bluuebunny/crossref_metadata_2025 huggingface dataset:
Hyperuricemia treatment in acute heart failure patients does not improve their long‐term prognosis: A propensity score matched analysis from the AHEAD registry
Authors: Pavlusova Marie , Jarkovsky Jiri , Benesova Klara , Vitovec Jiri , Linhart Ales , Widimsky Petr , Spinarova Lenka , Zeman Kamil , Belohlavek Jan , Malek Filip , Felsoci Marian , Kettner Jiri , Ostadal Petr , Cihalik Cestmir , Spac Jiri , Al‐Hiti Hikmet , Fedorco Marian , Fojt Richard , Kruger Andreas , Malek Josef , Mikusova Tereza , Monhart Zdenek , Bohacova Stanislava , Pohludkova Lidka , Rohac Filip , Vaclavik Jan , Vondrakova Dagmar , Vyskocilova Klaudia , Bambuch Miroslav , Dostalova Gabriela , Havranek Stepan , Svobodová Ivana , Dusek Ladislav , Spinar Jindrich , Miklik Roman , Parenica Jiri
Published: May 2019

Background

Hyperuricemia is associated with a poorer prognosis in heart failure (HF) patients. Benefits of hyperuricemia treatment with allopurinol have not yet been confirmed in clinical practice. The aim of our work was to assess the benefit of allopurinol treatment in a large cohort of HF patients.

Methods

The prospective acute heart failure registry (AHEAD) was used to select 3160 hospitalized patients with a known level of uric acid (UA) who were discharged in a stable condition. Hyperuricemia was defined as UA ≥500 μmoL/L and/or allopurinol treatment at admission. The patients were classified into three groups: without hyperuricemia, with treated hyperuricemia, and with untreated hyperuricemia at discharge. Two‐ and five‐year all‐cause mortality were defined as endpoints. Patients without hyperuricemia, unlike those with hyperuricemia, had a higher left ventricular ejection fraction, a better renal function, and higher hemoglobin levels, had less frequently diabetes mellitus and atrial fibrillation, and showed better tolerance to treatment with angiotensin‐converting enzyme inhibitors/angiotensin receptor blockers and/or beta‐blockers.

Results

In a primary analysis, the patients without hyperuricemia had the highest survival rate. After using the propensity score to set up comparable groups, the patients without hyperuricemia had a similar 5‐year survival rate as those with untreated hyperuricemia (42.0% vs 39.7%, P = 0.362) whereas those with treated hyperuricemia had a poorer prognosis (32.4% survival rate, P = 0.006 vs non‐hyperuricemia group and P = 0.073 vs untreated group).

Conclusion

Hyperuricemia was associated with an unfavorable cardiovascular risk profile in HF patients. Treatment with low doses of allopurinol did not improve the prognosis of HF patients.
Nonadherent behaviors among young women on adjuvant endocrine therapy for breast cancer
Authors: Wassermann Johanna , Gelber Shari I. , Rosenberg Shoshana M. , Ruddy Kathryn J. , Tamimi Rulla M. , Schapira Lidia , Borges Virginia F. , Come Steven E. , Meyer Meghan E. , Partridge Ann H.
Published: May 2019

Background

Young age is a known factor associated with suboptimal adherence to endocrine therapy (ET) for adjuvant breast cancer (BC) treatment. This study was aimed at assessing nonadherent behaviors and associated factors among young women with early‐stage hormone receptor–positive BC.

Methods

As part of a multicenter, prospective cohort of women with a diagnosis of BC at or under the age of 40 years, participants were surveyed 30 months after their diagnosis about adherent behaviors. Among those who reported taking ET, adherence was measured with a 3‐item Likert‐type scale: Do you ever forget to take your ET? If you feel worse when you take your ET, do you stop taking it? Did you take your ET exactly as directed by your doctor over the last 3 months? Women reporting at least 1 nonadherent behavior were classified as nonadherers. Variables with a P value <.20 were included in a multivariable logistic model.

Results

Among 384 women, 194 (51%) were classified as nonadherers. Univariate factors that retained significance in the multivariable model included educational level (odds ratio [OR], 0.50 for high vs low; P = .04), level of social support according to the Medical Outcome Study Social Support Survey (OR, 0.98 per 1 point; P = .01), and confidence with the decision regarding ET measured on a 0 to 10 numerical scale (OR, 0.63 for high vs low; P = .04).

Conclusions

Findings from this study could help to identify young patients at higher risk for nonadherence. Interventions adapted to the level of education and aimed at reinforcing support and patients' confidence in their decision to take ET could improve adherence and associated outcomes in this population.
Additive and interactive cumulative effects on boreal landbirds: winners and losers in a multi‐stressor landscape
Authors: Mahon C. Lisa , Holloway Gillian L. , Bayne Erin M. , Toms Judith D.
Published: May 2019

Stressors created by multiple resource industries can result in cumulative effects over time and space. Many studies have evaluated single stressors and assumed that cumulative effects can be understood by adding stressors together. However, there is growing evidence that interactive effects are important in structuring biological communities. We evaluated whether the effects of multiple stressors in the boreal forest (linear features, energy, forestry) combine additively or interactively by testing a candidate model set of 12 cumulative effects models of abundance for 27 landbird species. We fitted paired additive and interactive Generalized Additive Models and examined model predictions in the Athabasca Oil Sands Area of Alberta, Canada, and a theoretical no‐disturbance version of the study area. Of the 27 species examined, an additive disturbance model was the best for nine species, while an interactive disturbance model was the best for 11 species. In the current study area, disturbance models predicted strong increases in abundance for species associated with deciduous forest and open habitats (winning species) and moderate decreases for species associated with conifer forest (losing species). We found a 15% change in landbird community composition between the current study area, with 8.4% disturbance, and the theoretical no‐disturbance study area. Complex synergistic and antagonistic interactions among stressors were observed for 39% of landbird species, with the majority of interactions observed being synergistic. Stressors with relatively small disturbance areas, such as narrow linear disturbances, frequently interacted with other stressors to affect species’ responses, and energy sector stressors often had additive or interactive effects with forestry stressors. Interactive cumulative effects from multiple sectors will make it increasingly difficult for industry and land managers to manage impacts unless interactions among stressors are incorporated into cumulative effects assessments and regional land use planning processes.
Propagule pressure and genetic diversity enhance colonization by a ruderal species: a multi‐generation field experiment
Authors: Hovick Stephen M. , Whitney Kenneth D.
Published: May 2019

Colonization is a critical filter, setting the stage for short‐term and long‐term population success. Increased propagule pressure (e.g., more founding individuals) usually enhances colonization; however, this pattern may be driven by purely numeric effects, population genetic diversity effects, or both. To determine the independent and interactive effects of propagule pressure and genetic diversity, we conducted a seed addition experiment in the field using the ruderal annual Arabidopsis thaliana. Propagule pressure treatments spanned five levels, from 32 to 960 seeds per 0.25‐m2 plot. Founder populations were composed of one, four, or eight genotypes and exposed to ambient or reduced levels of interspecific competition. Genotype monocultures were included to quantify additive vs. non‐additive effects. Populations were followed for three generations, with abundance, population persistence and genotype retention (the proportion of introduced genotypes persisting over time) as the major response variables. Increased propagule pressure enhanced abundance immediately following introduction, particularly where nutrient availability was high and competition reduced. Greater propagule pressure also increased the likelihood of population persistence and genotype retention through three generations. However, most populations experienced rapid abundance declines over time, yielding no relationship between propagule pressure and third‐generation abundance across persisting populations. Under reduced competition, increased genetic diversity led to a marginal increase in persistence through the third generation that was more pronounced, and statistically significant, in low nutrient conditions. Genetic diversity did not affect persistence through the first generation, thus indicating that genetic diversity effects strengthened over time. Nevertheless, genotypic mixture populations fell short of expectations based on performance in monocultures (negative non‐additive effects). Increased genetic diversity was also associated with abundance declines, largely due to one particularly high‐performing genotype in the lowest diversity treatments (i.e., genotypic identity effects). Overall, our results indicate that increases in both propagule pressure and genetic diversity can enhance colonization success but are highly context dependent. They also highlight novel ways in which both factors can impact the retention of introduced genetic diversity over time. Our findings pinpoint the determinants of a fundamental population process and have key implications for applications where enhanced or suppressed colonization is desired, including ecological restoration and invasive species management.
Hydralazine and nitrates in the treatment of heart failure with reduced ejection fraction
Authors: Al‐Mohammad Abdallah
Published: May 2019

Hydralazine and nitrate combination was the first treatment that showed improved survival of patients with heart failure with reduced left ventricular ejection fraction (HFREF) in the Vasodilator Heart Failure Trial (V‐HeFT trial) in 1986. This showed a 34% reduction of mortality at 2 years of follow‐up in patients with advanced heart failure (New York Heart Association Class IV). The angiotensin‐converting enzyme inhibitor (ACEi), beta‐blockers, mineralocorticoid receptor antagonists, and most recently sacubitril–valsartan have superseded the combination of hydralazine and nitrates. However, the latter combination does have a place bridging the survival gap of Black patients with HFREF when added to their standard therapy. This was demonstrated in the African‐American Heart Failure Trial (A‐HeFT trial) in 2004 when the risk reduction in the Black patients was 43% compared with that in the placebo. This combination may have a potential use in patients with contraindications to the use of ACEi, angiotensin receptor blockers, and sacubitril–valsartan. This is suggested by both the European Society of Cardiology (ESC) Guidelines and the guidelines of the National Institute for Health and Care Excellence (NICE). In this perspective, the role of the combination of hydralazine and nitrates in the treatment of HFREF is reviewed through a synopsis of the evidence base consisting of three randomized controlled studies, several further analyses of subgroups within those trials, a systemic review, and two large observational studies of registry cohorts. The place of the combination in the treatment cascades proposed by heart failure guidelines of the ESC and NICE is explored. This perspective is to remind us of their appropriate roles, particularly given the findings of underuse of this combination in people of African ancestry in Europe.
Ruthenium‐Catalyzed C‐H Bond Activation/Arylation Accelerated by Biomass‐Derived Ligands
Authors: Binnani Chinky , Mandal Shyama Charan , Pathak Biswarup , Singh Sanjay K.
Published: May 2019

A variety of ligands are being explored extensively to achieve enhanced performance for ligand assisted C‐H bond activation/functionalization reactions. We explored here several readily available biomass‐derived ligands as effective additives to significantly enhance the catalytic activity of arene‐Ru(II) dimer for ortho C‐H bond arylation in a water‐based catalytic reaction. We achieved almost 7‐fold enhancement in the catalytic activity with [(η6‐p‐cymene)RuCl2]2 catalyst in the presence of levulinic acid ligand at 80 °C. Mass investigations revealed the in‐situ formation of a ruthenium‐levulinate complex, which presumably plays a crucial role in the formation of the important cycloruthenated intermediate by facilitating the initial activation of ortho C‐H bond of 2‐phenylpyridine. Density functional theoretical studies also inferred that the ligand assisted route is energetically more favorable, where the acetyl group is found to be involved in the deprotonation step.
Rose Hip Seed Oil: Methods of Extraction and Chemical Composition
Authors: Dąbrowska Mariola , Maciejczyk Ewa , Kalemba Danuta
Published: May 2019

Recently, there has been growing interest in the use of uncommon plant oils in the food and cosmetic industries. Oils obtained from Rosa canina L. and R. rubiginosa L. seeds are widespread on the market and recommended for pharmaceutical, cosmetic, and nutritional purposes. Both these oils are quite well investigated. However, Rosa L. genus includes numerous other species bearing fruits (hips) with seeds rich in active compounds. These rose species may also be a source of oil valuable for purposes above mentioned. Thus recent literature relating to rosehip seed oils, its extraction methods and composition are summarized to provide an overview of the published data on this subject. The goal of this article is to deliver necessary background with references for an up‐to‐date perspective of different rose species' seed oils, to review methods for their isolation, and thereby to compare oil extraction yield and composition.

Practical Applications: This review underscores the importance of rose hip seed oil as a product for healthier foods and other purposes.

Uncommon plant oils have recently gained popularity in the food and cosmetic industries. Oils obtained from Rosa canina and R. rubiginosa seeds are recommended for pharmaceutical, cosmetic, and nutritional purposes. Moreover, Rosa L. genus includes numerous other species' seeds rich in active compounds. Thus recent literature relating to rose hip seed oils, its extraction methods, and composition are summarized to provide an overview of the published data on this subject.
Synthesis of α‐Fluoroamides with a C–F Quaternary Stereogenic Center by Electrophilic Fluorination: One‐Pot Four‐Component Strategy
Authors: Krishna Swaroop Desireddy , Ravi Kumar Nagiri , Reddy Narra Srikanth , Punna Nagender , Jagadeesh Babu Nanubolu , Narsaiah Banda
Published: May 2019

An efficient method for the synthesis of α‐fluoroamides having C–F quaternary stereogenic center was achieved by a one‐pot four‐component strategy under mild reaction conditions. A variety of α‐fluoroamides was synthesized by using 1,3‐dicarbonyl, isocyanide, acetylenedicarboxylate and N‐fluorobenzenesulfonimide (NFSI) systems with good to excellent yields up to 93 %. The current protocol proceeds through the unstable 3‐fluoro 4H‐pyran intermediate, which is key for the reaction and further it can be hydrolyzed due to the high electronegativity of the fluorine atom to produce the desired α‐fluoroamides.
Palladium‐Catalyzed Decarboxylative Generation and Propargylation of 2‐Azaallyl Anions
Authors: Tang Shaojian , Wei Wenjing , Yin Dan , Poznik Michal , Chruma Jason J.
Published: May 2019

A palladium‐catalyzed decarboxylative propargylation (DcPg) of propargyl 2,2‐diphenylglycinate imines was developed. In this process, the nature of the propargyl ester and aryl imine components, as well as the catalyst system and solvent, had a significant impact on the ratio of desired propargylated products vs. allene and/or diene side products that arise via different modes of C–C bond formation. The resulting propargylated products can be transformed readily into useful (Z)‐homoallylic amines. Moreover, the regioisomeric diene products could be converted to pharmaceutically‐relevant diarylmethyl imines via a two‐step Diels‐Alder/oxidation process.
Improvement of lipid production in oleaginous yeast Rhodosporidium toruloides by ultraviolet mutagenesis
Authors: Guo Minrui , Cheng Shaobo , Chen Guogang , Chen Jiluan
Published: May 2019

The oleaginous yeast Rhodosporidium toruloides AS 2.1389 is viewed as desirable industrial microorganisms that can accumulate a high content of lipids for biodiesel production. In this study, we attempted to improve lipid accumulation in the yeast Rhodosporidium toruloides by UV irradiation mutagenesis and selection based on lithium chloride tolerance or ethanol–H2O2 tolerance. The biomass concentration, lipid yield and glucose consumption of mutant R. toruloides were determined. The transcription levels of lipid accumulation‐related genes in the wild‐type and mutant strains were also determined. The lithium chloride‐tolerant strain R‐ZL2 and the ethanol–H2O2‐resistant strain R‐ZY13 were generated by UV mutagenesis. The two mutant strains showed greater lipid productivity and lipid yield compared to the wild type. Transcriptional analysis revealed that IDP1, GPD1 and GND were expressed at significantly higher levels in the two high‐lipid‐producing mutants. In conclusion, lipid productivity and lipid yield in R. toruloides were successfully improved via UV mutagenesis and selection. We also identified some lipid accumulation‐related genes for improving lipid productivity through genetic engineering.
Effect of Supports on the Redox Performance of NiFe2O4 in a Chemical Looping Process
Authors: Ma Zhong , Zeng Dewang , Zhang Shuai , Xiao Rui
Published: May 2019

NiFe2O4 oxygen carrier (OC) presents higher oxygen carrying capacity than single metal oxides (NiO and Fe2O3). However, the redox ability of NiFe2O4 gets deactivated due to phase segregation. Herein, the investigation of the effect of supports (CeO2, CeZrO2, and ZrO2) on the phase stability and the redox performance of NiFe2O4 during the chemical looping (CL) process are presented. The structure of NiFe2O4‐based OCs is characterized using different characterization methods. The CL reaction is conducted in a fixed‐bed reactor at 900 °C under alternate 5% CO/N2 and 5% O2/N2 atmospheres. The results indicate that the redox performance and the phase stability of NiFe2O4‐based OCs are significantly affected by the supports. According to experimental results, CeO2 can improve the oxygen mobility of NiFe2O4. The CeO2–NiFe2O4 OC has the best performance in terms of both recyclability and phase stability during the redox cycles. The results show that CeO2–NiFe2O4 can reduce the tendency of Fe segregation due to the high concentration of oxygen vacancies. It can be reduced and reoxidized to the original crystalline phase of NiFe2O4. Nevertheless, the CeZrO2–NiFe2O4 and ZrO2–NiFe2O4 OCs have drawbacks related to serious sintering and phase segregation into Fe2O3.
Baseline Level of Hepatitis B Core Antibody Predicts Spontaneous Hepatitis B e Antigen (HBeAg) Seroconversion in HBeAg‐Positive Children With a Normal Alanine Aminotransferase Level
Authors: Chen Ho‐Sheng , Wu Jia‐Feng , Su Tung‐Hung , Chen Huey‐Ling , Hsu Hong‐Yuan , Xia Ning‐Shao , Chen Pei‐Jer , Chang Mei‐Hwei
Published: May 2019

It is not clear whether baseline hepatitis B core antibody (anti‐HBc) level in hepatitis B e antigen (HBeAg)‐positive children with a normal alanine aminotransferase (ALT) level is predictive of spontaneous HBeAg seroconversion. We investigated the correlation between anti‐HBc level and the natural course of chronic hepatitis B (CHB) virus (HBV) infection in children, particularly the ability of baseline anti‐HBc level to predict spontaneous HBeAg seroconversion during long‐term follow‐up. HBeAg‐positive children with untreated CHB and a normal ALT level were followed longitudinally. Anti‐HBc level was determined by double‐sandwich immunoassay. Effects of anti‐HBc levels and other parameters on spontaneous HBeAg seroconversion and the natural course of CHB were assessed. A total of 182 children (106 males) with a median age at enrollment of 10.6 years (interquartile range [IQR], 10.3‐15.3) were followed for a median of 19.8 years (IQR, 11.9‐21.9). Spontaneous HBeAg seroconversion occurred in 85 children (46.7%) during the follow‐up. A baseline anti‐HBc titer of >500 IU/mL (hazard ratio [HR] = 2.81), HBV genotype B and B + C (HR = 3.46), and a baseline hepatitis B surface antigen titer of ≤4.8 log10 IU/mL (HR = 3.09) were predictive of spontaneous HBeAg seroconversion, based on multivariable survival analysis (P < 0.001). In cases remaining HBeAg positive, their anti‐HBc levels increased gradually during follow‐up because of ongoing inflammation. Conclusion: Baseline anti‐HBc level is predictive of spontaneous HBeAg seroconversion in HBeAg‐positive children with a normal ALT level. Anti‐HBc level reflects anti‐HBV immune response in the HBeAg‐positive normal ALT phase of CHB.
The stipulation‐stimulation spiral: A model of system change
Authors: Kreindler Sara A.
Published: May 2019

This paper proposes a general model, based on what is known about the nature of (complex) systems, of how systems—in particular, health care systems—respond to attempted change. Inferences are drawn from a critical literature review and reinterpretation of two primary studies. The two fundamental system‐change approaches are “stipulation” and “stimulation”: stip(ulation) attempts to elicit a specific response from the system; stim(ulation) encourages the system to generate diverse responses. Each has a unique strength: stip's is precision, the ability to directly impact the desired outcome and only that outcome; stim's is resonance, the ability to take advantage of behavior already present within the system. Each approach's inherent strength is its complement's inherent weakness; thus, stip and stim often clash if attempted simultaneously but can reinforce each other if applied in alternation. Opposite patterns (the “stip‐stim spiral” vs “stip‐stim stalemate”) are observed to underpin successful vs failed system change: The crucial difference is whether decision‐makers respond to a need for precision/resonance by strengthening the appropriate approach (stipulation/stimulation, respectively), or merely by weakening its complement. With further validation, the model has the potential to yield a more fundamental understanding of why system‐change efforts fail and how they can succeed.
What, when, and who: Manager involvement in predicting employee resistance to acquisition integration
Authors: King David R. , Bauer Florian , (Derek) Weng Qingxiong , Schriber Svante , Tarba Shlomo
Published: May 2019

Applying sensemaking research to acquisition integration, we outline factors that influence employee resistance to acquisitions. While integration is widely viewed as important to acquisition outcomes, there is limited systematic study of how employees react to the integration process. Using survey data from Chinese acquirers and applying partial least squares structural equation modeling, we examine what changes with human and task integration with the speed of when changes are made to explore relationships with employee resistance. Consistent with a temporal perspective of acquisition processes and sensemaking we find slower task integration may mitigate employee resistance to acquisition integration. However, employee resistance to the speed that changes are made likely varies for who is involved, suggesting different roles for top and middle managers. Specifically, middle management involvement with slow human integration and top management involvement with fast task integration reduces employee resistance following an acquisition.
CYP3A4/5 mediates the metabolic detoxification of humantenmine, a highly toxic alkaloid from Gelsemium elegans Benth.
Authors: Sun Rongjin , Chen Minghao , Hu Yanxian , Lan Yao , Gan Lili , You Guoquan , Yue Min , Wang Hongmei , Xia Bijun , Zhao Jie , Tang Lan , Cai Zeng , Liu Zhongqiu , Ye Ling
Published: May 2019

Gelsemium elegans Benth., a well‐known toxic herbal plant, is widely used to treat rheumatic arthritis, inflammation and other diseases. Gelsemium contains humantenmine (HMT), which is an important bioactive and toxic alkaloid. Cytochrome P450 enzymes (CYPs) play important roles in the elimination and detoxification of exogenous substances. This study aimed to investigate the roles of CYPs in the metabolism and detoxification of HMT. First, metabolic studies were performed in vitro by using human liver microsomes, selective chemical inhibitors and recombinant human CYPs. Results indicated that four metabolites, including hydroxylation and oxidation metabolites, were found in human liver microsomes and identified based on their high‐resolution mass spectrum. The isoform responsible for HMT metabolism was mainly CYP3A4/5. Second, the toxicity of HMT on L02 cells in the presence of the nicotinamide adenine dinucleotide phosphate system (NADPH) was significantly less than that without NADPH system. A CYP3A4/5 activity inhibition model was established by intraperitoneally injecting ketoconazole in mice and used to evaluate the role of CYP3A4/5 in HMT detoxification. In this model, the 14‐day survival rate of the mice decreased to 17% after they were intragastrically treated with HMT, along with hepatic injury and increasing alanine aminotransferase (ALT) /aspartate aminotransferase (AST) levels. Overall, CYP3A4/5 mediated the metabolism and detoxification of HMT.
Downregulation of FGF Signaling by Spry4 Overexpression Leads to Shape Impairment, Enamel Irregularities, and Delayed Signaling Center Formation in the Mouse Molar
Authors: Marangoni Pauline , Charles Cyril , Ahn Youngwook , Seidel Kerstin , Jheon Andrew , Ganss Bernhard , Krumlauf Robb , Viriot Laurent , Klein Ophir D
Published: May 2019

FGF signaling plays a critical role in tooth development, and mutations in modulators of this pathway produce a number of striking phenotypes. However, many aspects of the role of the FGF pathway in regulating the morphological features and the mineral quality of the dentition remain unknown. Here, we used transgenic mice overexpressing the FGF negative feedback regulator Sprouty4 under the epithelial keratin 14 promoter (K14‐Spry4) to achieve downregulation of signaling in the epithelium. This led to highly penetrant defects affecting both cusp morphology and the enamel layer. We characterized the phenotype of erupted molars, identified a developmental delay in K14‐Spry4 transgenic embryos, and linked this with changes in the tooth developmental sequence. These data further delineate the role of FGF signaling in the development of the dentition and implicate the pathway in the regulation of tooth mineralization. © 2019 The Authors. JBMR Plus is published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.
Upregulation of microRNA‐196a improves cognitive impairment and alleviates neuronal damage in hippocampus tissues of Alzheimer's disease through downregulating LRIG3 expression
Authors: Yang Ke , Feng Shutao , Ren Jun , Zhou Wenbin
Published: May 2019

Purpose

This study is launched to uncover the inner function of microRNA‐196a (miR‐196a) on cognitive dysfunction and neuronal damage in Alzheimer's disease (AD) rats through regulating the PI3K/Akt signaling pathway.

Methods

The establishment of AD rat model was performed by a microinjection of Aβ25‐35. miR‐196a and LRIG3 expression was detected, and the putative binding site between them was also determined. The spatial learning and memory capability, the hippocampal neurons ultrastructure as well as the survival, and apoptosis of hippocampal neurons of rats were observed. The expression of apoptosis‐associated protein, oxidative stress index, and inflammatory factors as well as the PI3K/Akt pathway‐related factors was determined.

Results

Initially, decreased miR‐196a and increased LRIG3 were exhibited in hippocampus tissues of AD rats. In addition, restored miR‐196a and deleted LRIG3 ameliorated spatial learning and memory capability, suppressed the pathological injury, induced the survival, and suppressed the apoptosis of hippocampal neurons, as well as inhibited oxidative stress injury together with inflammatory injury in AD rats. Furthermore, upregulation of miR‐196a activated the PI3/Akt pathway in AD rats.

Conclusion

This current study suggests that upregulation of miR‐196a and downregulation of LRIG3 improve cognitive impairment and alleviate neuronal damage in hippocampus tissues in AD rats via the modulation of the PI3K/Akt pathway.
Neuropathological and genomic characterization of glioblastoma‐induced rat model: How similar is it to humans for targeted therapy?
Authors: Sharifzad Farzaneh , Yasavoli‐Sharahi Hamed , Mardpour Saeid , Fakharian Esmaeil , Nikuinejad Hassan , Heydari Yasaman , Mardpour Soura , Taghikhani Adeleh , khellat Reza , Vafaei Somayeh , Kiani Sahar , Ghavami Saeid , Łos Marek , Noureddini Mehdi , Ebrahimi Marzieh , Verdi Javad , Hamidieh Amir Ali
Published: May 2019

Glioblastoma multiforme (GBM) is a unique aggressive tumor and mostly develops in the brain, while rarely spreading out of the central nervous system. It is associated with a high mortality rate; despite tremendous efforts having been made for effective therapy, tumor recurrence occurs with high prevalence. To elucidate the mechanisms that lead to new drug discovery, animal models of tumor progression is one of the oldest and most beneficial approaches to not only investigating the aggressive nature of the tumor, but also improving preclinical research. It is also a useful tool for predicting novel therapies' effectiveness as well as side effects. However, there are concerns that must be considered, such as the heterogeneity of tumor, biological properties, pharma dynamic, and anatomic shapes of the models, which have to be similar to humans as much as possible. Although several methods and various species have been used for this approach, the real recapitulation of the human tumor has been left under discussion. The GBM model, which has been verified in this study, has been established by using the Rat C6 cell line. By exploiting bioinformatic tools, the similarities between aberrant gene expression and pathways have been predicted. In this regard, 610 common genes and a number of pathways have been detected. Moreover, while magnetic resonance imaging analysis enables us to compare tumor features between these two specious, pathological findings provides most of the human GBM characteristics. Therefore, the present study provides genomics, pathologic, and imaging evidence for showing the similarities between human and rat GBM models.
Pathophysiology of propionic and methylmalonic acidemias. Part 1: Complications
Authors: Haijes Hanneke A. , Jans Judith J. M. , Tas Simone Y. , Verhoeven‐Duif Nanda M. , van Hasselt Peter M.
Published: May 2019

Over the last decades, advances in clinical care for patients suffering from propionic acidemia (PA) and isolated methylmalonic acidemia (MMA) have resulted in improved survival. These advances were possible thanks to new pathophysiological insights. However, patients may still suffer from devastating complications which largely determine the unsatisfying overall outcome. To optimize our treatment strategies, better insight in the pathophysiology of complications is needed. Here, we perform a systematic data‐analysis of cohort studies and case‐reports on PA and MMA. For each of the prevalent and rare complications, we summarize the current hypotheses and evidence for the underlying pathophysiology of that complication. A common hypothesis on pathophysiology of many of these complications is that mitochondrial impairment plays a major role. Assuming that complications in which mitochondrial impairment may play a role are overrepresented in monogenic mitochondrial diseases and, conversely, that complications in which mitochondrial impairment does not play a role are underrepresented in mitochondrial disease, we studied the occurrence of the complications in PA and MMA in mitochondrial and other monogenic diseases, using data provided by the Human Phenotype Ontology. Lastly, we combined this with evidence from literature to draw conclusions on the possible role of mitochondrial impairment in each complication. Altogether, this review provides a comprehensive overview on what we, to date, do and do not understand about pathophysiology of complications occurring in PA and MMA and about the role of mitochondrial impairment herein.
A one‐port automatic fixture removal method for de‐embedding
Authors: Xie Chengcheng , Xu Ruimin
Published: May 2019

Traditional calibration methods and measurement‐based de‐embedding processes require the design of calibration kits and measurement standards, and the processes are cumbersome and costly. Even the simple automatic fixture removal (AFR) with 2x‐through fixtures still needs a through line to extract the fixtures' characteristics, and there are some restrictions. With one‐port AFR (1xAFR), the open fixture's time domain response (TDR) could be gated and windowed, then extracted to fixture's through S‐parameter. When the fixture is connected to device under test (DUT), its response could be de‐embedded from the blended S‐parameter and the DUT's S‐parameter could be obtained. In this paper, the basic principle and extraction process of 1xAFR are described, and two measurement cases are demonstrated to verify 1xAFR's ease of use and accuracy.
Physical exercise and human adipose‐derived mesenchymal stem cells ameliorate motor disturbances in a male rat model of Parkinson's disease
Authors: Cucarián Jaison D. , Berrío Jenny P. , Rodrigues Cristiano , Zancan Mariana , Wink Márcia R. , de Oliveira Alcyr
Published: May 2019

Parkinson's disease (PD) is a disabling and highly costly neurodegenerative condition with worldwide prevalence. Despite advances in treatments that slow progression and minimize locomotor impairments, its clinical management is still a challenge. Previous preclinical studies, using mesenchymal stem cell (MSC) transplantation and isolated physical exercise (EX), reported beneficial results for treatment of PD. Therefore, this experimental randomized study aimed to elucidate the therapeutic potential of combined therapy using adipose‐derived human MSCs (ADSCs) grafted into the striatum in conjunction with aerobic treadmill training, specifically in terms of locomotor performance in a unilateral PD rat model induced by 6‐hydroxydopamine (6‐OHDA). Forty‐one male Wistar rats were categorized into five groups in accordance with the type of treatment to which they were subjected (Sham, 6‐OHDA − injury, 6‐OHDA + exercise, 6‐OHDA + cells, and 6‐OHDA + combined). Subsequently, dopaminergic depletion was assessed by the methylphenidate challenge and the specified therapeutic intervention was conducted in each group. The foot fault task was performed at the end of the experiment to serve as an assessment of motor skills. The results showed that despite disturbances in motor balance and coordination, locomotor dysfunction was ameliorated in all treatment categories in comparison to the injury group (sign test, p < 0.001, effect size: 0.71). The exercise alone and combined groups were the categories that exhibited the best recovery in terms of movement performance (p < 0.001). Overall, this study confirms that exercise is a powerful option to improve motor function and a promising adjuvant intervention for stem cell transplantation in the treatment of PD motor symptoms.

Open Practices

This article has been awarded Open Data. All materials and data are publicly accessible at https://figshare.com/s/18a543c101a17a1d5560. Learn more about the Open Practices badges from the Center for Open Science: https://osf.io/tvyxz/wiki.
Comparison between the active tropical cyclone seasons over the Arabian Sea and Bay of Bengal
Authors: Sattar Abdus M. , Cheung Kevin K. W.
Published: May 2019

Climatologically, tropical cyclone (TC) activity in the North Indian Ocean (NIO) is asymmetric between the Arabian Sea (AS) and Bay of Bengal (BoB) basin. For the 172 TCs formed over NIO during 1983–2015, only 56 formed over AS and the rest (116) over BoB. During the period, AS was very active in a few years (but with quiet BoB season), and the opposite occurred in some others. It is found that this contrast occurred mostly during the post‐monsoon season of October–December. The meteorological and climate factors that accounted for these contrasting AS and BoB TC seasons are analysed. While climate variability such as the El Niño Southern Oscillation and Indian Ocean Dipole have known influences to NIO TC activity, results reveal that no single climate mode can well explain the TC development concentrating on AS or BoB only. Instead, it is found that variability of the northeast monsoon is an important factor responsible for the difference between the two basins. Excess moisture is available over the AS due to anomalous low‐level flow from the equatorial IO in the years in which there are more TCs in that basin, and dryer condition is over the BoB. In these years, there is likely excess northeast monsoon rainfall. The relationship is opposite between post‐monsoon BoB TC activity and the northeast monsoon. Nevertheless, the anomalous flow during active AS TC seasons is similar to that occurs during positive Indian Ocean Dipole, and thus this climate variability may be responsible for redistributing the moisture content in the NIO.
Subdividing the Holocene Series/Epoch: formalization of stages/ages and subseries/subepochs, and designation of GSSPs and auxiliary stratotypes
Authors: WALKER MIKE , Head Martin J. , Lowe John , Berkelhammer Max , BjÖrck Svante , Cheng Hai , Cwynar Les C. , Fisher David , Gkinis Vasileios , Long Antony , Newnham Rewi , Rasmussen Sune Olander , Weiss Harvey
Published: May 2019

The Holocene, which currently spans ~11 700 years, is the shortest series/epoch within the geological time scale (GTS), yet it contains a rich archive of evidence in stratigraphical contexts that are frequently continuous and often preserved at high levels of resolution. On 14 June 2018, the Executive Committee of the International Union of Geological Sciences formally ratified a proposal to subdivide the Holocene into three stages/ages, along with their equivalent subseries/subepochs, each anchored by a Global boundary Stratotype Section and Point (GSSP). The new stages are the Greenlandian (Lower/Early Holocene Subseries/Subepoch) with its GSSP in the Greenland NGRIP2 ice core and dated at 11 700 a b2k (before 2000 CE); the Northgrippian (Middle Holocene Subseries/Subepoch) with its GSSP in the Greenland NGRIP1 ice core and dated at 8236 a b2k; and the Meghalayan (Upper/Late Holocene Subseries/Subepoch) with its GSSP in a speleothem from Mawmluh Cave, north‐eastern India, with a date of 4250 a b2k. We explain the nomenclature of the new divisions, describe the procedures involved in the ratification process, designate auxiliary stratotypes to support the GSSPs and consider the implications of the subdivision for defining the Anthropocene as a new unit within the GTS.
A combined fuzzy multicriteria decision‐making approach for evaluating hospital website quality
Authors: Perçin Selçuk
Published: May 2019

Developments in the health care industry in the last decade have forced companies to improve their website quality with the goal of attaining a sustainable competitive advantage through e‐business models. Here, we evaluate and measure the website quality of hospitals while considering the interactions among evaluation criteria. For this purpose, the fuzzy decision making trial and evaluation laboratory (DEMATEL) method, which copes with the interactions among the evaluation criteria, is presented. In addition, the generalized Choquet fuzzy integral (GCFI), non‐additive information fusion technique, is proposed to aggregate the experts' preferences and to calculate the overall website quality of hospitals. Finally, a sensitivity analysis is used to observe the changes in evaluation results of hospitals when assigning different weight combinations to the evaluation criteria. The proposed model is the first to evaluate the website quality of hospitals operating in Turkey.
Telomerase insufficiency induced telomere erosion accumulation in successive generations in dyskeratosis congenita family
Authors: He Caixia , Jing Shuang , Dai Congling , Tu Chaofeng , Tan Zhenhua , Du Juan , Lu Guang‐Xiu , Lin Ge , Zeng Sicong
Published: May 2019

Background

Dyskeratosis congenita (DC) is a rare heritable bone marrow failure syndrome that is associated with telomere dysfunction, and has high genetic heterogeneity and varied features.

Objective

This study aimed to identify the underlying genetic etiology of a DC family with more severe symptoms in the younger generation and to explore the relationship between the genetic causes and the severity of DC phenotype.

Methods

Whole‐exome sequencing was performed on the proband to screen the candidate causative gene. The protein structure was then predicted by SWISS‐MODEL software. Telomere length (TL) assay was performed on family members along with large‐scale population controls. The prenatal diagnosis (PND) was performed on the fetus of parents with secondary pregnancy.

Results

Novel heterozygous mutations in TERT (NM_198253.2), c.1796G>A (p.Arg599Gln), c.2839T>C (p.Ser947Pro), and c.3346G>C (p.Glu1116Gln) were identified in the proband. His TL was below the first percentile of the peers, which also appeared on the fetus with epidermal dyskeratosis through PND. The TL data of large‐scale population and members of the DC family implied the accumulation of telomere erosion in successive generations in this family.

Conclusions

Our study identified three clinical pathologic TERT mutations and implied that telomere erosion might be accumulated through successive generations, contributing to the severity of DC in the younger generation.
Identification of the Apoptosis and Autophagy Bi‐functional Proteins
Authors: Wang Peiran , Zhang Zhichao
Published: May 2019

Although autophagy and apoptosis, two main kinds of programmed cell death, constitute distinct cellular processes with often opposing outcomes, there have been shown a complex interplay between them in recent years. This interplay is surely critical to the overall fate of the cell. However, a full‐scale identification of those bi‐functional proteins involved in both functions is currently beyond reach by existing databases or traditional biological experiments. And that makes the interplay impossible to be well understood. Here we built a large, comprehensiveness apoptosis and autophagy related PPI (protein‐protein interaction) network and then used topology clustering to undergo a network analysis workflow. Finally, we concluded a list of 151 apoptosis and autophagy bi‐functional proteins from this network. By this way we showed a global view on these bi‐functional proteins about their unique characteristics and provided clues of new functions of some proteins which are not focused in present researches.
People with type 2 diabetes struggling for self‐management: A part study from the randomized controlled trial in RENEWING HEALTH
Authors: Ribu Lis , Rønnevig Marit , Corbin Juliet
Published: May 2019

Aim

To develop a theoretical explanation for the daily life problems and challenges perceived by those living with type 2 diabetes.

Design and methods

We used a grounded theory approach with a constant comparative method to discover a framework with the core concept of struggling between “ought to do” and “want to do” and related concepts.

Results

The struggle to self‐manage and maintain new habits can be more or less difficult depending on the patient's perceived conditions. We identified three situations illustrated in a diagram: one where there is less struggle to let go of old habits, a second where there is more of a struggle to balance between what individuals want to do and what they ought to do and a third where they are giving up struggling. Study findings show that healthcare personnel must consciously seek to understand how patients perceive their own situation.
Daily Self‐Weighing to Prevent Holiday‐Associated Weight Gain in Adults
Authors: Kaviani Sepideh , vanDellen Michelle , Cooper Jamie A.
Published: May 2019

Objective

Holiday weight gain is reported to be 0.4 to 1.5 kg and may contribute to annual weight gain. The objective of this study was to test the efficacy of daily self‐weighing (DSW) using visual graphical feedback (GF) to prevent holiday weight gain.

Methods

A total of 111 adults were randomly assigned into a control or DSW + GF group and completed the preholiday visit (v1; before Thanksgiving), the postholiday visit (v2; after New Year’s Day), and the follow‐up visit (v3; 14 weeks after v2). The participants in the DSW + GF group performed DSW with Wi‐Fi scales during the holidays and were told to try not to gain weight above baseline weight.

Results

There was no change in weight with DSW + GF, whereas the control group gained weight from v1 to v2 (−0.13 ± 0.27 kg vs. 2.65 ± 0.33 kg, P < 0.001, respectively). In the control group, weight change was similar between individuals with overweight or obesity (OW/OB) versus individuals with normal weight (2.71 ± 0.48 kg vs. 2.62 ± 0.43 kg, not significant, respectively). For DSW + GF, individuals with OW/OB lost weight whereas those with normal weight maintained weight during the holidays (−1.46 ± 0.62 kg vs. 0.33 ± 0.27 kg, P = 0.01, respectively). The control group lost weight during the follow‐up (−1.14 ± 0.43 kg, P = 0.01; v2 to v3) but retained 57% of weight gain; therefore, weight gain from v1 to v3 was significant (1.51 ± 0.39 kg, P < 0.001).

Conclusions

DSW + GF was a successful approach to prevent holiday weight gain, with those with OW/OB responding most favorably to DSW + GF.
Histidine‐rich glycoprotein augments natural killer cell function by modulating PD‐1 expression via CLEC‐1B
Authors: Nishimura Yoshito , Wake Hidenori , Teshigawara Kiyoshi , Wang Dengli , Sakaguchi Masakiyo , Otsuka Fumio , Nishibori Masahiro
Published: May 2019

Augmentation of natural killer (NK) cell cytotoxicity is one of the greatest challenges for cancer immunotherapy. Although histidine‐rich glycoprotein (HRG), a 75‐kDa glycoprotein with various immunomodulatory activities, reportedly elicits antitumor immunity, its effect on NK cell cytotoxicity is unclear. We assessed NK cell cytotoxicity against K562 cells. We also measured concentrations of cytokines and granzyme B in the cell supernatant. The proportion of CD56bright NK cells and NK cell surface PD‐1 expression was assessed with flow cytometry. The neutralizing effects of anti‐C‐type lectin‐like receptor (CLEC) 1B against HRG were also measured. NK cell morphological changes were analyzed via confocal microscopy. HRG significantly increased NK cell cytotoxicity against K562 cell lines. HRG also increased the release of granzyme B and the proportion of CD56bright NK cells. Further, HRG was able to decrease NK cell surface PD‐1 expression. The effects of HRG on NK cells were reversed with anti‐CLEC‐1B antibodies. Additionally, we confirmed NK cell nuclear morphology and F‐actin distribution, which are involved in the regulation of cytotoxic granule secretion. Because both PD‐1 and CLEC‐1B are associated with prognosis during malignancy, HRG incorporates these molecules to exert the antitumor immunity role. These facts indicate the potential of HRG to be a new target for cancer immunotherapy.