bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metformin inhibits mTOR–HIF‐1α axis and profibrogenic and inflammatory biomarkers in thioacetamide‐induced hepatic tissue alterations
Authors: Al‐Hashem Fahaid , Al‐Humayed Suliman , Amin Shaimaa N. , Kamar Samaa S. , Mansy Soheir S. , Hassan Sarah , Abdel‐Salam Lubna O. , Ellatif Mohamed Abd , Alfaifi Mohammed , Haidara Mohamed A. , Al‐Ani Bahjat 
Published: October 2018

AbstractThe potential inhibitory effect of the antidiabetic and anti‐inflammatory drug, metformin on thioacetamide (TAA)‐induced hepatotoxicity associated with the inhibition of mammalian target of rapamycin (mTOR)–hypoxia‐inducible factor‐1α (HIF‐1α) axis has not been investigated before. Therefore, we tested whether metformin can protect against liver injuries including fibrosis induced by TAA possibly via the downregulation of mTOR–HIF‐1α axis and profibrogenic and inflammatory biomarkers. Rats either injected with TAA (200 mg/kg; twice a week for 8 weeks) before being killed after 10 weeks (model group) or were pretreated with metformin (200 mg/kg) daily for 2 weeks before TAA injections and continued receiving both agents until the end of the experiment, at Week 10 (protective group). Using light and electron microscopy examinations, we observed in the model group substantial damage to the hepatocytes and liver tissue such as collagen deposition, infiltration of inflammatory cells, and degenerative cellular changes with ballooned mitochondria that were substantially ameliorated by metformin. Metformin also significantly (
p < 0.05) inhibited TAA‐induced HIF‐1α, mTOR, the profibrogenic biomarker α‐smooth muscle actin, tissue inhibitor of metalloproteinases‐1, tumor necrosis factor‐α (TNF‐α), interleukin‐6 (IL‐6), alanine aminotransferase (ALT) and aspartate aminotransferase in harvested liver homogenates and blood samples. In addition, a significant (
p < 0.01) positive correlation between hypoxia scoring (HIF‐1α) and the serum levels of TNF‐α (
r = 0.797), IL‐6 (
r = 0.859), and ALT (
r = 0.760) was observed. We conclude that metformin protects against TAA‐induced hepatic injuries in rats, which is associated with the inhibition of mTOR–HIF‐1α axis and profibrogenic and inflammatory biomarkers; thus, may offer therapeutic potential in humans.
Using theory of change frameworks to develop evaluation strategies for research engagement: results of a pre‐pilot study
Authors: MacQueen Kathleen M , Eley Natalie T , Frick Mike , Hamilton Carol 
Published: October 2018

AbstractIntroductionInadequate community and stakeholder engagement can lead to accusations that research is unethical and can delay or slow research or translation of results to practice. Such experiences have led major funders as well as regulatory and advisory bodies to establish minimal requirements for community and stakeholder engagement in HIV and other clinical research. However, systematic efforts to formally evaluate the contributions and impact of particular practices are lacking.MethodsA theory of change framework aligned with Good Participatory Practice for TB clinical trials was used to develop a set of measures for use in a minimally burdensome survey of trial implementing sites. The survey was pre‐piloted with three TB trial sites in North America, South America and Asia to assess the feasibility of surveying global research sites in a systematic way, and to see if the measures captured informative variation in the use of engagement strategies and desired outcomes. Surveys were conducted at baseline and six months. In‐depth interviews were conducted with site staff prior to the baseline survey to understand how sites conceptualized the concepts underlying the framework and the extent to which they viewed their work as aligned with the framework.ResultsSurvey measures captured considerable variability in the intensity and variety of engagement strategies, both across sites and within sites over time, and moderate variability in outcomes. Interviews indicated that underlying concepts were often unfamiliar to staff at baseline, but the goals of engagement aligned well with existing values.ConclusionsBrief, targeted surveys of trial sites to characterize use of broad strategies, specific practices and some outcomes are a feasible option for evaluating good participatory practice. Additional testing is warranted to assess and enhance validity, reliability and predictive value of indicators. Options for collecting outcome measures through additional objective means should be explored.
Village community mobilization is associated with reducedHIVincidence in young South African women participating in theHPTN068 study cohort
Authors: Lippman Sheri A , Leddy Anna M , Neilands Torsten B , Ahern Jennifer , MacPhail Catherine , Wagner Ryan G , Peacock Dean , Twine Rhian , Goin Dana E , Gómez‐Olivé F Xavier , Selin Amanda , Tollman Stephen M , Kahn Kathleen , Pettifor Audrey 
Published: October 2018

AbstractIntroductionAdolescent girls and young women (AGYW) in South Africa bear a disproportionate burden ofHIV. Community mobilization (CM), defined as community members taking collective action to achieve a common goal related to health, equity and rights, has been associated with increasedHIVtesting and condom use and has been called a ‘critical enabler’ for addressing theHIVepidemic. However, limited research has examined whetherCMis associated withHIVincidence amongAGYW.MethodsWe examine the association ofCMwith incidentHIVamongAGYW(ages 13 to 21) enrolled in theHPTN068 cohort in the Agincourt Health and socio‐Demographic Surveillance System, South Africa. This analysis includes 2292 participants residing in 26 villages where cross‐sectional, population‐based surveys were conducted to measureCMamong 18‐ to 35‐year‐old residents in 2012 and 2014.HPTN068 participants completed up to five annual visits that included anHIVtest (2011 to 2016). Household‐level data were collected fromAGYWparents/guardians and census data is updated annually. Mean village‐levelCMscores were created using a validated community mobilization measure with seven components (social cohesion, social control, critical consciousness, shared concerns, organizations and networks, leadership and collective action). We used pooled generalized estimating equation regression with a Poisson distribution to estimate risk ratios (RR) for the association of village‐levelCMscore andCMcomponents with incidentHIVinfection, accounting for village‐level clustering and adjusting for key covariates.ResultsThere were 194 incident infections over the follow‐up period. For every additional standard deviation of village‐levelCMthere was 12% lowerHIVincidence (RR: 0.88, 95%CI: 0.79, 0.98) after adjusting for individual, household and community characteristics.CMcomponents associated with lowerHIVincidence included critical consciousness (RR: 0.88;CI: 0.79, 0.97) and leadership (RR: 0.87;CI: 0.79, 0.95); while not statistically significant, social cohesion (RR: 0.91;CI: 0.81, 1.01), shared concerns (RR: 0.90;CI: 0.81, 1.00), and organizations and networks (RR: 0.91;CI: 0.79, 1.03) may also play a protective role.ConclusionsThese results suggest that having strong community social resources will reduceAGYW's risk ofHIVacquisition. Work to mobilize communities, focusing on building social cohesion, shared concerns, critical consciousness, and effective and accountable leadership, can fortify prevention programming forAGYW.
Synthesis, Characterization, and Evaluation of Surface and Thermal Properties and Cytotoxicity of 2‐Hydroxy‐3‐Phenoxypropyl Imidazolium Bola‐Type Gemini Amphiphiles
Authors: Aggarwal Rajni , Singh Sukhprit , Saini Vedangana , Kaur Gurcharan 
Published: October 2018

AbstractA library of imidazolium‐based gemini cationic bola amphiphiles was synthesized using a regioselective ring‐opening reaction of glycidyl phenyl ether with imidazole under solvent‐free conditions. The corresponding hexafluorophosphate (PF6−) and tetrafluoroborate (BF4−) counterion‐containing amphiphiles were also synthesized and characterized using nuclear magnetic resonance (NMR) and mass spectroscopy. The micellar and interfacial parameters like the critical micelle concentration (CMC), surface pressure at the CMC (Пcmc), surface tension at CMC (
γcmc), counterion binding (β), maximum surface excess concentration (
Γmax), minimum area per molecule (
Amin), standard free energy of micellization () and adsorption (), and Kraft temperature were evaluated using surface tension and conductometry methods in aqueous solution as well as in buffer solution. Dynamic light scattering (DLS) was used to determine the size of the micelles formed in the aqueous solution. Cytotoxicity tests were carried out on the C6 glioma cancerous brain cell line using the MTT assay (3‐(4, 5‐dimethylthiazole‐2‐yl)‐2, 5‐diphenyltetrazolium bromide) to evaluate the IC50 value of all the synthesized amphiphiles. Thermal stability of these amphiphiles was also evaluated using a thermal gravimetric analyzer (TGA). Economic way of synthesis, moderate thermal stability, a low value of CMC, and cytotoxicity of these amphiphiles will inspire new research in the field of nanobiotechnology and pharmaceutical industries.
A Breakthrough for Fiber Lasers
Authors: Kliner Dahv A. V. , Victor Brian 
Published: October 2018

AbstractThe sheet metal cutting market is dominated by fiber lasers because of their unmatched combination of productivity, precision, and cost‐effectiveness. Fiber lasers in the 2 – 4 kW range have become the workhorses for many fabrication shops, offering faster and more precise cutting of thin metal than legacy cutting technologies, such as CO2 lasers and plasma torches. Many fiber laser systems are, however, designed for cutting a limited range of metal thicknesses. Specifically, a small, tightly focused laser beam provides the fastest cutting speeds for thin gauges, but for thicker plates this small beam has significant limitations in edge quality and maximum thickness. Alternatively, a larger beam can improve the edge quality for thick plate because of the wider kerf, but with a substantial speed penalty for cutting thin sheet.
ALDH2 Polymorphism rs671, but Not ADH1B Polymorphism rs1229984, Increases Risk for Hypo‐HDL‐Cholesterolemia in a/a Carriers Compared to the G/G Carriers
Authors: Imatoh Takuya , Yengo Loic , Rocheleau Ghislain , Kamimura Seiichiro , Maeda Shiro , Miyazaki Motonobu , Froguel Philippe 
Published: October 2018

AbstractIt has been reported that polymorphisms within the gene‐encoding enzymes related to alcohol metabolism are associated with levels of serum HDL‐cholesterol (HDL‐C) in East Asian populations. We evaluated the effects of genetic variants within the aldehyde dehydrogenase‐2 (ALDH2) gene and the alcohol dehydrogenase‐1B (ADH1B) gene on changes in the lipid profile in an 11‐year longitudinal study. We genotyped rs1229984 within ADH1B and rs671 within ALDH2. We combined the genetic data with longitudinal clinical and biochemical data from 2002 to 2013 and designed a retrospective longitudinal study of 1436 Japanese males. There were significant negative relationships between rs671 within ALDH2 and HDL‐C levels according to multiple linear regression analysis. Next, we assessed the association between the development of hypo‐HDL cholesterolemia and rs1229984 within ADH1B or rs671 within ALDH2. In logistic regression analysis, rs671 A allele homozygote carriers have 2.65 times higher risk of developing hypo‐HDL cholesterolemia than G allele homozygote carriers. Even after adjusting for possible confounding factors, a significant association was observed. However, no association between rs1229984 within ADH1B and the development of hypo‐HDL cholesterolemia was observed. Rs671 within ALDH2 but not rs1229984 within ADH1B was associated with lower HDL‐C levels in Japanese males.
Schweinfurthins: Lipid Modulators with Promising Anticancer Activity
Authors: Koubek Emily J. , Weissenrieder Jillian S. , Neighbors Jeffrey D. , Hohl Raymond J. 
Published: October 2018

AbstractThe schweinfurthin family of compounds displays exciting potent and differential cytotoxicity against human cancer cell lines. Currently, the effect of schweinfurthins on tumor development and progression is being explored in animal models of cancer with promising results. The first schweinfurthin family member, vedelianin, was isolated in 1992, followed by other schweinfurthins in 1998. This opened up the door for the synthesis of additional analogs. At present, the focus of research lies on delineating the mechanism of schweinfurthin action and identifying the nature of sensitivity. It appears that many of the intracellular effects of schweinfurthins are due to, or impacted by, the effect of schweinfurthins on lipid metabolism, synthesis, and homeostasis. These effects include impaired trafficking from the trans‐golgi network, disruption of lipid rafts, changes in oxysterol‐binding protein activity, and interference with the isoprenoid biosynthesis pathway (IBP). Cancer cells are known to rely heavily on fatty acid, lipid, and sterol synthesis for growth and proliferation. Therefore, compounds that target these needs, such as schweinfurthins, display promise as novel therapeutics. This timely review will take an in‐depth look at the history of schweinfurthins, their synthesis, where the research presently stands, and the questions that remain.
Detection of Endogenous Phosphatidylinositol 4,5–bisphosphate in Phytophthora cinnamomi
Authors: Howard Jeff M. , Beech Peter L. , Callahan Damien L. 
Published: October 2018

AbstractPlant diseases caused by Phytophthora species are serious threats to agriculture and the natural environment. Genome sequencing has revealed the lack of a gene for canonical phospholipase C (PLC), an enzyme that was hitherto thought to be ubiquitous in eukaryotes. PLC acts in the hydrolysis of phosphatidylinositol 4,5–bisphosphate (PtdIns‐4,5‐P2), a membrane‐bound phospholipid critical for signal initiation in many cellular processes. Previous studies have not provided evidence of endogenous PtdIns‐4,5‐P2 in Phytophthora and, in the absence of canonical PLC, argued for redundancy or loss in the PLC pathway in Phytophthora. Using liquid chromatography mass spectrometry, we have detected endogenous PtdIns‐4,5‐P2 in Phytophthora cinnamomi. This is the first identification of the phospholipid in the genus, and is significant because it indicates that the signal transduction pathway of the PLC product, inositol 1,4,5‐trisphosphate (IP3), may have been retained in Phytophthora incorporating an as‐yet unidentified homolog or analog of PLC.
Prairie Lakes: Model Systems for Integrating Ecology and Human Dimensions for Better Management
Authors: Nanayakkara Lushani 
Published: October 2018

AbstractSuccessfully managing the impacts of changing environmental conditions on complex socio‐ecological systems requires identifying, quantifying, and understanding the multitude of threats facing such systems. Research that transcends disciplinary boundaries is the best means of accomplishing this task. This article discusses key findings of previous studies conducted in the prairie region of Saskatchewan, Canada, the multitude of threats facing lake ecosystems, and the need to consider human dimensions to effectively address these issues.
Polymer Brush Decorated MOF Nanoparticles Loaded with AIEgen, Anticancer Drug, and Supramolecular Glue for Regulating and In Situ Observing DOX Release
Authors: Chen Shuai , Chen Qixian , Dong Shuqi , Ma Jianbiao , Yang Ying‐Wei , Chen Li , Gao Hui 
Published: October 2018

AbstractUiO‐66‐based metal–organic framework nanoparticles functionalized with abundant polycationic segments as polymer brushes on surface are created to load negatively charged functional entities composed of anticancer drug, doxorubicin (DOX), and aggregation‐induced emissive luminogen, a tetraphenylethene (TPE) derivative, followed by further modification with cucurbit[7]uril (CB[7]) as a supramolecular glue with the aim of pursuing a pH‐responsive release function of the loaded functional components. The subsequent investigations verified the constructed formulation capable of promoting the stability and cellular uptake of the nanoparticles. The fluorescence resonance energy transfer between TPE donor and DOX acceptor enables in situ observation of pH‐responsive DOX release. Significantly, CB modification appears to facilitate intracellular release of the DOX payload, eventually accounting for potent cytotoxicity to the treated cells.
Did California Paid Family Leave Impact Infant Health?
Authors: Pihl Ariel Marek , Basso Gaetano 
Published: October 2018

AbstractThe effects of paid parental leave policies on infant health have yet to be established. In this paper we investigate these effects by exploiting the introduction of California Paid Family Leave (PFL), the first program in the U.S. that specifically provides working parents with paid time off for bonding with a newborn. We measure health using the full census of infant hospitalizations in California and a set of control states, and implement a differences‐in‐differences approach. Our results suggest a decline in infant admissions, which is concentrated among those causes that are potentially affected by closer childcare (and to a lesser extent breastfeeding). Other admissions that are unlikely to be affected by parental leave do not exhibit the same pattern.
Pandemic 2009 influenza A (H1N1)‐associated deaths among children in China: A retrospective analysis
Authors: Lu Zhiwei , Zheng Yuejie , He Yanxia , Chen Huizhong , Wang Heping , Cao Ling , Zhao Deyu , Ji Wei , Shang Yunxiao , Li Changchong , Chen Zhimin , Zhao Shunying , Nong Guangmin , Chen Qiang , Liu Enmei , Wan Chaomin , Wang Ying , Yang Tong , Wang Zhenhua , Deng Li , Lu Quan 
Published: October 2018

AbstractImportanceA cluster of influenza‐associated deaths occurred among children during pandemic 2009 influenza A (H1N1) in China, but the risk factors and causes for death have not been clarified.ObjectiveWe describe the clinical findings regarding 2009 influenza A (H1N1)‐associated pediatric deaths in China, including the risk factors for death.MethodsThe definition of 2009 influenza A (H1N1)‐associated pediatric death is death in a child who is younger than 14 years and has laboratory‐confirmed influenza. We collected data of total 810 hospitalized patients with 2009 influenza A (H1N1) infection from September 2009 to February 2010 in 17 hospitals across China. The clinical characteristics, laboratory abnormalities, and treatment course were retrospectively studied.ResultsOf the 810 patients hospitalized with 2009 influenza A (H1N1) infection, 19 (2.3%) died. Ten patients died from severe pneumonia and acute respiratory distress syndrome; eight died from encephalopathy/encephalitis; one died from secondary fungal meningitis. Patients who died were more likely than patients who survived to have neutrophilia, lymphopenia, elevated C‐reactive protein, and elevations of lactate dehydrogenase, creatine kinase, creatine kinase‐MB, aspartate aminotransferase and alanine aminotransferase. There were no significant differences in the median age, median time from onset of illness to admission, underlying chronic disease, and initiation of antiviral therapy within 48 hours of illness onset, between patients who died and those who survived.InterpretationThe risk factors for pediatric death associated with 2009 influenza A (H1N1) infection are different from those of seasonal influenza. The most common causes of death are viral pneumonia, acute respiratory distress syndrome, and encephalopathy/encephalitis.
Long‐term outcome of acute central nervous system infection in children
Authors: Chen Tianming , Liu Gang 
Published: October 2018

AbstractImportanceCentral nervous system infection is a severe illness in children. Little is known about the long‐term outcome in children with central nervous system infection of various etiologies.ObjectiveThe aims of this study were to investigate the long‐term outcomes of childhood acute central nervous system infection and to examine possible prognostic factors.MethodsOf 172 children who were treated for acute central nervous system infection from January 2009 through December 2009, 139 were eligible for follow‐up evaluations. A structured interview was conducted with the parents 3.8–4.7 years after hospital discharge. The global outcome was determined in all patients using the Pediatric Version of the Glasgow Outcome Scale–Extended. Clinical features of the acute episode were retrieved from medical records.ResultsThe outcome was favorable in 109 of 139 patients (78%), 38 (27%) were mildly impaired, six (4%) were moderately impaired, 14 (10%) were severely impaired and two (1%) were in a vegetative state. There were eight deaths. The most frequent symptoms were difficulty concentrating (16%), epilepsy (12%), limb paralysis (12%), memory impairment (10%), speech disorders (9%), irritability (9%). Significant risk factors for epilepsy included the presence of recurrent seizures or status epilepticus, the existence of pure spikes in the electroencephalogram, brain parenchyma abnormalities on neuroimaging and herpes simplex virus encephalitis (HSVE). A multivariate analysis identified three factors that were independently associated with poor outcome: coma, brain parenchyma abnormalities on neuroimaging and HSVE.InterpretationMost children with acute central nervous system infection experienced a favorable outcome 3.8–4.7 years after discharge from the hospital. Minor to severe disability persists in a high proportion of cases. Coma, brain parenchymal abnormalities on neuroimaging and HSVE may predict poor long‐term outcome.
The advances of genetics research on Hirschsprung's disease
Authors: Ke Juntao , Zhu Ying , Miao Xiaoping 
Published: October 2018

AbstractHirschsprung's disease (HSCR) is a rare and complex congenital disorder characterized by the absence of the enteric neurons in lower digestive tract with an incidence of 1/5 000. Affected infant usually suffer from severe constipation with megacolon and distended abdomen, and face long‐term complications even after surgery. In the last 2 decades, great efforts and progresses have been made in understanding the genetics and molecular biological mechanisms that underlie HSCR. However, only a small fraction of the genetic risk can be explained by the identified mutations in the previously established genes. To search novel genetic alterations, new study designs with advanced technologies such as genome/exome‐wide association studies (GWASs/EWASs) and next generation sequencing (NGS) on target genes or whole genome/exome, were applied to HSCR. In this review, we summaries the current development of the genetics researches on HSCR based on GWASs/EWASs and NGS, focusing on the newly discovered variants and genes, and their potential roles in HSCR pathogenesis.