bluuebunny/crossref_metadata_2025 huggingface dataset:
The Application of a Continuous Grignard Reaction in the Preparation of Fluconazole
Authors: Korwar Sudha , Amir Somi , Tosso Perrer N. , Desai Bimbisar K. , Kong Caleb J. , Fadnis Swara , Telang Nakul S. , Ahmad Saeed , Roper Thomas D. , Gupton B. Frank
Published: September 2017

The application of continuous methods in the synthesis of active pharmaceutical ingredients continues to receive significant attention in the academic as well as the industrial research communities. One of the major advantages of continuous methods is the ability to safely access kinetic synthons as well as highly reactive reagents that are typically unavailable through traditional batch methods. In this work, we report the high‐yielding, clean formation of an aryl‐turbo Grignard and its selective addition to a highly‐enolizable 1,3‐dichloroacetone, for the continuous synthesis of a key intermediate for fluconazole, a widely‐prescribed anti‐fungal agent. In addition, process optimization of the final API was also carried out to arrive at a semi‐continuous method to this essential medicine.
Astrocytic signaling supports hippocampal–prefrontal theta synchronization and cognitive function
Authors: Sardinha Vanessa Morais , Guerra‐Gomes Sónia , Caetano Inês , Tavares Gabriela , Martins Manuella , Reis Joana Santos , Correia Joana Sofia , Teixeira‐Castro Andreia , Pinto Luísa , Sousa Nuno , Oliveira João Filipe
Published: September 2017

Astrocytes interact with neurons at the cellular level through modulation of synaptic formation, maturation, and function, but the impact of such interaction into behavior remains unclear. Here, we studied the dominant negative SNARE (dnSNARE) mouse model to dissect the role of astrocyte‐derived signaling in corticolimbic circuits, with implications for cognitive processing. We found that the blockade of gliotransmitter release in astrocytes triggers a critical desynchronization of neural theta oscillations between dorsal hippocampus and prefrontal cortex. Moreover, we found a strong cognitive impairment in tasks depending on this network. Importantly, the supplementation with d‐serine completely restores hippocampal–prefrontal theta synchronization and rescues the spatial memory and long‐term memory of dnSNARE mice. We provide here novel evidence of long distance network modulation by astrocytes, with direct implications to cognitive function.
Preferential encoding of movement amplitude and speed in the primary motor cortex and cerebellum
Authors: Stark‐Inbar Alit , Dayan Eran
Published: September 2017

Voluntary movements require control of multiple kinematic parameters, a task carried out by a distributed brain architecture. However, it remains unclear whether regions along the motor system encode single, or rather a mixture of, kinematic parameters during action execution. Here, rapid event‐related functional magnetic resonance imaging was used to differentiate brain activity along the motor system during the encoding of movement amplitude, duration, and speed. We present cumulative evidence supporting preferential encoding of kinematic parameters along the motor system, based on blood‐oxygenation‐level dependent signal recorded in a well‐controlled single‐joint wrist‐flexion task. Whereas activity in the left primary motor cortex (M1) showed preferential encoding of movement amplitude, the anterior lobe of the right cerebellum (primarily lobule V) showed preferential encoding of movement speed. Conversely, activity in the left supplementary motor area (SMA), basal ganglia (putamen), and anterior intraparietal sulcus was not preferentially modulated by any specific parameter. We found no preference in peak activation for duration encoding in any of the tested regions. Electromyographic data was mainly modulated by movement amplitude, restricting the distinction between amplitude and muscle force encoding. Together, these results suggest that during single‐joint movements, distinct kinematic parameters are controlled by largely distinct brain‐regions that work together to produce and control precise movements. Hum Brain Mapp 38:5970–5986, 2017. © 2017 Wiley Periodicals, Inc.
Deficits in voluntary pursuit and inhibition of risk taking in sensation seeking
Authors: Zheng Ya , Li Qi , Tian Moqian , Nan Weizhi , Yang Guochun , Liang Jin , Liu Xun
Published: September 2017

Sensation seeking has been associated with substance use and other risk‐taking behaviors. The present functional magnetic resonance imaging (fMRI) study investigated the neural correlates underlying risk taking in sensation seeking. Twenty‐eight high sensation seekers (HSS; 14 female and 14 male young adults) and 28 low sensation seekers (LSS; 14 female and 14 male young adults) performed an interactive, sequential gambling task that allowed for voluntary pursuit or inhibition of risk taking. Behaviorally, HSS versus LSS exhibited a stronger tendency toward risk taking. Comparison of the groups revealed that when taking risks, HSS relative to LSS exhibited reduced fMRI responses in brain areas involved in risk processing, such as the dorsomedial prefrontal cortex and the thalamus. Importantly, during the voluntary inhibition of risk taking, HSS relative to LSS showed greater fMRI responses in brain areas implicated in cognitive control (the bilateral anterior cingulate cortex) and negative emotion (the right anterior insula). These findings suggest that risk taking in sensation seeking may be driven by both a hypoactive neural system in the voluntary pursuit of risk taking and a hyperactive neural system in the voluntary inhibition of risk taking, thus providing implications for future prevention programs targeting sensation‐seeking behaviors.Hum Brain Mapp 38:6019–6028, 2017. ©2017 Wiley Periodicals, Inc.
Src kinase inhibition reduces inflammatory and cytoskeletal changes in ΔF508 human cholangiocytes and improves cystic fibrosis transmembrane conductance regulator correctors efficacy
Authors: Fiorotto Romina , Amenduni Mariangela , Mariotti Valeria , Fabris Luca , Spirli Carlo , Strazzabosco Mario
Published: September 2017

Cystic fibrosis transmembrane conductance regulator (CFTR), the channel mutated in cystic fibrosis (CF), is expressed by the biliary epithelium (i.e., cholangiocytes) of the liver. Progressive clinical liver disease (CF‐associated liver disease; CFLD) occurs in around 10% of CF patients and represents the third leading cause of death. Impaired secretion and inflammation contribute to CFLD; however, the lack of human‐derived experimental models has hampered the understanding of CFLD pathophysiology and the search for a cure. We have investigated the cellular mechanisms altered in human CF cholangiocytes using induced pluripotent stem cells (iPSCs) derived from healthy controls and a ΔF508 CFTR patient. We have devised a novel protocol for the differentiation of human iPSC into polarized monolayers of cholangiocytes. Our results show that iPSC‐cholangiocytes reproduced the polarity and the secretory function of the biliary epithelium. Protein kinase A/cAMP‐mediated fluid secretion was impaired in ΔF508 cholangiocytes and negligibly improved by VX‐770 and VX‐809, two small molecule drugs used to correct and potentiate ΔF508 CFTR. Moreover, ΔF508 cholangiocytes showed increased phosphorylation of Src kinase and Toll‐like receptor 4 and proinflammatory changes, including increased nuclear factor kappa‐light‐chain‐enhancer of activated B cells activation, secretion of proinflammatory chemokines (i.e., monocyte chemotactic protein 1 and interleukin‐8), as well as alterations of the F‐actin cytoskeleton. Treatment with Src inhibitor (4‐amino‐5‐(4‐chlorophenyl)‐7‐(t‐butyl)pyrazolo[3,4‐d]pyramidine) decreased the inflammatory changes and improved cytoskeletal defects. Inhibition of Src, along with administration of VX‐770 and VX‐809, successfully restored fluid secretion to normal levels. Conclusion: Our findings have strong translational potential and indicate that targeting Src kinase and decreasing inflammation may increase the efficacy of pharmacological therapies aimed at correcting the basic ΔF508 defect in CF liver patients. These studies also demonstrate the promise of applying iPSC technology in modeling human cholangiopathies. (Hepatology 2018;67:972–988)
‘Brexit’ and International Insolvency Beyond the Realm of Mutual Trust
Authors: Carballo Piñeiro Laura
Published: September 2017

The outcome of the referendum held in the UK in June 2016 is of far‐reaching and unpredictable consequences. This article focuses on the particular field of international insolvency with a view to identifying some of them, all arising out of the fact that the UK will be leaving the EU area of justice and the strong cooperation based on mutual trust between member states. This will make UK–EU insolvency cases clearly less efficient and effective. The consequences of Brexit could be mitigated by the already existing coordination among the international instruments dealing with these matters, in particular the European Insolvency Regulation and the UNCITRAL Model Law on Cross‐Border Insolvency. However, not all EU member states have in place rules dealing with these issues as regards to third states. In order to lessen the impact of Brexit in this sensitive area of law, the implementation of the Model Law in order to deal with extra‐EU cross‐border insolvency could be of avail. Copyright © 2017 INSOL International and John Wiley & Sons, Ltd
From ‘Prisoner's Dilemma’ to Reluctance to Use Judicial Discretion: The Enemies of Cooperation in European Cross‐Border Cases
Authors: Mangano Renato
Published: September 2017

This article will focus on Articles 41–44 of the Recast European Insolvency Regulation (Regulation 2015/848) and the dynamic of cooperation and communication between courts and insolvency practitioners. Two main ideas will be maintained. The first is that cooperation requires a legal framework which is certain—otherwise, prescriptions imposing duties of cooperation and communication might produce ‘prisoner's dilemmas’ and, paradoxically, unwillingness to cooperate. The second idea is that prescriptions imposing duties of cooperation and communication have an intrinsic open texture—this characteristic ontologically requires courts and insolvency practitioners to make choices between different rulings and activities. These findings imply that while interventions, both at European level and at national level, aiming at making the legal framework more certain are always welcome, interventions aiming at better specifying contents and extension of duties of cooperation and communication could be to a certain extent useless and even counterproductive. Copyright © 2017 INSOL International and John Wiley & Sons, Ltd.
Fabrication of tough poly(ethylene glycol)/collagen double network hydrogels for tissue engineering
Authors: Chen Jing‐Xiao , Yuan Jing , Wu Ya‐Ling , Wang Ping , Zhao Peng , Lv Guo‐Zhong , Chen Jing‐Hua
Published: September 2017

In this study, a series of poly(ethylene glycol)/collagen (PEG/Col) double network (DN) hydrogel is fabricated from PEG and Col. Results of the compressive strength test indicate that the strength and toughness of these DN hydrogels are significantly enhanced. The fracture strength of PEG/Col DN hydrogels increases by 9‐ to 12‐fold compared with that of PEG single network (SN) hydrogel, and by 36‐ to 48‐fold compared with that of Col SN hydrogel. Taking advantage of both PEG and Col building blocks, the PEG/Col DN hydrogels possess a strengthened skeleton. Moreover, the water‐storage capability and favorable biocompatibility of Col are effectively maintained. Given that the DN hydrogels can provide the appropriate environment for the adhesion, growth, and proliferation of MC3T3‐E1 cells, PEG/Col DN hydrogels have potential as a load‐bearing tissue repair material. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 192–200, 2018.
Gelatin methacrylate scaffold for bone tissue engineering: The influence of polymer concentration
Authors: Celikkin Nehar , Mastrogiacomo Simone , Jaroszewicz Jakub , Walboomers X. Frank , Swieszkowski Wojciech
Published: September 2017

Gelatin methacrylate (GelMA) is an inexpensive, photocrosslinkable, cell‐responsive hydrogel which has drawn attention for a wide range of tissue engineering applications. The potential of GelMA scaffolds was demonstrated to be tunable for different tissue engineering (TE) applications through modifying the polymer concentration, methacrylation degree, or UV light intensity. Despite the promising results of GelMA hydrogels in tissue engineering, the influence of polymer concentration for bone tissue engineering (BTE) scaffolds was not established yet. Thus, in this study, we have demonstrated the effect of polymer concentration in GelMA scaffolds on osteogenic differentiation. We prepared GelMA scaffolds with 5 and 10% polymer concentrations and characterized the scaffolds in terms of porosity, pore size, swelling characteristics, and mechanical properties. Subsequent to the scaffolds characterization, the scaffolds were seeded with bone marrow derived rat mesenchymal stem cells and cultured in osteogenic media to evaluate the possible osteogenic differentiation effect exerted by the polymer concentration. After 7, 14, 21, and 28 days, DNA content, calcium deposition, and alkaline phosphatase (ALP) activity of scaffolds were evaluated quantitatively by colorimetric bioassays. Furthermore, the distribution of the calcium deposition within the scaffolds was attained qualitatively and quantitatively by microcomputer tomography (µCT). Our data suggest that GelMA hydrogels prepared with 5% polymer concentration has promoted homogeneous extracellular matrix calcification and it is a great candidate for BTE applications. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 201–209, 2018.
Evaluation of osteogenic inductivity of a novel BMP2‐mimicking peptide P28 and P28‐containing bone composite
Authors: Sun Tingfang , Qu Yanzhen , Cui Wei , Yang Liang , Ji Yanhui , Yu Wei , Navinduth Ramphul , Shao Zengwu , Yang Hu , Guo Xiaodong
Published: September 2017

We developed a novel BMP2‐mimicking peptide P28, which possesses two distinct special structural elements—seven repetitive aspartic acids and phosphorylated serine designed to promote affinity to hydroxyapatite as well as nucleation of apatite crystallization and mineralization. In this work, we systematically studied the osteogenic inductivity of P28 in vitro and in vivo in comparison with BMP2. We confirmed its effects on proliferation, recruitment, and osteogenic differentiation of MC3T3‐E1 cells in vitro. Furthermore, we loaded P28 into a biomimetic bone composite nanohydroxyapatite/collagen/poly(l‐lactide) (nHAC/PLA) and evaluated its ability to promote bone regeneration in vivo using a rabbit femoral condyle defect model. The micro‐CT reconstruction and quantification analysis and the histological analysis indicated that P28/nHAC/PLA bone composite was capable of repairing bone defects. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 210–220, 2018.
Evaluation of chemical stability of polymers of XIENCE everolimus‐eluting coronary stents in vivo by pyrolysis‐gas chromatography/mass spectrometry
Authors: Kamberi Marika , Pinson David , Pacetti Stephen , Perkins Laura E. L. , Hossainy Syed , Mori Hiroyoshi , Rapoza Richard J. , Kolodgie Frank , Virmani Renu
Published: September 2017

The polymers poly(vinylidene fluoride‐co‐hexafluoropropylene) (PVDF‐HFP) and poly(n‐butyl methacrylate) (PBMA) are employed in manufacturing the XIENCE family of coronary stents. PBMA serves as a primer and adheres to both the stent and the drug coating. PVDF‐HFP is employed in the drug matrix layer to hold the drug everolimus on the stent and control its release. Chemical stability of the polymers of XIENCE stents in the in‐vivo environment was evaluated by pyrolysis‐gas chromatography with mass spectrometry (Py‐GC/MS) detection. For this evaluation, XIENCE stents explanted from porcine coronary arteries and from human coronary artery specimens at autopsy after 2–4 and 5–7 years of implantation, respectively, were compared to freshly manufactured XIENCE stents (controls). The comparison of pyrograms of explanted stent samples and controls showed identical fragmentation fingerprints of polymers, indicating that PVDF‐HFP and PBMA maintained their chemical integrity after multiple years of XIENCE coronary stent implantation. The findings of the present study demonstrate the chemical stability of PVDF‐HFP and PBMA polymers of the XIENCE family of coronary stents in the in‐vivo environment, and constitute a further proof of the suitability of PVDF‐HFP as a drug carrier for the drug eluting stent applications. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1721–1729, 2018.
Leptin induces matrix metalloproteinase 7 expression to promote ovarian cancer cell invasion by activating ERK and JNK pathways
Authors: Ghasemi Ahmad , Hashemy Seyed Isaac , Aghaei Mahmoud , Panjehpour Mojtaba
Published: September 2017

Leptin, an adipokine secreted by adipose tissue, induces cell invasion and metastasis. MMP7 is a member of the matrix metalloproteinase family that plays an important role in cell invasion. Here we evaluate the possible role and underlying mechanism of MMP7 in the leptin‐mediated cell invasion in ovarian cancer cell lines. All experiments were carried out in cultured SKOV3, OVCAR3, and CaoV‐3 ovarian cell lines. MMP7 expression was determined using the Western blot following treatment to various concentrations of leptin for defined time intervals. The activation of ERK, JNK, and P38 MAP kinases were determined using Western blotting. Wound healing and BD matrigel invasion assays were used to measure cell migration and invasion. The siRNA approach and pharmacological inhibitors of ERK and JNK pathway were used to confirm the receptor‐dependent effect of leptin and a role for ERK and JNK pathway. Zymography assay was employed to determine MMP2 and MMP9 activation. Results show that leptin induces ERK1/2 and JNK1/2 activation and subsequently promotes MMP7 expression in SKOV3 (4.8 ± 0.14 fold of control, P < 0.01) and OVCAR3 (3.1 ± 0.19 fold of control, P < 0.01) ovarian cancer cell lines. These effects was reversed by knockdown of OB‐Rb and/or pre‐incubation with PD98059 (ERK1/2 inhibitor), SP600125 (JNK1/2 inhibitor). Gelatin zymography showed that MMP7 gene silencing attenuated leptin‐induced MMP9 activation in SKOV3 cell line. Taken together, our results suggest new evidences for a modulatory effect of leptin in regulation of ovarian cancer cell invasion by stimulating MMP7 expression via ERK and JNK pathways.
Transplantation of hypoxic preconditioned neural stem cells benefits functional recovery via enhancing neurotrophic secretion after spinal cord injury in rats
Authors: Fan Wei‐li , Liu Peng , Wang Guan , Pu Jun‐gang , Xue Xin , Zhao Jian‐hua
Published: September 2017

Spinal cord injury (SCI) is a debilitating, costly, and common pathological condition that affects the function of central nervous system (CNS). To date, there are few promising therapeutic strategies available for SCI. To look for a suitable therapeutic strategy, we have developed a sublethal hypoxic preconditioning procedure using Fluorescence‐activated cell sorting (FACS) analysis, LDH releasing, and cell viability assays in vitro. Meanwhile, we have examined the benefits of neural stem cells (NSCs) transplantation prior to hypoxic preconditioning on functional recovery and potential mechanism via MRI screening, H&E, and Nissl staining, immunofluorescence staining and Elisa assays. Our data showed that transplantation of hypoxic prconditioned NSCs could enhance neuronal survival, especially 5‐TH+ and ChAT+ neurons, in the injured spinal cord to reinforce functional benefits. The hypoxia exposure upregulated HIF‐1α, neurotrophic and growth factors including neurotrophin‐3 (NT‐3), glial cell‐derived neurotrophic factor (GDNF), and brain‐derived neurotrophic factor (BDNF) in vitro and in vivo. Furthermore, functional recovery, including locomotor and hypersensitivities to mechanical and thermal stimulation assessed via behavioral and sensory tests, improved significantly in rats with engraftment of NSCs after hypoxia exposure from day 14 post‐SCI, compared with the control and N‐NSCs groups. In short, the approach employed in this study could result in functional recovery via upregulating neurotrophic and growth factors, which implies that hypoxic preconditioning strategy could serve as an effective and feasible strategy for cell‐based therapy in the treatment of SCI in rats.
Further results on almost resolvable cycle systems and the Hamilton–Waterloo problem
Authors: Wang L. , Lu S. , Cao H.
Published: September 2017

In this paper, we almost completely solve the existence of almost resolvable cycle systems with odd cycle length. We also use almost resolvable cycle systems as well as other combinatorial structures to give some new solutions to the Hamilton–Waterloo problem.
Distribution of Mycobacterium tuberculosis in Korea in the preceding decade
Authors: Jeon Jae‐Sik , Kim Jae Kyung , Choi Qute , Kim Jong Wan
Published: September 2017

Background

Tuberculosis (TB) is an infectious disease caused by the bacillus Mycobacterium tuberculosis (MTB); it is transmitted among people through air. The aim of this study was to assess the prevalence of TB and its clinical trends by collecting and analyzing data on specimens in Korea.

Methods

All clinical specimens referred to the Dankook University Hospital Laboratory in Cheonan, Korea, from September 2005 to June 2016 were tested to isolate MTB using solid and liquid cultures, acid‐fast bacilli (AFB) smears, and polymerase chain reactions (PCR).

Results

In total, 146 150 specimens were collected; the mean TB positivity rate was 7.8%. The highest positivity rate was observed among patients 30‐39 years of age (12.6%), followed by those 20‐29 years of age (12.2%). The mean positivity rate was highest in 2010 and lowest in 2016 (10.7% and 6.7%, respectively). When comparing 2015‐2011, we saw a decrease in the number of TB‐positive patients of 3.4%; this represented an annual decrease in 0.9%.

Conclusion

Our data revealed a trend for a decrease in TB prevalence over time. Moreover, TB positivity rates were highest among the younger age groups in our study. Therefore, rapid diagnosis and treatment of TB in younger individuals are crucial.
Neutrophil extracellular traps in acrolein promoted hepatic ischemia reperfusion injury: Therapeutic potential of NOX2 and p38MAPK inhibitors
Authors: Arumugam Suyavaran , Girish Subbiah Kesthuru , Kemparaju Kempaiah , Thirunavukkarasu Chinnasamy
Published: September 2017

Neutrophil is a significant contributor to ischemia reperfusion (IR) induced liver tissue damage. However, the exact role of neutrophils in IR induced innate immune activation and liver damage is not quite clear. Our study sheds light on the role of chronic oxidative stress end products in worsening the IR inflammatory process by neutrophil recruitment and activation following liver surgery. We employed specific inhibitors for molecular targets—NOX2 (NADPH oxidase 2) and P38 MAPK (Mitogen activated protein kinase) signal to counteract neutrophil activation and neutrophil extracellular trap (NET) release induced liver damage in IR injury. We found that acrolein initiated neutrophil chemotaxis and induced NET release both in vitro and in vivo. Acrolein exposure caused NET induced nuclear and mitochondrial damage in HepG2 cells as well as aggravated the IR injury in rat liver. Pretreatment with F‐apocynin and naringin, efficiently suppressed acrolein induced NET release in vitro. Notably, it suppressed the expression of inflammatory cytokines, P38MAPK‐ERK activation, and apoptotic signals in rat liver exposed to acrolein and subjected to IR. Moreover, this combination effectively attenuated acrolein induced NET release and hepatic IR injury. In the current study we have shown that the acrolein accumulation in liver due to chronic stress, is responsible for neutrophil recruitment and its activation leading to NET induced liver damage during surgery. Our study shows that therapeutic targeting of NOX2 and P38MAPK signaling in patients with chronic hepatic disorders would improve post operative hepatic function and survival.
RNA binding protein Musashi‐2 regulates PIWIL1 and TBX1 in mouse spermatogenesis
Authors: Sutherland Jessie M. , Sobinoff Alexander P. , Fraser Barbara A. , Redgrove Kate A. , Siddall Nicole A. , Koopman Peter , Hime Gary R. , McLaughlin Eileen A.
Published: September 2017

RNA‐binding proteins (RBP) are important facilitators of post‐transcriptional gene regulation. We have previously established that nuclear overexpression of the RBP Musashi‐2 (MSI2) during male germ cell maturation is detrimental to sperm cell development and fertility. Herein we determine the genes and pathways impacted by the upregulation of Msi2. Microarray analysis and qPCR confirmed differential gene expression in factors fundamental to the cell cycle, cellular proliferation, and cell death. Similarly, comparative protein expression analysis via iTRAQ, immunoblot, and immunolocalization, identified differential expression and localization of important regulators of transcription, translation, RNA processing, and spermatogenesis. Specifically, the testis‐expressed transcription factor, Tbx1, and the piRNA regulator of gamete development, Piwil1, were both found to be targeted for translational repression by MSI2. This study provides key evidence to support a fundamental role for MSI2 in post‐transcriptional regulation during male gamete development.
Overexpression of miR‐216b: Prognostic and predictive value in acute myeloid leukemia
Authors: Zhang Ting‐juan , Wu De‐hong , Zhou Jing‐dong , Li Xi‐xi , Zhang Wei , Guo Hong , Ma Ji‐chun , Deng Zhao‐qun , Lin Jiang , Qian Jun
Published: September 2017

Accumulating studies have shown that miR‐216b acted as a tumor suppressor and was down‐regulated in solid tumors. However, little studies revealed the role or clinical implication of miR‐216b in blood cancers. Herein, we reported miR‐216b expression and its clinical significance in patients with acute myeloid leukemia (AML). In the current study, we analyzed bone marrow (BM) miR‐216b expression in 115 de novo AML patients examined by real‐time quantitative PCR. Notably, BM miR‐216b expression was significantly up‐regulated in AML patients, and could serve as a potential biomarker distinguishing AML from controls. No significant correlations of BM miR‐216 expression were found with sex, age, white blood cells, hemoglobin, platelets, BM blasts, French–American–British classifications, and karyotypes. Significantly, patients with high miR‐216b expression tended to have a lower frequency of FLT3‐ITD mutation and higher incidence of U2AF1 and IDH1/2 mutations. Moreover, complete remission (CR) rate and overall survival were negatively affected by BM miR‐216b overexpression among cytogenetically normal AML (CN‐AML). Cox regression analyses showed that high BM miR‐216b expression may act as an independent risk factor in CN‐AML patients. Among the follow‐up patients, BM miR‐216b level in CR phase was markedly lower than in diagnosis time, and was returned in relapse phase. Collectively, our findings indicated that miR‐216b overexpression was a frequent event in de novo AML, and independently conferred a poor prognosis in CN‐AML. Moreover, miR‐216b expression was a valuable biomarker correlated with disease recurrence in AML.
Global analysis of gene expression profiles in the submandibular salivary gland of klotho knockout mice
Authors: Kwon Sung‐Min , Kim Soo‐A , Yoon Jung‐Hoon , Yook Jong‐In , Ahn Sang‐Gun
Published: September 2017

Salivary dysfunction commonly occurs in many older adults and is considered a physiological phenomenon. However, the genetic changes in salivary glands during aging have not been characterized. The present study analyzed the gene expression profile in salivary glands from accelerated aging klotho deficient mice (klotho−/−, 4 weeks old). Microarray analysis showed that 195 genes were differentially expressed (z‐score > 2 in two independent arrays) in klotho null mice compared to wild‐type mice. Importantly, alpha2‐Na+/K+‐ATPase (Atp1a2), Ca2+‐ATPase (Atp2a1), epidermal growth factor (EGF), and nerve growth factor (NGF), which have been suggested to be regulators of submandibular salivary gland function, were significantly decreased. When a network was constructed from the differentially expressed genes, proliferator‐activated receptor‐γ (PPAR γ), which regulates energy homeostasis and insulin sensitivity, was located at the core of the network. In addition, the expression of genes proposed to regulate various PPAR γ‐related cellular pathways, such as Klk1b26, Egfbp2, Cox8b, Gpx3, Fabp3, EGF, and NGFβ, was altered in the submandibular salivary glands of klotho−/− mice. Our results may provide clues for the identification of novel genes involved in salivary gland dysfunction. Further characterization of these differentially expressed genes will be useful in elucidating the genetic basis of aging‐related changes in the submandibular salivary gland.
Addressing Antiretroviral Therapy‐Associated Drug‐Drug Interactions in Patients Requiring Treatment for Opportunistic Infections in Low‐Income and Resource‐Limited Settings
Authors: Chastain Daniel B. , Franco‐Paredes Carlos , Stover Kayla R.
Published: September 2017

An increasing number of human immunodeficiency virus (HIV)‐infected patients are achieving virologic suppression on antiretroviral therapy (ART) limiting the use of primary and secondary antimicrobial prophylaxis. However, in low‐income and resource‐limited settings, half of those infected with HIV are unaware of their diagnosis, and fewer than 50% of patients on ART achieve virologic suppression. Management of comorbidities and opportunistic infections among patients on ART may lead to inevitable drug‐drug interactions (DDIs) and even toxicities. Elderly patients, individuals with multiple comorbidities, those receiving complex ART, and patients living in low‐income settings experience higher rates of DDIs. Management of these cytochrome P450‐mediated, nonmediated, and drug transport system DDIs is critical in HIV‐infected patients, particularly those in resource‐limited settings with few options for ART. This article critically analyzes and provides recommendations to manage significant DDIs and drug toxicities in HIV‐infected patients receiving ART.
Seasonal variation and correlation between corticosterone and the antioxidant uric acid during stress in the Northern Cardinal (Cardinalis cardinalis)
Authors: Haskins Jonathan W. , Spizzoucco Frank A. , Walker Brian G.
Published: September 2017

Glucocorticoids modify metabolism and other physiological processes in order to mount an appropriate response to stress. This stress response is affected by a combination of seasonal changes, life‐history events, and environmental factors. Determining seasonal variability and the potential connection between stress hormones and metabolism is fundamental in understanding seasonal physiological changes in animals. Here, we compared an indicator of stress (corticosterone) with an indicator of metabolic activity (uric acid—a non‐enzymatic antioxidant and end product of protein metabolism) during capture and restraint in Northern Cardinals (Cardinalis cardinalis) during fall, winter, spring, and summer. Baseline corticosterone, the acute change in corticosterone (Δ10‐corticosterone), and integrated corticosterone during capture stress were significantly different among seasons. For all corticosterone measurements birds captured in summer consistently had the lowest values while spring birds were highest. The lower corticosterone stress response in summer may decrease the likelihood of abandonment and thus protect investment in eggs/chicks. Higher glucocorticoid secretion in spring may benefit birds competing for nesting sites. No differences in uric acid levels (baseline, 60 min, and acute change over 60 min‐ Δ60‐uric acid) were found among seasons. While plasma uric acid significantly decreased over an hour in all seasons examined, there were no significant correlations between baseline corticosterone and uric acid, time‐60 corticosterone and uric acid, and Δ10‐corticosterone and Δ60‐uric acid. We conclude that the relationship between corticosterone and metabolism, as measured by uric acid, is indirect, and seasonal variation occurs with corticosterone secretion but not with uric acid, as measured here.
Quasi‐graphic matroids*
Authors: Geelen Jim , Gerards Bert , Whittle Geoff
Published: September 2017

Frame matroids and lifted‐graphic matroids are two interesting generalizations of graphic matroids. Here, we introduce a new generalization, quasi‐graphic matroids, that unifies these two existing classes. Unlike frame matroids and lifted‐graphic matroids, it is easy to certify that a 3‐connected matroid is quasi‐graphic. The main result is that every 3‐connected representable quasi‐graphic matroid is either a lifted‐graphic matroid or a frame matroid.
Packing odd T‐joins with at most two terminals
Authors: Abdi Ahmad , Guenin Bertrand
Published: September 2017

Take a graph G, an edge subset , and a set of terminals where is even. The triple is called a signed graft. A T‐join is odd if it contains an odd number of edges from Σ. Let ν be the maximum number of edge‐disjoint odd T‐joins. A signature is a set of the form where and is even. Let τ be the minimum cardinality a T‐cut or a signature can achieve. Then and we say that packs if equality holds here.

We prove that packs if the signed graft is Eulerian and it excludes two special nonpacking minors. Our result confirms the Cycling Conjecture for the class of clutters of odd T‐joins with at most two terminals. Corollaries of this result include, the characterizations of weakly and evenly bipartite graphs, packing two‐commodity paths, packing T‐joins with at most four terminals, and a new result on covering edges with cuts.
Berge–Fulkerson coloring for C(8)‐linked graphs
Authors: Hao Rong‐Xia , Zhang Cun‐Quan , Zheng Ting
Published: September 2017

It is conjectured by Berge and Fulkerson that every bridgeless cubic graph has six perfect matchings such that each edge is contained in exactly two of them.
Let G be a cubic graph and be a 2‐factor of G such that is odd if and only if for some integer k. The 2‐factor F is C(8)‐linked
if, for every , there is a circuit of length 8 with edge sequence where and . And the cubic graph G is C(8)‐linked if it contains a C(8)‐linked 2‐factor. It is proved in this article that every C(8)‐linked cubic graph is Berge–Fulkerson colorable.
It is also noticed that many classical families of snarks (including some high oddness snarks) are C(8)‐linked. Consequently, the Berge–Fulkerson conjecture is verified for these infinite families of snarks.
One‐way infinite 2‐walks in planar graphs
Authors: Biebighauser Daniel P. , Ellingham M. N.
Published: September 2017

We prove that every 3‐connected 2‐indivisible infinite planar graph has a 1‐way infinite 2‐walk. (A graph is 2‐indivisible if deleting finitely many vertices leaves at most one infinite component, and a 2‐walk is a spanning walk using every vertex at most twice.) This improves a result of Timar, which assumed local finiteness. Our proofs use Tutte subgraphs, and allow us to also provide other results when the graph is bipartite or an infinite analog of a triangulation: then the prism over the graph has a spanning 1‐way infinite path.
Serum lactate in liver resection with intermittent Pringle maneuver: the “square‐root‐ shape
Authors: Giustiniano Enrico , Procopio Fabio , Costa Guido , Rocchi Laura , Ruggieri Nadia , Cantoni Stefania , Zito Paola C. , Gollo Yari , Torzilli Guido , Raimondi Ferdinando
Published: September 2017

Background

Serum lactate (sLac) concentration during liver resection with intermittent hepatic hilum clamping (i.e. Pringle maneuver, PM) was retrospectively investigated.

Methods

A total of 133 patients who underwent liver resection were enrolled. We analyzed the sLac peri‐operatively. Correlations were searched between the PM and lactatemia and its variations (i.e. lactate clearance, cLac) and other factors which it might be related to. Lactatemia in triplicate intraoperatively was recorded, just after the awakening, and 1 and 2 h later. The cLac between two consecutive measurements [(sLac1 − sLac2)/sLac1] was computed.

Results

A reliable dependence of sLac was found from the cumulative PM. More than 76 min of cumulative Pringle Time (cPT) exposed patients to a worse cLac at the end of the resection phase (P < 0.0001). We found cPT >76 min, global operation time >365 min and bleeding >225 ml to be predictors of hyperlactatemia (sLac >4 mmol/L). Normal liver resulted as a risk factor for hyperlactatemia and steatosis was not (P = 0.030 vs. P = 0.325). Finally, cLac showed a “square‐root‐ shape, just like the mathematical operation sign.

Conclusions

Lactatemia during liver resection depends on the duration of PM, bleeding and the duration of the operation. Normal liver may expose the patient to the risk of hyperlactatemia.
Convenient Synthesis of Piperazine Substituted Quinolones
Authors: Fathalla Walid , Pazdera Pavel
Published: September 2017

A series of 1‐[(4‐hydroxy‐2‐oxo‐1‐phenyl‐1,2‐dihydroquinolin‐3‐yl)carbonyl]‐4‐(substituted) piperazines 3a–c and methyl 2‐[(4‐hydroxy‐2‐oxo‐1‐phenyl‐1,2‐dihydroquinolin‐3‐yl)carbonylamino] alkanoates 5a–d has been developed by the direct condensation of ethyl [4‐hydroxy‐2‐oxo‐1‐phenyl‐1,2‐dihydro‐3‐quinoline] carboxylate 2 with N1‐monosubstituted piperazine hydrochlorides or amino acid ester hydrochloride in the presence of triethyl amine. The quinolone amino acid esters 5a–d were the key intermediate for the preparation of a series of 1‐[2‐((4‐hydroxy‐2‐oxo‐1‐phenyl‐1,2‐dihydroquinolin‐3‐yl)carbonylamino)alkylcarbony]‐4‐substituted piperazine derivatives 8–11 (a‐d) via azide coupling method with amino acid ester hydrochloride.
Synthesis and Evaluation of Novel [1,2,4]Triazolo[1,5‐c]quinazoline Derivatives as Antibacterial Agents
Authors: Zeydi Masoud Mohammadi , Montazeri Naser , Fouladi Mahdi
Published: September 2017

A series of new 2‐aryl‐5‐methyl‐[1,2,4]triazolo[1,5‐c]quinazoline derivatives (5a–5g) have been synthesized by the reaction of 3‐amino‐2‐methylquinazolin‐4‐(3H)‐one (3) with aromatic nitriles in potassium tert‐butoxide under reflux conditions. 3‐Amino‐2‐methylquinazolin‐4‐(3H)‐one (3) was synthesized by the reaction 2‐methyl‐4H‐benzo[d][1,3]oxazin‐4‐one (2) with hydrazine hydrate. The chemical structure of products was confirmed by IR, 1H, 13C NMR and elemental analysis. These compounds were screened for antibacterial [Staphylococcus aureus (ATCC 25923), Bacillus cereus (ATCC 11778), Micrococcus luteus (ATCC 9341), Escherichia coli (ATCC 25922), and Pseudomonas aeruginosa (ATCC 27853)] activities, using the zone inhibition method.
1H‐1,2,3‐triazole‐tethered 8‐OMe Ciprofloxacin and Isatin Hybrids: Design, Synthesis and in vitro Anti‐mycobacterial Activities
Authors: Xu Zhi , Song Xu‐Feng , Qiang Min , Lv Zao‐Sheng
Published: September 2017

A new class of 1H‐1,2,3‐triazole‐tethered 8‐OMe ciprofloxacin (8‐OMe CPFX) isatin hybrids 5a–l was designed, synthesized and screened for their in vitro anti‐mycobacterial activities against Mycobacterium tuberculosis H37Rv and multi‐drug‐resistant tuberculosis (MDR‐TB). All targets (minimum inhibitory concentration (MIC): 0.20–8.0 μg/mL) exhibited promising inhibitory activity against MTB H37Rv and MDR‐TB. Among them, conjugate 5h (MIC: 0.20 μg/mL), was 2–16 times more potent in vitro than the references CPFX (MIC: 3.12 μg/mL), 8‐OMe CPFX (MIC: 1.56 μg/mL) and RIF (MIC: 0.39 μg/mL) against MTB H37Rv. The most potent hybrid 5l (MIC: 0.25 μg/mL) was 8–256 times more active than the three references (MIC: 2.0–64 μg/mL) against MDR‐TB. Both of them warrant further investigations.
Diversity‐oriented Multicomponent Synthesis of Bisquinolones under Green Conditions
Authors: Bandi Madhu , Reddy Ch.Venkata Ramana
Published: September 2017

A diversity‐oriented green and eco‐friendly synthesis of bisquinolones have been developed by simply condensation of N‐methylquinolone (1), with various benzaldehydes 2a–n and aniline (3) under catalyst‐free conditions. An exciting feature of this communication is the product formation that depends on the intermediate (II) generated in the reaction mechanism.
Hepatitis B among immigrants from Myanmar: Genotypes and their clinical relevance
Authors: Schulz Thomas R. , Edwards Rosalind , Thurnheer M Christine , Yuen Lilly , Littlejohn Margaret , Revill Peter , Chu Melissa , Tanyeri Firuz , Wade Amanda , Biggs Beverley‐Ann , Sasadeusz Joseph
Published: September 2017

Hepatitis B virus (HBV) from 76 adult immigrants in Australia from Myanmar was characterized to determine the prevalence of different HBV genotypes and subgenotypes. A mutational analysis was then performed to determine the presence of clinically significant mutations and correlate them to clinical outcomes. Initial genotyping revealed 68 patients with genotype C (89.5%) and eight patients with genotype B (10.5%). Phylogenetic analysis revealed the large majority of the genotype C infections were of subgenotype C1 (67/68). Sequencing of the HBV polymerase gene (and overlapping surface gene) revealed no mutations associated with antiviral resistance. HBV surface gene mutations were detected in 10 patients with subgenotype C1. HBV BCP/PC sequencing was obtained for 71/76 (93%) patients. BCP and/or PC mutations were identified in 57/71 (80%) of PCR positive patients. Treatment had been commenced for 15/76 (18%) patients, a further 26 untreated patients were in a stage of disease where HBV treatment would be considered standard of care. It was identified that genotype C1 is the predominant sub‐genotype in this population. Genotype C is known to be associated with increased risk of development of HCC. This highlights the need for screening for HCC given the potential for the development of liver cancer. It was also identified that people with HBV were potentially not receiving optimal therapy in a timely fashion.
Achieving interfragmentary compression without special drilling technique or screw design
Authors: Eastman Jonathan , Deafenbaugh Bradley , Christiansen Blaine , Garcia‐Nolen Tanya , Lee Mark
Published: September 2017

Traditional fracture fixation teaching suggests that fully threaded screws do not provide interfragmentary compression unless placed through a glide hole. Based on this assumption, pelvic surgeons typically use fully threaded screws in the treatment of comminuted transforaminal sacral fractures to limit iatrogenic neuroforaminal stenosis. Clinical experience with fully threaded screws suggests that interfragmentary compression actually does occur. We hypothesized that the use of a fully threaded screw does not produce any interfragmentary compression and that there is no difference in insertional torque between partially threaded and fully threaded screws. To test this hypothesis, fully and partially threaded 7.0 millimeter (mm) cannulated screws were placed across two synthetic bone blocks fabricated to simulate normal and osteoporotic bone. We compared two groups of normal and osteoporotic blocks for compression achieved and maximal insertional torque generated with fully threaded and partially threaded screw insertion. A micro computed tomography (CT) scan of the composite blocks was obtained to investigate for structural changes created during screw insertion. For both groups, compression was achieved with fully threaded screws and the maximal insertional torque was higher using fully threaded screws. Micro CT analysis demonstrated local bone damage with structural disruption in the near segment of the fully threaded screw path in comparison to the partially threaded. Clinical significance: this study demonstrates that compression is generated using fully threaded screws without using a predrilled glide hole. The insertional torque required to generate compression with fully threaded screws is increased but is clinically applicable. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1099–1105, 2018.
The seating mechanics of head‐neck modular tapers in vitro: Load‐displacement measurements, moisture, and rate effects
Authors: Ouellette Eric S. , Shenoy Aarti A. , Gilbert Jeremy L.
Published: September 2017

The mechanically assisted crevice corrosion performance of head‐neck modular tapers is a significant concern in orthopedic biomaterials. Fretting crevice corrosion processes in modular tapers are thought to be influenced by a wide array of factors including seating mechanics of the junction, hence there is a need for in vitro test methods that can assess their performance. This study presented a test method to directly measure the load‐displacement seating mechanics of modular tapers and used this method to compare the seating mechanics for different tapers, moisture, seating loads and seating rates. Seating mechanics were explored whereby the instantaneous load‐displacement behavior of the head seating onto the neck is captured and used to define the mechanics of seating. Two distinct taper design/material combinations were assembled wet or dry using axially applied loads (500, 1,000, 2,000, and 4,000 N) at two loading rates of 100 and 104 N/s (n = 5 for each condition) using a servohydraulic test frame. The results showed that pull‐off strength scaled with seating load and ranged between 43% and 68% of seating load depending on sample and wetness. Tapers seated wet had higher pull‐off strengths (2,200 ± 300 N) than those seated dry (1,800 ± 200 N, p < 0.05). Seating mechanics (load‐displacement plots) varied due to sample type and due to wetness with differences in seating energy, seating stiffness, and seating displacement. These results show the detailed mechanics of seating during assembly and provide significant insight into the complex interplay of factors associated with even “ideal” seating (axial, quasistatic) loading. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1164–1172, 2018.
Spatial Variation of Soil Seed Bank under Cushion Plants in a Subalpine Degraded Grassland
Authors: Niknam Parisa , Erfanzadeh Reza , Ghelichnia Hassan , Cerdà Artemi
Published: September 2017

Cushion plants can affect wind speed and sediment movement patterns that probably modify the water and sediment redistribution along slopes and increase the accumulation of seeds under and around their canopies. This study was carried out to assess the spatial variability of soil seed bank (SSB) and seed bank composition around cushion plants to estimate the SSB potential for restoration of degraded area. Twenty cushions of Onobrychis cornuta were selected in a mountainous rangelands in northern Alborz in Iran, measuring density, richness and composition of SSB at four locations of each cushion (upslope edge, downslope edge, centre and outside). SSB composition and density were determined by seedling emergence method. The results showed that the locations of cushions had significant effect on density and richness of the SSBs. The highest SSB density and richness were observed in the centre and upslope edge of the cushions, while there was no significant differences of density and richness between downslope edge and outside (bare grassland soil) of the cushions. In addition, the results showed that seed bank composition was highly correlated between the four locations in the same cushion. We concluded that cushion plants can act as seed traps specially trapping seeds dispersed by barochory and hydrochory and therefore play an important role in conservation and recovery of degraded areas. Copyright © 2017 John Wiley & Sons, Ltd.