bluuebunny/crossref_metadata_2025 huggingface dataset:
Investigation of the in vivo metabolism of harpagoside and distribution of its metabolites in rats by HPLC‐IT‐TOF‐MSn
Authors: Wang Jing‐Zhe , Zhang Yi‐Fan , Xu Feng , Shang Ming‐Ying , Liu Guang‐Xue , Cai Shao‐Qing
Published: February 2018

Harpagoside, an iridoid glycoside, is the major bioactive constituent of the traditional Chinese medicine Scrophulariae Radix. High‐performance liquid chromatography with a diode array detector combined with electrospray ionization ion trap time‐of‐flight multistage mass spectrometry (HPLC‐ESI‐IT‐TOF‐MSn) was used to profile and identify the metabolites of harpagoside in rats in vivo and to study the distribution of these metabolites in rats for the first time. A total of 45 metabolites were identified, 37 of which were postulated to be new compounds. The number of detected metabolites in the heart, liver, spleen, lung, kidney, stomach and small intestine was 2, 9, 6, 16, 4, 16 and 6, respectively, which indicated that the target organs of harpagoside should be spleen, lung and stomach. The main types of metabolic reactions of harpagoside in rats are hydrolysis, reduction, sulfuric acid addition, hydroxylation, methoxylation, sulfate substitution, methylation, glucose conjugation and amino acid conjugation. Furthermore, 23 metabolites were determined to have bioactivities based on the literature and ‘PharmMapper’ analysis. These findings are useful for better comprehension of the effective forms, target organs and pharmacological effects of harpagoside. Moreover, these findings provide a reference for studying the metabolism and distribution of iridoid compounds.
Simultaneous determination of evodiamine and its four metabolites in rat plasma by LC–MS/MS and its application to a pharmacokinetic study
Authors: Wang Cuiyun , Yue Fang , Ai Guangfeng , Yang Jie
Published: February 2018

A simple and sensitive liquid chromatography tandem mass spectrometry method was validated for simultaneous quantification of evodiamine and its metabolites 10‐hydroxyevodiamine (M1), 18‐hydroxyevodiamine (M2), 10‐hydroxyevodiamine‐glucuronide (M3) and 18‐hydroxy‐ evodiamine‐glucuronide (M4) in rat plasma for the first time. The analytes were extracted with acetonitrile and separated on a C18 column within 3 min. The detection was achieved in positive selected reaction monitoring mode with precursor‐to‐product transitions at m/z 304.1 → 161.1 for evodiamine, m/z 320.1 → 134.1 for M1, m/z 320.1 → 150.1 for M2, m/z 496.2 → 134.1 for M3, m/z 496.2 → 171.1 for M4 and m/z 349.2 → 305.1 for camptothecin (internal standard). The linearity was evident over the tested concentration ranges with correlation coefficients >0.9991. The lower limits of quantification for evodiamine, M1, M2, M3 and M4 were 0.1, 0.1, 0.1, 0.25 and 0.25 ng mL−1, respectively. Extraction recoveries and matrix effects of the analytes were within the ranges of 84.51–97.21 and 90.13–103.30%, respectively. The accuracy (relative error) ranged from −8.14 to 7.23% while the intra‐ and inter‐day precisions (relative standard deviation) were < 9.31%. The validated assay was successfully applied for the pharmacokinetic study of evodiamine, M1, M2, M3 and M4 in rat. The current study will be helpful in understanding the in vivo disposition of evodiamine.
Spectrum–effect relationship between HPLC fingerprints and hypolipidemic effect of Curcuma aromatica
Authors: Liu Meiqiong , Wu Youjiao , Huang Shushi , Liu Huagang , Feng Jie
Published: February 2018

Curcuma aromatica is used as a traditional Chinese medicine, and it is mainly distributed in Guangxi, China. In this study, 10 batches of C. aromatica were collected from different origins in Guangxi. The fingerprints were established by HPLC technique to investigate the quality stability of C. aromatica. The spectrum–effect relationship between HPLC fingerprints and hypolipidemic effect of C. aromatica was assessed by similarity analysis, gray relational analysis and multiple linear regression analysis. From the results, the similarity values between each batch of C. aromatica and reference fingerprint were >0.880, indicating the good quality stability of the 10 batches of C. aromatica. Twenty common peaks were selected as the fingerprints to evaluate the quality and hypolipidemic effect of C. aromatica. The results of spectrum–effect relationship showed that peaks 10, 18, 13, 15 and 17 in the fingerprints were closely related to hypolipidemic effect. This study successfully established the spectrum–effect relationship between HPLC fingerprints and hypolipidemic effect of C. aromatica, which provided methods for quality control and more effectively studies on bioactive compounds of C. aromatica. It could also provide a new simple and effective method for utilizing the fingerprints to optimize the Chinese prescription and develop traditional Chinese medicine.
The relevance of personal characteristics and gender diversity for (eco‐)innovation activities at the firm‐level: Results from a linked employer–employee database in Germany
Authors: Horbach Jens , Jacob Jojo
Published: February 2018

The burgeoning literature on the determinants of eco‐innovation has not yet considered the influence of the personal characteristics of a firm's employees. The paper opens this “black box” of unexplained heterogeneity: it has often been observed that firms with broadly similar characteristics take different decisions concerning eco‐innovations. In fact, latent variables such as the greenness of a firm may be explained by the personal characteristics (gender, family status, geographic origins, education, etc.) of the firm's staff and decision‐makers. The linked employer–employee database of the Institute for Employment Research (IAB) in Germany makes such an analysis possible based on data for 2010–2012. The results of an econometric analysis show that having a large proportion of highly qualified women and a mixed‐gender management board are positively correlated with innovation activities in the environmental sector. The results further confirm that export‐oriented firms are more likely to innovate, firms characterized by staff overaging innovate to a lesser extent and greater competition pressure encourages innovation.
Signaling good by doing good: How does environmental corporate social responsibility affect international expansion?
Authors: Xu Xiaodong , Zeng Saixing , Chen Hongquan
Published: February 2018

This study investigates the mechanisms through which environmental corporate social responsibility (CSR) facilitates international expansion. It is currently believed that environmental CSR can allow firms to establish trusting relationships with external stakeholders and build competitive advantages. However, the question of whether and how environmental CSR affects export performance needs to be answered. We focus on two aspects of environmental CSR: energy conservation and emission reduction. We argue that firms with better performance in energy conservation and emission reduction are more likely to obtain international certification to pursue international expansion, as a signal of desirable attributes. By using 425 listed companies from environmentally sensitive industries between 2008 and 2012 in China, we find that a high level of energy conservation and emission reduction has a significant and indirect effect on export performance, which is mediated by their signaling behavior.
Central nervous system relapse in patients over 80 years with diffuse large B‐cell lymphoma: an analysis of two LYSA studies
Authors: Cabannes‐Hamy Aurélie , Peyrade Frederic , Jardin Fabrice , Emile Jean‐François , Delwail Vincent , Mounier Nicolas , Haioun Corinne , Perrot Aurore , Fitoussi Olivier , Lara Diane , Delarue Richard , André Marc , Offner Fritz , Ghesquières Hervé , Pascal Laurent , Soussain Carole , Lazarovici Julien , Schiano Jean‐Marc , Gaulard Philippe , Tilly Hervé , Thieblemont Catherine ,   the LYSA,   the lymphoma study association
Published: February 2018

CNS relapse is reported in 2–5% of diffuse large B‐cell lymphoma (DLBCL) patients, dramatically decreasing overall survival (OS). Very few studies address incidence and risk factors of CNS relapse in very elderly patients, a challenging population to treat given their commonly associated comorbidities. A retrospective analysis was performed of 270 DLBCL patients >80 years treated between 2004 and 2013 in two multicentre phase II LYSA trials (LNH03‐7B, LNH09‐7B) evaluating the addition of rituximab or ofatumumab to mini‐CHOP as front‐line therapy. No patients received CNS prophylaxis. CNS relapse was evaluated according to cumulative incidence, patient characteristics, risk factors, and survival. Median age was 83 years (range: 79–95). After a median follow‐up of 28.7 months, eight patients had CNS relapse (3.0%). Median time between inclusion and CNS relapse was 19.2 months (range: 3.2–32.6). Patients survived a median of 1.5 months after CNS relapse (range: 0.4–4.1). Median OS from relapse was significantly lower in CNS relapse patients (1.5 months, 95% CI: 0.4–3.5) compared to patients with non‐CNS relapse (6.6 months; 95% CI: 4.6–11.9). No baseline characteristics were associated with CNS relapse. The proportion of patients with CNS disease did not differ significantly between patients with low‐intermediate risk according to CNS‐IPI and patients with high risk (3% vs. 2.8%, P = 1.00). CNS relapse cumulative incidence in very elderly treatment‐naive patients is 1.8% at 2 years and is associated with poor survival. This population had a long median time to CNS relapse. Absence of prophylaxis did not strongly impact CNS relapse incidence.
Improving work‐life balance for ATs can reduce school's risk, liability
Authors: Neal Timothy
Published: February 2018

Athletic training in the college athletics setting has its challenges. Given the amount and year‐round nature of activities the athletic trainer is expected to cover, combined with team travel; meetings with coaches, staff, administrators, and recruits; and texts and emails coming in at all hours from coaches and student‐athletes, ATs have little time off. Add in the pressure of providing health care to a population expecting quick results to maintain their rigorous training, practicing, and seasonal competition (traditional and nontraditional season), plus the potential for litigation with every decision, ATs are set up for burnout, mistakes, and attitude challenges. ATs miss family functions, holidays, semester breaks, opportunities for professional development and continuing education, and summer vacations due to workload expectations. Athletics departments should pay attention to the red flag of concern raised by the potential liability that can result from overworked, under‐paid ATs trying to keep up with 80‐plus‐hour workweeks.
Discover 5 ways to develop a gratitude practice
Authors: Costa Karen
Published: February 2018

A growing body of research is looking at the positive impacts of gratitude. Harvard Mental Health newsletter detailed the connections between gratitude practices and individual well‐being, employee motivation, happiness, and fundraising initiatives. Gratitude feels good, motivates us, makes us happier, increases our generosity, and is equally beneficial to both giver and receiver.
Was student‐athlete with learning disability subjected to outrageous verbal abuse by his coaches?
Authors: Gelpi Aileen
Published: February 2018

In spite of his learning disability, Tulane University student Brandon Purcell was able to become a kicker on the football team in 2013.
Learn from others who have launched new sport programs
Authors: McCarthy Claudine
Published: February 2018

Drew Watson first became director of athletics at Southeastern University in 2013, the same year the school announced it would launch its inaugural season of football.
Human Appeasing Pheromone (HAP) influence on behavior and psychopathological residual symptoms of patients with complex psychiatric disorders
Authors: Piccinni Armando , Veltri Antonello , Marazziti Donatella , Mucci Federico , Cozzi Alessandro , Pageat Patrick
Published: February 2018

Key Clinical Message

This article is a case‐report series showing the effectiveness of a three‐month exposure to a synthetic analogue of Human Appeasing Pheromone as add‐on strategy to psychopharmacological treatment on behavioral and residual symptoms of three patients suffering from severe psychiatric disorders with complex clinical pictures.
A Polycarboxyl‐Decorated FeIII‐Based Xerogel‐Derived Multifunctional Composite (Fe3O4/Fe/C) as an Efficient Electrode Material towards Oxygen Reduction Reaction and Supercapacitor Application
Authors: Devi Bandhana , Venkateswarulu Mangili , Kushwaha Himmat Singh , Halder Aditi , Koner Rik Rani
Published: February 2018

Low cost, non‐noble metal catalysts with a good oxygen reduction reaction (ORR) activity comparable to that of platinum and also having good energy storage properties are highly desirable but challenging. Several challenges are associated with the development of such materials. Herein, we demonstrate a new polycarboxyl‐functionalised FeIII‐based gel material, synthesised following a solvothermal method and the development of its composite (Fe3O4/Fe/C) by annealing at optimised temperature. The developed composite displayed excellent electrocatalytic activity for the oxygen reduction reaction with an onset potential of 0.87 V (vs. RHE) and a current density value of −5 mA cm−2, which are comparable with commercial 20 wt % Pt/C. In addition, as one of the most desirable properties, the composite exhibits a better methanol tolerance and greater durability than Pt/C. The same material was explored as an energy storage material for supercapacitors, which showed a specific capacitance of 245 F g−1 at a current density of 1 A g−1. It is expected that this Fe3O4/Fe/C composite with a disordered graphitised carbon matrix will pave a horizon for developing energy conversion and energy storage devices.
The Hydrophobic Effect Applied to Organic Synthesis: Recent Synthetic Chemistry “in Water”
Authors: Lipshutz Bruce H. , Ghorai Subir , Cortes‐Clerget Margery
Published: February 2018

Recent developments over the past few years in aqueous micellar catalysis are discussed. Applications to problems in synthesis are highlighted, enabled by the use of surfactants that self‐aggregate in water into micelles as nanoreactors. These include amphiphiles that have been available for some time, as well as those that have been newly designed. Reactions catalyzed by transition metals, including Pd, Cu, Rh, and Au, are of particular focus.
High‐Nuclearity Heterometallic tert‐Butylethynide Clusters Assembled with tert‐Butylphosphonate
Authors: Duan Guang‐Xiong , Xie Yun‐Peng , Jin Jun‐Ling , Bao Li‐Piao , Lu Xing , Mak Thomas C. W.
Published: February 2018

tert‐Butylphosphonic acid and lanthanide precursors were employed to construct two high‐nuclearity hybrid silver(I)–ytterbium(III) phosphonate clusters: compound 1 consists of a Ag16 ethynide cluster fused with a trinuclear hydroxoytterbium phosphonate cluster, whereas compound 2 is composed of two Ag16 ethynide clusters bridged by a hexanuclear oxo/hydroxoytterbium phosphonate cluster. Using transition‐metal‐substituted lacunary polyoxotungstates in place of the lanthanide reactant, new phosphonate‐functionalized silver(I)–copper(II) ethynide clusters [Ag34Cu6 (3) and Ag37Cu6 (4)] and silver(I) ethynide clusters [Ag51 (5) and Ag72 (6)] were obtained. The structures of complexes 3–6 feature core–shell arrangements, in which silver(I)–copper(II) or silver(I) ethynide cluster shells stabilized by peripheral phosphonate ligands enclose different kinds of tungstate core templates.
Magnetic Reduced Graphene Oxide/Nickel/Platinum Nanoparticles Micromotors for Mycotoxin Analysis
Authors: Molinero‐Fernández Águeda , Jodra Adrián , Moreno‐Guzmán María , López Miguel Ángel , Escarpa Alberto
Published: February 2018

Magnetic reduced graphene oxide/nickel/platinum nanoparticles (rGO/Ni/PtNPs) micromotors for mycotoxin analysis in food samples were developed for food‐safety diagnosis. While the utilization of self‐propelled micromotors in bioassays has led to a fundamentally new approach, mainly due to the greatly enhanced target–receptor contacts owing to their continuous movement around the sample and the associated mixing effect, herein the magnetic properties of rGO/Ni/PtNPs micromotors for mycotoxin analysis are additionally explored. The micromotor‐based strategy for targeted mycotoxin biosensing focused on the accurate control of micromotor‐based operations: 1) on‐the‐move capture of free aptamers by exploiting the adsorption (outer rGO layer) and catalytic (inner PtNPs layer) properties and 2) micromotor stopped flow in just 2 min by exploiting the magnetic properties (intermediate Ni layer). This strategy allowed fumonisin B1 determination with high sensitivity (limit of detection: 0.70 ng mL−1) and excellent accuracy (error: 0.05 % in certified reference material and quantitative recoveries of 104±4 % in beer) even in the presence of concurrent ochratoxin A (105–108±8 % in wines). These results confirm the developed approach as an innovative and reliable analytical tool for food‐safety monitoring, and confirm the role of micromotors as a new paradigm in analytical chemistry.
Recent Advances in the Synthesis of β‐Functionalized Ketones by Radical‐Mediated 1,2‐Rearrangement of Allylic Alcohols
Authors: Weng Wei‐Zhi , Zhang Bo
Published: February 2018

β‐Functionalized ketones are a highly important and valuable class of compounds that have gained increasing attention from organic chemists due to their intensive uses as versatile synthetic intermediates and building blocks in complex molecule assembly and natural product synthesis. Accordingly, there is continuing interest in the development of new approaches for the synthesis of β‐functionalized ketones. In recent years, radical‐mediated 1,2‐rearrangement reactions of allylic alcohols, which proceed through cationic (semipinacol) rearrangements or radical (neophyl) rearrangements, have presented an attractive and powerful strategy to access various diversely β‐functionalized ketones. Interestingly, this strategy allows for the direct installation of a variety of valuable functional groups at the β‐position of cyclic and acyclic ketones by employing different radical precursors. However, a review focusing on the preparation of β‐functionalized ketones by radical‐mediated 1,2‐rearrangement reactions of allylic alcohols has not been summarized to date. This Minireview highlights recent progress made in this highly active and interesting research area, and the corresponding mechanisms will also be discussed.
1,8‐Diphenyl‐9,10‐Bis(arylethynyl)phenanthrenes: Synthesis, Distorted Structure, and Optical Properties
Authors: Konishi Akihito , Morinaga Atsushi , Fukuhara Gaku , Nishijima Masaki , Mori Tadashi , Kida Toshiyuki , Yasuda Makoto
Published: February 2018

The synthesis and optical properties of 1,8‐diphenyl‐9,10‐bis(arylethynyl)phenanthrenes, which are distorted phenanthrenes, are reported. The presence of the two phenyl groups at the 1,8‐positions of phenanthrene significantly distorts the molecular geometries, as was evidenced by X‐ray crystallography. The congested substitution pattern in the K region results in a distorted aromatic framework, which leads to a redshift in the emission spectrum. These observations are in stark contrast to 9,10‐bis(phenylethynyl)phenanthrene with no phenyl groups at the 1,8‐positions. A large Stokes shift suggested extensive structural relaxation between the phenyl and arylethynyl units in the excited state, which was supported by theoretical calculations.
A General Approach to Access Morphologies of Polyoxometalates in Solution by Using SAXS: An Ab Initio Modeling Protocol
Authors: Li Mu , Wang Weiyu , Yin Panchao
Published: February 2018

Herein, we reported a general protocol for an ab initio modeling approach to deduce structure information of polyoxometalates (POMs) in solutions from scattering data collected by the small‐angle X‐ray scattering (SAXS) technique. To validate the protocol, the morphologies of a serious of known POMs in either aqueous or organic solvents were analyzed. The obtained particle morphologies were compared and confirmed with previous reported crystal structures. To extend the feasibility of the protocol to an unknown system of aqueous solutions of Na2MoO4 with the pH ranging from −1 to 8.35, the formation of {Mo36} clusters was probed, identified, and confirmed by SAXS. The approach was further optimized with a multi‐processing capability to achieve fast analysis of experimental data, thereby, facilitating in situ studies of formations of POMs in solutions. The advantage of this approach is to generate intuitive 3D models of POMs in solutions without confining information such as symmetries and possible sizes.
Styrene Polymerization under Ambient Conditions by using a Transient 1,3,2‐Diazaphospholane‐2‐oxyl Complex
Authors: Heurich Tobias , Qu Zheng‐Wang , Kunzmann Robert , Schnakenburg Gregor , Engeser Marianne , Nožinović Senada , Streubel Rainer
Published: February 2018

A combined theoretical and experimental study on the formation and reactivity of a P‐OTEMP (P‐bound TEMPO (TEMPO=2,2,6,6‐tetramethyl‐piperidin‐1‐oxyl)) substituted 1,3,2‐diazaphospholane W(CO)5 complex is presented, including DFT‐based mechanistic details. The complex possesses a thermally labile O−N bond that cleaves homolytically yielding the transient 1,3,2‐diazaphospholane‐2‐oxyl complex [(CO)5W(R2PO.)], which acts as a radical initiator for styrene polymerization under ambient conditions.
Open Chain Polyarsenides of the Lanthanides
Authors: Schoo Christoph , Köppe Ralf , Piesch Martin , Gamer Michael T. , Konchenko Sergey N. , Scheer Manfred , Roesky Peter W.
Published: February 2018

The reaction of [(Cp′′′Co)2(μ,η2:2‐As2)2] with the decamethylsamarocenes [Cp*2Sm(THF)2] or [Cp*2Sm], or the bis(tetramethyl‐n‐propyl)samarocene [(C5Me4(n‐propyl))2Sm] resulted in the mixed d/f polyarsenides [(Cp′′′Co)2As4Sm(η5‐C5Me4R)2] (R=Me, n‐propyl). They are the first structural representatives of open chain‐like polyarsenides as ligands in the coordination sphere of lanthanides. Their formation can be explained by an intramolecular As–As coupling within the cobalt polyarsenide complex after reduction by the divalent samarium complex. Density functional theory calculations give insight into the structural change of the (As2)2 unit in [{Cp′′′Co(μ,η2:2‐As2)}2] upon reduction.
Beyond symptomatic relief for chemotherapy‐induced peripheral neuropathy: Targeting the source
Authors: Ma Jiacheng , Kavelaars Annemieke , Dougherty Patrick M. , Heijnen Cobi J.
Published: February 2018

Chemotherapy‐induced peripheral neuropathy (CIPN) is a serious adverse side effect of many chemotherapeutic agents, affecting >60% of patients with cancer. Moreover, CIPN persists long into survivorship in approximately 20% to 30% of these patients. To the authors' knowledge, no drugs have been approved to date by the US Food and Drug Administration to effectively manage chemotherapy‐induced neuropathic pain. The majority of the drugs tested for the management of CIPN aim at symptom relief, including pain and paresthesia, yet are not very efficacious. The authors propose that there is a need to acquire a more thorough understanding of the etiology of CIPN so that effective, mechanism‐based, disease‐modifying interventions can be developed. It is important to note that such interventions should not interfere with the antitumor effects of chemotherapy. Mitochondria are rod‐shaped cellular organelles that represent the powerhouses of the cell, in that they convert oxygen and nutrients into the cellular energy “currency” adenosine triphosphate. In addition, mitochondria regulate cell death. Neuronal mitochondrial dysfunction and the associated nitro‐oxidative stress represent crucial final common pathways of CIPN. Herein, the authors discuss the potential to prevent or reverse CIPN by protecting mitochondria and/or inhibiting nitro‐oxidative stress with novel potential drugs, including the mitochondrial protectant pifithrin‐μ, histone deacetylase 6 inhibitors, metformin, antioxidants, peroxynitrite decomposition catalysts, and anti‐inflammatory mediators including interleukin 10. This review hopefully will contribute toward bridging the gap between preclinical research and the development of realistic novel therapeutic strategies to prevent or reverse the devastating neurotoxic effects of chemotherapy on the (peripheral) nervous system. Cancer 2018;124:2289‐98. © 2018 American Cancer Society.
Adverse mental health outcomes in a population‐based cohort of survivors of childhood cancer
Authors: Nathan Paul C. , Nachman Alex , Sutradhar Rinku , Kurdyak Paul , Pole Jason D. , Lau Cindy , Gupta Sumit
Published: February 2018

BACKGROUND

The elevated risk for physical late effects in childhood cancer survivors (CCS) is well documented, but their risk for mental health problems is less well described.

METHODS

The authors assembled a cohort of all 5‐year CCS who were diagnosed before age 18 years and treated in an Ontario pediatric cancer center between 1987 and 2008. Patients were matched to population controls and linked to health administration databases. The authors calculated rates of mental health care visits (family physician, psychiatrist, emergency department, hospitalization) and the risk for a severe mental health event (emergency department, hospitalization, suicide). Outcomes were compared using recurrent event and survival analyses.

RESULTS

Compared with 20,269 controls, 4117 CCS had a higher rate of mental health visits (adjusted relative rate [RR], 1.34; 95% confidence interval [CI], 1.12‐1.52). Higher rates were associated with female gender (RR, 1.39; CI, 1.10‐1.75; P = .006) and being diagnosed at ages 15 to 17.9 years (compared with ages 0‐4 years: RR, 1.81; 95% CI, 1.17‐2.80; P = .008). Cancer type, treatment intensity, and treatments targeting the central nervous system were not significant predictors. Survivors were at increased risk for a severe event compared with controls (adjusted hazard ratio, 1.13; 95% CI, 1.00‐1.28; P = .045). CCS who were diagnosed with cancer at age 4 years or younger were at greatest risk: 16.3% (95% CI, 13.2%‐19.8%) had experienced a severe event by age 28 years.

CONCLUSIONS

CCS experienced higher rates of mental health visits and a greater risk for a severe event than the general population. Survivors of adolescent cancer have a higher rate of mental health visits overall, whereas survivors of cancer before age 4 years have a markedly elevated risk of severe events. Cancer 2018;124:2045‐57. © 2018 American Cancer Society.
T‐cell–depleted haploidentical stem cell transplantation results improve with time in adults with acute leukemia: A study from the Acute Leukemia Working Party of the European Society of Blood and Marrow Transplantation (EBMT)
Authors: Sestili Simona , Labopin Myriam , Ruggeri Annalisa , Velardi Andrea , Ciceri Fabio , Maertens Johan , Kanz Lothar , Aversa Franco , Lewalle Philippe , Bunjes Donald , Mohty Mohamad , Nagler Arnon
Published: February 2018

BACKGROUND

T‐cell–depleted, haploidentical transplantations (haplos) are commonly offered to patients who have high‐risk, acute leukemia in the absence of a human leukocyte antigen (HLA) full‐matched donor.

METHODS

To determine the effect of transplantation period, the authors divided 308 adults with de novo, acute leukemia who underwent T‐cell–depleted haplo from 2005 to 2015 into 2 groups, according the year in which they underwent transplantation (2005‐2011 [n = 191] and 2012‐2015 [n = 117]).

RESULTS

The median age was 41 years in patients who underwent transplantation before 2012 and 46 years in those who underwent transplantation after 2012 (P = .04). Most patients had acute myeloid leukemia (75% vs 69%; P = .26) and were in first complete remission (CR1) (55% vs 64%; P = .12) at the time of transplantation. The cumulative incidence of grade 2, 3, and 4 acute graft‐versus‐host disease (GvHD) and chronic GvHD were not different between the 2 groups (acute GvHD: 20% vs 22% cumulative incidence in patients who underwent haplo before and after 2012, respectively [P = .67]; chronic GvHD: 19% vs 11% cumulative incidence, respectively; P = .12]. The 2‐year relapse incidence was 20%, the nonrelapse mortality (NRM) rate was 48%, and no difference was observed over time (21% vs 19% [P = .72] and 54% vs 38% [P = .11] for patients who underwent haplo before and after 2012, respectively). The main cause of NRM was infection. Haplo after 2012 (hazard ratio [HR], 0.57; P = .01), younger age (HR, 0.82; P = .02), and receipt of a reduced‐intensity conditioning (RIC) regimen (HR, 0.53; P = .01) were independently associated with lower NRM. The 2‐year overall survival rate was 36% and improved after 2012 (29% vs 47% before 2012; P = .02); and it was higher for patients who underwent transplantation in CR1 (41% vs 29%; P = .01). In multivariate analysis, haplo after 2012 (HR, 0.54; P = .003) and receipt of a RIC regimen (HR, 0.54; P = .005) were independently associated with better overall survival. Similarly, leukemia‐free survival and GvHD‐free/relapse‐free survival (GRFS) improved over time: the leukemia‐free survival rate was 31% (25% vs 43% in the groups who underwent transplantation before and after 2012, respectively; P = .05), and the GRFS rate was 24% (19% vs 34%, respectively; P = .09). In addition, leukemia‐free survival and GRFS improved among patients who received a RIC regimen.

CONCLUSIONS

The outcome of patients with acute leukemia who underwent T‐cell–depleted haplo has improved over time. Cancer 2018;124:2142‐50. © 2018 American Cancer Society.
Relapse and survival after transplantation for complex karyotype acute myeloid leukemia: A report from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation and the University of Texas MD Anderson Cancer Center
Authors: Ciurea Stefan O. , Labopin Myriam , Socie Gerard , Volin Liisa , Passweg Jakob , Chevallier Patrice , Beelen Dietrich , Milpied Noel , Blaise Didier , Cornelissen Jan J. , Fegueux Nathalie , Polge Emmanuelle , Kongtim Piyanuch , Rondon Gabriela , Esteve Jordi , Mohty Mohamad , Savani Bipin N. , Champlin Richard E. , Nagler Arnon
Published: February 2018

BACKGROUND

Despite recent advances in allogeneic hematopoietic stem cell transplantation (AHSCT), the outcome of patients who have acute myeloid leukemia (AML) with a complex karyotype (CK) remains poor. The objective of this study was to identify prognostic factors associated with post‐transplantation survival in a large cohort of patients with CK AML.

METHODS

In total, data on 1342 consecutively patients who underwent transplantation for CK (≥3 chromosomal abnormalities) AML were provided by the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation and from the University of Texas MD Anderson Cancer Center database were included in the analysis. The median patient age was 52 years. The donors were human leukocyte antigen‐matched related donors (N = 749), matched unrelated donors (N = 513), and mismatched unrelated donors (N = 80).

RESULTS

Relapse was the main cause of treatment failure. Overall, 51% of patients relapsed, 17.6% died of treatment‐related mortality, and 31.3% survived leukemia‐free. In multivariate analysis, the factors associated with an increased risk of relapse were age (>40 years; hazard ratio [HR], 1.1 per 10 years;P= .02), secondary AML (HR, 1.35;P= .01), active disease at transplantation (HR, 1.98;P< .001), and deletion/monosomy 5 (HR, 1.5;P< .001); whereas age (HR, 1.15 per 10 years;P< .001), secondary AML (HR, 1.36;P= .001), active disease at transplantation (HR, 1.99;P< .001), deletion/monosomy 5 (HR, 1.24;P= .008), and deletion/monosomy 7 (HR, 1.44;P< .001) predicted for leukemia‐free survival.

CONCLUSIONS

Disease relapse remains the most common cause of treatment failure for patients with CK AML after transplantation. Novel approaches to decrease the relapse rate and improve survival are needed in these patients.Cancer2018;124:2134‐41. ©2018 American Cancer Society.
Induction and Measurement of Cytotoxic T Lymphocyte Activity
Authors: Wonderlich John , Shearer Gene , Livingstone Alexandra , Brooks Andrew , Soloski Mark J. , Presby Matthew M.
Published: February 2018

Cytotoxic T cells (CTLs) are important immune effector cells in the adaptive immune response. It has been well documented that CTLs are important in host immune responses to viral and bacterial intracellular pathogens, tumors, and transplanted tissues. The properties of CTLs have been studied extensively in murine models, and their roles validated in the human setting. Frequently, the presence of these cells correlates well with protective immunity, so the ability to readily measure the activity of these cells is an important immunological measurement. In this unit, several assays are described that are commonly utilized to induce CTLs and to measure CTL activity both in vitro and in vivo. These assays are adaptable to many experimental and/or disease models, and in the case of the in vitro assays can be applied to measure CTL activity in human samples. © 2018 by John Wiley & Sons, Inc.
Sporulation and Germination of Paenibacillus larvae Cells
Authors: Mahdi Osama S. , Fisher Nathan A.
Published: February 2018

Endospores are metabolically dormant cells formed by a variety of Gram‐positive bacteria within the phylum Firmicutes in response to nutrient limiting or otherwise unfavorable growth conditions. American foulbrood disease (AFB) is a serious disease of honeybees that is caused by the introduction of Paenibacillus larvae endospores into a honeybee colony. Progression to fulminant disease and eventual collapse of the colony requires multiple rounds of endospore germination, vegetative replication, endospore formation, and subsequent spread within the colony. This unit includes protocols for the in vitro sporulation and germination of P. larvae to assist investigators in the study of these processes. © 2018 by John Wiley & Sons, Inc.
Poliovirus Replicon RNA Generation, Transfection, Packaging, and Quantitation of Replication
Authors: Viktorova Ekaterina G. , Khattar Sunil , Samal Siba , Belov George A.
Published: February 2018

Poliovirus is a prototype member of the Enterovirus genus of the Picornaviridae family of small positive strand RNA viruses, which include important human and animal pathogens. Quantitative assessment of viral replication is very important for investigation of the virus biology and the development of anti‐viral strategies. The poliovirus genome structure allows replacement of structural genes with a reporter protein, such as a luciferase or a fluorescent protein, whose signals can be detected and quantified in vivo, thus permitting observation of replication kinetics in live cells. This paper presents protocols for poliovirus replicon RNA production, purification, packaging and transfection, as well as techniques for monitoring Renilla luciferase replication signal in living cells. © 2018 by John Wiley & Sons, Inc.
Association between intrusive negative autobiographical memories and depression: A meta‐analytic investigation
Authors: Mihailova Stella , Jobson Laura
Published: February 2018

The study investigated several associations between depression and intrusive negative autobiographical memories. A systematic literature search identified 23 eligible studies (N = 2,582), which provided 59 effect sizes. Separate meta‐analyses indicated that depression was moderately, positively associated with intrusive memory frequency, memory distress, maladaptive memory appraisals, memory avoidance, and memory rumination. Intrusive memory vividness was not significantly associated with depression. There were insufficient data to examine the relationship between depression and memory vantage perspective. Between‐study heterogeneity was high for intrusive memory frequency and memory avoidance, and the percentage of females in studies significantly moderated the relationship between these variables and depression. An additional exploratory meta‐analysis (3 studies; N = 257) indicated that intrusive memories were experienced more frequently by those with posttraumatic stress disorder than those with depression. Overall, the findings suggest that intrusive memories warrant clinical attention as they may contribute to the maintenance of depressive symptomatology.
A Convenient Split‐Intein Tag Method for the Purification of Tagless Target Proteins
Authors: Cooper Merideth A. , Taris Joseph E. , Shi Changhua , Wood David W.
Published: February 2018

In this work, we describe a novel self‐cleaving tag technology based on a highly modified split‐intein cleaving element. In this system, the N‐terminal segment of an engineered split intein is expressed in E. coli and covalently immobilized onto a capture resin, while the smaller C‐terminal intein segment is fused to the N‐terminus of the desired target protein. The tagged target can then be expressed in an appropriate expression system, without concern for premature intein cleaving. During the purification, strong association between the intein segments effectively captures the tagged target onto the capture resin while simultaneously generating a cleaving‐competent intein complex. Once the complex is purified by washing the column, intein‐mediated cleavage and release of the tagless target is induced with a simple shift in buffer pH from 8.5 to 6.2. The result is a convenient and effective method for the purification of traceless and tagless target proteins, which can be used in characterization and functional studies. © 2018 by John Wiley & Sons, Inc.
Phenotypic and Functional Evaluation of Hematopoietic Stem and Progenitor Cells in Toxicology of Heavy Metals
Authors: Li Qian , Yang Zhengli , Zhao Yifan , Jia Xiaodong , Zhou Zhijun , Zhang Yubin
Published: February 2018

All blood cells are differentiated from hematopoietic stem and progenitor cells (HSPCs), a process known as hematopoiesis that can be influenced by a variety of environmental factors. In this unit, we introduce a couple of protocols including phenotypic analysis, mixed bone marrow (BM) chimera and rescue assays, colony‐forming unit (CFU), and in vitro OP9 stromal cell differentiation assays for evaluating HSPCs in the BM of mice, and provide some examples of their implications in mouse models treated with heavy metals. The protocols for evaluating hematopoietic stem cells (HSCs) comprise phenotypic analysis and functional transplantation assays. The protocols for assessing hematopoietic progenitor cells (HPCs) consist of phenotypic analysis and in vitro differentiation assays. The main techniques applied in these protocols include flow cytometry (phenotypic analysis and sorting), irradiation, transplantation, and cell culture. © 2018 by John Wiley & Sons, Inc.
Exploring the Influence of Reaction Parameters on the Preparation of Calcium Carbonate by Spontaneous Precipitation
Authors: Wu Zhi Gang , Wang Jian , Guo Yang , Jia Yan Rong
Published: February 2018

Different polymorph and morphology of CaCO3 powder are prepared by spontaneous precipitation method in the presence of sodium citrate and NaOH at ambient temperature. The influence of spontaneous precipitation reaction parameters such as aging time, pH value, the concentration of complexing agent sodium citrate on the crystal phase, particle size and morphology of the precipitated calcium carbonate is studied in this paper. The prepared samples are characterized by scanning electron microscopy (SEM) and X‐ray diffraction (XRD). The results show that the aging time, the pH of the solution and the concentration of sodium citrate turned out to be important for the morphologies and crystal phase of CaCO3. Increasing the aging time, the content of vaterite decreases slightly, whereas the opposite effect is observed for increasing pH. When pH value is 13, pure calcite irregular nanoparticles can be prepared. In the presence of sodium citrate, the content of vaterite increases as the increasing of sodium citrate. When the concentration of sodium citrate is increased to 0.1 m, uniform vaterite microsphere with 5 µm size can be obtained.
Investigation of Selected Alcohols as Antisolvents in the Crystallization Behavior of Ammonium Dihydrogen Phosphate from Aqueous Solutions
Authors: Sangwal Keshra , Mielniczek‐Brzóska Ewa
Published: February 2018

Measurements of temperatures Tw of water at initial temperature 30 °C and temperature Ts of aqueous ADP solutions saturated at 30 °C against the content x of three alcohols (i.e. methanol, ethanol and n‐butanol) added as antisolvents at different rates reveal regions of constant temperature in the maxima of the Tw(x) plots in water and in the vicinity of occurrence of three‐dimensional (3D) nucleation of the Ts(x) plots in the solutions. These regions of constant temperature, represented by the antisolvent content x, lie between x1 and x2 such that Δx = (x2−x1) > 0. It is found that the antisolvent content range Δx decreases with an increase in the maximum constant temperatures in the Tw(x) and Ts(x) plots. From an analysis of the data of x1 and x2 for different maximum temperatures obtained from the Tw(x) and Ts(x) plots it is argued that the maximum value of Δx is related to the withdrawal of the heat of reactions by the cooling system. However, in the case of ADP solutions, the value of Δx representing the width of the maxima due to 3D nucleation in the Ts(x) plots is also related to the reorganization of crystalline clusters to form stable 3D nuclei during antisolvent crystallization.
An intrusion detection system based on combining probability predictions of a tree of classifiers
Authors: Ahmim Ahmed , Derdour Makhlouf , Ferrag Mohamed Amine
Published: February 2018

Intrusion detection system (IDS) represents an unavoidable tool to secure our network. It is considered as a second defense line against the different form of attacks. The principal limits of the current IDSs are their inability to combine the detection of the new form of attacks with high detection rate and low false alarm rate. In this paper, we propose an intrusion detection system based on the combination of the probability predictions of a tree of classifiers. Specifically, our model is composed of 2 layers. The first one is a tree of classifiers. The second layer is a classifier that combines the probability predictions of the tree. The built tree contains 4 levels where each node of this tree represents a classifier. The first node classifies the connections in 2 clusters: Denial of Service attacks and Cluster 2. Then, the second node classifies the connections of the Cluster 2 in Probing attacks and Cluster 3. The third node classifies the connections of the Cluster 3 in Remote‐to‐Local attacks and Cluster 4. Finally, the last node classifies the connections of the Cluster 4 in User‐to‐Root attacks and Normal connections. The second layer contains the last classifier that combines the probability predictions of the first layer and take the final decision. The experiments on KDD'99 and NSL‐KDD show that our model gives a low false alarm rate and the highest detection rate. Furthermore, our model is more precise than the recent intrusion detection system models with accuracy equal to 96.27% for KDD'99 and 89.75% for NSL‐KDD.
Learning of hierarchical serial patterns emerges in infancy
Authors: Lewkowicz David J. , Schmuckler Mark A. , Mangalindan Diane M. J.
Published: February 2018

Recursive, hierarchically organized serial patterns provide the underlying structure in many cognitive and motor domains including speech, language, music, social interaction, and motor action. We investigated whether learning of hierarchical patterns emerges in infancy by habituating 204 infants to different hierarchical serial patterns and then testing for discrimination and generalization of such patterns. Results indicated that 8‐ to 10‐month‐old and 12‐ to 14‐month‐old infants exhibited sensitivity to the difference between hierarchical and non‐hierarchical structure but that 4‐ to 6‐month‐old infants did not. These findings demonstrate that the ability to perceive, learn, and generalize recursive, hierarchical, pattern rules emerges in infancy and add to growing evidence that general‐purpose pattern learning mechanisms emerge during the first year of life.
Engage community to create awareness of accessibility
Authors: Hope Joan
Published: February 2018

When Catherine E. Johnson, J.D., M.A., became director of the ADA Resource Center for Equity and Accessibility at the University of Kansas, she planned a series of efforts to improve the Hawk Route, an accessible route across campus.
Help your students understand access at your institution
Authors: Gaddy Stephanie
Published: February 2018

Helping students understand the difference between access and success can be a challenge. Essentially, all college students with disabilities are entitled to equal access to all courses and activities offered at the college. However, equal access does not mean equal success, and this is where the confusion might occur. This confusion can result in disappointment, frustration, and maybe even anger for students.
Closed captioning is a valuable resource to all students, as long as they can find the captions
Authors: Sutton Halley
Published: February 2018

Nearly all students take courses with video components, but only a little more than half of students know how to find out if course videos have captions, according to a study conducted by Katie Linder, Ph.D., research director at Oregon State University Ecampus. According to Linder, 99.7 percent of students surveyed reported having at least one course, either face to face or online, that made heavy use of videos, but only 55.9 percent of those students were able to determine if those videos offered closed captioning.
Micro‐environment and intracellular metabolism modulation of adipose tissue macrophage polarization in relation to chronic inflammatory diseases
Authors: Zhu Xiao , Tu Yixuan , Chen Hainan , Jackson Ampadu O. , Patel Vaibhav , Yin Kai
Published: February 2018

The accumulation and pro‐inflammatory polarization of immune cells, mainly macrophages, in adipose tissue (AT) are considered crucial factors for obesity‐induced chronic inflammatory diseases. In this review, we highlighted the role of adipose tissue macrophage (ATM) polarization on AT function in the obese state and the effect of the micro‐environment and intracellular metabolism on the dynamic switch of ATMs into their pro‐inflammatory or anti‐inflammatory phenotypes, which may have distinct influences on obesity‐related chronic inflammatory diseases. Obesity‐associated metabolic dysfunctions, including those of glucose, fatty acid, cholesterol, and other nutrient substrates such as vitamin D and iron in AT, promote the pro‐inflammatory polarization of ATMs and AT inflammation via regulating the interaction between ATMs and adipocytes and intracellular metabolic pathways, including glycolysis, fatty acid oxidation, and reverse cholesterol transportation. Focusing on the regulation of ATM metabolism will provide a novel target for the treatment of obesity‐related chronic inflammatory diseases, including insulin resistance, cardiovascular diseases, and cancers.