bluuebunny/crossref_metadata_2025 huggingface dataset:
Oil resistance and low‐temperature characteristics of plasticized nitrile butadiene rubber compounds
Authors: Kim Do Young , Kim Gi Hong , Nam Gi Myeong , Kang Dong Gug , Seo Kwan Ho
Published: April 2019

The mechanical properties and oil resistance of nitrile butadiene rubber as an automotive material are investigated under low‐temperature conditions. We discuss the effects of various plasticizers, such as dioctyl adipate, adipic acid ester, polyether ester, and adipic acid polyester. The mechanical properties after thermal oxidation aging, as well as oil resistance and low‐temperature characteristics of the compounds, are measured using a moving die rheometer, universal testing machine, differential scanning calorimeter, low‐temperature retraction tester, and gehman torsional stiffness tester. We focus on how the oil resistance and low‐temperature characteristics are affected by the plasticizer type and plasticizer content. The results demonstrate that nitrile butadiene rubber compounds are affected by the low molecular weight and viscosity of the plasticizer. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019, 136, 47851.
Methyl ketone production by Pseudomonas putida is enhanced by plant‐derived amino acids
Authors: Dong Jie , Chen Yan , Benites Veronica Teixeira , Baidoo Edward E.K. , Petzold Christopher J. , Beller Harry R. , Eudes Aymerick , Scheller Henrik V. , Adams Paul D. , Mukhopadhyay Aindrila , Simmons Blake A. , Singer Steven W.
Published: April 2019

Plants are an attractive sourceof renewable carbon for conversion to biofuels and bio‐based chemicals. Conversion strategies often use a fraction of the biomass, focusing on sugars from cellulose and hemicellulose. Strategies that use plant components, such as aromatics and amino acids, may improve the efficiency of biomass conversion. Pseudomonas putida is a promising host for its ability to metabolize a wide variety of organic compounds. P. putida was engineered to produce methyl ketones, which are promising diesel blendstocks and potential platform chemicals, from glucose and lignin‐related aromatics. Unexpectedly, P. putida methyl ketone production using Arabidopsis thaliana hydrolysates was enhanced 2–5‐fold compared with sugar controls derived from engineered plants that overproduce lignin‐related aromatics. This enhancement was more pronounced (~seven‐fold increase) with hydrolysates from nonengineered switchgrass. Proteomic analysis of the methyl ketone‐producing P. putida suggested that plant‐derived amino acids may be the source of this enhancement. Mass spectrometry‐based measurements of plant‐derived amino acids demonstrated a high correlation between methyl ketone production and amino acid concentration in plant hydrolysates. Amendment of glucose‐containing minimal media with a defined mixture of amino acids similar to those found in the hydrolysates studied led to a nine‐fold increase in methyl ketone titer (1.1 g/L).
A validated RP‐HPLC method for the evaluation of the influence of grapefruit juice on liver S9 activation of sacubitril
Authors: Moussa Bahia Abbas , Hashem Hanaa M.A. , Mahrouse Marianne Alphonse , Tarek Mahmoud Sally
Published: April 2019

Grapefruit juice inhibits esterase enzyme. Therefore, a possible interaction with ester prodrugs should be taken into consideration. In this study, the influence of grapefruit juice on sacubitril (SAC) rat liver S9 activation by esterase enzyme was evaluated. An RP‐HPLC method was developed and validated for estimation of SAC in rat liver S9 fraction using a C18 Cyano column as stationary phase and acetonitrile–sodium di‐hydrogen phosphate buffer (0.02 m, pH 4 adjusted by o‐phosphoric acid, 40:60, v/v), as mobile phase at a flow rate of 1 mL/min and UV detection at 254 nm. The method was successfully applied to an in vitro study in which SAC was incubated with rat liver S9 fraction prepared from rats that had previously ingested grapefruit juice for a week. The calculated SAC concentration after incubation was compared with that of SAC incubated with rat liver S9 fraction from the rat control group. The statistical significance between the results of test and control incubation sets was assessed. In conclusion, the current study demonstrated that grapefruit juice decreased SAC hydrolysis, hence delaying its activation to sacubitrilat (active form) in gut lumen. Based on this food–drug interaction, it may be required that grapefruit juice should be consumed with caution in patients receiving SAC.
What is hindering change? Anticipating the barriers to the adoption of enzyme‐based textile processing in a developing country
Authors: Rahman Mahfuzur , Billah Md Morsaline , Hack‐Polay Dieu
Published: April 2019

The study aimed to examine the barriers to embracing enzymatic processing in the garment industry in a developing country. We used the case of Bangladesh, which has the largest garment sector in the world. The research used semistructured interviews with 10 high‐profile figures in the industry, comprising scientists, manufacturers, enzyme traders, and policymakers. We found economic, sociocultural, informational, and policy‐related barriers to the adoption of enzymatic processing. Attending to each element would benefit manufacturers primarily; this will help identify its strengths and weaknesses to ensure the effective implementation of enzymatic textile processing to obtain optimum results. The study also found that manufacturers' desire to help improve environmental performance is a factor, which could motivate them in adopting green manufacturing innovation. It is expected that regulatory frameworks that encourage innovation—particularly from high social responsiveness and compliances as well as economic and financial incentives—would motivate manufacturers to develop sustainable environmental management strategies that enhance their ability to compete in global markets.
Democratizing health insurance services; accelerating social inclusion through technology policy of health insurance firms
Authors: Nayak Bishwajit , Bhattacharyya Som Sekhar , Krishnamoorthy Bala
Published: April 2019

Technology plays an important role in reducing inequalities in health care delivery and enhancing quality of life. Health insurance firms require a potent technology policy to understand social determinants of health insurance that can lead to more innovative approaches to social inclusivity initiatives. This paper explicates critical factors of technology policy of health insurance firms that can contribute to better social inclusion and move towards universal health care. Through structured survey questionnaire, data were collected from 125 senior health insurance executives from India for identifying factors important for technology policy. A technology policy scale comprising six distinct factors is developed for health insurance firms using exploratory factor analysis. The factors are “organizational technology strategy,” “technology value drivers,” “technology utilization,” “firm agility in technology,” “firm technology capabilities,” and “customer focus through technology.” The factors identified in this study can be utilized and integrated with enabling technologies such as machine learning, internet of things, big data analytics, and digital phenotyping for creation of electronic health records that are critical for risk management of health insurance firms. This would help to promote healthy lifestyles and disease prevention strategies to strengthen universal health care for society. This paper looks at the factors that are essential in framing a technology policy for the health insurance sector. It provides reasons on how the factors contribute in the evolving health insurance field and can increase the rate of social inclusion for health care. And, finally, it helps in distinguishing how technology requirements and utilization in health insurance is different from other businesses.
Hybrid approach to ventricular septal defect enlargement
Authors: Patel Neil D. , Justino Henri , Ing Frank F.
Published: April 2019

The need for creation or enlargement of a ventricular septal defect (VSD) is a rare occurrence. It is most frequently required in patients with double‐outlet right ventricle who develop restriction of a remote muscular VSD or obstruction of a perimembranous VSD secondary to atrioventricular (AV) valve attachments to the interventricular septum. Surgical and transcatheter options for VSD creation or enlargement are associated with several risks including heart block, AV valve injury, and perforation. We report the first description of a hybrid approach to VSD creation and enlargement in two patients.
Influence of Solvents on Solution‐Mediated Polymorphic Transformation of the Polymorphs of L‐Histidine
Authors: Wantha Lek , Punmalee Neeranuch , Flood Adrian E.
Published: April 2019

Solution‐mediated polymorphic transformation (SMPT) of the metastable polymorph B of L‐histidine (L‐his) into the stable polymorph A in water‐antisolvent solutions was performed. Methanol, acetone, and acetonitrile served as antisolvents. The SMPT was studied via nucleated batch antisolvent crystallization process by determining the change of the fraction of the stable polymorph A of L‐his in the crystal phase with time during the crystallization process. The fraction of the stable polymorph A of L‐his was assessed offline by Raman spectroscopy. The transformation time depended on the fractions of form A obtained at the initial stage of crystallization. The transformation rate of the metastable polymorph B into the stable polymorph A at lower antisolvent volume fraction was faster than at higher antisolvent volume fraction. The transformation time of polymorph B into polymorph A in water‐acetonitrile solution was the shortest compared to the other solutions.
Kinetic Control of a Self‐Assembly Pathway towards Hidden Chiral Microcoils
Authors: Guo Yongxian , Liu Yin , Gong Yanjun , Xiong Wei , Zhang Chuang , Zhao Jincai , Che Yanke
Published: April 2019

Manipulating the self‐assembly pathway is essentially important in the supramolecular synthesis of organic nano‐ and microarchitectures. Herein, we design a series of photoisomerizable chiral molecules, and realize precise control over pathway complexity with external light stimuli. The hidden single‐handed microcoils, rather than the straight microribbons through spontaneous assembly, are obtained through a kinetically controlled pathway. The competition between molecular interactions in metastable photostationary intermediates gives rise to a variety of molecular packing and thereby the possibility of chirality transfer from molecules to supramolecular assemblies.
A Highly Luminescent Tetrahydrocurcumin IrIII Complex with Remarkable Photoactivated Anticancer Activity
Authors: Colombo Alessia , Fontani Mattia , Dragonetti Claudia , Roberto Dominique , Williams J. A. Gareth , Scotto di Perrotolo Rossella , Casagrande Francesca , Barozzi Sara , Polo Simona
Published: April 2019

Curcumin has chemopreventative properties against a variety of tumours, but has poor bioavailability. Here, two new bis‐cyclometallated iridium(III) complexes have been prepared, featuring the natural product curcumin (CUR) or its reduced form, tetrahydrocurcumin (THC), as bidentate, anionic O O‐binding ligands. The iridium THC complex is highly luminescent in deoxygenated solution and efficiently generates singlet oxygen under aerated conditions, whereas in the CUR analogue, other non‐radiative decay pathways are competitive. The complexes are rapidly taken up by a variety of human tumour cell lines from solutions of micromolar concentration. They show negligible cytotoxicity in the absence of irradiation. When briefly irradiated with visible light, Ir‐THC becomes highly phototoxic, inducing rapid apoptosis within 2 h. The results show the high potential of such complexes as sensitizers in photodynamic therapy (PDT).
Radical Cation Diels‐Alder Reactions of Non‐Conjugated Alkenes as Dienophiles by Electrocatalysis
Authors: Ozaki Atsushi , Yamaguchi Yusuke , Okada Yohei , Chiba Kazuhiro
Published: April 2019

Summary of main observation and conclusion

Radical cation Diels‐Alder reactions provide a powerful method for the construction of six‐membered ring systems between both electron‐rich dienes and dienophiles. However, the most recent examples of this class have been limited to β‐methylstyrenes as dienophiles; the use of non‐conjugated alkenes remains challenging. The present study describes the serendipitous development of novel radical cation Diels‐Alder reactions by electrocatalysis that use non‐conjugated alkenes as dienophiles. The key to successful transformation involves highly substituted cyclohexenyl radical cations that are stable enough to be reduced by intermolecular single electron transfer.
Aryl and Arylalkyl Substituted 3‐Hydroxypyridin‐2(1H)‐ones: Synthesis and Evaluation as Inhibitors of Influenza A Endonuclease
Authors: Sagong Hye Yeon , Bauman Joseph D. , Nogales Aitor , Martínez‐Sobrido Luis , Arnold Eddy , LaVoie Edmond J.
Published: April 2019

Seasonal influenza infections are associated with an estimated 250–500 000 deaths annually. Resistance to the antiviral M2 ion‐channel inhibitors has largely invalidated their clinical utility. Resistance to neuraminidase inhibitors has also been observed in several influenza A virus (IAV) strains. These data have prompted research on inhibitors that target the cap‐snatching endonuclease activity of the polymerase acidic protein (PA). Baloxavir marboxil (Xofluza®), recently approved for clinical use, inhibits cap‐snatching endonuclease. Resistance to Xofluza® has been reported in both in vitro systems and in the clinic. An X‐ray crystallographic screening campaign of a fragment library targeting IAV endonuclease identified 5‐chloro‐3‐hydroxypyridin‐2(1H)‐one as a bimetal chelating agent at the active site. We have reported the structure–activity relationships for 3‐hydroxypyridin‐2(1H)‐ones and 3‐hydroxyquinolin‐2(1H)‐ones as endonuclease inhibitors. These studies identified two distinct binding modes associated with inhibition of this enzyme that are influenced by the presence of substituents at the 5‐ and 6‐positions of 3‐hydroxypyridin‐2(1H)‐ones. Herein we report the structure–activity relationships associated with various para‐substituted 5‐phenyl derivatives of 6‐(p‐fluorophenyl)‐3‐hydroxypyridin‐2(1H)‐ones and the effect of using naphthyl, benzyl, and naphthylmethyl groups as alternatives to the p‐fluorophenyl substituent on their activity as endonuclease inhibitors.
Is there still a role for stem cell transplantation in multiple myeloma?
Authors: Mina Roberto , Lonial Sagar
Published: April 2019

High‐dose chemotherapy and autologous stem cell transplantation (ASCT) are a standard of care for transplant‐eligible patients with newly diagnosed multiple myeloma (MM). The introduction of novel agents, which range from immunomodulatory drugs and proteasome inhibitors to monoclonal antibodies and have now been integrated into both induction and salvage regimens, has dramatically revolutionized the treatment landscape of MM and challenged the role of high‐dose chemotherapy and ASCT in treating MM. These advances have led to a number of provocative questions. First, what is the current role of stem cell transplantation (SCT) in comparison with standard‐dose therapy incorporating novel agents? Second, should ASCT be performed upfront (“early”) or later (“delayed”) in the course of the disease? Third, should single or double ASCT be performed? Fourth, is allogeneic SCT still an option for patients with MM? This article provides an overview of available data and evidence‐based responses regarding the role of SCT in MM.
Inotuzumab ozogamicin in combination with low‐intensity chemotherapy (mini‐HCVD) with or without blinatumomab versus standard intensive chemotherapy (HCVAD) as frontline therapy for older patients with Philadelphia chromosome‐negative acute lymphoblastic leukemia: A propensity score analysis
Authors: Jabbour Elias J. , Sasaki Koji , Ravandi Farhad , Short Nicholas J. , Garcia‐Manero Guillermo , Daver Naval , Kadia Tapan , Konopleva Marina , Jain Nitin , Cortes Jorge , Issa Ghayas C. , Jacob Jovitta , Kwari Monica , Thompson Philip , Garris Rebecca , Pemmaraju Naveen , Yilmaz Musa , O’Brien Susan M. , Kantarjian Hagop M.
Published: April 2019

Background

The outcome of older patients with newly diagnosed, Philadelphia chromosome (Ph)‐negative acute lymphoblastic leukemia (ALL) is poor. The combination of targeted therapy with low‐intensity chemotherapy is safe and effective. The objective of the current analysis was to compare the outcome of patients who received a combination of inotuzumab ozogamicin plus low‐intensity chemotherapy (mini–hyperfractionated cyclophosphamide, vincristine, and dexamethasone [mini‐HCVD]) with or without blinatumomab versus the outcome of those who received the standard, intensive, hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (HCVAD) regimen.

Methods

The authors analyzed 135 older patients with newly diagnosed, Ph‐negative ALL who were treated prospectively with standard HCVAD (n = 77) or with the combination of inotuzumab ozogamicin plus mini‐HCVD with or without blinatumomab (n = 58). A propensity score analysis was conducted using 1:1 matching using the nearest neighbor matching method.

Results

Propensity score matching identified 38 patients in each cohort. The antibody plus low‐intensity chemotherapy combination induced higher response rates (98% vs 88%), with lower rates of early death (0% vs 8%) and lower rates of death in complete remission (5% vs 17%). With propensity score matching, the 3‐year event‐free survival rates for patients who received HCVAD and those who received the combination of inotuzumab ozogamicin plus mini‐HCVD with or without blinatumomab were 34% and 64%, respectively (P = .003), and the 3‐year overall survival rates were 34% and 63%, respectively (P = .004). By multivariate analysis, age (P = .019; hazard ratio, 1.045) and the combination of inotuzumab plus mini‐HCVD with or without blinatumomab (P = .020; hazard ratio, 0.550) were identified as independent prognostic factors for survival.

Conclusions

The combination of inotuzumab ozogamicin plus mini‐HCVD with or without blinatumomab is safe and effective in older patients with newly diagnosed, Ph‐negative ALL and confers a better outcome compared with standard HCVAD chemotherapy.
Complexing‐Coprecipitation Method to Synthesize Catalysts of Cobalt, Nitrogen‐Doped Carbon, and CeO2 Nanosheets for Highly Efficient Oxygen Reduction
Authors: Wang Xiaoqing , Xu Jijian , Wu Zongxiao , Zhi Mingjia , Hong Zhanglian , Huang Fuqiang
Published: April 2019

The oxygen reduction reaction (ORR) is the key cathode reaction in renewable‐energy technologies. Developing highly efficient, low‐cost, methanol‐tolerant and durable ORR catalysts is highly needed. In this research, we reported a simple complexing‐coprecipitation method to synthesize CeO2 nanosheets encapsulated by a nitrogen‐doped carbon (NC) layer with uniformly dispersed Co nanoparticles catalysts on the surface. In particular, the 0.5Co‐NC‐CeO2 sample exhibits high ORR catalytic activity with an onset potential of 875 mV (vs. RHE), a diffusion‐limited current density of 4.72 mA/cm2 and a positive half‐wave potential of 817 mV (vs RHE), while 20% Pt/C presents an onset potential of 934 mV (vs. RHE), a diffusion limited current density of 5.8 mA/cm2 and half‐wave potential of 850 mV (vs. RHE). In addition, the catalyst 0.5Co‐NC‐CeO2 also possesses a robust durability, that is the half‐wave potential exhibits a negative shift of only 17 mV after 1000 cycles. The enhanced ORR performance can be attributed to the synergistic effect among Co, the nitrogen‐doped carbon layer and CeO2. The results demonstrated here have implications in designing non‐Pt ORR catalysts.
Association Between Tumor Size Kinetics and Survival in Patients With Urothelial Carcinoma Treated With Atezolizumab: Implication for Patient Follow‐Up
Authors: Tardivon Coralie , Desmée Solène , Kerioui Marion , Bruno René , Wu Benjamin , Mentré France , Mercier François , Guedj Jérémie
Published: April 2019

We characterized the association between tumor size kinetics and survival in patients with advanced urothelial carcinoma treated with atezolizumab (anti‐programmed death‐ligand 1, Tecentriq) using a joint model. The model, developed on data from 309 patients of a phase II clinical trial, identified the time‐to‐tumor growth and the instantaneous changes in tumor size as the best on‐treatment predictors of survival. On the validation dataset containing data from 457 patients from a phase III study, the model predicted individual survival probability using 3‐month or 6‐month tumor size follow‐up data with an area under the receptor‐occupancy curve between 0.75 and 0.84, as compared with values comprised between 0.62 and 0.75 when the model included only information available at treatment initiation. Including tumor size kinetics in a relevant statistical framework improves the prediction of survival probability during immunotherapy treatment and may be useful to identify most‐at‐risk patients in “real‐time.”
Rapid Quantification of NETs In Vitro and in Whole Blood Samples by Imaging Flow Cytometry
Authors: Lelliott Patrick M. , Momota Masatoshi , Lee Michelle S.J. , Kuroda Etsushi , Iijima Norifumi , Ishii Ken J. , Coban Cevayir
Published: April 2019

Neutrophil extracellular trap (NET) formation involves the release of DNA outside the cell to neutralize pathogens. Techniques such as live microscopy, flow cytometry, and intravital imaging allow the characterization of NETs, but these either cannot be applied in vivo, lack specificity or require invasive procedures. We developed an automated analysis method to rapidly acquire and characterize cells as NETs or NET precursors, as opposed to cells undergoing other forms of cell death, using imaging flow cytometry. NETs were maintained in solution using a novel three‐dimensional cell culture system in which cells are suspended at the interface of two liquids of different density. Critically, we identify NETs using an image analysis algorithm based on morphological data showing the extrusion of DNA beyond the cell boundaries. In vitro, we used this technique to demonstrate different requirements for NET formation in human and mouse neutrophils. We also measured NETs in whole blood during infection of mice with the malaria parasite Plasmodium yoelii. We expect this technique will provide a valuable approach to better understand the process of NET formation and its importance in disease. © 2019 International Society for Advancement of Cytometry
Effects of SGLT2 inhibitors on fractures and bone mineral density in type 2 diabetes: An updated meta‐analysis
Authors: Li Xiaoyu , Li Ting , Cheng Ying , Lu Yunhong , Xue Mei , Xu Linxin , Liu Xiangyang , Yu Xiaochen , Sun Bei , Chen Liming
Published: April 2019

Background

The aim of the study is to update and determine the effects of sodium glucose cotransporter 2 (SGLT2) inhibitor therapy on fracture and bone mineral density (BMD) in patients with type 2 diabetes mellitus (T2DM).

Methods

We identified 27 eligible randomized controlled trials (RCTs) that compared the efficacy and safety of SGLT2 inhibitors to a placebo in 20 895 T2DM participants, with an average duration of 64.22 weeks. The relative risk (RR) of bone fracture and weighted mean difference (WMD) of changes in the BMD from baseline were determined to evaluate the risk of fracture. The degree of heterogeneity was evaluated by the I2 statistic, and publication bias was estimated using a funnel plot and Egger test.

Results

The pooled RR was 1.02 (95% CI [0.81, 1.28]) with low heterogeneity, indicating that SGLT2 inhibitor treatment was not correlated with a higher risk of fracture. Additionally, no increased risk was found for patients with different ages, sexes, and levels of HbA1c and some biochemical indicators. Three trials with 1303 patients reported a change in the BMD from baseline. SGLT2 inhibitor treatment did not decrease the BMD at four skeletal sites (lumbar spine, femoral neck, total hip, and distal forearm), and the overall WMD was 0.08 (95% CI [−0.09, 0.26]). No significant publication bias was detected.

Conclusions

No increased risk for bone fracture was detected in patients with T2DM treated with SGLT2 inhibitors in this meta‐analysis. SGLT2 inhibitor therapy did not appear to affect bone health, but more long‐term detailed data are needed to validate this conclusion.
Changing landscapes of Southeast Asia and rodent‐borne diseases: decreased diversity but increased transmission risks
Authors: Morand Serge , Blasdell Kim , Bordes Frédéric , Buchy Philippe , Carcy Bernard , Chaisiri Kittipong , Chaval Yannick , Claude Julien , Cosson Jean‐François , Desquesnes Marc , Jittapalapong Sathaporn , Jiyipong Tawisa , Karnchanabanthoen Anamika , Pornpan Pumhom , Rolain Jean‐Marc , Tran Annelise
Published: April 2019

The reduction in biodiversity from land use change due to urbanization and agricultural intensification appears to be linked to major epidemiological changes in many human diseases. Increasing disease risks and the emergence of novel pathogens result from increased contact among wildlife, domesticated animals, and humans. We investigated the relationship between human alteration of the environment and the occurrence of generalist and synanthropic rodent species in relation to the diversity and prevalence of rodent‐borne pathogens in Southeast Asia, a hotspot of threatened and endangered species, and a foci of emerging infectious diseases. We used data from an extensive pathogen survey of rodents from seven sites in mainland Southeast Asia in conjunction with past and present land cover analyses. At low spatial resolutions, we found that rodent‐borne pathogen richness is negatively associated with increasing urbanization, characterized by increased habitat fragmentation, agriculture cover and deforestation. However, at a finer spatial resolution, we found that some major pathogens are favored by environmental characteristics associated with human alteration including irrigation, habitat fragmentation, and increased agricultural land cover. In addition, synanthropic rodents, many of which are important pathogen reservoirs, were associated with fragmented and human‐dominated landscapes, which may ultimately enhance the opportunities for zoonotic transmission and human infection by some pathogens.
Molecular identification of natural hybridization betweenMelastoma malabathricumandMelastoama beccarianumin Sarawak, Malaysia
Authors: Wu Renzhi , Zou Peishan , Tan Guangwen , Hu Zhenyang , Wang Yongqi , Ning Zulin , Wu Wei , Liu Ying , He Shaoyun , Zhou Renchao
Published: April 2019

Hybridization is very common in flowering plants and it plays a significant role in plant evolution and adaptation.MelastomaL. (Melastomataceae) comprises about 80–90 species in tropical Asia and Oceania, among which 41 species occur in Borneo. Natural hybridization is frequently reported inMelastomain China, but so far there have been no confirmed cases of hybridization in Southeast Asia (including Borneo), where most species occur. Here, we identified a case of natural hybridization betweenMelastoma malabathricumL. andMelastoma beccarianumCogn. in Sarawak, Malaysia, by using sequence data of three nuclear genes and one chloroplast intergenic spacer.Melastoma malabathricumis the most widespread species of this genus, occurring in almost the whole range of this genus, whileM. beccarianumis a local species endemic to northern Borneo. Our results showed that natural hybridization and introgression occur betweenM. malabathricumandM. beccarianum, and the introgression was asymmetrical, mainly fromM. malabathricumtoM. beccarianum. As adaptive traits can be transferred by introgression, our study suggests that natural hybridization should be a significant mechanism for the evolution and adaptation ofMelastomain Southeast Asia. However, introgression from the common speciesM. malabathricumto the relatively rare speciesM. beccarianummay cause the decline ofM. beccarianum, incurring conservation concern. With a large number of species ofMelastomaand almost year‐around flowering in Southeast Asia, more cases of natural hybridization are expected to be found and identified in near future.
Temporal and spatial variation in distribution of fish environmental DNA in England’s largest lake
Authors: Lawson Handley Lori , Read Daniel S. , Winfield Ian J. , Kimbell Helen , Johnson Harriet , Li Jianlong , Hahn Christoph , Blackman Rosetta , Wilcox Rose , Donnelly Rob , Szitenberg Amir , Hänfling Bernd
Published: April 2019

Environmental DNA offers great potential as a biodiversity monitoring tool. Previous work has demonstrated that eDNA metabarcoding provides reliable information for lake fish monitoring, but important questions remain about temporal and spatial repeatability, which is critical for understanding the ecology of eDNA and developing effective sampling strategies. Here, we carried out comprehensive spatial sampling of England's largest lake, Windermere, during summer and winter to (1) examine repeatability of the method, (2) compare eDNA results with contemporary gill‐net survey data, (3) test the hypothesis of greater spatial structure of eDNA in summer compared to winter due to differences in water mixing between seasons, and (4) compare the effectiveness of shore and offshore sampling for species detection. We find broad consistency between the results from three sampling events in terms of species detection and abundance, with eDNA detecting more species than established methods and being significantly correlated with rank abundance determined by long‐term data. As predicted, spatial structure was much greater in the summer, reflecting less mixing of eDNA than in the winter. For example Arctic charr, a deep‐water species, was only detected in deep, midlake samples in the summer, while littoral or benthic species such as minnow and stickleback were more frequently detected in shore samples. By contrast in winter, the eDNA of these species was more uniformly distributed. This has important implications for design of sampling campaigns, for example, deep‐water species could be missed and littoral/benthic species overrepresented by focusing exclusively on shoreline samples collected in the summer.
Anodic Mechanism of 1,1′‐Bis(diphenylphosphino)ferrocenedicarbonylnickel Determined by Low‐Temperature Spectroelectrochemistry
Authors: Ringenberg Mark R. , Döttinger Florian
Published: April 2019

[Ni(CO)2(dppf)] [1] {dppf = 1,1′‐bis(diphenylphosphino)ferrocene} was made by reductive carbonylation of [NiCl2(dppf)] with [Fe(CO)5], similar to our recent report in Organometallics, 2019, 38, 586–592. Complex [1] showed two oxidation waves in the cyclic voltammogram. UV/Vis‐NIR spectroelectrochemistry (SEC) and IR SEC at –30 °C as well as computational support by means of DFT was used to assign the oxidation state of both metal atoms after oxidation. The monocation [1]+ showed a strong NIR absorption band which was described as an IVCT [NiI→FeII] and inverse IVCT (iIVCT) or hole transfer [FeII→NiI] based on time dependence DFT (TD‐DFT). The IR SEC spectrum of [1]+ showed multiple bands associated with two similar configurations, one which had the spin delocalized over both metal atoms and a second configuration where the spin is primarily Ni localized. The second oxidation to [1]2+ occurred at the Ni atom and resulted in release of a CO ligand followed by the formation of dimeric complex determined by low temperature IR SEC.
Post‐wildfire sediment cascades: A modeling framework linking debris flow generation and network‐scale sediment routing
Authors: Murphy Brendan P. , Czuba Jonathan A. , Belmont Patrick
Published: April 2019

Wildfires represent one of the largest disturbances in watersheds of the Intermountain West. Yet, we lack models capable of predicting post‐wildfire impacts on downstream ecosystems and infrastructure. Here we present a novel modeling framework that links new and existing models to simulate the post‐wildfire sediment cascade, including spatially explicit predictions of debris flows, storage of debris flow sediment within valleys, delivery of debris flow sediment to active channels, and the downstream routing of sediment through river networks. We apply the model to sediment dynamics in Clear Creek watershed following the 2010 Twitchell Canyon Fire in the Tushar Mountains of southern Utah. The debris flow generation model performed well, correctly predicting 19 out of 20 debris flows from the largest catchments, with only four false positives and two false negatives at observed rainfall intensities. In total, the model predicts the occurrence of 160 post‐wildfire debris flows across the Clear Creek watershed, generating more than 650 000 m3 of sediment. Our new storage and delivery model predicts the vast majority of this sediment is stored within valleys, and only 13% is delivered to the river network. The sediment routing model identifies numerous sediment bottlenecks within the network, which alter transport dynamics and may be hotspots for aggradation and aquatic habitat alteration. The volume of sediment exported from the watershed after seven years of simulation totals 17% of that delivered, or 2% of the total generated debris flow sediment. In the case of the Twitchell Canyon Fire, this highlights that significant post‐wildfire sediment volumes can be stored in valleys (87%) and within the stream network (11%). Finally, we discuss useful insights that can be gleaned from the model framework, as well as the limitations and need for more monitoring and theory development in order to better constrain essential inputs, process rates, and morphodynamics. © 2019 John Wiley & Sons, Ltd.
Modeling and simulation of batteries and development of an energy storage system based in Riyadh, Saudi Arabia
Authors: Khan Salah Ud‐Din , Almutairi Zeyad Ammar
Published: April 2019

In this study, a renewable energy powered energy storage and utilization system is designed and modeled. The main objective of the study involves developing a theoretical‐simulation model for a coupled energy storage unit suitable for Saudi Arabia's climate conditions. The study commenced with the selection of the batteries most appropriate for a representative location in Riyadh, Kingdom of Saudi Arabia (KSA). Various parameters associated with performance and economic assessments of batteries were calculated via simulation. Photovoltaic (PV) panels were used as a renewable energy source. Feasibility studies of the PV panels were performed by considering the working conditions in the KSA. Finally, an integrated system composed of a PV system, a battery, and an end‐user was designed. A technical and economic model was developed for the coupled PV based energy storage and utilization unit. The simulation results obtained from the integrated system confirmed the suitability of practical demonstration (prototype) in the selected location. The current findings suggested the development of a working prototype of the theoretically proven energy storage system. This study paves the path to develop a method to conduct a feasible study of various other renewable energy‐driven storage systems.
Enhanced Microbial Bile Acid Deconjugation and Impaired Ileal Uptake in Pregnancy Repress Intestinal Regulation of Bile Acid Synthesis
Authors: Ovadia Caroline , Perdones‐Montero Alvaro , Spagou Konstantina , Smith Ann , Sarafian Magali H. , Gomez‐Romero Maria , Bellafante Elena , Clarke Louise C.D. , Sadiq Fouzia , Nikolova Vanya , Mitchell Alice , Dixon Peter H. , Santa‐Pinter Natalie , Wahlström Annika , Abu‐Hayyeh Shadi , Walters Julian R.F. , Marschall Hanns‐Ulrich , Holmes Elaine , Marchesi Julian R. , Williamson Catherine
Published: April 2019

Pregnancy is associated with progressive hypercholanemia, hypercholesterolemia, and hypertriglyceridemia, which can result in metabolic disease in susceptible women. Gut signals modify hepatic homeostatic pathways, linking intestinal content to metabolic activity. We sought to identify whether enteric endocrine signals contribute to raised serum bile acids observed in human and murine pregnancies, by measuring fibroblast growth factor (FGF) 19/15 protein and mRNA levels, and 7α‐hydroxy‐4‐cholesten‐3‐one. Terminal ileal farnesoid X receptor (FXR)‐mediated gene expression and apical sodium bile acid transporter (ASBT) protein concentration were measured by qPCR and western blotting. Shotgun whole‐genome sequencing and ultra‐performance liquid chromatography tandem mass spectrometry were used to determine the cecal microbiome and metabonome. Targeted and untargeted pathway analyses were performed to predict the systemic effects of the altered metagenome and metabolite profiles. Dietary CA supplementation was used to determine whether the observed alterations could be overcome by intestinal bile acids functioning as FXR agonists. Human and murine pregnancy were associated with reduced intestinal FXR signaling, with lower FGF19/15 and resultant increased hepatic bile acid synthesis. Terminal ileal ASBT protein was reduced in murine pregnancy. Cecal bile acid conjugation was reduced in pregnancy because of elevated bile salt hydrolase‐producing Bacteroidetes. CA supplementation induced intestinal FXR signaling, which was not abrogated by pregnancy, with strikingly similar changes to the microbiota and metabonome as identified in pregnancy. Conclusion: The altered intestinal microbiota of pregnancy enhance bile acid deconjugation, reducing ileal bile acid uptake and lowering FXR induction in enterocytes. This exacerbates the effects mediated by reduced bile acid uptake transporters in pregnancy. Thus, in pregnant women and mice, there is reduced FGF19/15‐mediated hepatic repression of hepatic bile acid synthesis, resulting in hypercholanemia.
Cholangiocyte‐Derived Exosomal Long Noncoding RNA H19 Promotes Hepatic Stellate Cell Activation and Cholestatic Liver Fibrosis
Authors: Liu Runping , Li Xiaojiaoyang , Zhu Weiwei , Wang Yanyan , Zhao Derrick , Wang Xuan , Gurley Emily C. , Liang Guang , Chen Weidong , Lai Guanhua , Pandak William M. , Robert Lippman H. , Bajaj Jasmohan S. , Hylemon Phillip B. , Zhou Huiping
Published: April 2019

Activation of hepatic stellate cells (HSCs) represents the primary driving force to promote the progression of chronic cholestatic liver diseases. We previously reported that cholangiocyte‐derived exosomal long noncoding RNA‐H19 (lncRNA‐H19) plays a critical role in promoting cholestatic liver injury. However, it remains unclear whether cholangiocyte‐derived lncRNA‐H19 regulates HSC activation, which is the major focus of this study. Both bile duct ligation (BDL) and Mdr2 knockout (Mdr2‐/‐) mouse models were used. Wild‐type and H19maternalΔExon1/+ (H19KO) mice were subjected to BDL. Mdr2‐/‐H19maternalΔExon1/+ (DKO) mice were generated. Exosomes isolated from cultured mouse and human cholangiocytes or mouse serum were used for in vivo transplantation and in vitro studies. Fluorescence‐labeled exosomes and flow cytometry were used to monitor exosome uptake by hepatic cells. Collagen gel contraction and bromodeoxyuridine assays were used to determine the effect of exosomal‐H19 on HSC activation and proliferation. Mouse and human primary sclerosing cholangitis (PSC)/primary biliary cholangitis (PBC) liver samples were analyzed by real‐time PCR, western blot analysis, histology, and immunohistochemistry. The results demonstrated that hepatic H19 level was closely correlated with the severity of liver fibrosis in both mouse models and human patients with PSC and PBC. H19 deficiency significantly protected mice from liver fibrosis in BDL and Mdr2‐/‐ mice. Transplanted cholangiocyte‐derived H19‐enriched exosomes were rapidly and preferentially taken up by HSCs and HSC‐derived fibroblasts, and promoted liver fibrosis in BDL‐H19KO mice and DKO mice. H19‐enriched exosomes enhanced transdifferentiation of cultured mouse primary HSCs and promoted proliferation and matrix formation in HSC‐derived fibroblasts. Conclusion: Cholangiocyte‐derived exosomal H19 plays a critical role in the progression of cholestatic liver fibrosis by promoting HSC differentiation and activation and represents a potential diagnostic biomarker and therapeutic target for cholangiopathies.
A multicenter retrospective comparison of induction chemoimmunotherapy regimens on outcomes in transplant‐eligible patients with previously untreated mantle cell lymphoma
Authors: Ng Zi Yun , Bishton Mark , Ritchie David , Campbell Robert , Gilbertson Michael , Hill Kate , Ratnasingam Sumita , Schwarer Anthony , Manos Kate , Shorten Sophie , Ng Melissa , Nelson Niles , Xin Liu , De Mel Widanalage Sanjay , Sunny Tenny , Purtill Duncan , Poon Michelle , Johnston Anna , Cochrane Tara , Lee Hui‐Peng , Hapgood Greg , Tam Constantine , Opat Stephen , Hawkes Eliza , Seymour John , Cheah Chan Yoon
Published: April 2019

Mantle cell lymphoma (MCL) is an uncommon and typically aggressive form of lymphoma. Although often initially chemosensitive, relapse is common. Several induction and conditioning regimens are used in transplant‐eligible patients, and the optimal approach remains unknown. We performed an international, retrospective study of transplant‐eligible patients to assess impact of induction chemoimmunotherapy and conditioning regimens on clinical outcomes. We identified 228 patients meeting inclusion criteria. Baseline characteristics were similar among the induction groups except for some variation in age. The type of induction chemoimmunotherapy received did not influence overall response rates (ORRs) (0.43), progression‐free survival (PFS) (P > .67), or overall survival (OS) (P > .35) on multivariate analysis (PFS and OS). Delivery of autologous stem cell transplant (ASCT) was associated with favorable PFS and OS (0.01) on univariate analysis only; this benefit was not seen on multivariate analysis—PFS (0.36) and OS (0.21). Compared with busulfan and melphalan (BuMel), the use of the carmustine, etoposide, cytarabine, melphalan (BEAM)–conditioning regimen was associated with inferior PFS (HR = 2.0 [95% CI 1.1‐3.6], 0.02) but not OS (HR = 1.1 [95% CI 0.5‐2.3], 0.81) on univariate analysis only. Within the limits of a retrospective study and modest power for some comparisons, type of induction therapy did not influence ORR, PFS, or OS for transplant‐eligible patients with MCL. International efforts are required to perform randomized clinical trials evaluating chemoimmunotherapy induction regimens.
Impact of 2016 WHO diagnosis of early and overt primary myelofibrosis on presentation and outcome of 232 patients treated with ruxolitinib
Authors: Palandri Francesca , Palumbo Giuseppe A. , Abruzzese Elisabetta , Iurlo Alessandra , Polverelli Nicola , Elli Elena , Bonifacio Massimiliano , Bergamaschi Micaela , Martino Bruno , Tiribelli Mario , Benevolo Giulia , Tieghi Alessia , Sgherza Nicola , Isidori Alessandro , Binotto Gianni , Crugnola Monica , Heidel Florian , Cavazzini Francesco , Bosi Costanza , Auteri Giuseppe , Cattaneo Daniele , Foà Robin , Lemoli Roberto M. , Cuneo Antonio , Krampera Mauro , Bartoletti Daniela , Cavo Michele , Vianelli Nicola , Breccia Massimo , Latagliata Roberto
Published: April 2019

The 2016 WHO criteria identified early primary myelofibrosis (PMF) as an individual entity with milder clinical features and better outcome compared with overt PMF. Here, we compared early and overt PMF patients treated with ruxolitinib in terms of baseline clinical/laboratory characteristics, response, and toxicity to treatment. We observed that early‐PMF patients achieve better and more stable spleen and symptoms responses, with significantly lower rates of hematological toxicities. No differences in overall and leukemia‐free survival were detected between the two cohorts. The application of 2016 WHO criteria is crucial to identify those PMF patients who deserve a stricter monitoring during treatment.
Transplantation of miR‐219 overexpressed human endometrial stem cells encapsulated in fibrin hydrogel in spinal cord injury
Authors: Jalali Monfared Marzie , Nasirinezhad Farinaz , Ebrahimi‐Barough Somayeh , Hasanzade Gholamreza , Saberi Hooshang , Tavangar Seyed Mohammad , Asadpour Shiva , Aryan Leila , Barabadi Zahra , Ai Jafar
Published: April 2019

Oligodendrocyte (OL) loss and demyelination occur after spinal cord injury (SCI). Stimulation of remyelination through transplantation of myelinating cells may be effective in improving function. For the repair strategy to be successful, the selection of a suitable cell and maintaining cell growth when cells are injected directly to the site of injury is important. In addition to selecting the type of cell, fibrin hydrogel was used as a suitable tissue engineering scaffold for this purpose. To test the relationship between myelination and functional improvement, the human endometrial stem cells (hEnSCs) were differentiated toward oligodendrocyte progenitor cells (OPCs) using overexpression of miR‐219. Adult female Wistar rats were used to induce SCI by using a compression model and were randomly assigned to the following four experimental groups: SCI, Vehicle, hEnSC, and OPC. Ten days after injury, miR‐219 overexpressed hEnSC‐derived OPCs encapsulated in fibrin hydrogel, as an injectable scaffold, were injected to the injury site. In this study, with a focus on promoting functional recovery after SCI, the Basso‐Beattie‐Bresnahan test was performed to evaluate the recovery of motor function every week for 10 weeks and the histological assay was then performed. Results showed that the rate of motor function recovery was significantly higher in OPC group compared to SCI and vehicle groups but no marked differences were found between OPC and hEnSC groups, although, the rate of myelination in the OPC group was significantly higher than the other groups. These results demonstrated that remyelination was not the cause of recovery of motor function.
siRNA‐mediated silencing of PAI‐1 gene acts as a promoter over the recanalization of endothelial progenitor cells in rats with venous thrombosis
Authors: Li Hang , Zhang Bo , Lu Shan , Ji De‐Gang , Ding Meng , Ye Yan‐Shuo , Sun Da‐Jun
Published: April 2019

With the changing lifestyle, venous thrombosis (VT) is becoming increasingly prevalent and poses a burden on the health economy. Endothelial progenitor cells (EPCs) are recruited into resolving VT. We aimed to investigate the effect of plasminogen activator inhibitor 1 (PAI‐1) silencing on the recanalization of VT in rat EPCs. EPCs and VT rat models were cultured and treated with negative control‐siRNA vector and PAI‐1‐siRNA vector, respectively. 4,5‐Dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay, wound‐healing test, and Matrigel‐induced tubular experiment were performed to detect the ability of cell proliferation, migration, and EPCs lumen formation. Immunohistochemistry was used to observe the recanalization of thrombus. The messenger RNA (mRNA) and protein expression of PAI‐1 and vascular endothelial growth factor (VEGF) were determined by reverse transcription quantitative polymerase chain reaction and Western blot analysis. PAI‐1‐siRNA enhances the luminal formation ability of EPCs and significantly promotes EPCs homing. In response to PAI‐1 gene silencing, tissues from inferior vena cava displayed reduced mRNA and protein expression of PAI‐1, increased VEGF expression as well as promoted lumen‐like structures. PAI‐1 gene silencing can promote the recanalization of VT by enhancement of the luminal formation ability of rats’ EPCs.