bluuebunny/crossref_metadata_2025 huggingface dataset:
Potential‐Responsive Surfaces for Manipulation of Cell Adhesion, Release, and Differentiation
Authors: Zhang Libing , Wang Zongjie , Das Jagotamoy , Labib Mahmoud , Ahmed Sharif , Sargent Edward H. , Kelley Shana O.
Published: August 2019

In living systems, interfacial molecular interactions control many biological processes. New stimuli‐responsive strategies are desired to provide versatile model systems that can regulate cell behavior in vitro. Described here are potential‐responsive surfaces that control cell adhesion and release as well as stem cell differentiation. Cell adhesion can be modulated dynamically by applying negative and positive potentials to surfaces functionalized with tailored monolayers. This process alters cell morphology and ultimately controls behavior and the fate of the cells. Cells can be detached from the electrode surface as intact clusters with different geometries using electrochemical potentials. Importantly, morphological changes during adhesion guide stem cell differentiation. The higher accessibility of the peptide under a positive applied potential causes phenotypic changes in the cells that are hallmarks of osteogenesis, whereas lower accessibility of the peptide promoted by negative potentials leads to adipogenesis.
Reactions in the Photocatalytic Conversion of Tertiary Alcohols on Rutile TiO2(110)
Authors: Courtois Carla , Eder Moritz , Schnabl Kordula , Walenta Constantin A. , Tschurl Martin , Heiz Ulrich
Published: August 2019

According to textbooks, tertiary alcohols are inert towards oxidation. The photocatalysis of tertiary alcohols under highly defined vacuum conditions on a titania single crystal reveals unexpected and new reactions, which can be described as disproportionation into an alkane and the respective ketone. In contrast to primary and secondary alcohols, in tertiary alcohols the absence of an α‐H leads to a C−C‐bond cleavage instead of the common abstraction of hydrogen. Surprisingly, bonds to methyl groups are not cleaved when the alcohol exhibits longer alkyl chains in the α‐position to the hydroxyl group. The presence of platinum loadings not only increases the reaction rate but also opens up a new reaction channel: the formation of molecular hydrogen and a long‐chain alkane resulting from recombination of two alkyl moieties. This work demonstrates that new synthetic routes may become possible by introducing photocatalytic reaction steps in which the co‐catalysts may also play a decisive role.
Differential Responsiveness of Monocyte and Macrophage Subsets to Interferon
Authors: Han Shuhong , Zhuang Haoyang , Lee Pui Y. , Li Mingjia , Yang Lijun , Nigrovic Peter A. , Reeves Westley H.
Published: August 2019

Objective

Peripheral blood mononuclear cells (PBMCs) in systemic lupus erythematosus (SLE) patients exhibit a gene expression program (interferon [IFN] signature) that is attributed to overproduction of type I IFNs by plasmacytoid dendritic cells. Type I IFNs have been thought to play a role in the pathogenesis of SLE. This study was undertaken to examine an unexpected influence of monocyte/macrophages on the IFN signature.

Methods

Proinflammatory (classic) and antiinflammatory (nonclassic) monocyte/macrophages were sorted from mice and analyzed by RNA sequencing and quantitative polymerase chain reaction (qPCR). Type I IFN‐α/β/ω receptor (IFNAR‐1) expression was determined by qPCR and flow cytometry. Macrophages were stimulated in vitro with IFNα, and pSTAT1was measured.

Results

Transcriptional profiling of peritoneal macrophages from mice with pristane‐induced SLE unexpectedly indicated a strong IFN signature in classic, but not nonclassic, monocyte/macrophages exposed to the same type I IFN concentrations. Ifnar1 messenger RNA and IFNAR surface staining were higher in classic monocyte/macrophages versus nonclassic monocyte/macrophages (P < 0.0001 and P < 0.05, respectively, by Student's t‐test). Nonclassic monocyte/macrophages were also relatively insensitive to IFNα‐driven STAT1 phosphorylation. Humans exhibited a similar pattern: higher IFNAR expression (P < 0.0001 by Student's t‐test) and IFNα‐stimulated gene expression (P < 0.01 by paired Wilcoxon's rank sum test) in classic monocyte/macrophages and lower levels in nonclassic monocyte/macrophages.

Conclusion

This study revealed that the relative abundance of different monocyte/macrophage subsets helps determine the magnitude of the IFN signature. Responsiveness to IFNα signaling reflects differences in IFNAR expression in classic (high IFNAR) compared to nonclassic (low IFNAR) monocyte/macrophages. Thus, the IFN signature depends on both type I IFN production and the responsiveness of monocyte/macrophages to IFNAR signaling.
Multidentate Anchors for Surface Functionalization
Authors: Li Zhong‐Qiu , Tang Jian‐Hong , Zhong Yu‐Wu
Published: August 2019

The bottom‐up functionalization of solid surfaces shows increasing importance for a wide range of interdisciplinary applications. Multidentate anchors with more than two contact points can bind to solid surfaces with strong chemisorption, well‐defined upright configuration, and tailored functionality. The surface functionalization using multidentate anchors with three (tripodal), four (quadripodal), or more binding points is summarized herein, with a focus on those beyond classical tripodal anchors. In particular, the molecular design on how to achieve multisite interaction between anchor and substrate and the introduction of functional groups to thin films are discussed.
Teaching progressions and learning progressions
Authors: Wolfson Adele J.
Published: August 2019

Just as students undergo “learning progressions” in moving from naivety to mastery of biochemical topics, faculty experience “teaching progressions” as they experiment with pedagogy, listen to students' feedback, and become members of a community of educators. An important element of both teaching and learning is assessment. Good assessment tools reflect the value we place on thoughtful instruction and in‐depth thinking. © 2019 International Union of Biochemistry and Molecular Biology, 47(5):493–497, 2019.
Plasmid production and purification: An integrated experiment‐based biochemistry and biotechnology laboratory course
Authors: Santos Tiago , Pereira Patrícia , Queiroz João A. , Cruz Carla , Sousa Fani
Published: August 2019

This laboratory experiment describes the production and purification of plasmid DNA for undergraduate biochemistry and biotechnology courses. This experiment performed in a one‐week period includes the protocols for plasmid pVAX1‐LacZ production in Escherichia coli DH5α cells and subsequent purification of supercoiled pVAX1‐LacZ. Firstly, the students use a growth medium that favors the replication of the plasmid resulting in a higher plasmid production during exponential growth. Afterwards, alkaline lysis is done to disrupt the bacterial cells and recover pVAX1‐LacZ plasmid. Lastly, they perform the purification of pVAX1‐LacZ supercoiled isoform by L‐histidine chromatography, followed by agarose gel electrophoresis to characterize the separation of supercoiled isoform from contaminants. The proposed experiment provides an opportunity for students to acquire these skills that are routinely used in biochemistry and biotechnology laboratories. © 2019 International Union of Biochemistry and Molecular Biology, 47(6):638–643, 2019.
Conceptualization of system dynamic for patchouli oil agroindustry development
Authors: Rahmayanti Dina , Hadiguna Rika Ampuh , Santosa Santosa , Nazir Novizar
Published: August 2019

Patchouli oil industry is one of the sectors that should be developed in Indonesia because Indonesia supplies around 90% patchouli oil in the world. This study aims to identify the data required for making agroindustry development decisions using system dynamic. This research was designing the stock flow diagrams (SFD) of patchouli oil from the plantation to the exporter. There are four types of SFD patchouli oil agroindustry, namely, plantation section, farmer section, collector section, and exporter section. The results of the study can identify the data needed as input for the dynamic system model. Input data must be determined first to run the model. Input data for each stage of SFD must be available if the government wants to do the development of patchouli oil agroindustry using a dynamic system model.
Virtualization and visualization of virtual memory system for effective teaching–learning
Authors: Bhat Wasim A. , Rashid Aazima , Wani Faiza F. , Altaf Fiza
Published: August 2019

In this paper we present a tool that virtualizes creation and execution of large address space programs, and visualizes working of virtual memory system in response to their virtualized execution to facilitate effective teaching–learning of the abstract concept and technical details of virtual memory system. The tool allows users to write large address space virtual programs using a small set of instructions, virtualize their execution and visualize the working of virtual memory system in response to their virtualized execution. We also evaluated students’ response towards the tool to investigate its teaching–learning effectiveness and acceptance by student community. The results suggest that with respect to the Technology Acceptance Model variables, students had positive values indicating a tendency to be favorable towards using the tool in their learning. Students exhibited high intention to use the tool, demonstrated a high positive attitude towards the tool, and showed high perceived usefulness of the tool to acquire complete, concrete and confident knowledge of virtual memory system.
Wavy mucosal tear in the sigmoid colon
Authors: Tominaga Kentaro , Yokoyama Junji , Hayashi Kazunao , Tsuchiya Atsunori , Terai Shuji
Published: August 2019

Although linear mucosal tears have been reported, we found a relatively rare case of wavy mucosal tear in collagenous colitis. This may be related to the mutual weak adhesiveness between the epithelium and collagen band. This complication necessitates great care to be taken while performing colonoscopy in patients suspected of collagenous colitis.
Magnetic Fields Enhanced the Performance of Tubular Dichalcogenide Micromotors at Low Hydrogen Peroxide Levels
Authors: de la Asunción‐Nadal Víctor , Jurado‐Sánchez Beatriz , Vázquez Luis , Escarpa Alberto
Published: August 2019

Propulsion at the microscale has attracted significant research interest. In this work, a numerical simulation to explain the speed boost of up to 34 % experienced by transition metal dichalcogenides (TMD) based micromotors under the effect of applied magnetic fields is described. The simulations show that, when an external magnetic field is applied, the flow regime changes from turbulent to laminar. This causes an increase in the residence time of the fuel over the catalyst surface, which enhances the oxygen production. The more efficient generation and growth of the bubbles lead to an increase of the capillary force exerted by them. Interestingly, the effect is more pronounced as the level of fuel decrease. The validity of the model is also proven by comparing both theoretical and experimental results. Interestingly, the speed enhancement in magnetic mode depends on geometrical factors only, as a similar phenomenon was observed in a variety of microjets with a variable surface roughness. The understanding of such phenomena will open new avenues for understanding and controlling the motion behavior of high‐towing‐force catalytic micromotors.
Engineering Migration Pathway for Effective Separation of Photogenerated Carriers on Multicomponent Heterojunctions Coated with Nitrogen‐Doped Carbon
Authors: Zhuang Yuan , Sun Liming , Zeng Suyuan , Zhan Wenwen , Wang Xiao‐Jun , Zhao Yanli , Han Xiguang
Published: August 2019

Multicomponent NiTiO3/A‐TiO2/R‐TiO2 photocatalysts coated with nitrogen‐doped carbon (N‐C/NiTiO3/A‐TiO2/R‐TiO2) for efficient H2 production were fabricated by directly pyrolyzing NH2‐MIL‐125(Ni/Ti) metal–organic framework microrods. Owing to the synergistic effect of the N‐doped carbon coating layer and multicomponent heterojunctions, the H2 production rate of N‐C/NiTiO3/A‐TiO2/R‐TiO2 was even higher than that of its Pt‐containing counterpart (Pt/NiTiO3/A‐TiO2/R‐TiO2). N‐C/NiTiO3/A‐TiO2 and N‐C/NiTiO3/R‐TiO2 as control photocatalysts were also prepared by simply adjusting the calcination temperature of NH2‐MIL‐125(Ni/Ti) in air atmosphere. The H2 production rate followed the order of N‐C/NiTiO3/A‐TiO2/R‐TiO2>N‐C/NiTiO3/A‐TiO2>N‐C/NiTiO3>R‐TiO2, which indicates that the multicomponent heterojunction plays a key role in photocatalytic H2 generation. The mechanism for the influence of the multicomponent heterojunction on photocatalytic activity was investigated in combination with molecular simulations, which showed that N‐C/NiTiO3/A‐TiO2/R‐TiO2 has a so‐called double type II heterojunction providing a perfect step‐by‐step migration pathway for effective separation of photogenerated electrons and holes. This work presents a simple and effective method for synthesizing efficient multicomponent photocatalysts.
Acid‐Assisted Direct Olefin Metathesis of Unprotected Carbohydrates in Water
Authors: Timmer Brian J. J. , Ramström Olof
Published: August 2019

The ability to use unprotected carbohydrates in olefin metathesis reactions in aqueous media is demonstrated. By using water‐soluble, amine‐functionalized Hoveyda–Grubbs catalysts under mildly acidic aqueous conditions, the self‐metathesis of unprotected alkene‐functionalized α‐d‐manno‐ and α‐d‐galactopyranosides could be achieved through minimization of nonproductive chelation and isomerization. Cross‐metathesis with allyl alcohol could also be achieved with reasonable selectivity. The presence of small quantities (2.5 vol %) of acetic acid increased the formation of the self‐metathesis product while significantly reducing the alkene isomerization process. The catalytic activity was furthermore retained in the presence of large amounts (0.01 mm) of protein, underlining the potential of this carbon–carbon bond‐forming reaction under biological conditions. These results demonstrate the potential of directly using unprotected carbohydrate structures in olefin metathesis reactions under mild conditions compatible with biological systems, and thereby enabling their use in, for example, drug discovery and protein derivatization.
Metal‐Free Fast Azidation by Using Tetrabutylammonium Azide: Effective Synthesis of Alkyl Azides and Well‐Defined Azido‐End Polymethacrylates
Authors: Wang Chen‐Gang , Chong Amerlyn Ming Liing , Lu Yunpeng , Liu Xu , Goto Atsushi
Published: August 2019

An effective method to synthesize azido‐end polymethacrylates from tetrabutylammonium azide (BNN3) in a nonpolar solvent (toluene) was developed. Several low‐mass alkyl halides were reacted with BNN3 in toluene as model reactions and the rate constants of these reactions were determined, to confirm fast BNN3 azidation for tertiary and secondary halides. The end‐group transformation of halide‐end polymethacrylates was effective and nearly quantitative. Notably, the combination of organocatalyzed living (or reversible deactivation) radical polymerization and BNN3 azidation enabled the metal‐free synthesis of azido‐end polymethacrylates, including single‐azido‐end and multi‐azido‐end functional homopolymers and block copolymers. The rapid and quantitative reaction without the requirement for a large excess of BNN3, metal‐free and polar‐solvent‐free nature, and broad polymer scope are attractive features of this azidation.
Photochemical Alkene Isomerization for the Synthesis of Polysubstituted Furans and Pyrroles under Neutral Conditions
Authors: Walker Johannes C. L. , Werrel Simon , Donohoe Timothy J.
Published: August 2019

A photochemical approach to polysubstituted heterocycles using UV‐induced alkene isomerization is described. The method allows for the synthesis of disubstituted furans and pyrroles under mild and neutral conditions and also provides access to a class of trisubstituted furans pertinent to natural‐product synthesis. The method has broad functional‐group tolerance and many richly decorated heterocycles have been prepared incorporating functional groups that are unstable under Brønsted and Lewis acidic conditions.
Negishi Coupling for Highly Selective Syntheses of Allenes via Ligand Effect and Mechanistic Study via SAESI‐MS/MS
Authors: Zheng Yangguangyan , Miao Bukeyan , Qin Anni , Xiao Junzhe , Liu Qi , Li Gen , Zhang Li , Zhang Fang , Guo Yinlong , Ma Shengming
Published: August 2019

Summary of main observation and conclusion

β‐H elimination is an intrinsic problem in transition metal‐catalyzed reactions. We describe herein an interesting ligand effect for Et2Zn acting as either ethyl provider or H provider, respectively: by applying SPhos or Gorlos‐Phos as the ligand, β‐H elimination has been successfully controlled in the corresponding Negishi coupling reaction affording different poly‐substituted allenes in good yields and excellent selectivities. SAESI‐MS (Solvent Assisted Electrospray Ionization Mass Spectrometry) has been applied to successfully capture the highly reactive organometallic intermediates, which show the different coordination behaviors of Pd with SPhos or Gorlos‐Phos as the ligand in the catalytic cycle. In addition, the different reactivities of Int 1 and Int 2 towards the formation of the final allene products have been demonstrated via SAESI‐MS/MS experiments. These MS studies visualized the whole catalytic cycle for the Negishi coupling reaction while nicely explain the observed reactivity and selectivity.
Diagnostic value of biopsy sampling in predicting histology in patients with diffuse malignant pleural mesothelioma
Authors: Chirieac Lucian R. , Hung Yin P. , Foo Wai Chin , Hofer Matthias D. , VanderLaan Paul A. , Richards William G. , Sugarbaker David J. , Bueno Raphael
Published: August 2019

Background

The classification of diffuse malignant mesothelioma into epithelioid, biphasic, and sarcomatoid types is based on histologic patterns. The diagnosis is made on biopsies, and because of intratumoral heterogeneity, they may not be representative of the entire tumor. The number and volume of biopsies needed to reach diagnostic accuracy in diffuse malignant mesothelioma and their prognostic value remain unclear.

Methods

This study examined 759 consecutive patients with pleural diffuse malignant mesothelioma treated by pleurectomy/decortication or extrapleural pneumonectomy for the presence of epithelioid and/or sarcomatoid histology and classified both the presurgery biopsies (core‐needle or thoracoscopic) and surgical resection specimens. The number and volume of biopsies were correlated with pre‐ and postsurgery histologies and overall survival.

Results

Diffuse malignant mesothelioma was classified as epithelioid (76%), biphasic (18%), sarcomatoid (5%), or indeterminate (1%) in biopsies and as epithelioid (64%), biphasic (32%), and sarcomatoid (4%) in surgical resection specimens (overall concordance, 80.6%). The positive likelihood ratios were 2.4, 13.6, and 90.1 for biopsies with epithelioid, biphasic, and sarcomatoid histologies, respectively. Concordant histologies between biopsies and resections were associated with a higher number of biopsies (median tissue blocks for concordant histologies vs discordant histologies, 3 vs 2; P < .002) but were less associated with a higher volume (median, 1.2 vs 1.1 cm3; P = .06). In a multivariate analysis, overall survival was independently predicted by histology in the resection specimen (P < .0001) but not in the biopsy (P = .09).

Conclusions

In contrast to epithelioid histology, sarcomatoid histology in biopsies is highly accurate. Despite intratumoral heterogeneity, the accuracy of histologic classification increases with the number of tissue blocks examined, emphasizing the diagnostic value of extensive sampling by presurgery biopsies.
Synthesis, Photophysics and Redox Properties of Aza‐BODIPY Dyes with Electron‐Donating Groups
Authors: Obłoza Magdalena , Łapok Łukasz , Pędziński Tomasz , Stadnicka Katarzyna M. , Nowakowska Maria
Published: August 2019

A series of novel aza‐BODIPY dyes substituted with p‐(dimethylamino)phenyl groups were synthesized and their spectral and electrochemical properties were compared. In particular, the impact of p‐(Me2N)Ph‐ groups on these characteristics was of consideration. For two aza‐BODIPYs studied, a near‐IR absorption band was observed at circa λabs=796 nm. Due to the pronounced intramolecular charge transfer (ICT) exerted by the presence of strongly electron‐donating p‐(Me2N)Ph‐ substituents, the compounds studied were weakly emissive with the singlet lifetimes (τS) in the picosecond range. Nanosecond laser photolysis experiments of the brominated aza‐BODIPYs revealed T1→Tn absorption spanning from ca. 350 nm to ca. 550 nm with the triplet lifetimes (τT) ranged between 6.0 μs and 8.5 μs. The optical properties of the aza‐BODIPYs studied were pH‐sensitive. Upon protonation of the dimethylamino groups with trifluoroacetic acid in toluene, a stepwise disappearance of the NIR absorption band at λabs=790 nm was observed with the concomitant appearance of a blue‐shifted absorption band at λabs=652 nm, which was accompanied by a prominent emission band at λfl=680 nm. The transformation from a non‐emissive to an emissive compound is associated with the inhibition of the ICT. As estimated by CV/DPV measurements, all aza‐BODIPYs studied exhibited two irreversible oxidation and two quasi‐reversible reduction processes. All compounds studied exhibit extremely high photostability and thermal stability.
A switch‐controlled multimode narrowband receiver RF front‐end
Authors: Li Xiaolong , Wang Jianrong , Zhu Ningning , Zhu Jin , Zheng Wei
Published: August 2019

This work illustrates a flexible and convenient method to build a multimode narrowband receiver RF front‐end by means of controlled switches, switched capacitors, and switched inductors. The front‐end comprises a dual‐gain‐mode narrowband low‐noise amplifier (LNA) and a dual‐linearity‐mode mixer. A four‐mode receiver RF front‐end constructed with the dual‐gain‐mode LNA and the dual‐linearity‐mode mixer operating in frequency band range from 1800 to 2050 MHz was demonstrated with an IBM 90‐nm CMOS process. The front‐end achieves a 1/1.6 dB noise figure, 30/20 dB power gain, and 16/−10 dBm third‐order input intercept point while draws a 5.9/3.6 mA current from a 1.8‐V supply voltage at the low noise mode and high linearity mode, respectively. The proposed technique can be employed to build an intelligent mobile system.
Peritoneal involvement by salpingoliths clinical significance and cytological challenges of interpretation
Authors: El Hussein Siba , Guerrero Dominick , Khader Samer N.
Published: August 2019

We present a case of salpingoliths detected in peritoneal washing, during an elective bilateral salpingo‐oophorectomy, in a 32 years old woman with history of familial BRCA gene mutation. Salpingoliths are psammoma body‐like types of calcification that originate from the fallopian tubes and can be encountered in peritoneal washings. Unlike psammoma bodies, salpingoliths have been tagged to benign and hyperplastic processes more often than neoplastic processes. Misinterpreting salpingoliths as psammoma bodies in peritoneal washings can be misleading for both cytopathologists and clinicians, especially as in the presented case, where there is a high risk for ovarian carcinoma. In this article, we aim to shed light on this rare finding, and report theories explaining its pathogenesis, in addition we provide an example of its challenging cytological presentation, to increase awareness among cytopathologists.
Blood‐based biomarkers for Down syndrome and Alzheimer's disease: A systematic review
Authors: Petersen Melissa E. , O'Bryant Sid E.
Published: August 2019

Down syndrome (DS) occurs due to triplication of chromosome 21. Individuals with DS face an elevated risk for development of Alzheimer's disease (AD) due to increased amyloid beta (Aβ) resulting from the over‐expression of the amyloid precursor protein found on chromosome 21. Diagnosis of AD among individuals with DS poses particular challenges resulting in an increased focus on alternative diagnostic methods such as blood‐based biomarkers. The aim of this review was to evaluate the current state of the literature of blood‐based biomarkers found in individuals with DS and particularly among those also diagnosed with AD or in prodromal stages (mild cognitive impairment [MCI]). A systematic review was conducted utilizing a comprehensive search strategy. Twenty‐four references were identified, of those, 22 fulfilled inclusion criteria were selected for further analysis with restriction to only plasma‐based biomarkers. Studies found Aβ to be consistently higher among individuals with DS; however, the link between Aβ peptides (Aβ1‐42 and Aβ1‐40) and AD among DS was inconsistent. Inflammatory‐based proteins were more reliably found to be elevated leading to preliminary work focused on an algorithmic approach with predominantly inflammatory‐based proteins to detect AD and MCI as well as predict risk of incidence among DS. Separate work has also shown remarkable diagnostic accuracy with the use of a single protein (NfL) as compared to combined proteomic profiles. This review serves to outline the current state of the literature and highlights the potential plasma‐based biomarkers for use in detecting AD and MCI among this at‐risk population.
Evolution of mitral regurgitation in patients with heart failure referred to a tertiary heart failure clinic
Authors: de Groot – de Laat Lotte E. , Huizer Jessy , Lenzen Mattie , Spitzer Ernest , Ren Ben , Geleijnse Marcel L. , Caliskan Kadir
Published: August 2019

Aims

Significant mitral regurgitation (MR) is an important predictor for all‐cause mortality and heart failure (HF) hospitalizations independent of left ventricular ejection fraction (LVEF). The aims of this study were to investigate (i) in how many patients referred to a tertiary outpatient HF clinic HF therapy could be optimized, (ii) the effect of optimized treatment on MR severity, and (iii) whether a reduction in MR resulted in improvement of symptoms.

Methods and results

Forty‐seven referred patients with therapy‐resistant symptomatic chronic HF with an LVEF <40% and at least moderate MR were analysed on admission and after optimization of HF treatment after 6–18 months. The patients were classified as a volume responder when LV end‐systolic volume (LVESV) decreased ≥15%, as LVEF responder when LVEF increased by ≥5% points, as clinical responder when New York Heart Association (NYHA) class improved at least one category, and as MR responder when MR severity improved at least one category to maximally moderate. After 14 ± 4 months of treatment optimization, optimal doses of angiotensin‐converting enzyme inhibitors/angiotensin receptor blocker were seen in 18 (38%) patients compared with three (6%) at baseline (P < 0.001), and optimal doses of beta‐blockers were seen in 14 (30%) patients compared with four (9%) at baseline (P < 0.001). In total, 68% of the patients were clinical responders, 57% MR responders, 34% volumetric responders, and 49% LVEF responders. NYHA class improved from 2.9 ± 0.6 to 2.0 ± 0.9 (P < 0.001), MR class from 5.2 ± 0.8 to 3.6 ± 1.5 (P < 0.001), LVEF from 24% ± 9% to 31% ± 12% (P < 0.01), and LVESV non‐significantly improved. The positive predictive value of MR response to NYHA response was 88%; the negative predictive value was 53%, agreement 69%, and kappa 0.39. The positive predictive value of LVEF response to NYHA response was 76%; the negative predictive value was 44%, agreement 60%, and kappa 0.21. The positive predictive value of LVESV volume response to NYHA response was 75%; the negative predictive value was 39%, agreement 51%, and kappa 0.12.

Conclusions

Although this study was limited by a small number of patients, initiation and up‐titration of recommended HF therapy in patients referred to our tertiary HF outpatient clinic resulted in significant MR reduction in over half of the patients, emphasizing the importance of optimal medical treatment in these very sick cardiac patients with otherwise grave prognosis. MR reduction was best correlated to NYHA improvement.
Oral modified release morphine for breathlessness in chronic heart failure: a randomized placebo‐controlled trial
Authors: Johnson Miriam J. , Cockayne Sarah , Currow David C. , Bell Kerry , Hicks Kate , Fairhurst Caroline , Gabe Rhian , Torgerson David , Jefferson Laura , Oxberry Stephen , Ghosh Justin , Hogg Karen J. , Murphy Jeremy , Allgar Victoria , Cleland John G.F. , Clark Andrew L.
Published: August 2019

Aims

Morphine is shown to relieve chronic breathlessness in chronic obstructive pulmonary disease. There are no definitive data in people with heart failure. We aimed to determine the effectiveness and cost‐effectiveness of 12 weeks morphine therapy for the relief of chronic breathlessness in people with chronic heart failure compared with placebo.

Methods and results

Parallel group, double‐blind, randomized, placebo‐controlled, phase III trial of 20 mg daily oral modified release morphine was conducted in 13 sites in England and Scotland: hospital/community cardiology or palliative care outpatients. The primary analysis compared between‐group numerical rating scale average breathlessness/24 hours at week 4 using a covariance pattern linear mixed model. Secondary outcomes included treatment‐emergent harms (worse or new). The trial closed early due to slow recruitment, randomizing 45 participants [average age 72 (range 39–89) years; 84% men; 98% New York Heart Association class III]. For the primary analysis, the adjusted mean difference was 0.26 (95% confidence interval, −0.86 to 1.37) in favour of placebo. All other breathlessness measures improved in both groups (week 4 change‐from‐baseline) but by more in those assigned to morphine. Neither group was excessively drowsy at baseline or week 4. There were no between‐group differences in quality of life (Kansas) or cognition (Montreal) at any time point. There was no exercise‐related desaturation and no change between baseline and week 4 in either group. There was no change in vital signs at week 4. The natriuretic peptide measures fell in both groups but by more in the morphine group [morphine 2169 (1092, 3851) pg/mL vs. placebo 2851 (1694, 5437)] pg/mL. There was no excess serious adverse events in the morphine group. Treatment‐emergent harms during the first week were more common in the morphine group; all apart from 1 were ≤ grade 2.

Conclusions

We could not answer our primary objectives due to inadequate power. However, we provide novel placebo‐controlled medium‐term benefit and safety data useful for clinical practice and future trial design. Morphine should only be prescribed in this population when other measures are unhelpful and with early management of side effects.
CuO‐Catalyzed 1,3‐Addition of Diaryliodonium Triflates to Diazo Esters for the Stereoselective Synthesis of Triflate‐Substituted β‐Aryloxyl Acrylates
Authors: Lin Jia‐Jia , Zhou Jun , Wu Panpan , Chen Chao
Published: August 2019

CuO‐catalyzed 1,3‐addition of diaryliodonium triflates to diazo esters was realized. This new strategy forms a series of triflate‐substituted β‐aryloxyl acrylate compounds with good tolerance of functional groups and excellent regioselectivity. Mild reaction conditions are enough, and strong acids or bases are not required. Easy manipulation and good step‐economy are further advantages. The alkenyl triflate products can be further modified via cross‐coupling reactions to generate derivatized products.
Beta‐lactoglobulin Electrochemical Detection Based with an Innovative Platform Based on Composite Polymer
Authors: Lettieri Mariagrazia , Hosu Oana , Adumitrachioaie Alina , Cristea Cecilia , Marrazza Giovanna
Published: August 2019

In this work, we present a new electrochemical disposable platform based on poly(aniline‐co‐anthranilic acid) (PANI/PAA) composite polymer coupled with an aptamer for sensitive detection of β‐lactoglobulin. Firstly, PANI/PAA film was electrodeposited on the graphite screen‐printed electrode surface by cyclic voltammetry. The co‐polymer modified electrode was then employed as platform for the covalent immobilization of an amino‐modified aptamer. Various β‐lactoglobulin solutions, with a fixed amount of biotinylated oligonucleotide complementary sequence, were dropped onto the aptasensor surface. A streptavidin‐alkaline phosphatase conjugate was then employed to trace the affinity reaction. After the addition of 1‐naphthyl‐phosphate enzymatic substrate, 1‐naphthol electroactive product was detected by differential pulse voltammetry. A decrease in the signal was obtained when the target concentration was increased, in according to a signal‐off approach. After optimization of key experimental parameters, a dose‐response curve was obtained between 0.01–1.0 μg mL−1 β‐lactoglobulin concentration range. The limit of detection of 0.053 μg L−1 was obtained. Milk samples spiked with β‐lactoglobulin were analyzed.
Perspectives of dementia from Asian communities living in New Zealand: A focus group of Asian health care professionals
Authors: Cheung Gary , Appleton Kerry , Boyd Michal , Cullum Sarah
Published: August 2019

Objective

The number of Asian New Zealanders with dementia is growing. The objective of this study was to explore with a group of Asian health care professionals about public attitudes towards dementia in Asian communities in New Zealand, the stigma of dementia, and how best to develop culturally appropriate services for Asian people and families living with dementia.

Methods

A focus group was conducted with a group of bilingual Asian health care professionals. A topic guide was developed based on the discussion at a prior meeting with the Cross Cultural Interest Group. The data were independently analysed by three researchers using the thematic qualitative methodology.

Results

Eleven overseas‐born Asian health care professionals (Chinese: n = 9, 82%) participated in the focus group. Four main themes emerged from the data: (a) cultural interpretations of dementia; (b) stigma; (c) filial piety; and (d) inequity in the availability of resources.

Conclusion

Our findings suggest that much work is needed to destigmatise dementia in New Zealand Asian communities, through psychoeducation, public awareness, and the availability of readily accessible services that can meet their cultural and language needs.
Significance and management of incidentally diagnosed metastatic papillary thyroid carcinoma in cervical lymph nodes in neck dissection specimens
Authors: Mandapathil Magis , Lennon Paul , Ganly Ian , Patel Snehal G. , Shah Jatin P.
Published: August 2019

Background

The management of patients with incidentally discovered metastatic thyroid cancer in cervical lymph nodes in neck dissection specimens for other pathologies is unclear.

Methods

Retrospective review of neck dissection specimens for nonthyroid malignancy during a 30‐year period was undertaken to identify incidental metastatic papillary thyroid cancer (PTC).

Results

Twenty‐six patients had an incidental finding of PTC in lymph node(s) in neck dissection specimens. Subsequent ultrasound of the thyroid showed nodules in 20 patients. Eleven (42%) underwent total thyroidectomy, 1 (4%) had a lobectomy, and 14 (54%) were kept under active surveillance only. At a median follow‐up of 48 months (range 10‐189 months), all patients who had undergone surgery and those under surveillance were free of PTC recurrence.

Conclusion

Evaluation for detection of a primary thyroid tumor is essential in all patients with incidentally discovered metastatic PTC. Decision regarding surgery or surveillance is dependent on clinical and radiological tumor features and patient factors.
An analytical approach to ascertain saturation‐excess versus infiltration‐excess overland flow in urban and reference landscapes
Authors: Stewart Ryan D. , Bhaskar Aditi S. , Parolari Anthony J. , Herrmann Dustin L. , Jian Jinshi , Schifman Laura A. , Shuster William D.
Published: August 2019

Uncontrolled overland flow drives flooding, erosion, and contaminant transport, with the severity of these outcomes often amplified in urban areas. In pervious media such as urban soils, overland flow is initiated via either infiltration‐excess (where precipitation rate exceeds infiltration capacity) or saturation‐excess (when precipitation volume exceeds soil profile storage) mechanisms. These processes call for different management strategies, making it important for municipalities to discern between them. In this study, we derived a generalized one‐dimensional model that distinguishes between infiltration‐excess overland flow (IEOF) and saturation‐excess overland flow (SEOF) using Green–Ampt infiltration concepts. Next, we applied this model to estimate overland flow generation from pervious areas in 11 U.S. cities. We used rainfall forcing that represented low‐ and high‐intensity events and compared responses among measured urban versus predevelopment reference soil hydraulic properties. The derivation showed that the propensity for IEOF versus SEOF is related to the equivalence between two nondimensional ratios: (a) precipitation rate to depth‐weighted hydraulic conductivity and (b) depth of soil profile restrictive layer to soil capillary potential. Across all cities, reference soil profiles were associated with greater IEOF for the high‐intensity set of storms, and urbanized soil profiles tended towards production of SEOF during the lower intensity set of storms. Urban soils produced more cumulative overland flow as a fraction of cumulative precipitation than did reference soils, particularly under conditions associated with SEOF. These results will assist cities in identifying the type and extent of interventions needed to manage storm water produced from pervious areas.
OptCAM: An ultra‐fast all‐optical architecture for DNA variant discovery
Authors: Maleki Ehsan , Koohi Somayyeh , Kavehvash Zahra , Mashaghi Alireza
Published: August 2019

Nowadays, the accelerated expansion of genetic data challenges speed of current DNA sequence alignment algorithms due to their electrical implementations. Essential needs of an efficient and accurate method for DNA variant discovery demand new approaches for parallel processing in real time. Fortunately, photonics, as an emerging technology in data computing, proposes optical correlation as a fast similarity measurement algorithm; while complexity of existing local alignment algorithms severely limits their applicability. Hence, in this paper, employing optical correlation for global alignment, we present an optical processing approach for local DNA sequence alignment to benefit both high‐speed processing and operational parallelism, inherently exist in optics. The proposed method, named as OptCAM, utilizes amplitude and wavelength of the optical signals, to accurately locate mutations through three main procedures. Furthermore, an all‐optical implementation of the OptCAM method is proposed consisting of three units, corresponding to the three OptCAM procedures. Performing considerably fast processes by passing optical signals through high‐throughput photonic devices, OptCAM avoids various limitations of electrical implementations. Accuracy and efficiency of the OptCAM method and its optical implementation are validated through numerical simulation by a gold standard simulation benchmark. The results indicate the proposed method is significantly faster than its electrical counterparts, in both single node and grid computation.
Novel biomimetic fiber incorporated scaffolds for tissue engineering
Authors: Yongcong Fang , Zhang Ting , Liverani Liliana , Boccaccini Aldo R. , Sun Wei
Published: August 2019

From a structural perspective, an ideal scaffold ought to possess interconnected macro pores with sizes from 10 to 100 μm to facilitate cell infiltration and tissue formation, as well as similar topography to the natural extracellular matrix (ECM) which would have an impact on cell behavior such as cell adhesion and gene expression. For that purpose, here we developed a fabrication process to incorporate electrospun short fibers within freeze‐dried scaffolds for tissue engineering applications. Briefly, PCL short fibers were first produced from electrospun fibers with ultrasonication method. They were then evenly dispersed in gelatin solution and freeze‐dried to obtain fiber incorporated scaffolds. The resulting scaffolds exhibited hierarchical structure including major pores with sizes ranging from 50 to 150 μm and the short fibers dispersed in the thin walls of major pores, mimicking the fibrous feature of natural ECM. The short fibers were proven to modify the mechanical properties of scaffold and to facilitate cell adhesion and proliferation on the scaffold. As a promising scaffold for tissue engineering and regenerative medicine, the fiber incorporated scaffold may have further biomedical applications, in which the short fibers can act as drug release vehicles for growth factors or other biomolecules to promote vascularization.
Facilitating Adolescent Well‐Being: A Review of the Challenges and Opportunities and the Beneficial Roles of Parents, Schools, Neighborhoods, and Policymakers
Authors: Pechmann Cornelia , Catlin Jesse R. , Zheng Yu
Published: August 2019

Adolescents face exceptional challenges and opportunities that may have a lifelong impact on their consumption and personal and societal well‐being. Parents, community members (schools and neighborhoods), and policymakers play major roles in shaping adolescents and influencing their engagement in consumption behaviors that are either developmentally problematic (e.g., drug use and unhealthy eating) or developmentally constructive (e.g., academic pursuits and extracurricular activities). In this article, we discuss two main topics: (a) the challenges and opportunities that characterize adolescence, based primarily on research in epidemiology and neuroscience, and (b) the ways that parents, community members, and policymakers can facilitate positive adolescent development, based on research from many disciplines including marketing, psychology, sociology, communications, public health, and education. Our goal is to summarize the latest scientific findings that can be used by various stakeholders to help adolescents navigate this turbulent period and become well‐adjusted, thriving adults.
Causation of human ulcerative colitis: A lead from an animal model that mirrors human disease
Authors: Roediger William E W
Published: August 2019

Most models of experimental colitis do not replicate human ulcerative colitis and do not help in defining the causation of human ulcerative colitis. Inducing pantothenic acid deficiency in pigs produces an ideal model in terms of extent, histology, and chronicity of human ulcerative colitis. Comparing metabolic changes in human ulcerative colitis with metabolic changes in experimental colitis in pigs provided a guide for the search of initiating factors of human ulcerative colitis. Observations showed that bacterial nitric oxide with bacterial hydrogen sulphide reproduced the metabolic changes of human ulcerative colitis. Decreasing colon‐produced nitric oxide and hydrogen sulphide by bacteria through diet and medication resulted in pronounced therapeutic improvement, both clinically and histologically, of human ulcerative colitis.
Synthesis, Crystal Structure, Antifungal Activity, and Docking Study of Difluoromethyl Pyrazole Derivatives
Authors: Qiao Li , Zhai Zhi‐Wen , Cai Peng‐Peng , Tan Cheng‐Xia , Weng Jian‐Quan , Han Liang , Liu Xing‐Hai , Zhang Yong‐Gang
Published: August 2019

Nine novel difluoromethylpyrazole acyl urea derivatives were synthesized via seven steps conveniently. All the structures were determined by 1H‐NMR, 13C‐NMR, HRMS, and X‐ray diffraction. The in vivo fungicidal activities were determined against Corynespora mazei, Botrytis cinerea, Fusarium oxysporum, and Pseudomonas syringae, respectively. The bioassay results indicated that some of them displayed good control effective (around 50 and 80%) against P. syringae and B. cinerea at 50 mg/L, respectively, which is better than control. It is possible that difluoromethylpyrazole acyl urea derivatives can be a leading compound for the development of new fungicides against the two fungi with further structure optimization. Furthermore, docking model was studied to establish structure–activity relationship of difluoromethylpyrazole acyl urea derivatives.
Emergent productivity regimes of river networks
Authors: Koenig Lauren E. , Helton Ashley M. , Savoy Philip , Bertuzzo Enrico , Heffernan James B. , Hall Robert O. , Bernhardt Emily S.
Published: August 2019

High‐resolution data are improving our ability to resolve temporal patterns and controls on river productivity, but we still know little about the emergent patterns of primary production at river‐network scales. Here, we estimate daily and annual river‐network gross primary production (GPP) by applying characteristic temporal patterns of GPP (i.e., regimes) representing distinct river functional types to simulated river networks. A defined envelope of possible productivity regimes emerges at the network‐scale, but the amount and timing of network GPP can vary widely within this range depending on watershed size, productivity in larger rivers, and reach‐scale variation in light within headwater streams. Larger rivers become more influential on network‐scale GPP as watershed size increases, but small streams with relatively low productivity disproportionately influence network GPP due to their large collective surface area. Our initial predictions of network‐scale productivity provide mechanistic understanding of the factors that shape aquatic ecosystem function at broad scales.
Proteome analysis of tissues by mass spectrometry
Authors: Dapic Irena , Baljeu‐Neuman Lucia , Uwugiaren Naomi , Kers Jesper , Goodlett David R. , Corthals Garry L.
Published: August 2019

Tissues and biofluids are important sources of information used for the detection of diseases and decisions on patient therapies. There are several accepted methods for preservation of tissues, among which the most popular are fresh‐frozen and formalin‐fixed paraffin embedded methods. Depending on the preservation method and the amount of sample available, various specific protocols are available for tissue processing for subsequent proteomic analysis. Protocols are tailored to answer various biological questions, and as such vary in lysis and digestion conditions, as well as duration. The existence of diverse tissue‐sample protocols has led to confusion in how to choose the best protocol for a given tissue and made it difficult to compare results across sample types. Here, we summarize procedures used for tissue processing for subsequent bottom‐up proteomic analysis. Furthermore, we compare protocols for their variations in the composition of lysis buffers, digestion procedures, and purification steps. For example, reports have shown that lysis buffer composition plays an important role in the profile of extracted proteins: the most common are tris(hydroxymethyl)aminomethane, radioimmunoprecipitation assay, and ammonium bicarbonate buffers. Although, trypsin is the most commonly used enzyme for proteolysis, in some protocols it is supplemented with Lys‐C and/or chymotrypsin, which will often lead to an increase in proteome coverage. Data show that the selection of the lysis procedure might need to be tissue‐specific to produce distinct protocols for individual tissue types. Finally, selection of the procedures is also influenced by the amount of sample available, which range from biopsies or the size of a few dozen of mm2 obtained with laser capture microdissection to much larger amounts that weight several milligrams.