bluuebunny/crossref_metadata_2025 huggingface dataset:
Endopiriform neurons projecting to ventral CA1 are a critical node for recognition memory
Authors: Yamawaki Naoki , Login Hande , Feld-Jakobsen Solbjørg Østergaard , Molnar Bernadett Mercedesz , Kirkegaard Mads Zippor , Moltesen Maria , Okrasa Aleksandra , Radulovic Jelena , Tanimura Asami
Published: November 2024

The claustrum complex is viewed as fundamental for higher order cognition; however, the circuit organization and function of its neuroanatomical subregions are not well understood. We demonstrated that some of the key roles of the CLA complex can be attributed to the connectivity and function of a small group of neurons in its ventral subregion, the endopiriform (EN). We identified a subpopulation of EN neurons by their projection to the ventral CA1 (EN
vCA1-proj.
neurons), embedded in recurrent circuits with other EN neurons and the piriform cortex. Although the EN
vCA1-proj.
neuron activity was biased toward novelty across stimulus categories, their chemogenetic inhibition selectively disrupted the memory-guided but not innate responses of mice to novelty. Based on our functional connectivity analysis, we suggest that EN
vCA1-proj.
neurons serve as an essential node for recognition memory through recurrent circuits mediating sustained attention to novelty, and through feed forward inhibition of distal vCA1 neurons shifting memory-guided behavior from familiarity to novelty.
Clinical efficacy and safety of organ-sparing cystectomy: a systematic review and meta-analysis
Authors: Zhang Yi , Peng Lei , Zhang Yang , Li Hangxu , Li Songbei , Zhang Shaohua , Shi Jianguo
Published: November 2024

Background

The clinical safety and efficacy of organ-sparing cystectomy (OSC) are subjects of ongoing debate, particularly concerning the potential increased risk of recurrence when retaining additional organs and its effectiveness in preserving sexual and urinary functions.

Methods

Adhering to the PRISMA 2020 statement and AMSTAR Guidelines, we conducted a systematic literature search up to February 2024 using PubMed, Embase, and Web of Science. The comparison focused on the clinical safety and effectiveness of OSC and standard radical cystectomy (SRC) in the treatment of bladder tumors. Our assessment covered several dimensions: Surgical safety outcomes (operation time, length of stay (LOS), estimated blood loss (EBL), and complications), oncological safety outcomes (recurrence rate, positive surgical margin rate, overall survival, and cancer-specific survival), and functional efficacy outcomes (daytime and nighttime urinary incontinence at 6 and 12 months, clean intermittent catheterization (CIC) rate, and erectile function within and after 1 year).

Results

The analysis included 19 eligible studies, encompassing 2,057 patients (1,189 OSC patients and 768 SRC patients). OSC demonstrated significant benefits in terms of erectile function and urinary continence without impacting CIC rates. No significant differences were observed in recurrence rate, positive surgical margin rate, overall survival, and cancer-specific survival. Furthermore, OSC and SRC were comparable in surgical safety outcomes, including operating time, LOS, EBL, and complications.

Conclusions

OSC offers notable advantages in erectile function and urinary continence. Despite limited clinical practice and potential selection bias, urologists may still consider OSC more based on their experience and specific patient factors.
An Overview on Prospects of Biotransformation of Organic Waste: The Fuel of Future
Authors: Roshni Choubey , Gracy Charles
Published: November 2024

Organic wastes can come straight from the source or be derived from MSW (Municipal Solid Waste) or food processing waste. Municipal organic waste primarily consists of lignocelluloses. It is widely known that the high stability of the components makes lignocellulose hydrolysis ineffective. Environmentally acceptable and effective alternatives to landfilling and incineration for the treatment of organic pollutants include thermal disintegration and biological treatment methods. However, the qualities of the waste also play a role in this. Anaerobic digestion, followed by aerobic stabilisation, biogas production, and anaerobic digestion allow for the co-generation of electrical and thermal energy as well as the manufacture of premium natural fertiliser. Enzymatic hydrolysis is the initial stage of a valorisation process to improve the production of fuels through fermentations. In this regard, MOW pre-treatment is essential to boost the effectiveness of biological processes.
In this paper, several organic wastes, pre-treatment processes and microbial degradation techniques are reviewed and analysed. Also, the limitations of various techniques are pointed out. The fundamental scientific features are highlighted and details are given on the technological parameters. An insight towards challenges faced in biodegradation of lignocellulosic waste material is provided. Researches reveal the fact that there is vast hope in the availability of sugars after pre-treatment which may be very crucial for biofuel generation.
Nfat5 is involved in the hyperosmotic regulation of Tmem184b: a putative modulator of ibuprofen transport in renal MDCK I cells
Authors: Rasmussen Rune Nørgaard , Christensen Kenneth Vielsted , Holm René , Nielsen Carsten Uhd
Published: March 2019

Nuclear factor of activated T cells 5 (NFAT5) is a transcription factor involved in the regulation of several genes involved in the response to extracellular hyperosmolality. Recently, the uptake of ibuprofen by an as yet unknown carrier was suggested in Madin‐Darby canine kidney (MDCK) I cells exposed to hyperosmolality. We therefore speculated that Nfat5 could be involved in the regulation of this ibuprofen carrier. Reverse transfection with siRNA against Nfat5 was used to knock down Nfat5 in MDCK I cells. The uptake of both radiolabelled taurine and ibuprofen was measured in MDCK I cells, first treated with siRNA against Nfat5 and afterwards cultivated with raffinose‐supplemented normal growth medium (500 mOsm) for 24 h. The siRNA transfection resulted in knockdown of Nfat5, and uptake of both taurine and ibuprofen was significantly decreased in transfected MDCK I cells. The decrease in ibuprofen uptake indicates that Nfat5 is involved in upregulation of the ibuprofen carrier. A transcriptome analysis of MDCK I cells treated with siRNA against Nfat5 revealed 989 genes upregulated by Nfat5 during hyperosmotic exposure. From these genes, the gene product transmembrane protein 184b was found to be regulated by Nfat5, and Tmem184b was the only potential gene product involved in the uptake of ibuprofen in MDCK I cells.

Dataset

The RNA sequencing dataset is available from the NCBI Gene Expression 452 Omnibus (https://www.ncbi.nlm.nih.gov/geo/) with the accession number GSE122074.
Neural correlates of early cognitive dysfunction in Parkinson's disease
Authors: Weil Rimona S. , Winston Joel S. , Leyland Louise‐Ann , Pappa Katerina , Mahmood Ribeya B. , Morris Huw R. , Rees Geraint
Published: March 2019

Objective

Dementia is a common and feared aspect of Parkinson's disease but there are no robust predictors of cognitive outcome. Visuoperceptual deficits are linked to risk of dementia in Parkinson's disease but whether they predict cognitive change is not known, and the neural substrates of visuoperceptual dysfunction in Parkinson's have not yet been identified.

Methods

We compared patients with Parkinson's disease and unaffected controls who underwent BOLD fMRI while performing our previously validated visuoperceptual task and tested how functional connectivity between task‐specific regions and the rest of the brain differed between patients who performed well and poorly in the task.

Results

We show that task performance at baseline predicts change in cognition in Parkinson's disease after 1 year. Our task‐based fMRI study showed that the performance in this task is associated with activity in the posterior cingulate cortex/precuneus. We found that functional connectivity between this region and dorsomedial prefrontal cortex was reduced in poor performers compared with good performers of this task.

Interpretation

Our findings suggest that functional connectivity is reduced between posterior and anterior hubs of the default mode network in Parkinson's patients who are likely to progress to worsening cognitive dysfunction. Our work implicates posterior default mode nodes and their connections as key brain regions in early stages of dementia in Parkinson's disease.
Ultrafast Pathways of the Photoinduced Insulator–Metal Transition in a Low‐Dimensional Organic Conductor
Authors: Smit Bart , Hüwe Florian , Payne Nancy , Olaoye Olufemi , Bauer Irene , Pflaum Jens , Schwoerer Markus , Schwoerer Heinrich
Published: March 2019

Among functional organic materials, low‐dimensional molecular crystals represent an intriguing class of solids due to their tunable electronic, magnetic, and structural ground states. This work investigates Cu(Me,Br‐dicyanoquinonediimine)2 single crystals, a charge transfer radical ion salt which exhibits a Peierls insulator‐to‐metal transition at low temperatures. The ultrafast electron diffraction experiments observe collective atomic motions at the photoinduced phase transition with a temporal resolution of 1 ps. These measurements reveal the photoinduced lifting of the insulating phase to happen within 2 ps in the entire crystal volume with an external quantum efficiency of conduction band electrons per absorbed photon of larger than 20. This huge cooperativity of the system, directly monitored during the phase transition, is accompanied by specific intramolecular motions. However, only an additional internal volume expansion, corresponding to a pressure relief, allows the metallic state for long times to be optically locked. The identification of the microscopic molecular pathways that optically drive the structural Peierls transition in Cu(DCNQI)2 highlights the tailored response to external stimuli available in these complex functional materials, a feature enabling high‐speed optical sensing and switching with outstanding signal responsivity.
Self‐Aligned Anisotropic Plasmonic Nanostructures
Authors: Feng Ji , Yang Fan , Wang Xiaojing , Lyu Fenglei , Li Zhiwei , Yin Yadong
Published: March 2019

Great opportunities emerge not only in the generation of anisotropic plasmonic nanostructures but also in controlling their orientation relative to incident light. Herein, a stepwise seeded growth method is reported for the synthesis of rod‐shaped plasmon nanostructures which are vertically self‐aligned with respect to the surface of colloidal substrates. Anisotropic growth of metal nanostructure is achieved by depositing metal seeds onto the surface of colloidal substrates and then selectively passivating the seed surface to induce symmetry breaking in the subsequent seed‐mediated growth process. The versatility of this method is demonstrated by producing nanoparticle dimers and linear trimers of Au, Au–Ag, Au–Pd, and Au–Cu2O. Further, this unique method enables the automatic vertical alignment of the resulting plasmonic nanostructures to the surface of the colloidal substrate, thereby making it possible to design magnetic/plasmonic nanocomposites that allow the dynamic tuning of the plasmon excitation by controlling their orientation using an external magnetic field. The controlled anisotropic growth of colloidal plasmonic nanostructures and their dynamic modulation of plasmon excitation further allow them to be conveniently fixed in a thin polymer film with a well‐controlled orientation to display polarization‐dependent patterns that may find important applications in information encryption.
Artificial Super Neutrophils for Inflammation Targeting and HClO Generation against Tumors and Infections
Authors: Zhang Chi , Zhang Lu , Wu Wei , Gao Fan , Li Run‐Qing , Song Wen , Zhuang Ze‐Nan , Liu Chuan‐Jun , Zhang Xian‐Zheng
Published: March 2019

Neutrophils are powerful effector leukocytes that play an important role in innate immune systems for opposing tumor progression and ameliorating pathogen infections. Inspired by their distinct functions against tumors and infections, the artificial “super neutrophils” are proposed with excellent inflammation targeting and hypochlorous acid (HClO) generation characteristics for targeting and eliminating malignant tumor cells and pathogens. The “super neutrophils” are fabricated by embedding glucose oxidase (GOx) and chloroperoxidase (CPO) into zeolitic imidazolate framework‐8 (ZIF‐8) for HClO generation via enzymatic cascades, and then encapsulating them with the neutrophil membrane (NM) for inflammation targeting. In vitro and in vivo results indicate that these artificial “super neutrophils” can generate seven times higher reactive HClO than the natural neutrophils for eradicating tumors and infections. The “super neutrophils” demonstrated here with easy fabrication and good neutrophil‐mimicking property exhibit great potential for biomedical applications.
Strongly Coupled W2C Atomic Nanoclusters on N/P‐Codoped Graphene for Kinetically Enhanced Sulfur Host
Authors: Shi Nianxiang , Xi Baojuan , Feng Zhenyu , Liu Jincheng , Wei Denghu , Liu Jing , Feng Jinkui , Xiong Shenglin
Published: March 2019

Lithium–sulfur batteries are deemed to be one of the most promising energy storage alternatives due to the high theoretical capacity and cost‐effectiveness. The significant challenge in exploring novel sulfur host materials is to simultaneously inhibit the shuttle effect and heighten the reaction kinetics. Herein, a novel hybrid host consisting of W2C atomic nanoclusters (NCs) grown on a N/P‐codoped graphene framework (W2C@N/P‐rGO) is designed and fabricated for the first use in lithium–sulfur batteries. By means of first‐principle calculations and the kinetics analysis including lithium ion diffusion coefficient and charge transfer resistance, the introduction of W2C atomic NCs benefits the enhancement of electrochemical kinetics on a polar hybrid conductor. Furthermore, the intense ability of chemically sequestrating the soluble polysulfides by W2C atomic NCs ensures the high utilization of sulfur, making the high capacity retention. With a high sulfur loading of 3.1 mg cm−2, the W2C@N/P‐rGO/sulfur composite cathode indicates a significantly enhanced electrochemical performance. This work may open up a new avenue to design novel host candidates for advanced lithium–sulfur batteries.
Printable High‐Aspect Ratio and High‐Resolution Cu Grid Flexible Transparent Conductive Film with Figure of Merit over 80 000
Authors: Chen Xiaolian , Nie Shuhong , Guo Wenrui , Fei Fei , Su Wenming , Gu Weibing , Cui Zheng
Published: March 2019

Figure of merit (FOM), the ratio of electrical conductance to optical transparency, is an important metric to evaluate transparent conductive film (TCF). The conductivity of commonly used flexible TCF such as indium tin oxide is generally limited and their FOM is lower than 300. In this study, a high‐performance copper (Cu) metal‐mesh TCF with the highest FOM ever reported, up to 8 × 104, is fabricated through an additive manufacturing process of blading a silver seed layer and selective electroplating of Cu. With this strategy, Cu metallic lines completely constrained in roll‐to‐roll imprinted microgrooves achieve high aspect ratio of 2 with 4 µm width and 8 µm depth, which has very clean and smooth edges. This embedded Cu metal mesh exhibits an ultralow sheet resistance down to 0.03 Ω □−1 at 86% optical transmittance. It is demonstrated that the Cu metal mesh has remarkable mechanical flexibility, high environmental stability at high temperature and humidity, and durability over repeated heating cycles. The Cu metal mesh is employed as a flexible transparent heater to attach to the windshield of a car, showing rapid heating at low voltage and effective removal of snow.
The final demise of Rodriguez lethal acrofacial dysostosis: A case report and review of the literature
Authors: Drivas Theodore G. , Taylor Jesse A. , Zackai Elaine H.
Published: March 2019

We evaluated a newborn with acrofacial dysostosis in whom a clinical diagnosis of Nager syndrome was entertained. Radiographs revealed hypoplasia of the scapulae and bilateral humeroradial synostosis, with absent ulna on the left and hypoplastic ulna on the right. The finding of bilateral humeroradial synostosis had not been seen in cases of Nager syndrome before and we considered other diagnoses. Humeroradial synostosis has been found in three cases of acrofacial dysostosis Rodriguez type, a syndrome characterized by mandibular hypoplasia, upper and lower extremity phocomelia, and oligodactyly of the upper limbs. More recently, haploinsufficiency of the SF3B4 gene has been identified as the cause of both Nager and Rodriguez syndrome, leading many to believe that Rodriguez syndrome represents a more severe end of a Nager syndrome spectrum. An SF3B4 mutation was found in our patient, prompting a review of the previous known cases of Rodriguez syndrome, which revealed no clustering of SF3B4 mutations, and four cases of Rodriguez syndrome with mutations identical to those in cases of Nager syndrome. Rodriguez syndrome was previously thought of as a lethal acrofacial dysostosis distinct from Nager syndrome. A number of more mild cases, as well as our case, intermediate between the two phenotypes, illustrate that Rodriguez syndrome is a severe manifestation of Nager syndrome, and is not lethal with aggressive medical care.
Synthetisch hergestellte, transient thermoresponsive Homopolymere mit einer oberen kritischen Lösungstemperatur für physiologisch relevante Anwendungen
Authors: Zhang Zhiyue , Li Hui , Kasmi Sabah , Van Herck Simon , Deswarte Kim , Lambrecht Bart N. , Hoogenboom Richard , Nuhn Lutz , De Geest Bruno G.
Published: March 2019

Interaktive Materialien, die auf einen Trigger hin ihre Morphologie ändern, aber sich genauso allmählich in völlig lösliche Komponenten zersetzen, können als attraktive Bausteine für eine neue Generation an Biomaterialien Anwendung finden. In dieser Arbeit stellen wir transient thermoresponsive Polymere vor, die eine obere kritische Lösungstemperatur (UCST) besitzen, aber graduell diese Eigenschaft nach Hydrolyse der Polymerseitenkette verlieren. Dabei können die Polymere ihre Morphologie und Löslichkeit unter physiologisch relevanten Bedingungen (Temperatur, pH, Ionenstärke) ändern. Während solches Verhalten zuvor bereits für Systeme mit einer unteren kritischen Lösungstemperatur (LCST) beschrieben wurde, blieb dies für UCST‐Polymere lange Zeit unerforscht. In dieser Arbeit zeigen wir, dass solche UCST‐Polymere im Gegensatz zu LCST‐Polymeren in wässriger Umgebung unterhalb ihrer kritischen Lösungstemperatur Koazervate ausbilden, in die sowohl ein hydrophiles Modellprotein als auch ein hydrophober Farbstoff eingelagert werden können. Wegen ihrer geringen Toxizität ist uns in vivo der Nachweis für die Einsetzbarkeit der Koazervate als Depots für Proteine, die über einen längeren Zeitraum hin freigesetzt werden, gelungen.
MOF‐on‐MOF: Oriented Growth of Multiple Layered Thin Films of Metal–Organic Frameworks
Authors: Ikigaki Ken , Okada Kenji , Tokudome Yasuaki , Toyao Takashi , Falcaro Paolo , Doonan Christian J. , Takahashi Masahide
Published: March 2019

The precise alignment of multiple layers of metal–organic framework (MOF) thin films, or MOF‐on‐MOF films, over macroscopic length scales is presented. The MOF‐on‐MOF films are fabricated by epitaxially matching the interface. The first MOF layer (Cu2(BPDC)2, BPDC=biphenyl‐4,4′‐dicarboxylate) is grown on an oriented Cu(OH)2 film by a “one‐pot” approach. Aligned second (Cu2(BDC)2, BDC=benzene 1,4‐dicarboxylate, or Cu2(BPYDC)2, BPYDC=2,2′‐bipyridine‐5,5′‐dicarboxylate) MOF layers can be deposited using liquid‐phase epitaxy. The co‐orientation of the MOF films is confirmed by X‐ray diffraction. Importantly, our strategy allows for the synthesis of aligned MOF films, for example, Cu2(BPYDC)2, that cannot be grown on a Cu(OH)2 surface. We show that aligned MOF films furnished with Ag nanoparticles show a unique anisotropic plasmon resonance. Our MOF‐on‐MOF approach expands the chemistry of heteroepitaxially oriented MOF films and provides a new toolbox for multifunctional porous coatings.
Electrospray Ionization Mass Spectrometry: A Powerful Platform for Noble‐Metal Nanocluster Analysis
Authors: Chen Tiankai , Yao Qiaofeng , Nasaruddin Ricca Rahman , Xie Jianping
Published: March 2019

Electrospray ionization mass spectrometry (ESI‐MS) is an analytical technique that measures the mass of a sample through “soft” ionization. Recent years have witnessed a rapid growth of its application in noble‐metal nanocluster (NC) analysis. ESI‐MS is able to provide the mass of a noble‐metal NC analyte for the analysis of their composition (n, m, q values in a general formula [MnLm]q), which is crucial in understanding their properties. This review attempts to present various developed techniques for the determination of the composition of noble metal NCs by ESI‐MS. Additionally, advanced applications that use ESI‐MS to further understand the reaction mechanism, complexation behavior, and structure of noble metal NCs are introduced. From the comprehensive applications of ESI‐MS on noble‐metal NCs, more possibilities in nanochemistry can be opened up by this powerful technique.
Hydrogen Peroxide Assisted Synthesis of Highly Luminescent Sulfur Quantum Dots
Authors: Wang Henggang , Wang Zhenguang , Xiong Yuan , Kershaw Stephen V. , Li Tianzi , Wang Yue , Zhai Yongqing , Rogach Andrey L.
Published: March 2019

An H2O2‐assisted top‐down approach is used to synthesize brightly luminescent, color‐tunable sulfur quantum dots (SQDs), with a photoluminescence quantum yield of up to 23 %. The formation of SQDs involves dissolution of bulk sulfur powder into small particles in an alkaline environment in the presence of polyethylene glycol, followed by H2O2‐assisted etching of polysulfide species, which has the advantage of the passivation of surface states. This synthetic strategy allows us to simultaneously control the final size of SQDs, to tune their emission color, and to improve their emission quantum yield by eliminating surface traps. Down‐conversion white light emitting diodes were also fabricated using blue emissive SQDs and orange emissive copper nanoclusters, with CIE color coordinates of (0.33, 0.32) and a high color rendering index of 91. The water‐soluble, highly luminescent SQDs are promising luminescent materials that can be produced from abundant precursor materials.
Promotional effect of acidic oxide on catalytic activity and N2 selectivity over CeO2 for selective catalytic reduction of NOx by NH3
Authors: Song Zhongxian , Liu Pan , Fu Yongmei , Liu Hongpan , Huang Zhenzhen , Kang Haiyan , Mao Yanli , Liu Biao , Guo Yifei
Published: March 2019

The CeO2, CeO2‐ZrO2 and CeO2‐WO3 catalysts were prepared by hydrothermal method and used to the selective catalytic reduction of NOx by NH3. The addition of ZrO2 or WO3 into CeO2 was favorable for pore structure, and then improved the number of active sites. Besides, the introduction of ZrO2 into CeO2 could improve the Lewis acid sites while WO3 could contribute to the generation of Brønsted and Lewis acid sites, which could improve the catalytic performance and N2 selectivity. The CeO2‐WO3 catalyst exhibited optimal catalytic activity with above 90% NOx conversion performance at 220–425 °C and approximately 100% N2 selectivity at 150–425 °C.
Yeast Systems Biology: Model Organism and Cell Factory
Authors: Nielsen Jens
Published: March 2019

For thousands of years, the yeast Saccharomyces cerevisiae (S. cerevisiae) has served as a cell factory for the production of bread, beer, and wine. In more recent years, this yeast has also served as a cell factory for producing many different fuels, chemicals, food ingredients, and pharmaceuticals. S. cerevisiae, however, has also served as a very important model organism for studying eukaryal biology, and even today many new discoveries, important for the treatment of human diseases, are made using this yeast as a model organism. Here a brief review of the use of S. cerevisiae as a model organism for studying eukaryal biology, its use as a cell factory, and how advances in systems biology underpin developments in both these areas, is provided.
Reduced cortical thickness related to single nucleotide polymorphisms in the major histocompatibility complex region in antipsychotic‐naive schizophrenia
Authors: Tao Bo , Xiao Yuan , Hu Na , Shah Chandan , Liu Lu , Gao Xin , Liu Jieke , Zhang Wenjing , Yao Li , Xu Heng , Hua Jun , Lui Su
Published: March 2019

Instructions

The aim of this study was to explore the relationships between changes in cortical thickness and single nucleotide polymorphisms (SNPs) in the major histocompatibility complex (MHC) region in a group of antipsychotic‐naive schizophrenia (AN‐SCZ) patients.

Methods

Twenty‐five AN‐SCZ patients and 51 healthy controls (HCs) participated in this study. General linear models were used to identify associations between the average cortical thicknesses of each brain region (N = 68) and each of the 11 SNPs in the MHC region in the AN‐SCZ patients and HCs. Next, we performed independent‐sample t tests to investigate whether cortical thickness was significantly lower in the AN‐SCZ patients than in HCs in the brain regions that were significantly associated with the SNPs. Finally, we examined the correlations between clinical symptoms and cortical thickness in the above brain areas in the whole AN‐SCZ group using Pearson correlation tests.

Results

Seven of the 11 SNPs within the MHC region were significantly associated with cortical thickness only in the AN‐SCZ patients; these included rs1635, rs1736913, rs2021722, rs204999, rs2523722, rs3131296, and rs9272105. The AN‐SCZ patients had significantly thinner cortical thicknesses in the above brain regions, especially the prefrontal cortex. Furthermore, the left entorhinal region was negatively correlated with Positive and Negative Symptom Scale (PANSS) activation scores in the AN‐SCZ group (r = −0.601, p = 0.03).

Conclusions

This study provides evidence demonstrating the potential effects of MHC risk variants in cortical thickness deficits in AN‐SCZ. These data also support the notion that the immune system plays critical roles in the pathology of schizophrenia, which is mediated via the modulation of the development of cerebral cortical structures.
A nimble organization and a flexible degree program: A term‐based competency‐based education case study
Authors: Herron Joshua , Garland Eleisha
Published: March 2019

Anderson University began re‐designing one of its online degrees using competency‐based education principles in 2015, using almost 2 years to develop the curriculum and implementation plans. The model is designed with maximum flexibility, letting students choose their path to competency at each course rather than developing both subscription and term models. In the term‐based model that the university uses, students are able to add courses within a term if they finish sooner mid‐session since courses allow for varying paces and paths all aligned to a set of program competencies developed through national standards for the profession and input from the program's advisory board. Investment by the university leadership, a dedicated implementation team, and a nimble organization allowed a successful program launch in fall 2018, overcoming many common barriers cited to achieve the benefits of increased program quality, alignment to competencies, higher retention and completion, and positive enrollment trends.
Highly Efficient Degradation of Perfluorooctanoic Acid over a MnOx‐Modified Oxygen‐Vacancy‐Rich In2O3 Photocatalyst
Authors: Wu Yaoyao , Li Yuqiong , Fang Chihhsiang , Li Chuanhao
Published: March 2019

Destructive removal of perfluoroalkyl substances (PFASs) from water has been an emerging concern, as the C−F bond cleavage requires energy‐consuming advanced oxidation approaches. The conventional photocatalyst materials exhibit insufficient PFAS degradation due to either a weak absorption ability towards PFASs or a limited reaction oxygen species (ROS) generation. Herein, In2O3, which has an excellent absorption ability towards perfluorooctanoic acid (PFOA), is chosen as the main catalyst materials. Oxygen vacancies are then generated on the surface of In2O3 to assist the PFOA adsorption. Further depositions of the MnOx cocatalyst on the surface of In2O3 are performed to enhance the ROS generation efficiency. Based on the above design, the MnOx‐modified oxygen‐vacancy‐rich In2O3 photocatalyst shows a remarkably improved PFOA photodegradation and defluorination efficiencies under the solar light irradiation as compared with the pristine and commercial In2O3. The photodegradation pathway of PFOA is investigated. The experimental results from the PFOA adsorption analysis and electron spin resonance (ESR) spectra confirm the enhanced adsorption ability and the higher ROS generation efficiency, respectively. The catalyst is further tested in the presence of different anions and cations, where rapid degradation of PFOA is also observed, indicating the potential of the composite materials applied in the practical treatment of PFAS‐contaminated water.
Stachyonic Acid: A Dengue Virus Inhibitor from Basilicum polystachyon
Authors: Tan Yuen P. , Houston Sevan D. , Modhiran Naphak , Savchenko Andrei I. , Boyle Glen M. , Young Paul R. , Watterson Daniel , Williams Craig M.
Published: March 2019

Stachyonic acid A, arising from the first in‐depth phytochemical investigation of the herb Basilicum polystachyon, was found to display potent inhibitory activity against dengue virus, with limited cytotoxicity. Andrographolide, a known dengue virus inhibitor and closely related labdane‐type diterpene, is structurally more complex but displayed poor antiviral activity in the PRNT assay, and increased cytotoxicity in comparison. Furthermore, a Diels–Alder reaction with PTAD identified the active pharmacophore of stachyonic acid to be the conjugated diene.
Total Synthesis of Lajollamycin B
Authors: Nishimaru Tatsuya , Eto Kohei , Komine Keita , Ishihara Jun , Hatakeyama Susumi
Published: March 2019

The first total synthesis of lajollamycin B, a structurally novel nitro‐tetraene spiro‐β‐lactone/γ‐lactone antibiotic, is described. The convergent synthesis involves the construction of the C8′–C11′ nitrodienylstannane and its coupling with the segment prepared from the C1′–C7′ ω‐iodoheptadienoic acid and the right‐hand heterocyclic fragment, which has been utilized for our previous syntheses of oxazolomycin A. The revision of the geometry of the terminal Δ10′, 11′‐double bond from E to Z is also described for the structure of natural lajollamycin B.
Sulfonimidamides and Imidosulfuric Diamides: Compounds from an Underexplored Part of Biologically Relevant Chemical Space
Authors: Zasukha Sergiy V. , Timoshenko Vadim M. , Tolmachev Andrey A. , Pivnytska Valentyna O. , Gavrylenko Oleksii , Zhersh Serhii , Shermolovich Yuriy , Grygorenko Oleksandr O.
Published: March 2019

Invited for the cover of this issue are Oleksandr Grygorenko and co‐workers at Enamine Ltd., Institute of Organic Chemistry NAS Ukraine, and Taras Shevchenko National University of Kyiv. The image depicts two novel reagents for the synthesis of sulfonimidamides and imidosulfuric diamides. Read the full text of the article at 10.1002/chem.201900440.
Rapid Photolysis‐Mediated Folding of Disulfide‐Rich Peptides
Authors: Patil Nitin A. , Karas John A. , Wade John D. , Hossain Mohammed Akhter , Tailhades Julien
Published: March 2019

Structure–activity relationship studies are a highly time‐consuming aspect of peptide‐based drug development, particularly in the assembly of disulfide‐rich peptides, which often requires multiple synthetic steps and purifications. Therefore, it is vital to develop rapid and efficient chemical methods to readily access the desired peptides. We have developed a photolysis‐mediated “one‐pot” strategy for regioselective disulfide bond formation. The new pairing system utilises two ortho‐nitroveratryl protected cysteines to generate two disulfide bridges in less than one hour in good yield. This strategy was applied to the synthesis of complex disulfide‐rich peptides such as Rho‐conotoxin ρ‐TIA and native human insulin.
A COEUR cohort study of SATB2 expression and its prognostic value in ovarian endometrioid carcinoma
Authors: Le Page Cécile , Köbel Martin , Meunier Liliane , Provencher Diane M , Mes‐Masson Anne‐Marie , Rahimi Kurosh
Published: March 2019

The aim of this study was to describe the expression of special AT‐rich sequence‐binding protein 2 (SATB2) in ovarian endometrioid carcinoma (EC). SATB2 is a nuclear matrix‐associated transcription factor that is associated with abnormal expression in certain cancers but has not been reported for ovarian carcinoma. SATB2 mRNA and protein expression was first assessed in a pilot cohort of 26 samples by Affymetrix microarray and by routine immunohistochemistry on a small tissue microarray. A large multicenter validation cohort representing the well‐characterized cases of 235 ovarian EC from the Canadian Ovarian Experimental Unified Resource (COEUR) was then used to validate this result and to assess the prognostic impact of SATB2 expression. SATB2 staining was scored as negative, weak, moderate, and strong intensity, and by percentage of stained cells. No SATB2 expression was observed in clear cell carcinomas but 10% (n = 3) of the ECs in the pilot cohort showed SATB2 expression. In the validation cohort, strong expression was observed in 11% of ECs, while weak or moderate expression levels were detected in 12% of cases. Evaluation of SATB2 expression with clinicopathological parameters revealed an association with patient age and Federation International of Gynecology and Obstetrics grade but not with disease stage or postoperative residual disease. Any expression of SATB2, independent of intensity, was also associated with longer survival and improved progression‐free survival with hazard ratio (HR) = 0.14 (95% CI 0.03–0.56) and HR = 0.16 (95% CI 0.02–1.24) respectively. A greater beneficial effect was observed in patients with stage III/IV disease compared to patients with stage I/II disease. Furthermore, direct comparison of SATB2 with other reported prognostic biomarkers such as progesterone receptor, CDX2 and β‐catenin within this cohort showed that SATB2 had the strongest association with survival. Given the current lack of accurate prognostic factors for these patients, SATB2 has promising clinical utility and warrants further study.
Genome‐Wide Association and Functional Studies Reveal Novel Pharmacological Mechanisms for Allopurinol
Authors: Brackman Deanna J. , Yee Sook Wah , Enogieru Osatohanmwen J. , Shaffer Christian , Ranatunga Dilrini , Denny Joshua C. , Wei Wei‐Qi , Kamatani Yoichiro , Kubo Michiaki , Roden Dan M. , Jorgenson Eric , Giacomini Kathleen M.
Published: March 2019

Allopurinol, which lowers uric acid (UA) concentration, is increasingly being recognized for its benefits in cardiovascular and renal disease. However, response to allopurinol is variable. We gathered samples from 4,446 multiethnic subjects for a genome‐wide association study of allopurinol response. Consistent with previous studies, we observed that the Q141K variant in ABCG2 (rs2231142), which encodes the efflux pump breast cancer resistance protein (BCRP), associated with worse response to allopurinol. However, for the first time this association reached genome‐wide level significance (P = 8.06 × 10−11). Additionally, we identified a novel association with a variant in GREM2 (rs1934341, P = 3.22 × 10−6). In vitro studies identified oxypurinol, the active metabolite of allopurinol, as an inhibitor of the UA transporter GLUT9, suggesting that oxypurinol may modulate UA reabsorption. These results provide strong evidence for a role of BCRP Q141K in allopurinol response, and suggest that allopurinol may have additional hypouricemic effects beyond xanthine oxidase inhibition.
The importance of inter‐individual variation in predicting species' responses to global change drivers
Authors: Guscelli Ella , Spicer John I. , Calosi Piero
Published: March 2019

Inter‐individual variation in phenotypic traits has long been considered as “noise” rather than meaningful phenotypic variation, with biological studies almost exclusively generating and reporting average responses for populations and species’ average responses. Here, we compare the use of an individual approach in the investigation of extracellular acid–base regulation by the purple sea urchin Paracentrotus lividus challenged with elevated pCO2 and temperature conditions, with a more traditional approach which generates and formally compares mean values. We detected a high level of inter‐individual variation in acid–base regulation parameters both within and between treatments. Comparing individual and mean values for the first (apparent) dissociation constant of the coelomic fluid for individual sea urchins resulted in substantially different (calculated) acid–base parameters, and models with stronger statistical support. While the approach using means showed that coelomic pCO2 was influenced by seawater pCO2 and temperature combined, the individual approach indicated that it was in fact seawater temperature in isolation that had a significant effect on coelomic pCO2. On the other hand, coelomic [HCO3−] appeared to be primarily affected by seawater pCO2, and less by seawater temperature, irrespective of the approach adopted. As a consequence, we suggest that individual variation in physiological traits needs to be considered, and where appropriate taken into account, in global change biology studies. It could be argued that an approach reliant on mean values is a “procedural error.” It produces an artefact, that is, a population's mean phenotype. While this may allow us to conduct relatively simple statistical analyses, it will not in all cases reflect, or take into account, the degree of (physiological) diversity present in natural populations.
Clinical implications of prolonged hyperglycaemia before basal insulin initiation in type 2 diabetes patients: An electronic medical record database analysis
Authors: Raccah Denis , Guerci Bruno , Ajmera Mayank , Davis Keith , Meyers Juliana , Lew Elisheva , Shaunik Alka , Blonde Lawrence
Published: March 2019

Aims

To assess the effect of duration of hyperglycaemia before basal insulin (BI) initiation on clinical outcomes in type 2 diabetes (T2D).

Materials and methods

Patients with T2D who initiated BI during 2009‐2013, had continuous enrolment for ≥2 years preceding and ≥1 year following BI initiation (“index date”), and had ≥1 glycated haemoglobin (A1C) measure not at target (ie, ≥7.0%) within 6 months preindex date were included in the study. Patients were stratified by preindex‐date duration of A1C ≥7.0%. Longitudinal A1C, weight, BMI, and diabetes medication were compared between cohorts for up to 15‐month follow‐up.

Results

Of 37 053 patients who initiated BI, 40.7%, 15.3%, 16.0%, and 28.0%, respectively, had uncontrolled A1C for <6, 6‐<12, 12‐<18 and 18‐24 months preindex date. Baseline characteristics were similar between cohorts. Baseline A1C values were similar across cohorts (9.2%‐9.6%). Mean follow‐up A1C values were higher with longer preindex‐date duration of uncontrolled A1C (8.0 ± 1.7%, 8.2 ± 1.6%, 8.5 ± 1.7%, and 8.6 ± 1.7% for <6, 6‐<12, 12‐<18, and 18‐24 months); attainment of A1C <7.0% worsened with increasing preindex‐date duration of A1C ≥7.0% (29.6%, 20.0%, 14.6%, and 11.5% for <6, 6‐<12, 12‐<18, and 18‐24 months).

Conclusions

These data suggest that longer duration of uncontrolled A1C before BI initiation increases the risk of not reaching glycaemic targets. However, target attainment was poor in all cohorts, highlighting inadequate glycaemic control as an important unmet need in US patients with T2D.
Influence of Common Anions on the Coordination of Metal Cations in Polyalcohols
Authors: Teichert Johannes , Ruck Michael
Published: March 2019

Polyalcohols (polyols), such as ethylene glycol, have mild reducing ability. They are used in the so‐called polyol process to produce metallic nanoparticles of various kinds. In these syntheses, the effective reduction potential of the polyol strongly depends on the presence of other anions. Those anions compete against the polyol molecules for the direct bonding to the metal cations. As an indicator for the coordination behavior of polyols, we crystallized and structurally characterized 19 new coordination compounds with Mn, Co, Ni, Cu, Zn, Cd, Pb, or Bi. 15 of these compounds comprise nitrate ions, the others acetate ions. Compared to the already known chloride and sulfate analogues, nitrate shows an intermediate coordination affinity towards the metal cations considered here. While no direct metal–nitrate coordination occurs with Co2+, Ni2+, and Zn2+, mixed nitrate–polyol coordination environments are found for Mn2+, Cu2+, Cd2+, and Bi3+. Because of its strong chelating property, the acetate ion always coordinates the metal cation, competing with the polyol. The first mononuclear and dinuclear metal acetate diol coordination compounds were obtained with Co2+ and Cu2+, respectively. The coordination affinity of nitrate and acetate ligands in solid metal polyol complexes fully corresponds with our recent observations of the anion‐dependent reduction behavior of copper(II) salts in polyols.
Monocationic Iridium(III) Complexes with Far‐Red Charge‐Transfer Absorption and Near‐IR Emission: Synthesis, Photophysics, and Reverse Saturable Absorption
Authors: Liu Bingqing , Lystrom Levi , Cameron Colin G. , Kilina Svetlana , McFarland Sherri A. , Sun Wenfang
Published: March 2019

The synthesis, photophysics, and reverse saturable absorption (RSA) of three monocationic iridium(III) complexes (Ir1–Ir3) bearing diimine (N^N) ligand with different degrees of π‐conjugation are reported. Spectroscopic methods, including UV/Vis absorption, emission, and transient absorption spectroscopy, and density functional theory calculations were carried out to understand the nature of the singlet and triplet optical transitions and the influence of N^N ligand π‐conjugation on the photophysical properties of the complexes. All complexes possessed predominant ligand–centered, 1π,π* absorption bands at 280–420 nm and weak charge‐transfer absorption bands at 420–610 nm for Ir1, 420–680 nm for Ir2, and 420–730 nm for Ir3. The extended π‐conjugation of the N^N ligand red–shifted the charge‐transfer absorption bands and increased the molar extinction coefficients of all of the absorption bands. All complexes were emissive in the far‐red to the near‐infrared regions, with the emission energies gradually decreasing when the π‐conjugation of the N^N ligand increased. However, the emission lifetime of Ir3 increased when its emitting state energy decreased. This was caused by the different nature of the T1 state in Ir3, which was the predominant N^N ligand–localized 3π,π* state compared to the charge‐transfer T1 states in Ir1 and Ir2. The different parentage of the T1 state in Ir3 also gave rise to a much broader and stronger triplet excited‐state absorption in the 420–800 nm regions. The varied ground‐state and triplet excited‐state absorption characteristics led to a different strength of the reverse saturable absorption (RSA) for ns laser pulses at 532 nm, with the RSA strength following the trend of Ir3 > Ir1 ≥ Ir2. Complex Ir3 is particularly attractive for its potential as a broadband reverse saturable absorber in view of its broader ground‐ and excited‐state absorption in the regions of 420–730 nm and longer–lived triplet excited state.
Quantitative analysis of microcystin variants by capillary electrophoresis mass spectrometry with dynamic pH barrage junction focusing
Authors: Yan Ping , Zhang Keke , Wang Lingyu , Tong Wenjun , Chen David D. Y.
Published: March 2019

Dynamic pH junction is an online focusing method in CE based on the electrophoretic mobility difference of analytes in the sample matrix and the background electrolyte. An advantage of this method over the conventional CE is that the sensitivity can be significantly improved. By injecting a long sample plug in the capillary and focusing the analytes at the pH boundary between the background electrolyte and sample matrix, the LOD can be improved by 10–100 folds. The dynamic pH junction method can be easily coupled with ESI‐MS. In this work, we used this method for the analysis of microcystins (MCs). The detection limits and dynamic ranges were studied. The separation was optimized by adjusting the injection time, and concentrations and pH values of the background electrolyte. The optimization of analyte focusing leads to enhanced detection response compared to conventional injections, achieving 200–400 fold higher averaged peak heights for four microcystin (MC) variants. More importantly, this method was successfully used for the quantitative analysis of microcystins (MCs) in crude algae samples from natural water bodies, making it promising for practical applications.
Enhanced Processing and Testing Concepts for New Active Materials for Lithium‐Ion Batteries
Authors: Bockwinkel Kai , Nowak Christine , Thiede Bastian , Nöske Markus , Dietrich Franz , Thiede Sebastian , Haselrieder Wolfgang , Dröder Klaus , Kwade Arno , Herrmann Christoph
Published: March 2019

Electrode manufacturing requires multiple process steps, e.g., dispersing and coating. In‐between these steps, intermediate products have to be transferred, stored, and handled. Especially for the development of new active materials or electrode formulations, the variety of parameters that need to be screened is enormous. In addition, these materials are initially tested in small batches, and it is not always possible to upscale the used processes. To evaluate the performance of different materials or differently processed materials, test cells are assembled. This usually requires manual work procedures, which are inherently sensitive to variations and untraceable errors. If the stochastic flaws are large enough, the effects of process variations are covered by these. It is therefore important to increase reproducibility in all process steps. Herein, new concepts for electrode production and automated sample preparation for highly reproducible production and more effective electrode development and screening of parameters are presented. A combined grinding and dispersion process for the production of silicon‐based anodes and an automated assembly system for efficient testing is presented. The processes are supported by methods of data mining to collect process data, ensure high reproducibility, and support research on new active materials.
Pyrolysis kinetics of a Wangqing oil shale using thermogravimetric analysis
Authors: Hua Zejia , Wang Qing , Jia Chunxia , Liu Qi
Published: March 2019

A thermogravimetric analyzer was used to study the pyrolysis characteristics of an oil shale at different heating rates. Friedman, Flynn–wall–Ozawa (FWO), and distributed activation energy model (DAEM) methods were used to calculate the kinetic parameters of low‐temperature pyrolysis of oil shale. The results show that as the heating rate increases, (a) the initial pyrolysis temperature, peak temperature, and final pyrolysis temperature of oil shale shift toward the high‐temperature region, (b) the range of devolatilization temperature increases, and (c) the peak value of oil shale weight loss increases. The apparent activation energies calculated using theFWOand Friedman methods change with the conversion rate, and the average activation energies are 233.71 and 234.61 kJ/mol, respectively. Kinetic parameters obtained from theDAEMcalculation of low‐temperature pyrolysis of oil shale have energy compensation effects. By combining F‐test and quantitative criterion test, it was found that the logisticDAEMmodel is suitable for solving oil shale kinetic parameters. The activation energy of low‐temperature pyrolysis of oil shale is 238.67 kJ/mol, and the reaction order n is 1.