bluuebunny/crossref_metadata_2025 huggingface dataset:
Ellagitannin HeT obtained from strawberry leaves is oxidized by bacterial membranes and inhibits the respiratory chain
Authors: Martos Gustavo G. , Mamani Alicia , Filippone María P. , Abate Pedro O. , Katz Néstor E. , Castagnaro Atilio P. , Díaz Ricci Juan C.
Published: December 2017

Plant secondary metabolism produces a variety of tannins that have a wide range of biological activities, including activation of plant defenses and antimicrobial, anti‐inflammatory and antitumoral effects. The ellagitannin HeT (1‐O‐galloyl‐2,3;4,6‐bis‐hexahydroxydiphenoyl‐β‐d‐glucopyranose) from strawberry leaves elicits a strong plant defense response, and exhibits antimicrobial activity associated to the inhibition of the oxygen consumption, but its mechanism of action is unknown. In this paper we investigate the influence of HeT on bacterial cell membrane integrity and its effect on respiration. A β‐galactosidase unmasking experiment showed that HeT does not disrupt membrane integrity. Raman spectroscopy analysis revealed that HeT strongly interacts with the cell membrane. Spectrochemical analysis indicated that HeT is oxidized in contact with bacterial cell membranes, and functional studies showed that HeT inhibits oxygen consumption, NADH and MTT reduction. These results provide evidence that HeT inhibits the respiratory chain.
Potential Effect Modifiers of the Association Between Physical Activity Patterns and Joint Symptoms in Middle‐Aged Women
Authors: Peeters Geeske , Edwards Kimberley L. , Brown Wendy J. , Barker Anna L. , Arden Nigel , Redmond Anthony C. , Conaghan Philip G. , Cicuttini Flavia , Mishra Gita D.
Published: December 2017

Objective

To examine whether body mass index (BMI), menopausal status, and hormone therapy (HT) use modify the association between physical activity (PA) patterns throughout middle age and the incidence and prevalence of joint symptoms in women in later middle age.

Methods

Data were from 6,661 participants (born 1946–1951) in the Australian Longitudinal Study on Women's Health. Surveys, with questions on joint pain and stiffness, PA, height and weight, menopausal symptoms, and HT use, were completed every 3 years from 1998 to 2010. PA patterns were defined as none or low, low or meeting guidelines, fluctuating, or meeting guidelines at all times (reference pattern). Logistic regression was used to examine the association between PA patterns and prevalent (in 2010) and cumulative incident (1998–2010) joint symptoms and effect modification by patterns in BMI, menopausal status, and HT.

Results

The groups representing fluctuating PA (odds ratio [OR] 1.34 [99% confidence interval (99% CI) 1.04–1.72]) and no or low PA (OR 1.60 [99% CI 1.08–2.35]) had higher odds of incident joint symptoms than those described as meeting guidelines at all times. Stratification by BMI showed that this association was statistically significant in the obese group only. No evidence for effect modification by menopausal status or HT use was found. The findings were similar for prevalent joint symptoms.

Conclusion

Maintaining at least low levels of PA throughout middle age was associated with a lower prevalence and incidence of joint symptoms later in life. This apparent protective effect of PA on joint symptoms was stronger in obese women than in under‐ or normal‐weight women, and not related to menopause or HT status.
Recent Progress on Piezotronic and Piezo‐Phototronic Effects in III‐Group Nitride Devices and Applications
Authors: Du Chunhua , Hu Weiguo , Wang Zhong Lin
Published: December 2017

Wurtzite‐structured III‐group nitrides, like GaN, InN, AlN, and their alloys, present both piezoelectric and semiconducting properties under straining owing to the polarization of ions in a crystal with non‐central symmetry. The piezoelectric polarization charges are created at the interface when a strain is applied. As a result, a piezoelectric potential (piezopotential) is produced, which is used as a “gate” to tune/control the charge transport behavior across a metal/semiconductor interface or a p‐n junction. This is called as piezotronic effect. A series of piezotronic devices and applications have been developed, such as piezotronic nanogenerators (NGs), piezotronic transistors, piezotronic logic devices, piezotronic electromechanical memories, piezotronic enhanced biochemical, and gas sensors and so on. With the flourished development of piezotronic effect, the piezo‐phototronic effect, as the three‐way coupling of piezoelectric polarization, semiconductor properties, and optical excitation, utilizes the piezopotential to modulate the energy band profile and control the carrier generation, transportation, separation, and/or recombination for improving performances of optoelectronic devices. This paper intends to provide an overview of the rapid progress in the emerging fields of piezotronics and piezo‐phototronics, covering from the fundamental principles to devices and applications. This study will provide important insight into the potential applications of GaN based electronic/optoelectronic devices in sensing, active flexible/stretchable electronics/optoelectronics, energy harvesting, human‐machine interfacing, biomedical diagnosis/therapy, and prosthetics.
Emerging Roles of Electrospun Nanofibers in Cancer Research
Authors: Chen Shixuan , Boda Sunil Kumar , Batra Surinder K. , Li Xiaoran , Xie Jingwei
Published: December 2017

This article reviews the recent progress of electrospun nanofibers in cancer research. It begins with a brief introduction to the emerging potential of electrospun nanofibers in cancer research. Next, a number of recent advances on the important features of electrospun nanofibers critical for cancer research are discussed including the incorporation of drugs, control of release kinetics, orientation and alignment of nanofibers, and the fabrication of 3D nanofiber scaffolds. This article further highlights the applications of electrospun nanofibers in several areas of cancer research including local chemotherapy, combinatorial therapy, cancer detection, cancer cell capture, regulation of cancer cell behavior, construction of in vitro 3D cancer model, and engineering of bone microenvironment for cancer metastasis. This progress report concludes with remarks on the challenges and future directions for design, fabrication, and application of electrospun nanofibers in cancer diagnostics and therapeutics.
Highly Deformable and See‐Through Polymer Light‐Emitting Diodes with All‐Conducting‐Polymer Electrodes
Authors: Kee Seyoung , Kim Nara , Park Byoungwook , Kim Bong Seong , Hong Soonil , Lee Jong‐Hoon , Jeong Soyeong , Kim Ahryun , Jang Soo‐Young , Lee Kwanghee
Published: December 2017

Despite the high expectation of deformable and see‐through displays for future ubiquitous society, current light‐emitting diodes (LEDs) fail to meet the desired mechanical and optical properties, mainly because of the fragile transparent conducting oxides and opaque metal electrodes. Here, by introducing a highly conductive nanofibrillated conducting polymer (CP) as both deformable transparent anode and cathode, ultraflexible and see‐through polymer LEDs (PLEDs) are demonstrated. The CP‐based PLEDs exhibit outstanding dual‐side light‐outcoupling performance with a high optical transmittance of 75% at a wavelength of 550 nm and with an excellent mechanical durability of 9% bending strain. Moreover, the CP‐based PLEDs fabricated on 4 µm thick plastic foils with all‐solution processing have extremely deformable and foldable light‐emitting functionality. This approach is expected to open a new avenue for developing wearable and attachable transparent displays.
Improved Efficiency and Stability of Perovskite Solar Cells Induced by CO Functionalized Hydrophobic Ammonium‐Based Additives
Authors: Wu Zhifang , Raga Sonia R. , Juarez‐Perez Emilio J. , Yao Xuyang , Jiang Yan , Ono Luis K. , Ning Zhijun , Tian He , Qi Yabing
Published: December 2017

Because of the rapid rise of the efficiency, perovskite solar cells are currently considered as the most promising next‐generation photovoltaic technology. Much effort has been made to improve the efficiency and stability of perovskite solar cells. Here, it is demonstrated that the addition of a novel organic cation of 2‐(6‐bromo‐1,3‐dioxo‐1H‐benzo[de]isoquinolin‐2(3H)‐yl)ethan‐1‐ammonium iodide (2‐NAM), which has strong Lewis acid and base interaction (between CO and Pb) with perovskite, can effectively increase crystalline grain size and reduce charge carrier recombination of the double cation FA0.83MA0.17PbI2.51Br0.49 perovskite film, thus boosting the efficiency from 17.1 ± 0.8% to 18.6 ± 0.9% for the 0.1 cm2 cell and from 15.5 ± 0.5% to 16.5 ± 0.6% for the 1.0 cm2 cell. The champion cell shows efficiencies of 20.0% and 17.6% with active areas of 0.1 and 1.0 cm2, respectively. Moreover, the hysteresis behavior is suppressed and the stability is improved. The result provides a promising route to further elevate efficiency and stability of perovskite solar cells by the fine tuning of triple organic cations.
Origin of Fracture‐Resistance to Large Volume Change in Cu‐Substituted Co3O4 Electrodes
Authors: Liu Heguang , Li Qianqian , Yao Zhenpeng , Li Lei , Li Yuan , Wolverton Chris , Hersam Mark C. , Wu Jinsong , Dravid Vinayak P.
Published: December 2017

The electrode materials conducive to conversion reactions undergo large volume change in cycles which restrict their further development. It has been demonstrated that incorporation of a third element into metal oxides can improve the cycling stability while the mechanism remains unknown. Here, an in situ and ex situ electron microscopy investigation of structural evolutions of Cu‐substituted Co3O4 supplemented by first‐principles calculations is reported to reveal the mechanism. An interconnected framework of ultrathin metallic copper formed provides a high conductivity backbone and cohesive support to accommodate the volume change and has a cube‐on‐cube orientation relationship with Li2O. In charge, a portion of Cu metal is oxidized to CuO, which maintains a cube‐on‐cube orientation relationship with Cu. The Co metal and oxides remain as nanoclusters (less than 5 nm) thus active in subsequent cycles. This adaptive architecture accommodates the formation of Li2O in the discharge cycle and underpins the catalytic activity of Li2O decomposition in the charge cycle.
Facile Synthesis of Ag‐Decorated Ni3S2 Nanosheets with 3D Bush Structure Grown on rGO and Its Application as Positive Electrode Material in Asymmetric Supercapacitor
Authors: Qi Jiqiu , Chang Yuan , Sui Yanwei , He Yezeng , Meng Qingkun , Wei Fuxiang , Ren Yaojian , Jin Yunxue
Published: December 2017

A facile and cost‐effective route is developed for synthesizing 3D bush structure of Ag nanoparticles‐decorated Ni3S2 grown on reduced graphene oxide (rGO) for the first time. In this composite, Ni3S2 exhibits nanosheet networks with porous feature. The electrochemical measurements display that the as‐prepared rGO/Ag/Ni3S2 composite possesses a superior areal capacitance of 5920 mF cm−2 at current density of 5 mA cm−2. 77.5% of the initial areal capacitance is retained as current density increased from 5 to 20 mA cm−2. Encouragingly, this electrode exhibits excellent cycle performance with 94% capacitance retention after 3000 cycles at a current density of 30 mA cm−2, whereas for rGO/Ni3S2 composite electrode, only 84.7% of the initial value is maintained. The enhanced conductivity and unique structure of rGO/Ag/Ni3S2 composite attribute to its superior electrochemical performance. In addition, an aqueous asymmetric supercapacitor is fabricated using rGO/Ag/Ni3S2 composite as positive electrode and the nitrogen‐doped graphene as negative electrode. The assembled device delivers high energy density of 28.7 Wh kg−1 at a power density of 425 W kg−1. This work may prompt the development and application of active materials decorated with highly conductive nanoparticles in supercapacitors.
Reduced 3d Transition Metal Oxides Work as Solid‐State Sources of Solvated Electrons and Directly Inject Electrons into Water for H2 Production under Mild Thermal or IR Excitation
Authors: Zhang Guan , Zou Jing , Xu Xiaoxiang
Published: December 2017

Stabilizing excess electrons in a solid provides great opportunities for the design of new materials with precisely tuned electronic and magnetic properties. Herein, it is demonstrated heavily reduced 3d transition metal oxides (HRTMOs) particles can be used as a kind of novel solid‐state sources of solvated electrons, which are capable of injecting electrons directly into water upon mild thermal or near infrared light (IR) excitation. The structural characteristics and electronic properties of the reduced metal oxides related with the stabilization of excess electrons are investigated in detail. As a proof‐of‐concept example, H2 generation from water triggered by thermal excitation is tested for evaluating the potential applications of solvated electrons and the characteristics of electrons trapping and release in 3d HRTMOs. The trapping and release of electrons, corresponding to defects formation upon reduction and defects removal upon oxidation, respectively, are facile and repeatable without reducing the storage capacity during multicycle tests. The special characteristics of thermal/IR‐driven electron injection from the metal oxides solids into solution have great application potentials in areas of energy conversion, organic synthesis, and medical treatment, etc.
Resistor Network Modeling of Conductive Domain Walls in Lithium Niobate
Authors: Wolba Benjamin , Seidel Jan , Cazorla Claudio , Godau Christian , Haußmann Alexander , Eng Lukas M.
Published: December 2017

Here the concept of a 2D resistor network (2D RN) is applied in order to model the electrical conductivity along sheet‐like domain walls (DWs) in single crystalline lithium niobate (sc‐LNO). The only input to the RN modeling approach is the DW inclination angle distribution, as measured previously with respect to the polar c‐axis. The simulations then show that a 2D network of Ohmic resistors not only adequately accounts for the different boundary conditions envisaged in experiments, but equally well provides a direct link between the local domain wall conductivity (DWC) and the DW inclination angle α. Moreover, the RN simulations can be directly compared to local‐scale transport measurements, as obtained by scanning probe techniques. The conceptual simplicity and the low computational effort make the present RN modeling approach a useful tool for both the advanced interpretation and evaluation of potential DWC ferroelectrics.
Auditory evoked potentials in children and adolescents with Down syndrome
Authors: Gregory Letícia , Rosa Rafael F. M. , Zen Paulo R. G. , Sleifer Pricila
Published: December 2017

Down syndrome, or trisomy 21, is the most common genetic alteration in humans. The syndrome presents with several features, including hearing loss and changes in the central nervous system, which may affect language development in children and lead to school difficulties. The present study aimed to investigate group differences in the central auditory system by long‐latency auditory evoked potentials and cognitive potential. An assessment of 23 children and adolescents with Down syndrome was performed, and a control group composed of 43 children and adolescents without genetic and/or neurological changes was used for comparison. All children underwent evaluation with pure tone and vocal audiometry, acoustic immitance measures, long‐latency auditory evoked potentials, and cognitive potential. Longer latencies of the waves were found in the Down syndrome group than the control group, without significant differences in amplitude, suggesting that individuals with Down syndrome have difficulty in discrimination and auditory memory. It is, therefore, important to stimulate and monitor these children in order to enable adequate development and improve their life quality. We also emphasize the importance of the application of auditory evoked potentials in clinical practice, in order to contribute to the early diagnosis of hearing alterations and the development of more research in this area.
A Brønsted‐Acidic Ionic Liquid Gel as an Efficient and Recyclable Heterogeneous Catalyst for the Synthesis of Bis(indolyl)methanes under Solvent‐Free Sonication
Authors: Tran Phuong Hoang , Nguyen Xuan‐Trang Thi , Chau Duy‐Khiem Nguyen
Published: December 2017

A Brønsted‐acidic ionic liquid gel was prepared from 1‐(4‐sulfonic acid)butyl‐3‐methylimidazolium hydrogen sulfate and tetraethoxysilane. Its structural characterization was accomplished by FTIR, TGA, SEM, EDS, and ICP‐OES. The ionic liquid gel promotes the synthesis of bis(indolyl)methanes. Interestingly, this catalyst allows the preparation of bis(indolyl)methanes in good to excellent yields within a short reaction time, through a clean and straightforward procedure. Moreover, the ionic liquid gel can be recovered by filtration and can be reused up to 5 times without any detectable loss of catalytic performance. Additionally, the method has a wide substrate scope and provides an accessible route for the large‐scale direct synthesis of bis(indolyl)methanes.
Iron‐Catalyzed Intramolecular Reductive Coupling of Unactivated Aldehydes and Arylalkenes with Isopropanol
Authors: Zheng Yan‐Long , Liu Yan‐Yao , Xu Xue‐Tao , Zhang Kun , Ye Mengchun
Published: December 2017

FeCl3‐catalyzed intramolecular reductive coupling of unactivated aldehydes and arylalkenes with isopropanol as a terminal reductant under mild and easy‐to‐handle conditions has been developed. A series of five‐, six‐, seven‐ and eight‐membered carbocyclic alcohols were synthesized in moderate to excellent yields with high regioselectivities.
Comparison of endoscopic and open resection of sinonasal squamous cell carcinoma: a propensity score–matched analysis of 652 patients
Authors: Kılıç Suat , Kılıç Sarah S. , Baredes Soly , Chan Woo Park Richard , Mahmoud Omar , Suh Jeffrey D. , Gray Stacey T. , Eloy Jean Anderson
Published: December 2017

Background

The use of endoscopic resection as an alternative to open surgery for sinonasal malignancies has increased in the past 20 years.

Methods

The National Cancer Database was queried for cases of sinonasal squamous cell carcinoma (SNSCC) without cervical or distant metastases that were treated surgically between 2010 and 2014. They were split into 2 groups based on surgical approach: open or endoscopic. Demographics, facility and insurance type, stage, tumor characteristics, postoperative treatment, 30‐day readmission rate, 30‐ and 90‐day mortality, and overall survival (OS) were compared between the 2 groups. Cox proportional hazard analysis was performed. Propensity score matching (PSM) was used to mimic a randomized, controlled trial.

Results

A total of 1,483 patients were identified: 353 (23.8%) received endoscopic and 1130 (76.2%) received open surgery. Age, gender, race, geographic region, tumor size, surgical margins, postoperative chemoradiation, and 30‐day readmissions did not vary significantly between the 2 groups. Open surgery was more common in academic centers (62.8% vs 54.2%; p = 0.004), less common for tumors of the ethmoid and sphenoid sinus (p < 0.0001), less common for stage IVB tumors, and associated with longer hospital stay (mean, 4.67 days vs 2.50 days; p < 0.0001). Five‐year OS (5Y‐OS) was not significantly different between the 2 approaches (p = 0.953; open: 5Y‐OS, 56.5%; 95% confidence interval, 51.3% to 61.6%; endoscopic: 5Y‐OS, 46.0%; 95% confidence interval, 33.2% to 58.8%). In the PSM cohort of 652 patients, there was also no significant difference in OS (p = 0.850).

Conclusion

Endoscopic surgery is an effective alternative to open surgery, even after accounting for confounding factors that may favor its use over the open approach. It is also associated with a shorter hospital stay.
Protection Group Effects During α,γ‐Diol Lignin Stabilization Promote High‐Selectivity Monomer Production
Authors: Lan Wu , Amiri Masoud Talebi , Hunston Christopher M. , Luterbacher Jeremy S.
Published: December 2017

Protection groups were introduced during biomass pretreatment to stabilize lignin's α,γ‐diol group during its extraction and prevent its condensation. Acetaldehyde and propionaldehyde stabilized the α,γ‐diol without any aromatic ring alkylation, which significantly increased final product selectivity. The subsequent hydrogenolysis catalyzed by Pd/C generated lignin monomers at near‐theoretical yields based on Klason lignin (48 % from birch, 20 % from spruce, 70 % from high‐syringyl transgenic poplar), and with high selectivity to a single 4‐n‐propanolsyringol product (80 %) in the case of the poplar. Unlike direct hydrogenation of native wood, hydrogenolysis of protected lignin with Ni/C also led to high selectivity to this single product (78 %), paving the way to high‐selectivity lignin upgrading with base metal catalysts. The use of extracted lignin facilitated valorization of polysaccharides, leading to high yields of all three major biomass polymers to a single major product.
Fabrication of Defined Polydopamine Nanostructures by DNA Origami‐Templated Polymerization
Authors: Tokura Yu , Harvey Sean , Chen Chaojian , Wu Yuzhou , Ng David Y. W. , Weil Tanja
Published: December 2017

A versatile, bottom‐up approach allows the controlled fabrication of polydopamine (PD) nanostructures on DNA origami. PD is a biosynthetic polymer that has been investigated as an adhesive and promising surface coating material. However, the control of dopamine polymerization is challenged by the multistage‐mediated reaction mechanism and diverse chemical structures in PD. DNA origami decorated with multiple horseradish peroxidase‐mimicking DNAzyme motifs was used to control the shape and size of PD formation with nanometer resolution. These fabricated PD nanostructures can serve as “supramolecular glue” for controlling DNA origami conformations. Facile liberation of the PD nanostructures from the DNA origami templates has been achieved in acidic medium. This presented DNA origami‐controlled polymerization of a highly crosslinked polymer provides a unique access towards anisotropic PD architectures with distinct shapes that were retained even in the absence of the DNA origami template.
The enhancement performances of cotton stalk fiber/PVC composites by sequential two steps modification
Authors: Li Ya‐Yu , Wang Bin , Wang Bo , Ma Ming‐Guo
Published: December 2017

In the present study, the cotton stalk fiber (CSF) was modified by sequential two steps of alkali and copper ethanolamine (CE) solution treatment. The unmodified and modified CSF/poly(vinyl chloride) (CSF/PVC) composites were prepared. The mechanical and physical performances of the various CSF/PVC composites were studied comparatively. By the modification of CE solution, all the tensile strength, tensile modulus, impact strength, water resistance, and heat distortion temperature of samples were enhanced continuously. The sample with comprehensive properties was obtained using 2% concentration of CE. The composites were also prepared with different CSF content. By increasing the CSF loading, all the tensile strength, elongation at breakage, tensile modulus, and heat distortion temperature of samples were enhanced. The existence of copper on the surface of CSF improved the thermal stability of the CSF/PVC composites. Water retention value, oil retention value, and scanning electron microscope were applied to reveal the components and microscopic change of the composites. The possible reaction mechanism of modification was proposed based on the experimental results and according to the previous literature. This method reported here may provide a new way for the fabrication of CSF/PVC composite in engineering applications. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018, 135, 46090.
Genetic diversity and population history ofTanichthys albonubes(Teleostei: Cyprinidae): Implications for conservation
Authors: Zhao Jun , Hsu Kui‐Ching , Luo Jin‐Zhen , Wang Chun‐Hui , Chan Bosco‐Puilok , Li Jie , Kuo Po‐Hsun , Lin Hung‐Du
Published: December 2017

Tanichthys albonubesis a cyprinid fish of South China and North Vietnam. Although this species has been sold worldwide in the aquarium trade for more than a century, it is listed as a second‐class state‐protected animal in China and classified as ‘extinct in nature’ in the China Red Data Book.

To investigate the population history ofT. albonubesand evaluate the genetic conditions among the wild and hatchery populations, mitochondrial genes (mtDNA, 2032 bp from the d‐loop and cytb), nuclear genes (nuDNA, 2241 bp from RAG1 and ENC1) and 13 microsatellite loci were used to assess the genetic structure throughout the range of this species.

In total, 358 specimens were collected from three hatcheries and all known wild populations. This study found that the discordant population structure among these genetic markers was accounted for by differences in the effective population sizes. The results indicated that (1) the three hatchery stocks originated from a single source in China and that the hatchery stock in China maintained almost all theT. albonubesgenetic diversity in the downstream reaches of the Pearl River; (2) the wild population near Baiyun Mountain originated from hatchery releases; (3) the population history reflects the complex geological history of South China; and (4) the habitat destruction and fragmentation that have resulted in small and isolated populations may have shaped the genetic structure ofT. albonubes.

The low‐level genetic diversity ofT. albonubessupports the need for conservation interventions. The geographically distinct genotypes indicate a need for the development of management strategies directed towards the conservation of localized populations. The genetic status of all populations, including the hatchery stocks, should be evaluated and monitored continuously.
Vulnerability of Cape Fold Ecoregion freshwater fishes to climate change and other human impacts
Authors: Shelton Jeremy M. , Weyl Olaf L.F. , Chakona Albert , Ellender Bruce R. , Esler Karen J. , Impson N. Dean , Jordaan Martine S. , Marr Sean M. , Ngobela Tumisho , Paxton Bruce R. , Van Der Walt Johannes A. , Dallas Helen F.
Published: December 2017

Native freshwater fish populations throughout South Africa's Cape Fold Ecoregion (CFE) are in decline as a result of human impacts on aquatic habitats, including the introduction of non‐native freshwater fishes. Climate change may be further accelerating declines of many species, although this has not yet been studied in the CFE. This situation presents a major conservation challenge that requires assigning management priorities through assessing species in terms of their vulnerability to climate change.

One factor hindering reliable vulnerability assessments and the concurrent development of effective conservation strategies is limited knowledge of the biology and population status of many species. This paper reports on a study employing a rapid assessment method used in the USA, designed to capitalize on available expert knowledge to supplement existing empirical data, to determine the relative vulnerabilities of different species to climate change and other human impacts. Eight local freshwater fish experts conducted vulnerability assessments on 20 native and 17 non‐native freshwater fish species present in the CFE.

Results show (1) that native species were generally classified as being more vulnerable to extinction than were non‐native species, (2) that the climate change impacts are expected to increase the vulnerability of most native, and some non‐native, species, (3) that vulnerability hotspots requiring urgent conservation attention occur in the Olifants‐Doring, upper Berg and upper Breede River catchments in the south west of the region, (4) that in addition to providing guidance for prioritizing management interventions, this study highlights the need for reliable data on the biology and distribution of many CFE freshwater fishes, and (5) that identification of priority areas for protection should be based on multiple sources of data.
Error‐related brain activity and anxiety symptoms in youth with autism spectrum disorder
Authors: Rosen Tamara E. , Lerner Matthew D.
Published: December 2017

Individuals with autism spectrum disorder (ASD) often experience symptoms associated with generalized anxiety disorder, obsessive‐compulsive disorder, and social anxiety disorder. In other populations, these same symptoms are associated with a larger error‐related negativity (ERN), an event‐related potential that reflects endogenous threat sensitivity. As such, it is possible that the ERN may relate to the clinical presentation of anxiety in ASD. However, studies examining these associations in youth with ASD have yielded mixed results. The present study aimed to clarify this relationship by examining the ERN in relation to these specific anxiety symptoms in ASD, and by accounting for typical covariates (e.g., age, verbal abilities, depression, ASD symptoms) of the ERN. Fifty‐one youth, ages 8–17, with ASD and intact cognitive ability completed a modified Flanker task, from which the ERN component was obtained. Measures of anxiety, verbal abilities, depression, and ASD symptoms were collected from participants and parents. Results revealed that greater self‐reported social anxiety symptoms, specifically performance fears but not humiliation/rejection fears, were associated with an increased neural response to errors, as measured by the ERN. This relationship remained after controlling for other anxiety symptoms, as well as age, verbal IQ, depression symptoms, and ASD symptoms. Findings suggest that heightened threat sensitivity may be characteristic of individuals with ASD who exhibit social fearfulness. Autism Res 2018, 11: 342–354. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.

Lay Summary

The error‐related negativity (ERN) is a physiological measure of the brain's response to errors which is thought to reflect threat sensitivity and has been implicated in anxiety disorders in individuals without autism spectrum disorder (ASD). The present study revealed that the ERN is related to social anxiety symptoms, specifically performance fears, in a sample of youth with ASD. Findings suggest that heightened threat sensitivity may be characteristic of individuals with ASD who exhibit social fearfulness.
A Rational Approach to Metal Loading of Organic Multi‐Site Polymers: Illusion or Reality?
Authors: Babel Lucille , Baudet Karine , Hoang Thi Nhu Y. , Nozary Homayoun , Piguet Claude
Published: December 2017

Since its identification as an independent topic after the first world war, the chemistry of (bio)polymers and macromolecules rapidly benefited from intense synthetic activities driven by contributors focusing on formulation and structural aspects. Satisfying rationalization and predictions concerning polymer organization, stability, and reactivity were, however, delayed until the late fifties, when physical chemists set the basis of an adapted thermodynamic modeling. The recent emergence of metal‐containing (bio)organic polymers (i.e., metallopolymers) thus corresponds to a logical extension of this field with the ultimate goal of combining the rich magnetic and optical properties of open‐shell transition metals with the processability and structural variety of polymeric organic scaffolds. Since applications as energy storage materials, drug delivery vectors, shape‐memory materials, and photonic devices can be easily envisioned for these materials, the development of metallopolymers is faced with some urgency in producing novel exploitable structures, while the rational control of their formation, organization, and transformation remains elusive. Caught between the sometimes antagonistic requirements of economic efficiency on one side and of scientific pertinence on the other side, the ongoing achievements in the control of the metal loadings of multi‐site polymers are highlighted here with some tutorial discussions of luminescent lanthanidopolymers as proof‐of‐concept.
The Role of Terminal Functionality in the Membrane and Antibacterial Activity of Peptaibol‐Mimetic Aib Foldamers
Authors: Adam Catherine , Peters Anna D. , Lizio M. Giovanna , Whitehead George F. S. , Diemer Vincent , Cooper James A. , Cockroft Scott L. , Clayden Jonathan , Webb Simon J.
Published: December 2017

Peptaibols are peptide antibiotics that typically feature an N‐terminal acetyl cap, a C‐terminal aminoalcohol, and a high proportion of α‐aminoisobutyric acid (Aib) residues. To establish how each feature might affect the membrane‐activity of peptaibols, biomimetic Aib foldamers with different lengths and terminal groups were synthesised. Vesicle assays showed that long foldamers (eleven Aib residues) with hydrophobic termini had the highest ionophoric activity. C‐terminal acids or primary amides inhibited activity, while replacement of an N‐terminal acetyl with an azide group made little difference. Crystallography showed that N3Aib11CH2OTIPS folded into a 310 helix 2.91 nm long, which is close to the bilayer hydrophobic width. Planar bilayer conductance assays showed discrete ion channels only for N‐acetylated foldamers. However long foldamers with hydrophobic termini had the highest antibacterial activity, indicating that ionophoric activity in vesicles was a better indicator of antibacterial activity than the observation of discrete ion channels.
A Highly Enantioselective Copper/Phosphoramidite‐Thioether‐Catalyzed Diastereodivergent 1,3‐Dipolar Cycloaddition of Azomethine Ylides and Nitroalkenes
Authors: Feng Bin , Chen Jia‐Rong , Yang Yun‐Fang , Lu Bin , Xiao Wen‐Jing
Published: December 2017

In contrast to the plethora of catalytic systems that enable access to any enantiomers of the chiral products by simply choosing between a pair of enantiomeric or pseudoenantiomeric chiral catalysts, few analogously effective protocols exist for the synthesis of compounds bearing multiple stereogenic centers with full control of the absolute and relative stereochemical configurations. Here, we report the application of our previously developed modular phosphoramidite‐thioether ligands for the copper‐catalyzed diastereodivergent asymmetric 1,3‐dipolar cycloaddition of azomethine ylides and nitroalkenes. Our catalytic system enables wide substrate scope, great stereochemical control, and high reaction efficiency.
A Water‐Stable Luminescent ZnII Metal‐Organic Framework as Chemosensor for High‐Efficiency Detection of CrVI‐Anions (Cr2O72− and CrO42−) in Aqueous Solution
Authors: Yao Zhao‐Quan , Li Guang‐Yu , Xu Jian , Hu Tong‐Liang , Bu Xian‐He
Published: December 2017

A new luminescent ZnII‐MOF with 1D triangular channels along the b axis, namely NUM‐5, has been successfully assembled and well characterized, which features good stability, especially in aqueous solution. Interestingly, this compound exhibits a fast, sensitive and selective luminescence quenching response towards CrVI (Cr2O72−/CrO42−) in aqueous solution. The detection limits towards Cr2O72− and CrO42− ions are estimated to be 0.7 and 0.3 ppm, respectively, which are among the lowest detection limits reported for the MOF‐based fluorescent probes that can simultaneously detect Cr2O72− and CrO42− in aqueous environment. The possible detection mechanism has been discussed in detail. Moreover, it can be easily regenerated after detection experiments, indicative of excellent recyclability. All these results suggest NUM‐5 to be a highly selective and recyclable luminescent sensing material for the quantitative detection of CrVI anions in aqueous solution.
Fluorine‐Directed Glycosylation Enables the Stereocontrolled Synthesis of Selective SGLT2 Inhibitors for Type II Diabetes
Authors: Sadurní Anna , Kehr Gerald , Ahlqvist Marie , Wernevik Johan , Sjögren Helena Peilot , Kankkonen Cecilia , Knerr Laurent , Gilmour Ryan
Published: December 2017

Inhibition of the sodium‐glucose co‐transporters (SGLT1 and SGLT2) is a validated strategy to address the increasing prevalence of type II diabetes mellitus. However, achieving selective inhibition of human SGLT1 or SGLT2 remains challenging. Orally available small molecule drugs based on the d‐glucose core of the natural product Gliflozin have proven to be clinically effective in this regard, effectively impeding glucose reabsorption. Herein, we disclose the influence of molecular editing with fluorine at the C2 position of the pyranose ring of Phlorizin analogues Remogliflozin Etabonate and Dapagliflozin (Farxiga®) to concurrently direct β‐selective glycosylation, as is required for biological efficacy, and enhance aspects of the physicochemical profile. Given the abundance of glycosylated pharmaceuticals in diabetes therapy that contain a β‐configured d‐glucose nucleus, it is envisaged that this strategy may prove to be expansive.
Bioenergy Carriers – From Smoothly Treated Biomass towards Solid and Gaseous Biofuels
Authors: Thrän Daniela , Billig Eric , Brosowski André , Klemm Marco , Seitz Stefanie B. , Witt Janet
Published: December 2017

Bioenergy carriers are used in different energy sectors. While the bioenergy supply from energy crops is limited, there is still reasonable unused potential from residues and waste. Improved qualities are necessary with regard to energy density, storability, energy content, flexible application, and related emissions. Especially solid and gaseous biofuels can be generated with reasonable effort and are suitable for utilizing the available waste and residual streams. These advanced bioenergy carriers can support the energy transition significantly, but need support for market introduction.
A Comprehensive Structural Overview of p38α Mitogen‐Activated Protein Kinase in Complex with ATP‐Site and Non‐ATP‐Site Binders
Authors: Astolfi Andrea , Manfroni Giuseppe , Cecchetti Violetta , Barreca Maria Letizia
Published: December 2017

Herein we review all the currently available ATP‐site and non‐ATP‐site ligands bound to p38α mitogen‐activated protein kinase (MAPK) available in the RCSB Protein Data Bank (PDB). The co‐crystallized inhibitors have been classified into different families according to their experimental binding mode and chemical structure, and the ligand–protein interactions are discussed using the most representative compounds. This systematic structural analysis could provide some take‐home lessons for drug discovery programs aimed at the rational identification and optimization of new p38α MAPK inhibitors.
Phase 2 study of treatment selection based on tumor thymidylate synthase expression in previously untreated patients with metastatic colorectal cancer: A trial of the ECOG‐ACRIN Cancer Research Group (E4203)
Authors: Meropol Neal J. , Feng Yang , Grem Jean L. , Mulcahy Mary F. , Catalano Paul J. , Kauh John S. , Hall Michael J. , Saltzman Joel N. , George Thomas J. , Zangmeister Jeffrey , Chiorean Elena G. , Cheema Puneet S. , O'Dwyer Peter J. , Benson Al B.
Published: December 2017

BACKGROUND

The authors hypothesized that patients with metastatic colorectal cancer (mCRC) who had tumors with low thymidylate synthase (TS‐L) expression would have a higher response rate to combined 5‐fluorouracil, leucovorin, and oxaliplatin (FOLFOX) plus bevacizumab (FOLFOX/Bev) than those with high TS (TS‐H) expression and that combined irinotecan and oxaliplatin (IROX) plus bevacizumab (IROX/Bev) would be more effective than FOLFOX/Bev in those with TS‐H tumors.

METHODS

TS protein expression was determined in mCRC tissue. Patients who had TS‐L tumors received FOLFOX/Bev, and those who had TS‐H tumors were randomly assigned to receive either FOLFOX/Bev or IROX/Bev. The primary endpoint was the response rate (complete plus partial responses).

RESULTS

In total, 211 of 247 patients (70% TS‐H) were registered to the treatment phase. Efficacy analyses included eligible patients who had started treatment (N = 186). The response rates for patients who received IROX/Bev (TS‐H), FOLFOX/Bev (TS‐H), and FOLFOX/Bev (TS‐L) were 33%, 38%, and 49%, respectively (P= nonsignificant). The median progression‐free survival (PFS) was 10 months (95% confidence interval [CI], 9‐12 months; 10 months in the IROX/Bev TS‐H group, 9 months in the FOLFOX/Bev TS‐H group, and 13 months in the FOLFOX/Bev TS‐L group). The TS‐L group had improved PFS compared with the TS‐H group that received FOLFOX/Bev (hazard ratio, 1.6; 95% CI, 1.0%‐2.4%;P= .04; Cox regression). The median overall survival (OS) was 22 months (95% CI, 20 29 months; 18 months in the IROX/Bev TS‐H group, 21 months in the FOLFOX/Bev TS‐H group, and 32 months in the TS‐L group). OS comparisons for the 2 TS‐H arms and for the FOLFOX/Bev TS‐H versus TS‐L arms were not significantly different.

CONCLUSIONS

TS expression was prognostic: Patients with TS‐L tumors who received FOLFOX/Bev had a longer PFS than those with TS‐H tumors, along with a trend toward longer OS. Patients with TS‐H tumors did not benefit more from IROX/Bev than from FOLFOX/Bev.Cancer2018;124:688‐97. ©2017 American Cancer Society.
Immune checkpoint inhibitors in advanced non–small cell lung cancer
Authors: Assi Hazem I. , Kamphorst Alice O. , Moukalled Nour M. , Ramalingam Suresh S.
Published: December 2017

The emergence of immune checkpoint inhibitors for the treatment of cancer has led to major changes to the therapeutic landscape of lung cancer. Improvements in overall survival relative to standard chemotherapy have been observed in the first‐line and second‐line therapy settings for patients with advanced non–small cell lung cancer (NSCLC) who are treated with immune checkpoint inhibitors. Consequently, every patient with advanced‐stage NSCLC is now a candidate for immune checkpoint inhibitor therapy. However, it is clear that the benefit from therapy is not universal, and identification of biomarkers to select therapy has assumed importance. In addition to programmed cell death receptor ligand 1 expression, both tissue‐based and blood‐based markers are under evaluation to select patients. In an era of increasing costs of care and potential for toxicities related to immune checkpoint inhibition, proper patient selection is critical to the optimal use of this new class of agents. In addition, development of novel combination approaches has also emerged as an important way to improve the efficacy of immune checkpoint inhibition. Studies in earlier stages of NSCLC are already underway with the hope of improving the cure rate. In this article, the authors review the current landscape of immune checkpoint inhibitors in the treatment of advanced NSCLC. Cancer 2018;124:248‐61. © 2017 American Cancer Society.
Comparative study of lung and extrapulmonary poorly differentiated neuroendocrine carcinomas: A SEER database analysis of 162,983 cases
Authors: Dasari Arvind , Mehta Kathan , Byers Lauren A. , Sorbye Halfdan , Yao James C.
Published: December 2017

BACKGROUND

Extrapulmonary neuroendocrine carcinomas (NECs) are poorly studied and are managed similar to lung NECs, which may not account for differences between the 2 groups of tumors as well as the heterogeneity within extrapulmonary NEC.

METHODS

Data from the Surveillance, Epidemiology, and End Results program between 1973 and 2012 were used to estimate the relative percentages of lung NECs and subgroups of extrapulmonary NECs, epidemiological patterns at these sites, and the median and 5‐year overall survival rates.

RESULTS

Of 162,983 NEC cases, 14,732 were extrapulmonary; of these, 5509 were gastrointestinal (37.44%), 4151 were of unknown primary (28.2%), and 5072 were of other sites (34.4%). Lung NEC had the highest percentage of small cell morphology (95.2%) and gastrointestinal NEC had the least (38.7%), with the rest being other morphologies. Significant differences were noted with regard to median age (range, 48‐74 years), percentage of cases of distant stage disease (24%‐77%), and incidence according to sex and race. The median survival of patients with lung NEC was 7.6 months, that for patients with gastrointestinal NEC was 7.5 months (range, 25.1 months for NEC at the small intestine to 5.7 months for NEC at the pancreas), and that for patients with unknown NEC was 2.5 months. The 5‐year survival rate for patients with local stage disease ranged from 58% to 60% for NECs of the female genital tract and small intestine to 25% for esophageal NECs. The primary tumor site remained statistically significant for survival even after adjusting for known prognostic variables (P<.0001).

CONCLUSIONS

To the authors' knowledge, the current study is the largest study of NECs performed to date and also the first with comprehensive epidemiological data. Significant differences in incidence patterns and large variations in survival depending on anatomical site and morphological subtype were noted. A curative approach is possible for patients with nonmetastatic NECs. Cancer 2018;124:807‐15. © 2017 American Cancer Society.
“Epigenetic” modification as therapy for acute myeloid leukemia
Authors: Schiffer Charles A.
Published: December 2017

The benefits and limitations of the treatment of acute myeloid leukemia/myelodysplasia with epigenetic modifiers are discussed.

See also pages 325‐34.
Dose, schedule, safety, and efficacy of guadecitabine in relapsed or refractory acute myeloid leukemia
Authors: Roboz Gail J. , Kantarjian Hagop M. , Yee Karen W. L. , Kropf Patricia L. , O'Connell Casey L. , Griffiths Elizabeth A. , Stock Wendy , Daver Naval G. , Jabbour Elias , Ritchie Ellen K. , Walsh Katherine J. , Rizzieri David , Lunin Scott D. , Curio Tania , Chung Woonbok , Hao Yong , Lowder James N. , Azab Mohammad , Issa Jean‐Pierre J.
Published: December 2017

BACKGROUND

Outcomes for patients with relapsed or refractory acute myeloid leukemia (AML) are poor. Guadecitabine, a next‐generation hypomethylating agent, could be useful in treating such patients.

METHODS

In this multicenter, open‐label, phase 2 dose‐expansion study, AML patients from 10 North American medical centers were first randomized (1:1) to receive subcutaneous guadecitabine at 60 or 90 mg/m2 on 5 consecutive days in each 28‐day cycle (5‐day regimen). Subsequently, another cohort was treated for 10 days with 60 mg/m2 (10‐day regimen).

RESULTS

Between June 15, 2012, and August 19, 2013, 108 patients with previously treated AML consented to enroll in the study, and 103 of these patients were treated; 5 patients did not receive the study treatment. A total of 103 patients were included in the safety and efficacy analyses (24 and 26 patients who were randomly assigned to 60 and 90 mg/m2/d, respectively [5‐day regimen] and 53 patients who were assigned to 60 mg/m2/d [10‐day regimen]). The 90 mg/m2 dose showed no benefit in clinical outcomes in comparison with 60 mg/m2 in the randomized cohort. Composite complete response (CRc) and complete response (CR) rates were higher with the 10‐day regimen versus the 5‐day regimen (CRc, 30.2% vs 16.0%; P = .1061; CR, 18.9% vs 8%; P = .15). Adverse events (grade ≥ 3) were mainly hematologic, with a higher incidence on the 10‐day regimen. Early all‐cause mortality was low and similar between regimens. Twenty patients (8 on the 5‐day regimen and 12 on the 10‐day regimen) were bridged to hematopoietic cell transplantation.

CONCLUSIONS

Guadecitabine has promising clinical activity and an acceptable safety profile and thus warrants further development in this population. Cancer 2018;124:325‐34. © 2017 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. This is an open access article under the terms of the Creative Commons Attribution NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.