bluuebunny/crossref_metadata_2025 huggingface dataset:
Firearm legislation and statewide suicide rates: The moderating role of household firearm ownership levels
Authors: Anestis Michael D. , Houtsma Claire , Daruwala Samantha E. , Butterworth Sarah E.
Published: May 2019

Firearm legislation is associated with statewide suicide rates; however, prior research has often relied upon older data and categorical legislative grades while also failing to consider the nuanced role of firearm ownership. Therefore, the robust literature base on legislation and suicide has not directly examined regarding the extent to which the value of legislation hinges upon the rate of firearm ownership in a given state. The current study examined 2015 US statewide firearm legislation strength scores from Giffords Law Center to Prevent Gun Violence and 2016 statewide suicide rates from the Centers for Disease Control and Prevention. Firearm legislation strength was inversely associated with statewide overall and firearm suicide rates, but not with non‐firearm suicide rates. Firearm ownership rates moderated the association between firearm legislation strength and statewide overall suicide rates. Specifically, firearm legislation strength was inversely associated with statewide overall suicide rates at mean and high levels of firearm ownership. Findings support the potential utility of firearm legislation as part of a national effort to decrease US suicide deaths, particularly in areas with higher firearm ownership rates.
Ser625 of msn2 transcription factor is indispensable for ethanol tolerance and alcoholic fermentation process
Authors: Vamvakas Sotirios‐Spyridon , Kapolos John , Farmakis Lambros , Koskorellou Gregoria , Genneos Fotios
Published: May 2019

The genetic modification of yeast strains can be used as an approach for the improvement of ethanol fermentation. msn2p transcription factor is implicated in yeast stress response and its activation is controlled by protein kinase A (PKA). PKA activation inhibits the translocation of msn2p to the nucleus. An in silico analysis of msn2 protein sequence revealed serine residue at position 625 as a potent target of PKA. Thus, substitution of this serine residue with alanine increases the susceptibility of the cells to ethanol challenge reducing IC50 from 3% vol/vol to 2.42% vol/vol. Additionally, cells carrying this substitution were shown a significantly reduced fermentation rate at 30°C and 18°C increasing the total fermentation time by approximately two and three times, respectively. These results clearly indicate that Ser625 is absolutely necessary for yeast to retain its fermentation ability and ethanol tolerance.
Anatomical structures at risk using different approaches for sacrospinous ligament fixation
Authors: De Decker Albert , Fergusson Rosalie , Ondruschka Benjamin , Hammer Niels , Zwirner Johann
Published: May 2019

For 50 years now, sacrospinous ligament fixation (SSLF) has been used to treat pelvic organ prolapse consequent on altered integrity of the pelvic myofascial structures. It is usually performed vaginally, but it has recently been performed laparoscopically through either an anterior or a posterior approach, with the broad ligament as a landmark to differentiate the two. In the present study, these two laparoscopic approaches were assessed using Thiel‐embalmed cadavers. The anterior and posterior approaches were compared in terms of the closest distance to anatomical structures at risk, including pelvic viscera, the obturator nerve, and vascular structures. The posterior approach was more often closer to the investigated vessels and the rectum. The obturator nerve and the ureter were close to both the anterior and posterior approaches. The urinary bladder was closer using the anterior approach. From an anatomical standpoint, therefore, the anterior laparoscopic approach for SSLF is more likely to cause injury to the urinary bladder, whereas the posterior approach is more prone to causing rectal and vessel injuries. This study illustrates, from a basic science perspective, the importance of combining fascia research, novel endoscopic or minimally invasive surgical exposures informed by anatomy, and contemporary trends in gynecology in order to improve patient outcomes. Clin. Anat. 33:522–529, 2020. © 2019 Wiley Periodicals, Inc.
Pediatric regional anesthesia: A review of the relevance of surface anatomy and landmarks used for peripheral nerve blockades in infants and children
Authors: Byun Sarang , Pather Nalini
Published: May 2019

In regional anesthesia, accurate knowledge of surface anatomy and landmarks are essential for successful nerve blockades with least possible complications. The long‐established anatomical landmarks used for peripheral nerve blockades in adult patients have also gained a place in pediatric anesthesia. Despite the continuing benefits and need for more effective peripheral techniques in pediatrics, there is a paucity of data on pediatric landmarks, and hence the absence of more appropriate techniques for the different age groups of children. Recent advancement in imaging has shown that there is a greater awareness for the different surface projections at various stages of postnatal development, as compared with that of adults. Thus, if adult landmarks are not appropriately adapted for use in children, complication rates may rise due to injuries to anatomical structures. This review evaluated the existing evidence of the pediatric nerve block landmarks in the reported literature, in order to highlight the limitations in our current understanding of pediatric surface anatomy and landmarks. A literature search was done using five databases to obtain 141 references. Only a few of these studies provided detailed reports of the relations of relevant nerves to anatomical landmarks. A few clinical imaging studies have provided new anatomical landmarks in children with reference to their age‐related growth and anatomy. Most landmarks need to be standardized in children of various ages, and furthermore, inconsistencies in the current descriptions of the surface landmarks need to be validated and standardized for use in pediatric clinical practice. Clin. Anat. 32:803–823, 2019. © 2019 Wiley Periodicals, Inc.
Dermatome and fasciatome
Authors: Stecco Carla , Pirri Carmelo , Fede Caterina , Fan Chenglei , Giordani Federico , Stecco Luigi , Foti Calogero , De Caro Raffaele
Published: May 2019

Increased knowledge of the rich innervation of the deep fascia and its anatomical organization indicates the need to reevaluate maps of the dermatome according to the new findings. The authors present a distinction between dermatome and fasciatome, basing their approach to the literature on nerve root stimulation and comparing dermatomeric and myomeric maps. The former represents the portion of tissue composed of skin, hypodermis, and superficial fascia supplied by all the cutaneous branches of an individual spinal nerve; the latter includes the portion of deep fascia supplied by the same nerve root and organized according to force lines to emphasize the main directions of movement. The dermatome is important for esteroception, whereas the fasciatome is important for proprioception. If they are altered, the dermatome shows clearly localized pain and the fasciatome irradiating pain according to the organization of the fascial anatomy. Clin. Anat. 32:896–902, 2019. © 2019 Wiley Periodicals, Inc.
Review legal analysis of President Trump's executive order on free speech
Authors: Rooksby Jacob
Published: May 2019

President Donald Trump signed an executive order in March aimed at holding colleges and universities that receive federal research funding accountable for protecting free speech on their campuses. The controversial order delivers on a campaign talking point by Trump that higher education hasn't been appropriately hospitable to a diversity of viewpoints, particularly conservative viewpoints, and that institutions ought to face consequences for stifling freedom of expression on their campuses.
Is assignment‐deadline flexibility an appropriate accommodation?
Authors: Masinter Michael R.
Published: May 2019

A growing number of students have sought accommodation letters authorizing extended time for completion of future curricular assignments, or, as it is sometimes known, assignment‐deadline flexibility, as an accommodation. These students don't seek after‐the‐fact extensions for last‐minute health crises, but instead seek advance accommodations available for use at their discretion.
Alcohol injection for nonsurgical management of tailgut cyst in a middle‐aged woman: A case report
Authors: Aljuhani Farrah , Almunami Bashair , Alsamahi Rawan , Malibary Nadim , Algaithy Zuhoor
Published: May 2019

Managing recurrent tailgut cyst in a patient who is refraining from the definitive surgical en bloc resection can be challenging. Therefore, in this case report we outlined a less invasive approach which is computed tomography‐guided aspiration with alcohol injection which resulted in prolongation of symptoms free period in our patient.
Au−Pd Selectivity‐switchable Alcohol‐oxidation Catalyst: Controlling the Duality of the Mechanism using a Multivariate Approach
Authors: da S. Melo Itaciara E. M. , de Sousa Samuel A. A. , dos S. Pereira Laíse N. , Oliveira Jefferson M. , Castro Karla P. R. , Costa Jean C. S. , de Moura Edmilson M. , de Moura Carla V. R. , Garcia Marco A. S.
Published: May 2019

Supported gold‐palladium nanoparticles are highly selective catalysts for the oxidation of alcohols. However, little is known about how integrated reaction conditions can affect the chemoselectivity of a specific catalytic system. Herein, a novel Au−Pd selectivity‐switchable catalyst supported on SrCO3 is reported; and a multivariate optimization was suggested as the key process to better understand the formation of the products. The optimization approach considered temperature, pressure, time of reaction, and Au : Pd molar ratio, and settled that the temperature and Au : Pd molar ratio showed an important effect on the ester yield, while just the metal molar ratio significantly influenced the selectivity for the aldehyde. Thus, taking into consideration the experimental data and optimized conditions, we were able to efficiently switch the selectivity by just changing the pressure of the system in a benzyl alcohol oxidation reaction. In addition, we proposed that the presence of O2 implies that there are two catalytic pathways, which leads to different selectivity, allowing us to bring some mechanistic insights dealing with the duality of the mechanism. Such outcomes are based on dense experimental results and characterizations (FT‐IR, Rietveld refinement, XPS, H2‐TPR, and EDS‐STEM). The catalyst was also very stable, presenting activity up to 6 runs without loss of activity and selectivity, under certain reaction conditions.
Cellulose as an Adhesive for the Synthesis of Carbon Aerogel with a 3D Hierarchical Network Structure for Capacitive Energy Storage
Authors: Cai Tailong , Kuang Liwen , Wang Chao , Jin Chunde , Wang Zhe , Sun Qingfeng
Published: May 2019

As an abundant biomaterial, lignin is often used as a low‐end material, because it has an inferior formability at normal temperature and a poor solubility in most solvents. In this study, an innovative lignin/cellulose carbon aerogel with a 3D hierarchical network structure composed of nanochains connecting nanospheres is successfully synthesized by dissolving cellulose and lignin in 1‐butyl‐3‐methylimidazolium chloride, regenerating in deionized water, freeze‐drying, and carbonizing. Cellulose, as the adhesive connects lignin by hydrogen bonds, increases the specific surface area and improves the graphitization degree. Consequently, the sample with 10 wt % cellulose (C‐10) has a high specific capacitance (166 F g−1 at 0.1 A g−1), low impedance (τ=5.56 ms), and excellent capacitance retention (98.6 % after 1000 cycles). The C‐10‐based flexible supercapacitor exhibits a stable output capability (≥99 %) at different bending angles, long cycle life (≥1000 cycles), and high energy density (102 Wh kg−1 at 175 W kg−1).
Advanced Polymer Designs for Direct‐Ink‐Write 3D Printing
Authors: Li Longyu , Lin Qianming , Tang Miao , Duncan Andrew J. E. , Ke Chenfeng
Published: May 2019

The rapid development of additive manufacturing techniques, also known as three‐dimensional (3D) printing, is driving innovations in polymer chemistry, materials science, and engineering. Among current 3D printing techniques, direct ink writing (DIW) employs viscoelastic materials as inks, which are capable of constructing sophisticated 3D architectures at ambient conditions. In this perspective, polymer designs that meet the rheological requirements for direct ink writing are outlined and successful examples are summarized, which include the development of polymer micelles, co‐assembled hydrogels, supramolecularly cross‐linked systems, polymer liquids with microcrystalline domains, and hydrogels with dynamic covalent cross‐links. Furthermore, advanced polymer designs that reinforce the mechanical properties of these 3D printing materials, as well as the integration of functional moieties to these materials are discussed to inspire new polymer designs for direct ink writing and broadly 3D printing.
Spectroscopy and Reactivity of Dialkoxy Acenes
Authors: Brega Valentina , Kanari Sare Nur , Doherty Connor T. , Che Dante , Sharber Seth A. , Thomas Samuel W.
Published: May 2019

Photochemical oxidation of acenes can benefit or impede their function, depending on the application. Although acenes with alkoxy substituents on reactive sites are important for applications as diverse as drug delivery and organic optoelectronics, the influence of chemical structure on their photochemical oxidation remains unknown. This paper therefore describes the synthesis, spectroscopic properties, and reactivity with singlet oxygen (1O2) of a series of dialkoxyacenes that vary in the number and types of fused rings in the (hetero)acene cores. Reductive alkylation of quinone precursors yielded target dialkoxyacenes with fused backbones ranging from benzodithiophene to tetracenothiophene. Trends of their experimental spectroscopic characteristics were consistent with time‐dependent density functional theory (TD‐DFT) calculations. NMR studies show that photochemically generated 1O2 oxidizes all but one of these acenes to the corresponding endoperoxides in organic solvent. The rates of these oxidations correlate with the number and types of fused arenes, with longer dialkoxyacenes generally oxidizing faster than shorter derivatives. Finally, irradiation of these acenes in acidic, oxidizing environments cleaves the ether bonds. This work impacts those working in organic optoelectronics, as well as those interested in harnessing photogenerated reactive oxygen species in functional materials.
Manipulation of Transmembrane Transport by Synthetic K+ Ionophore Depsipeptides and Its Implications in Glucose‐Stimulated Insulin Secretion in β‐Cells
Authors: García‐Calvo José , Torroba Tomás , Brañas‐Fresnillo Virginia , Perdomo Germán , Cózar‐Castellano Irene , Li Yu‐Hao , Legrand Yves‐Marie , Barboiu Mihail
Published: May 2019

The cyclic depsipeptide cereulide toxin it is a very well‐known potassium electrogenic ionophore particularly sensitive to pancreatic beta cells. The mechanistic details of its specific activity are unknown. Here, we describe a series of synthetic substituted cereulide potassium ionophores that cause impressive selective activation of glucose‐induced insulin secretion in a constitutive manner in rat insulinoma INS1E cells. Our study demonstrates that the different electroneutral K+ transport mechanism exhibited by the anionic mutant depsipeptides when compared with classical electrogenic cereulides can have an important impact of pharmacological value on glucose‐stimulated insulin secretion.
The Effect of Viscosity on the Diffusion and Termination Reaction of Organic Radical Pairs
Authors: Li Xiaopei , Ogihara Tasuku , Abe Manabu , Nakamura Yasuyuki , Yamago Shigeru
Published: May 2019

The effect of viscosity on the diffusion efficiency (Fdif) of an organic radical pair in a solvent cage and the termination mechanism, that is, the selectivity of disproportionation (Disp) and combination (Comb) of the geminated caged radical pair and the diffused radicals encountered, were investigated quantitatively by following the photolysis of dimethyl 2,2′‐azobis(2‐methylpropionate) (V‐601) in the absence and presence of PhSD. Fdif and Disp/Comb selectivity outside the cage [Disp(dif)/Comb(dif)] are highly sensitive to the viscosity. In contrast, the Disp/Comb selectivity inside the cage [Disp(cage)/Comb(cage)] is rather insensitive. The difference in viscosity dependence between Disp(cage)/Comb(cage) and Disp(dif)/Comb(dif) is explained by the spin state of the radical pair inside and outside the cage and the spin state dependent configurational changes of the radical pair upon their collision. Given that the configurational change of the radicals associates the displacement and reorganization of solvents around the radicals, the termination outside the cage, which requires larger change than that inside the cage, is highly viscosity dependent. Furthermore, while the bulk viscosity of each solvent shows good correlation with Fdif and Disp/Comb selectivity, microviscosity is the better parameter predicting Fdif and Disp(dif)/Comb(dif) selectivity regardless of the solvents.
Biomarkers to diagnose metastatic breast carcinoma to the pancreas: A case report and update
Authors: Shee Kevin , Strait Alexander M. , Liu Xiaoying
Published: May 2019

The patient is a 72‐year‐old female who presents with new onset jaundice. The patient has a past medical history significant for right‐sided estrogen receptor (ER)‐positive and left‐sided ER‐negative breast cancers in 2005 and 2009, respectively, and recent 1‐year history of ER‐positive right‐sided breast cancer with bone and brain metastases. CT scan and endoscopic ultrasound (EUS) revealed a new 2 cm mass in the head of the pancreas, leading to EUS‐guided fine‐needle aspiration of the lesion. Pathologic workup revealed adenocarcinoma with signet‐ring cells, representing either metastatic breast or primary pancreatic cancer. Immunohistochemistry and molecular diagnostic workup identified positive GATA‐binding protein 3 (GATA3) immunoreactivity and a mutation in Erb‐B2 receptor tyrosine kinase 2 (ERBB2), also known as human epidermal growth factor receptor 2 (HER2). Here, we review the diagnostic markers commonly used to differentiate metastatic breast vs primary pancreatic adenocarcinoma, and discuss the challenges of utilizing GATA3 immunoreactivity and ERBB2 mutations for diagnosis.
Excitatory/inhibitory balance across ontogeny contributes to age‐specific behavioral outcomes of ethanol‐like challenge in conditioned taste aversion
Authors: Dannenhoffer Carol A. , Spear Linda P.
Published: May 2019

Adolescent‐typical sensitivities to ethanol (EtOH) are characterized in part by reduced sensitivity to EtOH's aversive effects. Rodent studies have shown that adolescents are less sensitive than adults to aversive properties of EtOH in a conditioned taste aversion (CTA) paradigm. To the extent that EtOH exerts antagonist‐like actions upon glutamate receptors and/or agonist‐like actions upon γ‐aminobutyric acid (GABA) receptors, age differences in excitatory/inhibitory balance may regulate age‐specific EtOH sensitivities, such as attenuated sensitivity of adolescents to EtOH aversion. In our experiments, adolescent and adult Sprague‐Dawley rats were tested for CTA following challenge with one of the following pharmacological agents: glutamatergic AMPA1 receptor antagonist NBQX, glutamatergic N‐methyl‐d‐aspartate NR2B receptor antagonist ifenprodil, and extrasynaptic GABAA receptor agonist THIP to determine whether these induced age‐specific aversive sensitivities like those seen with EtOH. NBQX administration did not induce CTA. The highest dose of extrasynaptic GABAA agonist THIP induced CTA in adolescents but not adults, an opposite ontogenetic profile as seen following EtOH. Ifenprodil exerted an age‐specific pattern of CTA similar to that seen with EtOH in males, with adolescents being insensitive to ifenprodil's aversive effects relative to adults. Thus, only antagonism of NR2B receptors in male rats mimicked age‐specific sensitivities to the aversive effects of EtOH.
Temperature variations in simulated warming alter photosynthesis of two emergent plants in plateau wetlands, China
Authors: Xiao Derong , Yan Pengfei , Zhan Pengfei , Zhang Yun , Liu Zhenya , Tian Kun , Yuan Xingzhong , Wang Hang
Published: May 2019

Understanding the impact of temperature variations (i.e., maximum, minimum, and diurnal temperature ranges [DTRs]) on ecosystems is now recognized as being of paramount importance in global change ecology; the roles of different aspects of these temperature variations in influencing plant photosynthesis remain under‐studied. Here, we investigated the photosynthetic responses of two local dominant wetland plants to two simulated air‐warming scenarios (+2° ± 0.5°C and +3.5° ± 0.5°C) by using open‐top chambers in the northwest Yunnan plateau. During the growing season from 2014 to 2016, we explored photosynthetic parameters and the relationships linking photosynthesis to temperature variations. We found that open‐top chambers had increased the daily maximum temperature as well as DTRs. The photosynthetic responses of two plant species to warming were species‐specific during the first two years but species‐independent in the third year. The two warming scenarios did not significantly alter the linear relationships linking maximum net photosynthetic rate (Amax) to stomatal conductance (gs), intercellular CO2 concentration (Ci), and transpiration rate (Tr), despite changes in slopes and intercepts of the fitted lines. The DTRs between 0°C and 30°C were positively correlated with photosynthesis, while DTRs over 30°C were negatively correlated with photosynthesis. Our results provide experimental evidence that temperature variations play a greater role than increasing average temperature in explaining plant photosynthesis, and more attention should be paid to temperature variations when assessing the impact of climate warming on wetland ecosystem.
Interactive effects of hydrogeomorphology on fish community structure in a large floodplain river
Authors: Delong Michael D. , Thoms Martin C. , Sorenson Ethan
Published: May 2019

Biocomplexity is an emergent property of ecosystems that captures the interplay of structures and processes at multiple scales. These interactions can establish a dynamic habitat template that serves as a filter to define ecological organization across landscapes. Studies of biocomplexity in floodplain rivers typically focus on hydrological variability or geomorphic heterogeneity separately, with their interactions being an output rather than the direct focus of investigations. This study examines the interaction of hydrological variability and geomorphic heterogeneity across 25 off‐channel habitats (OCHs) of the Upper Mississippi River, USA. Questions posed were as follows: What are the interactive effects of hydrological variability and geomorphic heterogeneity shaping the physical habitat template of OCHs? and How does the organization of the physical habitat template influence fish community composition within OCHs? Three distinct OCH groups emerged from this study: where hydrological variability defined Group 1 (Lake group); Group 2 was organized via geomorphic heterogeneity (Backwater group); and a combination of hydrological and geomorphological variables defined Group 3 (Slackwater group). Thus, the differential interaction of hydrology and geomorphology defined the dynamic physical habitat template of OCHs in this riverine landscape. No significant difference between the association matrices of the hydrogeomorphic template and fish community composition for the 25 OCH sites was recorded. A priori grouping of fish into the three OCH groups revealed marked differences in fish community composition. A subset of hydrogeomorphic variables that defined the physical character of the OCHs acted as an environmental filter for the fish community composition of the three OCH groups. A conceptual model explaining hydrogeomorphic–ecological interactions across the OCHs of this floodplain river system is provided.
Sulfonate‐Ligated Coordination Polymers Incorporating Paramagnetic Transition Metals
Authors: Kawamura Airi , Filatov Alexander S. , Anderson John S.
Published: May 2019

The functionalized linker SNDC (4,8‐disulfonyl‐2,6‐naphthalenedicarboxylate) has been incorporated into 2D extended structures featuring FeII or CoII. These materials are isostructural and exhibit coordination via both the carboxylate and sulfonate groups of the SNDC linker. The variable temperature magnetic behavior of the FeII and CoII materials has also been measured. A simplified model of these systems implies weak (|J| < 5 cm–1) antiferromagnetic coupling, as is expected for a superexchange mechanism operating through the carboxylate paddlewheels. The combination of functionalized linkers, such as SNDC, with paramagnetic metal centers is a promising pathway towards functionalized materials, and the coordination polymers reported join a small class of known materials featuring SNDC.
Enhanced Separation Concept (ESC): Removing the Functional Subunit from the Electrode by Molecular Design
Authors: Brandl Thomas , El Abbassi Maria , Stefani Davide , Frisenda Riccardo , Harzmann Gero D. , van der Zant Herre S. J. , Mayor Marcel
Published: May 2019

A new concept to improve the reliability of functional single molecule junctions is presented using the E‐field triggered switching of FeIIbis‐terpyridine complexes in a mechanically controlled break junction experiment as model system. The complexes comprise a push‐pull ligand sensing the applied E‐field and the resulting distortion of the FeII ligand field is expected to trigger a spin‐crossover event reflected in a sudden jump of the transport current. By molecular engineering, the active centre of the complex is separated from the gold electrodes in order to eliminate undesired side‐effects. Two aspects are considered to isolate the central metal ion, namely the spacing by introducing additional alkynes, and the steric shielding achieved by bulky isopropyl groups. With this small series of model complexes, a pronounced correlation is observed between the occurrence of bistable junctions and the extent of separation of the central metal ion, affirming the hypothesized Enhanced Separation Concept (ESC).
Photocatalyzed Generation of Nitrosocarbonyl Intermediates Under Solar Light Irradiation
Authors: Basile Teresa , Capaldo Luca , Ravelli Davide , Quadrelli Paolo
Published: May 2019

Tetrabutylammonium decatungstate (TBADT) has emerged as a valuable photocatalyst for sunlight‐induced organic reactions. In this communication we wish to present its use for the photocatalytic oxidation of hydroxamic acids to generate fleeting nitrosocarbonyl intermediates. The reaction required a fine tuning of the conditions, especially in terms of solvent and additives, since an aqueous acetonitrile solution containing a mild base (NaHCO3) gave the best results. The obtained highly reactive nitrosocarbonyl species were then efficiently trapped with suitable dienes, such as cyclopentadiene and 1,3‐cyclohexadiene, to afford the corresponding Hetero Diels–Alder (HDA) cycloadducts in good yields. Dedicated photophysical experiments helped to elucidate the mechanistic scenario.
Renaissance of 1,2,5‐Oxadiazolyl Diazonium Salts: Synthesis and Reactivity
Authors: Zhilin Egor S. , Fershtat Leonid L. , Bystrov Dmitry M. , Kulikov Alexander S. , Dmitrienko Artem O. , Ananyev Ivan V. , Makhova Nina N.
Published: May 2019

A new approach for the synthesis and reactivity of the 1,2,5‐oxadiazolyl diazonium salts is represented. A simple and direct protocol to previously inaccessible furoxanyl and furazanyl diazonium salts was developed for the first time. Azo coupling reactions of thus obtained diazonium salts with a series of structurally diverse CH‐acids have been also successfully performed. Therefore, this study reveals new horizons for the use of furoxanyl and furazanyl diazonium salts in organic chemistry.
Combination of medical and health care based on digital smartphone‐powered photochemical dongle for renal function management
Authors: Fu Yusheng , Tan Haiyan , Wu Xiujian , Wu Xiaohe , Yang Yongzheng , Gao Yanling , Liu Ruowei , Qi Min , Chen Xiaoyun , Ning Yaochao , Sun Weidong , Chang Nianhuan , Ma Junjie , Cheng Kang , Yang Hongni , Li Qing , Wang Ping , Wu Chaoran , Xian Hong , Wang Li
Published: May 2019

Currently, the global healthcare market is increasing at high speed with the impendent global aging issue. Healthcare Industry 4.0 has emerged as an efficient solution towards the aging issue since it was integrated with ubiquitous medical sensors, big health processing platform, high bandwidth, speed technologies, and medical services, etc. It is believed to fulfil the requirement of the tremendously growing health market. The acquisition of medical data acts as the dominant precondition to implement the Healthcare Industry 4.0. In the same way, the widely available smartphone could serve as the best biomedical information collect station. In this study, a smartphone‐powered photochemical dongle is demonstrated to precisely estimate blood creatinine from the fingertip blood, which works as a highly compact reflectance spectral analyzer with an enzymatically dry chemical test strip. Comparing with conventional laboratory facility for the evaluation and treatment of chronic kidney disease (CKD), it implemented the platform of point care with agreed accuracy. In order to estimate the efficiency of treatment and recovery of the CKD, the proposed photochemical dongle would provide a flexible and rapid platform for point of care. Furthermore, the proposed measured technology is very promising method for remote CKD management.
Solar Water Splitting under Neutral Conditions Using Z‐Scheme Systems with Mo‐Doped BiVO4 as an O2‐Evolving Photocatalyst
Authors: Iwase Akihide , Udagawa Yuhei , Yoshino Shunya , Ng Yun Hau , Amal Rose , Kudo Akihiko
Published: May 2019

The photocatalytic water‐splitting system ideally consists of just photocatalyst powder and water without any additives. Herein, improvement of water‐splitting activity under neutral conditions is achieved by applying Mo‐doping and cocatalyst‐loading to BiVO4 of an O2‐evolving photocatalyst in a Z‐scheme system with Ru‐loaded SrTiO3 doped with Rh as a H2‐evolving photocatalyst and a reduced graphene oxide as an electron mediator. The strategies are based on the idea that the Z‐schematic electron migration process in the powdered Z‐scheme system with reduced graphene oxide is similar to that in the photoelectrochemical system. Although the reaction condition becomes out of the ideal states, adding Ca(NO3)2 and CaCl2 into the reactant solution further improves the water‐splitting activity due to the formation of aggregated photocatalyst particles to boost the electron transfer from Mo‐doped BiVO4 to Ru‐loaded SrTiO3 doped with Rh through the reduced graphene oxide.
Basinga: A cell‐by‐cell GIS toolbox for computing basin average scaling factors, cosmogenic production rates and denudation rates
Authors: Charreau Julien , Blard Pierre‐Henri , Zumaque Jéna , Martin Léo C.P. , Delobel Tony , Szafran Lucas
Published: May 2019

The calculation of denudation rates from the measured cosmogenic nuclide concentrations in river sediments requires assumptions and approximations. Several different approaches and numerical tools are available in the literature. A widely used analytical approach represents the muogenic production with one or two exponentials, assumes the attenuation length of muons to be constant and also neglects temporal variations in the Earth's magnetic field. The denudation rates are then calculated directly and analytically from the measured concentrations. A second numerical and iterative approach was more recently proposed and considers a more rigorous muogenic production law based on pre‐calculated variable attenuation length of muons and accounts for temporal changes of the magnetic field. It also assumes a specific distribution of denudation rates throughout the basin and uses an iterative approach to calculate the basin average denudation rates.

We tested the two approaches across several natural basins and found that both approaches provide similar denudation results. Hence, assuming exponential muogenic production and constant attenuation length of muons in the rock has little impact on the derived denudation rates. Therefore, unless a priori known distributions of denudation rates are to be tested, there does not appear to be any particular gain from using the second iterative method which is computationally less effective.

Based on these findings, we developed and describe here Basinga, a new ArcGIS® and QGIS toolbox which computes the basin average scaling factors, cosmogenic production rates and denudation rates for several tens of drainage basins together. Basinga follows either the Lal/Stone or the Lifton/Sato/Dunai scaling schemes and includes several optional tools for correcting for topographic shielding, ice cover and lithology. We have also developed an original method for correcting the cosmogenic production rates for past variations in the Earth's magnetic field. © 2019 John Wiley & Sons, Ltd.
Capturing the cross‐terms in multidimensional advection schemes
Authors: Kent James
Published: May 2019

Solving the advection equation is an important part of numerically modeling the atmosphere. Both accuracy and efficiency are desirable traits of an advection scheme. For multidimensional flow, forward‐in‐time advection schemes must properly capture the cross‐terms. Failure to capture the cross‐terms can result in reduced accuracy and even instabilities. We show how multidimensional forward‐in‐time schemes successfully capture the cross‐terms of two‐dimensional (2D) flow. We then introduce a method to improve the efficiency of the forward‐in‐time schemes for 2D flow. This method stacks the duplicated cross‐terms from one flux into the other, creating asymmetrized fluxes. Numerical testing shows that these asymmetrized flux calculation schemes perform to the same accuracy as the original forwards‐in‐time schemes but with a significant improvement in computational time. Finally, we show extensions of the method to three‐dimensional (3D) flow.
Real‐life activity of eribulin mesylate among metastatic breast cancer patients in the multicenter national observational ESME program
Authors: Jacot William , Heudel Pierre‐Etienne , Fraisse Julien , Gourgou Sophie , Guiu Séverine , Dalenc Florence , Pistilli Barbara , Campone Mario , Levy Christelle , Debled Marc , Leheurteur Marianne , Chaix Marie , Lefeuvre Claudia , Goncalves Anthony , Uwer Lionel , Ferrero Jean‐Marc , Eymard Jean‐Christophe , Petit Thierry , Mouret‐Reynier Marie‐Ange , Courtinard Coralie , Cottu Paul , Robain Mathieu , Mailliez Audrey
Published: May 2019

Eribulin mesylate (EM) was recently approved for metastatic breast cancer (MBC) chemotherapy (CT) in late lines by the FDA, with debated results in second line. We evaluated outcomes in breast cancer patients receiving EM as second, third and fourth line in a national real‐life cohort of 16,703 consecutive MBC patients initiating their first metastatic therapeutic line between 2008 and 2014. Primary and secondary objectives were overall survival (OS) and progression‐free survival (PFS). An imbalance was seen for HER2+ tumors and concomitant anti‐HER2 targeted therapies use, we thus performed a subanalysis in HER2− patients. PFS and OS were significantly better in EM patients in third and fourth lines, compared to “Other chemotherapies” patients (PFS: 4.14vs. 3.02 months,p = 0.0010; 3.61vs. 2.53 months,p = 0.0102, third and fourth‐line; OS: 11.27vs. 7.65 months,p = 0.0001; 10.91vs. 5.95 months,p < 0.0001, third and fourth‐line). No significant difference was reported in second‐line (PFS: 5.06vs. 4.14 months,p = 0.1171; OS: 13.99vs. 11.66 months,p = 0.151). Among HER2− patients, a significant difference was seen for all lines, including 2nd‐line (PFS: 4.57vs. 3.91 months,p = 0.0379; OS: 14.98vs. 10.51 months,p = 0.0113). In this large real‐world database, HER2‐negative MBC patients receiving EM in second or later CT line presented significantly better PFS and OS. This difference disappeared in second line in the overall population, probably because of the imbalance in HER2‐targeted treatments use. Our results mirror those of the published randomized trials. The effect of anti‐HER2 therapies addition in this setting still needs to be defined.
How well are Phase 2 cancer trial publications supported by preclinical efficacy evidence?
Authors: Pratte Michael , Ganeshamoorthy Sylviya , Carlisle Benjamin , Kimmelman Jonathan
Published: May 2019

Major ethics policies require that human studies be preceded by animal experiments. We probed the extent to which trials testing efficacy of cancer drugs cited preclinical efficacy studies testing the same drug and disease indication. Using a sample of Phase 2 trial publications for novel cancer monotherapies approved by Food and Drug Administration 2005–2007, we conducted a systematic analysis of citations to preclinical efficacy evidence within trial publications. Citations were classified based on whether they “matched” the drug and indication of the trial. Our sample included 179 Phase 2 publications published 2004–2016. At least one preclinical study was cited for 113 of 179 publications (63%); 56 (31%) cited matching preclinical studies, and 74 (41%) did not cite either matching preclinical or matching clinical trial evidence. When excluding evidence that would likely not have been available to investigators before trial launch, 45 trials (25%) cited matching preclinical studies; 91 (51%) did not cite any matched preclinical or clinical, preceding evidence. No relationship between citation of matching and preceding preclinical evidence and trial outcomes was observed (28.4% of nonpositive trials vs. 26.9% of positive trials, p ~ 1). This suggests that many Phase 2 trial publications do not cite matching preclinical efficacy studies. Limited citation either suggests its absence or its exclusion from a publication. To ensure trials rest on a sound ethical basis and that publications support valid inference, journal editors and referees might encourage more complete descriptions of preclinical evidence or, where appropriate, active disclosure of its absence.
Downregulation of hedgehog ligands in human simple steatosis may protect against nonalcoholic steatohepatitis: Is TAZ a crucial regulator?
Authors: Khajehahmadi Zohreh , Mohagheghi Sina , Nikeghbalian Saman , Geramizadeh Bita , Khodadadi Iraj , Karimi Jamshid , Ghaffari Mohammad Ebrahim , Tavilani Heidar
Published: May 2019

The conversion of simple steatosis into nonalcoholic steatohepatitis (NASH) in patients with nonalcoholic fatty liver disease (NAFLD) has attracted many attentions in recent years. The role of the hedgehog (HH) pathway in the regulation of lipogenesis has been addressed in the literature. This study aimed to investigate the levels of the sonic hedgehog (SHH) and Indian hedgehog (IHH) ligands and the correlation of these ligands with levels of proteins involved in the transforming growth factor‐β1 (TGF‐β1) pathway, as well as the evaluation of the transcriptional coactivator with PDZ binding motif (TAZ) expression in human simple steatosis, NASH cirrhosis, and controls. Patients were divided into two groups: the first group consisted of patients diagnosed with simple steatosis (n = 16) and the second group included those diagnosed with NASH cirrhosis (n = 15). As a control group, 18 histologically normal liver tissues were collected in this study. The expression of the TGF‐β1pathway components and SHH and IHH ligands were analyzed by means of the quantitative real‐time polymerase chain reaction and western blot analyses. A significant decrease was found in the hepatic expression of the SHH, IHH, and TGF‐β1 pathways along with the expression of TAZ in tissue specimens with simple steatosis in comparison with patients affected by NASH cirrhosis and controls. Also, the levels of SHH and IHH proteins were significantly correlated with the expression of proteins involved in the TGF‐β1 pathway. Moreover, the expression of the HH pathway ligands was positively associated with the expression of TAZ, supporting the notion that TAZ may play a role in the activation of the HH pathway thereby regulating the expression of its ligands. It seems that in patients with NAFLD, the downregulation of the HH pathway ligands may stem from steatosis; however, at the same time, it may prevent the conversion of simple steatosis into NASH in patients with liver diseases. © 2019 IUBMB Life, 71(9):1382–1390, 2019
Fabrication and properties of an injectable sodium alginate/PRP composite hydrogel as a potential cell carrier for cartilage repair
Authors: Gao Xiang , Gao Liyang , Groth Thomas , Liu Tianfeng , He Dongning , Wang Mingrui , Gong Fan , Chu Jiaqi , Zhao Mingyan
Published: May 2019

Three‐dimensional scaffolds like hydrogels can be employed as cell carriers for in vitro or in vivo colonization and have become a major research topic to replace damaged tissue. In the current study, a novel composite hydrogel composed of sodium alginate (SA) and platelet‐rich‐plasma (PRP) varying in blending ratios, cross‐linked with calcium ions, released from calcium carbonate‐D‐Glucono‐d‐lactone (CaCO3‐GDL) was successfully prepared. It was found that addition of PRP changed largely the physical properties and biological performance of the composite hydrogels, which was depending on the blending ratio. The gelation rate and swelling ratio of alginate hydrogels were significantly reduced by the addition of PRP, which produced also a more homogeneous gel structure. Field emission scanning electron microscopy (FE‐SEM) investigation confirmed the incorporation of PRP‐derived proteins in the hydrogel, where a porous structure with a pore size of 200–300 μm was found. On the other hand, an increase in surface roughness was observed after the addition of PRP. The compressive mechanical strength of SA/PRP composite hydrogel was enhanced in comparison to the pure SA gel. The composite hydrogels with the highest PRP content exhibited at a maximum compressive stress of 0.26 MPa a maximum strain of 55%, while the maximum compressive strain of pure SA hydrogels was only 45% at a stress of 0.08 MPa. It was also found that the in vitro degradation of the alginate gel was accelerated by the addition of PRP. In terms of cellular responses, all gels exhibited an excellent cytocompatibility. Indeed, the composite hydrogels supported bone marrow‐derived mesenchymal stem cells proliferation and their chondrogenesis with up‐regulation of chondrogenic marker genes Sox9 and Aggrecan. Overall, the present study suggests a great potential of SA/PRP composite hydrogels as cell carriers for cartilage tissue engineering.
Indocyanine green based fluorescent polymeric nanoprobes for in vitro imaging
Authors: Ege Zeynep R. , Akan Aydin , Oktar Faik N. , Lin Chi C. , Kuruca Durdane S. , Karademir Betul , Sahin Yesim M. , Erdemir Gokce , Gunduz Oguzhan
Published: May 2019

Indocyanine green (ICG) provides an advantage in the imaging of deep tumors as it can reach deeper location without being absorbed in the upper layers of biological tissues in the wavelengths, which named “therapeutic window” in the tissue engineering. Unfortunately, rapid elimination and short‐term stability in aqueous media limited its use as a fluorescence probe for the early detection of cancerous tissue. In this study, stabilization of ICG was performed by encapsulating ICG molecules into the biodegradable polymer composited with poly(l‐lactic acid) and poly(ε‐caprolactone) via a simple one‐step multiaxial electrospinning method. Different types of coaxial and triaxial structure groups were performed and compared with single polymer only groups. Confocal microscopy was used to image the encapsulated ICG (1 mg/mL) within electrospun nanofibers and in vitro ICG uptake by MIA PaCa‐2 pancreatic cancer cells. Stability of encapsulated ICG is demonstrated by the in vitro sustainable release profile in PBS (pH = 4 and 7) up to 21 days. These results suggest the potential of the ability of internalization and accommodation of ICG into the pancreatic cell cytoplasm from in vitro implanted ICG‐encapsulated multiaxial nanofiber mats. ICG‐encapsulated multilayer nanofibers may be promising for the local sustained delivery system to eliminate loss of dosage caused by direct injection of ICG‐loaded nanoparticles in systemic administration.
The microRNA‐141‐3p/CDK8 pathway regulates the chemosensitivity of breast cancer cells to trastuzumab
Authors: Song Wenqing , Wu Shiwu , Wu Qiong , Zhou Lei , Yu Lan , Zhu Bo , Gong Xiaomeng
Published: May 2019

Aims

This study was conducted to explore the function of microRNA‐141‐3p/cyclin‐dependent kinase 8 (miR‐141‐3p/CDK8) in regulating trastuzumab resistance of breast cancer cells.

Materials and Methods

Microarray analysis was performed to screen microRNAs that are differentially expressed in wild type and trastuzumab‐resistant (TR) breast cancer cell lines. TargetScan helped predict the target gene of miR‐141‐3p. The regulatory relationship was confirmed through a luciferase reporter assay, quantitative reverse transcriptase polymerase chain reaction, and Western blot analysis. The MTT assay, transwell invasion assay, and wound scratch assay were performed to measure the proliferative, invasive, and migratory ability of breast cancer cells, respectively. Tumor cell xenografts in nude mice were conducted to observe the effect of miR‐141‐3p on trastuzumab resistance in breast cancer cells in vivo. The enzyme‐linked immunosorbent assay was used to detect protein secretion.

Results

miR‐141‐3p was downregulated in the drug‐resistant cell lines. CDK8 was proved to be a target gene of miR‐141‐3p. Transfection of miR‐141‐3p or CDK8 small interfering RNA (siRNA) reversed the resistance to trastuzumab in TR cell lines and suppressed cell invasion and migration. Dysregulation of transforming growth factor beta (TGF‐β) was detected when the expression of CDK8 was silenced by CDK8 siRNA, and downregulation of TGF‐β had a notable effect on reducing the phosphorylation of SMAD2/SMAD3.

Conclusion

miR‐141‐3p could restore the sensitivity to trastuzumab in breast cancer cells by repressing CDK8, which might regulate the phosphorylation levels of SMAD2/SMAD3 via TGF‐β.