bluuebunny/crossref_metadata_2025 huggingface dataset:
Deciphering the Late Cretaceous‐Cenozoic Structural Evolution of the North Peruvian Forearc System
Authors: Espurt N. , Brusset S. , Baby P. , Henry P. , Vega M. , Calderon Y. , Ramirez L. , Saillard M.
Published: December 2017

The link between plate tectonics and the evolution of active margins is still an ongoing task to challenge since the acceptance of plate tectonic paradigm. This paper aims at deciphering the structural architecture and uplift history of the North Peruvian forearc system to better understand the evolution and the mechanics that govern the Late Cretaceous‐Cenozoic building of this active margin. In this study, we report surface structural geology data, interpretation of seismic reflection profiles, apatite fission track data, and the construction of two offshore‐onshore crustal‐scale balanced cross sections. The structure of the North Peruvian forearc system is dominated by an accretionary style with northwestward propagation of thrust‐related structural highs involving continental/oceanic basement rocks and off‐scrapped sediments. The thrust systems bound thick thrust‐top forearc depocenters mainly deformed by crustal normal to strike‐slip faults and thin‐skinned gravitational instabilities. The sequential restoration of the margin calibrated with apatite fission track data suggests a correlation between uplift, shortening, and plate convergence velocity during Late Cretaceous and Miocene. Pliocene‐Quaternary shortening and uplift of the coastal zone is rather related to the subduction of asperities during convergence rate decrease. The development of crustal normal to strike‐slip faulting and subsidence zones might be the consequence of slab flexure, local basal erosion along subduction fault, and/or oblique subduction associated with sediment loading control. We conclude that the evolution of the North Peruvian forearc system was controlled by subduction dynamics, strong sediment accumulation, and recent ridge subduction, and it recorded the orogenic loading evolution of the Andes over the Cenozoic.
Synthesis of In‐Plane Artificial Lattices of Monolayer Multijunctions
Authors: Chiu Kuan‐Chang , Huang Kuan‐Hua , Chen Chun‐An , Lai Ying‐Yu , Zhang Xin‐Quan , Lin Erh‐Chen , Chuang Meng‐Hsi , Wu Jenn‐Ming , Lee Yi‐Hsien
Published: December 2017

Recently, monolayers of van der Waals materials, including transition metal dichalcogenides (TMDs), are considered ideal building blocks for constructing 2D artificial lattices and heterostructures. Heterostructures with multijunctions of more than two monolayer TMDs are intriguing for exploring new physics and materials properties. Obtaining in‐plane heterojunctions of monolayer TMDs with atomically sharp interfaces is very significant for fundamental research and applications. Currently, multistep synthesis for more than two monolayer TMDs remains a challenge because decomposition or compositional alloying is thermodynamically favored at the high growth temperature. Here, a multistep chemical vapor deposition (CVD) synthesis of the in‐plane multijunctions of monolayer TMDs is presented. A low growth temperature synthesis is developed to avoid compositional fluctuations of as‐grown TMDs, defects formations, and interfacial alloying for high heterointerface quality and thermal stability of monolayer TMDs. With optimized parameters, atomically sharp interfaces are successfully achieved in the synthesis of in‐plane artificial lattices of the WS2/WSe2/MoS2 at reduced growth temperatures. Growth behaviors as well as the heterointerface quality are carefully studied in varying growth parameters. Highly oriented strain patterns are found in the second harmonic generation imaging of the TMD multijunctions, suggesting that the in‐plane heteroepitaxial growth may induce distortion for unique material symmetry.
In Situ Electrical Properties’ Investigation and Nanofabrication of Ag/Sb2Te3 Assembled Multilayers’ Film
Authors: Wu Zhenhua , Chen Xiang , Zhang Yan , Dun Chaochao , Carroll David L. , Hu Zhiyu
Published: December 2017

Nanopatterned fabrication and electrical properties of Ag/Sb2Te3 layer‐by‐layer assembled films are systematically investigated by a conductive atomic force microscope. Multilayers’ film composed by alternating Ag and Sb2Te3 with respective thicknesses of 5 and 10 nm shows a bipolar resistive switching behavior contributed by the silver conductive filaments. Designed cross‐plane nanofilament arrays with reconfigurable patterns are fabricated, which show a potential application in memristor and nanofabrication. Multilayers with the same thickness of Ag but increased thickness of Sb2Te3 (up to 20 nm) present a Fowler–Nordheim tunneling‐dominated current and show in‐plane snowflake silver dendrite on the surface. Further studies on the silver dendrite may bring potential applications in extensive fields such as multifunctional data storage and neuromorphic. By controlling the type (Sb2Te3, Bi2Te3, etc.) and thickness of solid electrolyte materials, electronic devices with specific functions and applications can be designed.
Oxidative Catalytic Spiroketalization Leading to Diastereoselective Synthesis of Spiro[benzofuran‐2,1′‐isochromene]s
Authors: Qiu Jiang‐Kai , Hao Wen‐Juan , Li Guigen , Jiang Bo
Published: December 2017

A new one‐pot, two‐step silver‐catalyzed spiroketalization of the in‐situ generated quinone imine ketals (QIKs) with β‐alkynyl ketones has been established, enabling multiple C−O and C−C bond‐forming reactions to access densely functionalized spiro[benzofuran‐2,1′‐isochromene] derivatives with generally good yields. The use of β‐alkynyl ketones bearing alkyl and aryl groups located at the α‐position of the carbonyl group could lead to highly diastereoselective spiro[chromane‐2,1′‐isochromene] derivatives. The reaction features broad substrate scope, mild oxidative catalytic conditions and excellent diastereoselectivity.

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Barium Bismuth Niobate Double Perovskite/Tungsten Oxide Nanosheet Photoanode for High‐Performance Photoelectrochemical Water Splitting
Authors: Weng Baicheng , Grice Corey R. , Ge Jie , Poudel Tilak , Deng Xunming , Yan Yanfa
Published: December 2017

Recently, a new method to effectively engineer the bandgap of barium bismuth niobate (BBNO) double perovskite was reported. However, the planar electrodes based on BBNO thin films show low photocurrent densities for water oxidation owing to their poor electrical conductivity. Here, it is reported that the photoelectrochemical (PEC) activity of BBNO‐based electrodes can be dramatically enhanced by coating thin BBNO layers on tungsten oxide (WO3) nanosheets to solve the poor conductivity issue while maintaining strong light absorption. The PEC activity of BBNO/WO3 nanosheet photoanodes can be further enhanced by applying Co0.8Mn0.2Ox nanoparticles as a co‐catalyst. A photocurrent density of 6.02 mA cm−2 at 1.23 V (vs reversible hydrogen electrode (RHE)) is obtained using three optically stacked, but electrically parallel, BBNO/WO3 nanosheet photoanodes. The BBNO/WO3 nanosheet photoanodes also exhibit excellent stability in a high‐pH alkaline solution; the photoanodes demonstrate negligible photocurrent density decay while under continuous PEC operation for more than 7 h. This work suggests a viable approach to improve the PEC performance of BBNO absorber‐based devices.
Surgical outcomes of laparoscopic distal gastrectomy compared to open distal gastrectomy: A retrospective cohort study based on a nationwide registry database in Japan
Authors: Yoshida Kazuhiro , Honda Michitaka , Kumamaru Hiraku , Kodera Yasuhiro , Kakeji Yoshihiro , Hiki Naoki , Etoh Tsuyoshi , Miyata Hiroaki , Yamashita Yuichi , Seto Yasuyuki , Kitano Seigo , Konno Hiroyuki
Published: December 2017

To clarify the safety profile of laparoscopic distal gastrectomy (LDG) for gastric cancer patients, the short‐term outcome of LDG was compared to that of open distal gastrectomy (ODG) by propensity score matching using data from the Japanese National Clinical Database (NCD). We conducted a retrospective cohort study of patients undergoing distal gastrectomy between January 2012 and December 2013. Using the data for 70 346 patients registered in the NCD, incidences of mortality and morbidities were compared between LDG patients and ODG patients in the propensity score matched stage I patients (ODG: n = 14 386, LDG: n = 14 386) and stage II‐IV patients (ODG: n = 3738, LDG: n = 3738), respectively. There was no significant difference in mortality rates between LDG and ODG at all stages. Operating time was significantly longer in LDG compared to ODG, whereas blood loss and incidences of superficial surgical site infection (SSI), deep SSI, and wound dehiscence were significantly higher in ODG at all stages. Interestingly, pancreatic fistula was found significantly more often in LDG (1%) compared to ODG (0.8%) (P = .01) in stage I patients; however, it was not different in stage II‐IV patients. The length of postoperative stay was significantly longer in patients undergoing ODG compared to LDG at all stages. LDG in general practice might be a feasible therapeutic option in patients with both advanced gastric cancer and those with early gastric cancer in Japan.
Arthrogryposis and pterygia as lethal end manifestations of genetically defined congenital myopathies
Authors: Ahmed Atif A. , Skaria Priya , Safina Nicole P. , Thiffault Isabelle , Kats Alex , Taboada Eugenio , Habeebu Sultan , Saunders Carol
Published: December 2017

Arthrogryposis multiplex congenita affects approximately 1 in 3,000 individuals of different ethnic backgrounds and displays an equal incidence in males and females. The underlying mechanism for congenital contracture of the joints is decreased fetal movement during intrauterine development. This disorder is associated with over 400 medical conditions and 350 known genes that display considerable variability in phenotypic expression. In this report, four fetal or perinatal autopsy cases of arthrogryposis were studied by gross morphology, microscopic histopathologic examination, and whole genome sequencing of postmortem DNA. Two stillborn sibling fetuses with arthrogryposis, pterygia, and amyoplasia had compound heterozygous pathogenic variants in NEB. A neonate with a histopathologic diagnosis of nemaline myopathy had a heterozygous de novo pathogenic variant in ACTA1. Another stillborn infant with pterygia and arthrogryposis had a heterozygous de novo likely pathogenic variant in BICD2. These cases demonstrate the utility of whole genome sequencing as the principal diagnostic method of lethal forms of skeletal muscle disorders that present with arthrogryposis and muscle amyoplasia/hypoplasia. Molecular diagnosis provides an opportunity for studying patterns of inheritance and for family counseling concerning future pregnancies.
Gram‐Scale Synthesis and Highly Regioselective Bromination of 1,1,9,9‐Tetramethyl[9](2,11)teropyrenophane
Authors: Unikela Kiran Sagar , Roemmele Tracey L. , Houska Václav , McGrath Kaitlin E. , Tobin David M. , Dawe Louise N. , Boeré René T. , Bodwell Graham J.
Published: December 2017

An improved synthetic pathway to the nanobelt‐like 1,1,9,9‐tetramethyl[9](2,11)teropyrenophane has been developed, and enables the synthesis of gram quantities of material. Key innovations are the development of a sequential chlorination/Friedel–Crafts alkylation reaction, a sequential iodination/Wurtz coupling reaction, and a room‐temperature teropyrene‐forming reaction. The teropyrenophane was found to form a very stable radical cation and undergo a completely regioselective fourfold bromination reaction.
Synthesis, spectroscopic evaluation, molecular modelling, thermal study and biological evaluation of manganese(II) complexes derived from bidentate N,O and N,S donor Schiff base ligands
Authors: Bargujar Savita , Chandra Sulekh , Chauhan Reeta , Rajor Hament K. , Bhardwaj Jyoti
Published: December 2017

Manganese(II) complexes having the general composition Mn(L)2X2 (where L = 3‐bromoacetophenone semicarbazone, 3‐bromoacetophenone thiosemicarbazone, 1‐tetralone semicarbazone, 1‐tetralone thiosemicarbazone, flavanone semicarbazone or flavanone thiosemicarbazone and X = Cl− or ½SO42−) were synthesized. All the complexes were characterized using elemental analyses, molar conductance and magnetic moment measurements, and mass, 1H NMR, infrared, electron paramagnetic resonance and electronic spectral studies. The molar conductance of the complexes in dimethylsulfoxide lies in the range 10–20 Ω−1 cm2 mol−1 indicating their non‐electrolytic nature. All the complexes show magnetic moments corresponding to five unpaired electrons. The possible geometries of the complexes were assigned on the basis of electron paramagnetic resonance, electronic and infrared spectral studies. Some of the synthesized ligands and their complexes were screened for their antifungal activities against fungi Macrophomina phaseolina, Botrytis cinerea and Phoma glomerata using the food poison technique and their antibacterial activities against Xanthomonas campestris pv. campestris and Ralstonia solanacearum using the paper disc diffusion method. They showed appreciable activities.
Hierarchical TiO2 nanosheet‐assembled nanotubes with dual electron sink functional sites for efficient photocatalytic degradation of rhodamine B
Authors: Zhang Chao , Zhou Yuming , Bao Jiehua , Zhang Yiwei , Zhao Shuo , Fang Jiasheng , Chen Wenxia , Sheng Xiaoli
Published: December 2017

A novel Pt–TiO2/Ag nanotube photocatalyst has been synthesized successfully via a facile method. TiO2 nanotubes are assembled with numerous ultrathin TiO2 nanosheets and show a highly open structure. The gaps between adjacent TiO2 nanosheets can serve as channels for the access of reactants, accelerating the mass transfer process. During the fabrication process of the Pt–TiO2/Ag nanotube photocatalyst, high‐quality Pt–SiO2 nanotubes are synthesized first with the structure‐directing effect of polyvinylpyrrolidone. Then a TiO2 layer is coated on the outside surface of the silica nanotubes. The introduced titanium species can be converted into TiO2 nanosheet structure during the subsequent hydrothermal treatment, gradually constructing nanosheet‐assembled nanotubes. Lastly, after the introduction of another electron sink function site of Ag through UV irradiation, the Pt–TiO2/Ag nanotube photocatalyst with dual electron sink functional sites is obtained. The specially doped Pt and Ag NPs can simultaneously inhibit the recombination process of photogenerated charge carriers and increase light utilization efficiency. Therefore, the as‐synthesized Pt–TiO2/Ag nanotube catalyst exhibits a high photocatalytic degradation performance for rhodamine B of 0.2 min−1, which is about 3.2 and 5.3 times as high as that of Pt–TiO2 and TiO2 nanotubes because of the enhanced charge carrier separation efficiency. Furthermore, in the unique nanoarchitecture, the nanotubes are assembled with numerous ultrathin TiO2 nanosheets, which can absorb abundant active species and dye molecules for photocatalytic reaction. On the basis of experimental results, a possible rhodamine B degradation mechanism is proposed to explain the excellent photocatalytic efficiency of the Pt–TiO2/Ag nanotube photocatalyst.
Dibenzothienopyrrolo[3,2‐b]pyrrole: The Missing Member of the Thienoacene Family
Authors: Tasior Mariusz , Czichy Małgorzata , Łapkowski Mieczysław , Gryko Daniel T.
Published: December 2017

Dibenzothienopyrrolo[3,2‐b]pyrrole and the corresponding bis(S,S‐dioxide) were synthesized by using a concise synthetic strategy. Despite the presence of six fused aromatic rings, π‐expanded pyrrolo[3,2‐b]pyrroles of this type absorb and emit at relatively short wavelengths, which reflects inefficient π conjugation due to the angular arrangement of the aromatic rings. They exhibit interesting and complex electrochemical behavior, which highlights their potential in organic electronics. Both heteroacenes undergo two‐stage oxidation while retaining the independence of each 1‐phenyl‐1H‐[1]benzothieno[3,2‐b]pyrrole, which was proved by in situ electron spin resonance measurements. Interestingly, electrochemically generated dicationdiradicals are not only distributed over the pyrrolo[3,2‐b]pyrrole scaffold, but also over the phenyl substituents located on nitrogen atoms.
Serum metabolomics of laryngeal cancer based on liquid chromatography coupled with quadrupole time‐of‐flight mass spectrometry
Authors: Zhang Xiaotao , Hou Hongwei , Chen Huan , Liu Yong , Wang An , Hu Qingyuan
Published: December 2017

The discovery of new laryngeal cancer‐related metabolite biomarkers could help to facilitate early diagnosis. A serum metabolomics study from laryngeal cancer patients and healthy individuals was conducted using liquid chromatography coupled with quadrupole time‐of‐flight mass spectrometry. Univariate and multivariate statistics were used to discriminate laryngeal cancer patients and healthy individuals. 1‐Palmitoyl‐sn‐glycero‐3‐phosphocholine (LysoPC 16:0), 1‐o‐hexadecyl‐2‐acetyl‐sn‐glycero‐3‐phosphocholine (PAF) and 1,2‐dipalmitoyl‐sn‐glycero‐3‐phosphocholine were found to be significantly different between the laryngeal cancer group and the healthy group. They are mainly involved in phospholipids catabolism, linoleic acid metabolism, α‐linoleic acid metabolism and arachidonic acid metabolism. The area under the curve of the biomarker combined by two metabolites (LysoPC 16:0 and PAF) was 0.935, the sensitivity was 0.962 and the specificity was 0.825. LysoPC 16:0 and PAF may show diagnostic potential for laryngeal carcinoma.
The anatomy of free fibula osteoseptocutaneous flap in neophalloplasty in transgender surgery
Authors: Zaheer Usman , Granger Andre , Ortiz Angelica , Terrell Mark , Loukas Marios , Schober Justine
Published: December 2017

The Free Fibula Osteoseptocutaneous flap is a reliable option when used in neophalloplastic procedures. It possesses intrinsic rigidity that is sufficient for penetrative intercourse, and satisfactory sensation. We review the pros and cons of this procedure, as well the anatomy and surgical steps involved. Surgical text descriptions were enhanced by the creation of new anatomic illustrations. Anatomy of the donor and recipient sites, as well as the surgical technique leading to creation of the neophallus are demonstrated in detail with new relevant illustrations. The free fibula osteoseptocutaneous flap provides the neophallus with many desirable characteristics. Its thick subcutaneous and fascial layer, along with the thicker fibula (compared to the radius), allows for a neophallus of greater diameter. Skin marking, flap lifting, and transfer to the perineum with all relevant neurovascular anastomosis; fibular artery is anastomosed with the femoral artery, while the fibular veins are anastomosed to branches of the saphenous vein, as well as neurorrhaphy of the dorsal nerves of the clitoris and the LSCN are demonstrated. The osteomatized fibula is fixed to the periosteum of the pubic symphysis as shown. Anatomical traits of the Free Fibula Osteoseptocutaneous flap allow intercourse without prosthesis. The donor‐site scar in this procedure can be covered by a long sock, and donor site morbidity is acceptable. Clin. Anat. 31:169–174, 2018. © 2018 Wiley Periodicals, Inc.
Role of mitochondrial dysfunction in the pathophysiology of DNA repair disorders
Authors: Prates Mori Mateus , de Souza‐Pinto Nadja Cristhina
Published: December 2017

DNA is constantly being damaged, either by endogenous or exogenous genotoxins. In that regard, DNA repair activities are essential for maintaining genomic stability and to life itself. Mutations in genes encoding DNA repair proteins cause severe human syndromes, but DNA repair defects have also been linked to several other diseases, notably to cancer and normal aging. Recently, new evidence has emerged indicating that some DNA repair diseases display mitochondrial and metabolic dysfunction through mechanisms that are yet being uncovered. These results suggest that mitochondria play an import role in the DNA damage response pathways and that damage accumulation may lead to mitochondrial dysfunction via metabolic imbalance and mitophagy impairment. Here we review the recent findings linking mitochondrial impairment and cell death to DNA damage accumulation in the context of DNA repair defects. In addition, the general involvement of DNA damage in cellular dysfunction suggests that these phenomena may be also involved in other human pathologies in which mitochondrial dysfunction and metabolic disruption play causative roles.
Regulation of osteogenesis of human amniotic mesenchymal stem cells by sodium butyrate
Authors: Fan Xiaoting , Li Lei , Ye Zhaoyang , Zhou Yan , Tan Wen‐Song
Published: December 2017

Human amniotic membrane‐derived mesenchymal stem cells (hAMSCs) draw great interests for regenerative medicine due to convenient availability and low immunogenicity. However, suboptimal culture conditions limit their application. In recent years, small molecules have proven powerful in regulating stem cell fates and can be applied to stimulate their function. In the present study, the impacts of sodium butyrate (NaBu), a histone deacetylase inhibitor (HDACi), on hAMSCs were investigated. It was shown that NaBu at a low concentration inhibited cell proliferation by arresting cell cycle at G0/G1 rather than inducing apoptosis. When NaBu was supplemented at a concentration of <1.0 mM for 3 days during osteogenic induction, significantly more mineralized nodules were generated and the expression of osteogenesis‐related genes (ALP, Runx2, Opn, and Ocn) and proteins (Col1a1, OPN, OCN, Runx2, and TAZ) were both significantly enhanced. However, a higher concentration (1.0 mM) and longer exposure time (14 days) of NaBu showed no such effects, which may be partially attributed to both the increased expression of histone deacetylase 8 (HDAC8) and reduced level of H3K9‐Ace, thus leading to the transcriptional inhibition during osteogenesis. Further, it was indicated that ERK might be involved in the stimulatory effects of NaBu. These findings may be helpful to develop an efficient culture process for hAMSCs towards bone regeneration.
Emergency transcatheter closure of a stented PDA in a patient with pulmonary atresia and intact ventricular septum: be ready for the unexpected!
Authors: Faccini Alessia , Butera Gianfranco
Published: December 2017

Key Clinical Message

Patients with congenital heart disease and duct‐dependent pulmonary circulation can undergo stenting of the patent ductus arteriosus (PDA). This case shows that, due to the physiological changes occurring after stent implantation, sometimes it is necessary to close the stented PDA rather than to redilate it.
Spontaneous pneumomediastinum in a term neonate – case report
Authors: Rocha Gustavo , Guimarães Hercília
Published: December 2017

Key Clinical Message

Pneumomediastinum after birth, without birth injury or resuscitation maneuvers, is an unusual situation that can present with grunting, deafening of cardiac sounds, and bulging of the hemithorax. If clinical condition allows, conservative approach is advised even if the pneumomediastinum does not spontaneously resolve in 1 or 2 days.
How Well Are We Applying Quantitative Methods to Reverse Translation to Inform Early Clinical Development?
Authors: Heatherington Anne C. , Kasichayanula Sreeneeranj , Venkatakrishnan Karthik
Published: December 2017

If we are to improve our low success rate and rising costs in the pharmaceutical industry, we need to use every tool available. Reverse translation can particularly inform discovery and early clinical development via appropriate quantitative integration of relevant data. This commentary reports on a crowd‐sourced survey (2017) that sought to evaluate the integration of reverse translation in pharma. The results indicate that these methods are being applied, to varying degrees, across most respondents.
Development and Qualification of a Drug‐Disease Modeling Platform to Characterize Clinically Relevant Endpoints in Type 2 Diabetes Trials
Authors: Gaitonde Puneet , Hurtado Felipe K. , Garhyan Parag , Chien Jenny Y. , Schmidt Stephan
Published: December 2017

Type 2 diabetes mellitus (T2DM) is a chronic, progressive disease characterized by persistently elevated blood glucose concentration (hyperglycemia). We developed a mechanistic drug‐disease modeling platform based on data from more than 4,000 T2DM subjects in seven phase II/III clinical trials. The model integrates longitudinal changes in clinically relevant biomarkers of glycemic control with information on baseline disease state, demographics, disease progression, and different therapeutic interventions, either when given alone or as add‐on combination therapy. The model was able to simultaneously characterize changes in fasting plasma glucose, fasting serum insulin, and glycated hemoglobin A1c following administration of sulfonylurea, metformin, and thiazolidinedione as well as disease progression in clinical trials ranging from 16–104 weeks of treatment. The mechanistic components of this generalized mechanism‐based platform, based on knowledge of pharmacology, insulin‐glucose homeostatic feedback, and diabetes pathophysiology, allows its application to be further expanded to other antidiabetic drug classes and combination therapies.
Is metformin poised for a second career as an antimicrobial?
Authors: Malik Faiza , Mehdi Syed Faizan , Ali Haroon , Patel Priya , Basharat Anam , Kumar Amrat , Ashok Fnu , Stein Joanna , Brima Wunnie , Malhotra Prashant , Roth Jesse
Published: December 2017

Metformin, a widely used antihyperglycaemic, has a good safety profile, reasonably manageable side‐effects, is inexpensive, and causes a desirable amount of weight loss. In 4 studies of patients with tuberculosis (1 prospective and 3 retrospective), metformin administration resulted in better outcomes. In mice with several models of endotoxemia, metformin diminished levels of proinflammatory cytokines and improved survival. Laboratory studies showed effectiveness of the drug on multiple pathogens, includingTrichinella spiralis,Staphylococcus aureus,Pseudomonas aeruginosa, hepatitis B virus, hepatitis C virus, and human immunodeficiency virus. Metformin administration in humans and mice produced major changes in the composition of the gut microbiota. These recently discovered microbe‐modulating properties of the drug have led investigators to predict wide therapeutic utility for metformin. The recent easing in United States Food and Drug Administration (FDA) guidelines regarding administration of metformin to patients with kidney disease, and reduced anxiety about patient safety in terms of lactic acidosis, increase the probability of broadening of metformin's usage as a treatment of infectious agents. In this text we review articles pertinent to metformin's effects on microorganisms, both pathogens and commensals. We highlight the possible role of metformin in a wide range of infectious diseases and a possible expansion of its therapeutic profile in this field. A systematic review was done of PubMed indexed articles that examined the effects of metformin on a wide range of pathogens. Metformin was found to have efficacy as an antimicrobial agent in patients with tuberculosis. Mice infected withTrypanosomiasis cruzihad higher survival when also treated with metformin. The drugin vitrowas active againstT. spiralis,S. aureus,P. aeruginosa, and hepatitis B virus. In addition there is emerging literature on its role in sepsis. We conclude that metformin may have a potential role in the therapy for multiple infectious diseases. Metformin, in addition to its traditional effects on glucose metabolism, provides anti‐microbial benefits in patients with tuberculosis and in a very wide range of other infections encounters in vitro and in vivo.
Microglial modulation of neuronal activity in the healthy brain
Authors: York Elisa M. , Bernier Louis‐Philippe , MacVicar Brian A.
Published: December 2017

Investigations on the role of microglia in the brain have traditionally been focused on their contributions to disease states. However, recent observations have now convincingly shown that microglia in the healthy brain are not passive bystanders, but instead play a critical role in both central nervous system development and homeostasis of synaptic circuits in the adult. Here, we review the various mechanisms by which microglia impact neuronal communication in the healthy adult brain, both by sensing nearby synaptic responses and by actively modulating neuronal function. © 2017 Wiley Periodicals, Inc. Develop Neurobiol 78: 593–603, 2018
Stereodivergent Syntheses of altro and manno Stereoisomers of 2‐Acetamido‐1,2‐dideoxynojirimycin
Authors: de la Fuente Alex , Verdaguer Xavier , Riera Antoni
Published: December 2017

A stereoselective synthesis of 2‐acetamido‐1,2‐dideoxyaltronojirimycin (8) and its manno epimer 9 is described. The synthetic approach is based on key bicyclic carbamate 7, which is easily accessible with high enantiomeric purity on a multigram scale by Sharpless asymmetric epoxidation of 1,4‐pentadien‐3‐ol or 2,4‐pentadien‐1‐ol. This procedure completes an efficient stereodivergent approach to five isomers of 2‐acetamido‐1,2‐dideoxyiminosugars in high overall yields starting from the same key intermediate 7. The approach described in this paper is based on control of the stereoselectivity of the sulfite ring‐opening reaction to give retention of configuration through anchimeric assistance from the endocyclic amine.
Synthesis of Carbohydrate Mimetics by Intramolecular 1,3‐Dipolar Cycloaddition of N‐(3‐Alkenyl)nitrones Derived from Unprotected d‐Aldopentoses
Authors: Malinowski Maciej , Rowicki Tomasz , Guzik Patrycja , Wielechowska Monika , Sas Wojciech
Published: December 2017

A concise synthesis of C‐furanosides has been achieved, starting from unprotected d‐xylose and d‐arabinose. Both sugars reacted with hydroxylamine 6 to give the respective nitrones. These underwent in‐situ intramolecular 1,3‐dipolar cycloaddition reactions to give, in each case, a pair of diastereomeric derivatives of 7‐oxa‐1‐aza‐bicyclo[2.2.1]heptane 7 and 8. The ratio of chromatographically separable diastereoisomers could be changed by carrying out the reaction in the presence of weak Lewis acid. Both d‐xylose‐derived stereoisomers 7a and 8a were converted into d‐erythro‐C‐furanosides by tosylation or mesylation followed by catalytic hydrogenolysis. On the other hand, the formation of d‐threo‐C‐furanosides from d‐arabinose derivatives 7b and 8b under similar conditions was accompanied by the formation of minor amounts of polyhydroxyquinolizidines as a result of competitive N‐alkylation. The polyhydroxyquinolizidine side‐products were useful for the assignment of the configuration of the new compounds.
Categorization Working Memory Span Task: Validation study of two Brazilian alternate versions
Authors: Brum Paula Schimidt , Borella Erika , Carretti Barbara , Guidotti Elena , Yassuda Mônica Sanches
Published: December 2017

Background

The Categorization Working Memory Span Task (CWMS task) is a complex working memory (WM) span test that has been used previously to assess age and individual differences in WM as well as the relationship between WM and complex aspects of cognition such as listening comprehension. Two alternate versions of the task have been developed to be used as outcome variables in WM training protocol, which mirrors the task involved in the CWMS task.

Objectives

(1) To translate and adapt the CWMS task for Brazilian Portuguese; (2) to test the equivalence of its 2 alternate versions; (3) to examine temporal stability; (4) to examine the influence of age and schooling on CWMS task; (5) to establish its relationship with other tests of WM.

Methods

Eighty‐one older adults completed version A, and 86 completed version B of the CWMS task. After 6 months, a subsample (n = 85) completed the same version of the task.

Results

Versions A and B of the task generated comparable scores. Both versions had adequate temporal stability, which was higher for the CWMS total recall, which is the classical variable in this task to represent WM performance, when compared to the other variables generated by the test. The CWMS task variables were moderately correlated with schooling and other cognitive tests (Mini Mental State Examination, Letter‐Number Sequencing, Spatial Span Backward, Digit Span Forward).

Conclusions

The 2 versions of the CWMS task were equivalent and stable temporally. The task was influenced by schooling and global cognition.
Carbon dioxide embolism during transoral robotic thyroidectomy: A case report
Authors: Kim Kyu Nam , Lee Dong Won , Kim Ji Yeon , Han Kyoung‐Hee , Tae Kyung
Published: December 2017

Background

Carbon dioxide (CO2) embolism is a serious, although rare, complication of remote access thyroidectomy using CO2 insufflation. Recently, we encountered a case of CO2 embolism during transoral thyroidectomy, and present it here with a review of the literature.

Methods and Results

A 59‐year‐old female patient with papillary thyroid carcinoma underwent transoral robotic thyroidectomy with CO2 insufflation. During skin flap elevation, the anterior jugular vein was lacerated. Simultaneously, an electrocardiogram (ECG) showed bradycardia with premature atrial complexes, followed by asystole. After 2 cycles of cardiopulmonary resuscitation with an injection of 1‐mg epinephrine, spontaneous circulation returned, and sinus tachycardia with ST segment elevation was noted in ECGs. The patient's vital signs returned to normal within 30 minutes, and normal sinus rhythm was observed. She was discharged on postoperative day 7, without neurologic and cardiac deficit.

Conclusion

The possibility of CO2 embolism during transoral thyroidectomy with CO2 insufflation should not be overlooked.
Printing inks of electroactive polymer PEDOT:PSS: The study of biocompatibility, stability, and electrical properties
Authors: Stříteský Stanislav , Marková Aneta , Víteček Jan , Šafaříková Eva , Hrabal Michal , Kubáč Lubomír , Kubala Lukáš , Weiter Martin , Vala Martin
Published: December 2017

Biocompatibility tests and a study of the electrical properties of thin films prepared from six electroactive polymer ink formulations based on poly(3,4‐ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS) were performed. The aim was to find a suitable formulation of PEDOT:PSS and conditions for preparing thin films in order to construct printed bioelectronic devices for biomedical applications. The stability and electrical properties of such films were tested on organic electrochemical transistor (OECT)‐based sensor platforms and their biocompatibility was evaluated in assays with 3T3 fibroblasts and murine cardiomyocytes. It was found that the thin films prepared from inks without an additive or any thin film post‐treatment provide limited conductivity and stability for use in biomedical applications. These properties were greatly improved by using ethylene glycol and thermal annealing. Addition or post‐treatment by ethylene glycol in combination with thermal annealing provided thin films with electrical resistance and a stability sufficient to be used in sensing of animal cell physiology. These films coated with collagen IV showed good biocompatibility in the assay with 3T3 fibroblasts when compared to standard cell culture plastics. Selected films were then used in assays with murine cardiomyocytes. We observed that these cells were able to attach to the PEDOT:PSS films and form an active sensor element. Spontaneously beating clusters were formed, indicating a good physiological status for the cardiomyocyte cells. These results open the door to construction of cheap printed electronic devices for biointerfacing in biomedical applications. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1121–1128, 2018.
Stat5 phosphorylation is responsible for the excessive potency of HB‐EGF
Authors: Heo Jeongyeon , Kim Jae Geun , Kim Sunghwan , Kang Hara
Published: December 2017

Heparin‐binding EGF‐like growth factor (HB‐EGF) is a potent growth factor involved in wound healing and tumorigenesis. Despite the sequence similarity between HB‐EGF and EGF, HB‐EGF induces cellular proliferation and migration more potently than EGF. However, the differential regulation by HB‐EGF and EGF has not been thoroughly elucidated. In this study, we compared signaling pathways activated by HB‐EGF and EGF to understand the details of the molecular mechanism of the high potency induced by HB‐EGF. HB‐EGF specifically induced the phosphorylation of EGFR‐Y1045 and activated Stat5, which is responsible for promoting cell proliferation, and migration. The competition of phosphorylated EGFR‐Y1045 inhibited Stat5 activation and consequently lowered the effect of HB‐EGF on cell proliferation, suggesting that the phosphorylation of EGFR‐Y1045 is essential for the activation of Stat5. The phosphorylation of EGFR‐Y1045 and Stat5 induced by HB‐EGF was prevented by sequestering the heparin‐binding domain, suggesting that the heparin‐binding domain is critical for HB‐EGF‐mediated signaling and cellular responses. In conclusion, the heparin‐binding domain of HB‐EGF was responsible for EGFR‐mediated Stat5 activation, resulting in a more potent cellular proliferation, and migration than that mediated by EGF. This molecular mechanism is useful for understanding ligand‐specific EGFR signaling and developing biomedicines for wound healing or cancer therapy.
T cell exhaustion in cancer: Mechanisms and clinical implications
Authors: Wang Jin‐Cheng , Xu Yong , Huang Zheng‐Ming , Lu Xiao‐Jie
Published: December 2017

During chronic viral infection or cancer, the immune system usually induces a corresponding immune response against pathogens or cancer cells so as to prevent worsening disease. T cell exhaustion in which reduced and dysfunctional effector T cells lead to immune escape is one of the mechanisms that pathogens or cancer cells get rid of control from the immune system. In this review, we discuss some mechanisms associated with T cell exhaustion and enumerate current methods of reversing T cell exhaustion. We also summarize current targeted treatment strategies and put forward following aspects that required to research.
Down‐regulation of FN1 inhibits colorectal carcinogenesis by suppressing proliferation, migration, and invasion
Authors: Cai Xun , Liu Chuan , Zhang Tie‐Ning , Zhu Yi‐Wen , Dong Xiao , Xue Peng
Published: December 2017

Fibronectin 1 (FN1) is involved in cell adhesion and migration processes including embryogenesis, wound healing, blood coagulation, host defense, metastasis, and implicated in various biochemical processes. However, its effects on the development and progression of human cancer, especially colorectal cancer (CRC), are unclear. To evaluate the relationship between the expression of FN1 and the histopathologic parameters of patients with CRC or the proliferation, migration, and invasion of colorectal cancer cell lines, we screened FN1 as a new candidate gene which promotes development of CRC, in an independent dataset (The Human Protein Atlas website). Here, we reported that FN1 was elevated in CRC tissues compared with normal colon tissues. Further, FN1 expression level was correlated with age, lymph vascular invasion, and survival rate. Knockdown of FN1 in two CRC cell lines, LOVO, and SW1116, significantly inhibited cell proliferation, migration and invasion, and induced cell apoptosis. Western blot analysis showed that down‐regulation of FN1 significantly decreased the expression of Bcl‐2, MMP‐9, Twist, and increased the expression of Bax, Caspase‐3, and E‐cadherin in LOVO and SW1116 cells. Then, we found that the protein ITGA5 was identified as a binding partner of FN1 and ITGA5 overexpression reversed FN1‐induced tumorigenesis of CRC in vitro. Taken together, FN1 suppressed apoptosis and promoted viability, invasion, and migration in CRC through interacting with ITGA5. FN1 may be a prognostic factor and potential target for CRC treatment.
B,N‐Codoped graphene as catalyst for the oxygen reduction reaction: Insights from periodic and cluster DFT calculations
Authors: Ricca Chiara , Labat Frédéric , Zavala Claudia , Russo Nino , Adamo Carlo , Merino Gabriel , Sicilia Emilia
Published: December 2017

A comprehensive theoretical study of the oxygen reduction reaction (ORR) over B,N‐codoped graphene has been carried out in the framework of DFT using two different approaches based on periodic or cluster models. The comparison and integration of the information provided by the two approaches allow achieving a more complete description of the studied phenomena, combining the advantages of both models. On one hand, the analysis of the structure, stability, and electronic properties of this catalyst permits to identify and characterize the active sites and provides insights into the origin of its high catalytic activity that should be found in the synergistic coupling of the opposite effects of the two B and N heteroatoms used as dopants. On the other hand, the study of the reaction mechanisms evidences that the process is thermodynamically favorable due to the overall high exothermicity, and that the 4e– transfer is the favorite ORR pathway, being the OH hydrogenation the rate‐determining step. Overall, all the reported results clearly underline the superior catalytic activity of B,N‐codoped graphene toward this reaction. © 2017 Wiley Periodicals, Inc.
Stem cells in lung repair and regeneration: Current applications and future promise
Authors: Zhu Yuqing , Chen Xiao , Yang Xu , EI‐Hashash Ahmed
Published: December 2017

Lung diseases are major cause of morbidity and mortality worldwide. The progress in regenerative medicine and stem cell research in the lung are currently a fast‐growing research topic that can provide solutions to these major health problems. Under normal conditions, the rate of cellular proliferation is relatively low in the lung in vivo, compared to other major organ systems. Lung injury leads to the activation of stem/progenitor cell populations that re‐enter the cell cycle. Yet, little is known about stem cells in the lung, despite common thoughts that these cells could play a critical role in the repair of lung injuries. Nor do we fully understand the cellular and architectural complexity of the respiratory tract, and the diverse stem/progenitor cells that are involved in the lung repair and regeneration. In this review, we discuss the conceptual framework of lung stem/progenitor cell biology, and describe lung diseases, in which stem cell manipulations may be physiologically significant. In addition, we highlight the challenges of lung stem cell‐based therapy.
Role of Nrf2 in preventing oxidative stress induced chloride current alteration in human lung cells
Authors: Canella Rita , Benedusi Mascia , Martini Marta , Cervellati Franco , Cavicchio Carlotta , Valacchi Giuseppe
Published: December 2017

The lung tissue is one of the main targets of oxidative stress due to external sources and respiratory activity. In our previous work, we have demonstrated in that O3 exposure alters the Cl− current–voltage relationship, with the appearance of a large outward rectifier component mainly sustained by outward rectifier chloride channels (ORCCs) in human lung epithelial cells (A549 line). In the present study, we have performed patch clamp experiments, in order to identify which one of the O3 byproducts (4hydroxynonenal (HNE) and/or H2O2) was responsible for chloride current change. While 4HNE exposition (up to 25 μM for 30′ before electrophysiological analysis) did not reproduce O3 effect, H2O2 produced by glucose oxidase 10 mU for 24 hr before electrophysiological analysis mimicked O3 response. This result was confirmed treating the cell with catalase (CAT) before O3 exposure (1,000 U/ml for 2 hr): CAT was able to rescue Cl− current alteration. Since CAT is regulated by Nrf2 transcription factor, we pre‐treated the cells with the Nrf2 activators, resveratrol and tBHQ. Immunochemical and immunocytochemical results showed Nrf2 activation with both substances that lead to prevent OS effect on Cl− current. These data bring new insights into the mechanisms involved in OS‐induced lung tissue damage, pointing out the role of H2O2 in chloride current alteration and the ability of Nfr2 activation in preventing this effect.
Mesenchymal stromal cells prevent bleomycin‐induced lung and skin fibrosis in aged mice and restore wound healing
Authors: Rubio Gustavo A. , Elliot Sharon J. , Wikramanayake Tongyu C. , Xia Xiaomei , Pereira‐Simon Simone , Thaller Seth R. , Glinos George D. , Jozic Ivan , Hirt Penelope , Pastar Irena , Tomic‐Canic Marjana , Glassberg Marilyn K.
Published: December 2017

Fibrosis can develop in nearly any tissue leading to a wide range of chronic fibrotic diseases. However, current treatment options are limited. In this study, we utilized an established aged mouse model of bleomycin‐induced lung fibrosis (BLM) to test our hypothesis that fibrosis may develop simultaneously in multiple organs by evaluating skin fibrosis and wound healing. Fibrosis was induced in lung in aged (18–22‐month‐old) C57BL/6 male mice by intratracheal BLM administration. Allogeneic adipose‐derived mesenchymal stromal cells (ASCs) or saline were injected intravenously 24 hr after BLM administration. Full thickness 8‐mm punch wounds were performed 7 days later to study potential systemic anti‐fibrotic and wound healing effects of intravenously delivered ASCs. Mice developed lung and skin fibrosis as well as delayed wound closure. Moreover, we observed similar changes in the expression of known pro‐fibrotic factors in both lung and skin wound tissue, including miR‐199 and protein expression of its corresponding target, caveolin‐1, as well as phosphorylation of protein kinase B. Importantly, ASC‐treated mice exhibited attenuation of BLM‐induced lung and skin fibrosis and accelerated wound healing, suggesting that ASCs may prime injured tissues and prevent end‐organ fibrosis.
Differential mechanisms of adenosine‐ and ATPγS‐induced microvascular endothelial barrier strengthening
Authors: Bátori Róbert , Kumar Sanjiv , Bordán Zsuzsanna , Cherian‐Shaw Mary , Kovács‐Kása Anita , MacDonald Justin A. , Fulton David J. R. , Erdődi Ferenc , Verin Alexander D.
Published: December 2017

Maintenance of the endothelial cell (EC) barrier is critical to vascular homeostasis and a loss of barrier integrity results in increased vascular permeability. While the mechanisms that govern increased EC permeability have been under intense investigation over the past several decades, the processes regulating the preservation/restoration of the EC barrier remain poorly understood. Herein we show that the extracellular purines, adenosine (Ado) and adenosine 5′‐[γ‐thio]‐triphosphate (ATPγS) can strengthen the barrier function of human lung microvascular EC (HLMVEC). This ability involves protein kinase A (PKA) activation and decreases in myosin light chain 20 (MLC20) phosphorylation secondary to the involvement of MLC phosphatase (MLCP). In contrast to Ado, ATPγS‐induced PKA activation is accompanied by a modest, but significant decrease in cyclic adenosine monophosphate (cAMP) levels supporting the existence of an unconventional cAMP‐independent pathway of PKA activation. Furthermore, ATPγS‐induced EC barrier strengthening does not involve the Rap guanine nucleotide exchange factor 3 (EPAC1) which is directly activated by cAMP but is instead dependent upon PKA‐anchor protein 2 (AKAP2) expression. We also found that AKAP2 can directly interact with the myosin phosphatase‐targeting protein MYPT1 and that depletion of AKAP2 abolished ATPγS‐induced increases in transendothelial electrical resistance. Ado‐induced strengthening of the HLMVEC barrier required the coordinated activation of PKA and EPAC1 in a cAMP‐dependent manner. In summary, ATPγS‐induced enhancement of the EC barrier is EPAC1‐independent and is instead mediated by activation of PKA which is then guided by AKAP2, in a cAMP‐independent mechanism, to activate MLCP which dephosphorylates MLC20 resulting in reduced EC contraction and preservation.