bluuebunny/crossref_metadata_2025 huggingface dataset:
Lead‐Free Metal Halide Perovskite Nanocrystals: Challenges, Applications, and Future Aspects
Authors: Ghosh S. , Pradhan B.
Published: February 2019

Lead halide perovskite materials have shown strong promise in energy harvesting and generation over the past five years. However, their poor ambient stability and lead toxicity issues hinder optoelectronic applications. In the quest for alternatives, metal halide perovskites with lower toxicity and more stable metals have recently emerged. The divalent Pb2+ could be replaced with isoelectronic Sn2+, but Sn2+ tends to oxidize rapidly in presence of air to Sn4+, forming a defect in the structure. However, Sn2+‐based perovskites have been stabilized in 2D structures. Recently Sn4+ based halide perovskites nanocrystals with have been reported with poor luminescence. The replacement of Pb2+ with isoelectronic trivalent elements (Sb3+, Bi3+) results in A3B2X9 type defect‐order perovskite structure, which shows promises for optoelectronic applications. The perovskite nanocrystals of Sb, Bi have been reported in the form of dimers and layered structures. In addition to these, double perovskites, where two divalent Pb2+ are replaced with a monovalent and a trivalent cation have been reported very recently. In this Focus Review, we give a brief summary of different non‐lead perovskite nanocrystals starting from synthesis, characterization, stability, properties to applications, along with potential future directions.
Efficient Passivation of Ag Nanowires with 11‐Mercaptoundecanoic Acid Probed Using In Situ Total‐Internal‐Reflection Surface‐Enhanced Raman Scattering Spectroscopy
Authors: Plissonneau Marie , Madeira Alexandra , Talaga David , Bonhommeau Sébastien , Servant Laurent , Vallée Renaud A. L. , Labrugère Christine , Goldthorpe Irene A. , Pautrot‐D'Alencon Lauriane , Le Mercier Thierry , Treguer‐Delapierre Mona
Published: February 2019

A promising passivation strategy of one class of Ag nanostructures of high interest for optoelectronics, namely Ag nanowires (AgNWs), with 11‐mercaptoundecanoic acid (MUA) is described. Combining XPS, electron microscopy and original in‐situ total‐internal‐reflection (TIR) surface‐enhanced Raman scattering (SERS) spectroscopic measurements, the substitution of polyvinylpyrrolidone (PVP) molecules on as‐synthesized PVP‐coated AgNWs by their MUA counterparts is clearly demonstrated. The relevance of the SERS approach to examine the anchoring of the MUA onto the silver surface of specific AgNWs with pentagonal cross‐sections is supported by FDTD simulations. In particular, the TIR‐SERS technique reveals that the PVP‐MUA substitution process can be divided into two main steps, namely (i) the desorption of PVP molecules associated with the anchoring of MUA molecules via the formation of Ag−OOC and Ag−S bonds (accomplished within 40 min), and (ii) the subsequent reorientation of MUA molecules to form only Ag−S bonds (finished in 90 min). The resulting passivation of AgNWs with MUA significantly improves their resistance to corrosion, which is crucial for future commercial applications.
Randomized Phase I Trial to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Topical Daprodustat in Healthy Volunteers and in Patients With Diabetic Foot Ulcers
Authors: Olson Eric , Mahar Kelly M. , Morgan Lisa , Fillmore Christina , Holland Claire , Lavery Lawrence
Published: February 2019

Daprodustat, a small‐molecule inhibitor of prolyl hydroxylases, prevents breakdown of hypoxia‐inducible factor (HIF), leading to increased transcription of HIF‐responsive genes. This randomized, placebo‐controlled study evaluated the safety, tolerability, and pharmacokinetics of a topical formulation of daprodustat in healthy volunteers (intact skin) and in patients with diabetic foot ulcers (DFUs) following single and/or 14‐day repeat‐dose administration. In the diabetic patients, exploratory assessments of wound area, volume, and depth were made to qualitatively assess effectiveness. Systemic absorption via topical application was limited across doses up to 1.0% at 100 mg/cm2 for 14 days. Systemic pharmacokinetics were quantifiable in a few samples from a few patients. Because only sporadic concentrations were observed versus pharmacokinetic profiles, pharmacokinetic parameters were not determined. Wound area, depth, and volume showed consistent but weak improvements in the treatment arm; however, the variability in response and small sample size of the standard‐of‐care and placebo arms limited the ability to assess trends in wound healing compared with the daprodustat arm. Overall, topically applied daprodustat was well tolerated, raised no safety concerns, and provided limited to nonquantifiable systemic exposures. The healing of DFUs will need to be evaluated in studies designed to test this hypothesis over a longer treatment duration.
Retracted: The mechanism and experimental study on the interference of high voltage lines to navigation system
Authors: Fan Linjing , Pan Xuchao , Huang Zhengxiang , Zu Xudong
Published: February 2019

Retraction: Linjing Fan Xuchao Pan Zhengxiang Huang Xudong Zu., The mechanism and experimental study on the interference of high voltage lines to navigation system. Concurrency and Computation: Practice and Experience. 2019;e4718, https://doi.org/10.1002/cpe.4718. The above article, published online on 4th February 2019 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the authors, the Editor, Professor Geoffrey Fox, and John Wiley and Sons Ltd. The retraction has been agreed due to inadequacies in the theoretical simulation resulting in foundational errors that are cannot be addressed through an erratum.
Tailoring the Molecular Skeleton of Aza‐BODIPYs to Design Photostable Red‐Light‐Emitting Laser Dyes
Authors: Prieto‐Castañeda Alejandro , Avellanal‐Zaballa Edurne , Gartzia‐Rivero Leire , Cerdán Luis , Agarrabeitia Antonia R. , García‐Moreno Inmaculada , Bañuelos Jorge , Ortiz María J.
Published: February 2019

The front cover artwork is provided by Maria Cristina Devesa, the Organic Chemistry Group from the Universidad Complutense de Madrid (UCM), the Molecular Spectroscopy Group from Universidad del País Vasco (UPV/EHU) and the Laser Materials Group from Instituto Rocasolano (CSIC). The image shows the bright and stable deep‐red emission from the designed aza‐BODIPY chromophores. Such laser emission can be pushed towards the near‐infrared upon a rational selection of the substitution pattern of the fluorophore. Read the full text of the Article at 10.1002/cptc.201800225.
Using functional traits to predict species growth trajectories, and cross‐validation to evaluate these models for ecological prediction
Authors: Thomas Freya M. , Yen Jian D. L. , Vesk Peter A.
Published: February 2019

Modeling plant growth using functional traits is important for understanding the mechanisms that underpin growth and for predicting new situations. We use three data sets on plant height over time and two validation methods—in‐sample model fit and leave‐one‐species‐out cross‐validation—to evaluate non‐linear growth model predictive performance based on functional traits. In‐sample measures of model fit differed substantially from out‐of‐sample model predictive performance; the bestfittingmodels were rarely the bestpredictivemodels. Careful selection of predictor variables reduced the bias in parameter estimates, and there was no single best model across our three data sets. Testing and comparing multiple model forms is important. We developed an R package with a formula interface for straightforward fitting and validation of hierarchical, non‐linear growth models. Our intent is to encourage thorough testing of multiple growth model forms and an increased emphasis on assessing model fit relative to a model's purpose.
Effects of distance on detectability of Arctic waterfowl using double‐observer sampling during helicopter surveys
Authors: Alisauskas Ray T. , Conn Paul B.
Published: February 2019

Aerial survey is an important, widely employed approach for estimating free‐ranging wildlife over large or inaccessible study areas. We studied how a distance covariate influenced probability of double‐observer detections for birds counted during a helicopter survey in Canada’s central Arctic. Two observers, one behind the other but visually obscured from each other, counted birds in an incompletely shared field of view to a distance of 200 m. Each observer assigned detections to one of five 40‐m distance bins, guided by semi‐transparent marks on aircraft windows. Detections were recorded with distance bin, taxonomic group, wing‐flapping behavior, and group size. We compared two general model‐based estimation approaches pertinent to sampling wildlife under such situations. One was based on double‐observer methods without distance information, that provide sampling analogous to that required for mark–recapture (MR) estimation of detection probability,, and group abundance,, along a fixed‐width strip transect. The other method incorporated double‐observer MR with a categorical distance covariate (MRD). A priori, we were concerned that estimators from MR models were compromised by heterogeneity indue to un‐modeled distance information; that is, more distant birds are less likely to be detected by both observers, with the predicted effect thatwould be biased high, andbiased low. We found that, despite increased complexity, MRD models (ΔAICc range: 0–16) fit data far better than MR models (ΔAICc range: 204–258). However, contrary to expectation, the more naïve MR estimators ofwere biased low in all cases, but only by 2%–5% in most cases. We suspect that this apparently anomalous finding was the result of specific limitations to, and trade‐offs in, visibility by observers on the survey platform used. While MR models provided acceptable point estimates of group abundance, their far higher stranded errors (0%–40%) compared to MRD estimates would compromise ability to detect temporal or spatial differences in abundance. Given improved precision of MRD models relative to MR models, and the possibility of bias when using MR methods from other survey platforms, we recommend avian ecologists use MRD protocols and estimation procedures when surveying Arctic bird populations.
Precision gain versus effort with joint models using detection/non‐detection and banding data
Authors: Sanderlin Jamie S. , Block William M. , Strohmeyer Brenda E. , Saab Victoria A. , Ganey Joseph L.
Published: February 2019

Capture–recapture techniques provide valuable information, but are often more cost‐prohibitive at large spatial and temporal scales than less‐intensive sampling techniques. Model development combining multiple data sources to leverage data source strengths and for improved parameter precision has increased, but with limited discussion on precision gain versus effort. We present a general framework for evaluating trade‐offs between precision gained and costs associated with acquiring multiple data sources, useful for designing future or new phases of current studies.We illustrated how Bayesian hierarchical joint models using detection/non‐detection and banding data can improve abundance, survival, and recruitment inference, and quantified data source costs in a northern Arizona, USA, western bluebird (Sialia mexicana) population. We used an 8‐year detection/non‐detection (distributed across the landscape) and banding (subset of locations within landscape) data set to estimate parameters. We constructed separate models using detection/non‐detection and banding data, and a joint model using both data types to evaluate parameter precision gain relative to effort.Joint model parameter estimates were more precise than single data model estimates, but parameter precision varied (apparent survival > abundance > recruitment). Banding provided greater apparent survival precision than detection/non‐detection data. Therefore, little precision was gained when detection/non‐detection data were added to banding data. Additional costs were minimal; however, additional spatial coverage and ability to estimate abundance and recruitment improved inference. Conversely, more precision was gained when adding banding to detection/non‐detection data at higher cost. Spatial coverage was identical, yet survival and abundance estimates were more precise. Justification of increased costs associated with additional data types depends on project objectives.We illustrate a general framework for evaluating precision gain relative to effort, applicable to joint data models with any data type combination. This framework evaluates costs and benefits from and effort levels between multiple data types, thus improving population monitoring designs.
Use of classical bird census transects as spatial replicates for hierarchical modeling of an avian community
Authors: Jiménez‐Franco María V. , Kéry Marc , León‐Ortega Mario , Robledano Francisco , Esteve Miguel A. , Calvo José F.
Published: February 2019

New monitoring programs are often designed with some form of temporal replication to deal with imperfect detection by means of occupancy models. However, classical bird census data from earlier times often lack temporal replication, precluding detection‐corrected inferences about occupancy. Historical data have a key role in many ecological studies intended to document range shifts, and so need to be made comparable with present‐day data by accounting for detection probability. We analyze a classical bird census conducted in the region of Murcia (SE Spain) in 1991 and 1992 and propose a solution to estimating detection probability for such historical data when used in a community occupancy model: the spatial replication of subplots nested within larger plots allows estimation of detection probability. In our study, the basic sample units were 1‐km transects, which were considered spatial replicates in two aggregation schemes. We fit two Bayesian multispecies occupancy models, one for each aggregation scheme, and evaluated the linear and quadratic effect of forest cover and temperature, and a linear effect of precipitation on species occupancy probabilities. Using spatial rather than temporal replicates allowed us to obtain individual species occupancy probabilities and species richness accounting for imperfect detection. Species‐specific occupancy and community size decreased with increasing annual mean temperature. Both aggregation schemes yielded estimates of occupancy and detectability that were highly correlated for each species, so in the design of future surveys ecological reasons and cost‐effective sampling designs should be considered to select the most suitable aggregation scheme. In conclusion, the use of spatial replication may often allow historical survey data to be applied formally hierarchical occupancy models and be compared with modern‐day data of the species community to analyze global change process.
Characteristics and development trends of ecohydrology in lakes and reservoirs: Insights from bibliometrics
Authors: Peng Kai , Deng Jianming , Gong Zhijun , Qin Boqiang
Published: February 2019

Ecohydrology, an interdisciplinary subject connecting ecology and hydrology, has developed rapidly in recent years. Because lakes and reservoirs are responsible for the drinking water supply of billions of people and water issues are becoming increasingly severe, the importance of these water bodies is self‐evident. Lake (reservoir) ecohydrology has thus attracted considerable attention. This study aimed to analyse the characteristics and development trends of ecohydrology using a bibliometric analysis based on the Science Citation Index database. A total of 21,753 papers from 1900 to 2017 on lake (reservoir) ecohydrology were published in 2,323 journals, and the large majority of them were published in the past three decades. Most research has been concentrated in Europe (40.0%) and North America (31.0%). Among these studies, a few key lakes, for example, Lake Taihu, Lake Erie, Lake Michigan, and Lake Ontario, have been analysed in detail by numerous researchers. The results of a word frequency analysis show that the topics related to ecohydrology have transformed from the microcosmic perspective to the macroscopic perspective, and major topics includeeutrophication,global change,models, andecosystem management. The results of a principal component analysis show that the scope of lake (reservoir) ecohydrology research in Europe and North America has stagnated in recent years, whereas in China, ecohydrology research has developed rapidly over the same period. The development of ecohydrology research around the world is not even, and we need to push for more research on major lakes that are outside of Europe, the United States, and China.
Not even wrong: the spurious measurement of biodiversity's effects on ecosystem functioning
Authors: Pillai Pradeep , Gouhier Tarik C.
Published: February 2019

Understanding how biodiversity influences ecosystem functioning is one of the central goals of modern ecology. The early and often acrimonious debates about the relationship between biodiversity and ecosystem functioning were largely resolved following the advent of a statistical partitioning scheme that decomposed the net effect of biodiversity on ecosystem functioning into a “selection” effect and a “complementarity” effect. Here we show that both the biodiversity effect and its statistical decomposition into selection and complementarity are fundamentally flawed because these methods use a naïve null expectation based on neutrality, likely leading to an overestimate of the net biodiversity effect, and because they fail to account for the nonlinear abundance‐ecosystem‐functioning relationships widely observed in nature. Furthermore, under nonlinearity no such statistical scheme can be devised to partition the biodiversity effect. We also present an alternative approach that provides a more reasonable starting point for estimating biodiversity effects. Overall, our results suggest that all studies conducted since the early 1990s are likely to have overestimated the positive effects of biodiversity on ecosystem functioning.
Sr4N[CN2][C2N]: The First Carbodiimide Acetonitriletriide
Authors: Jach Franziska , Höhn Peter , Prots Yurii , Ruck Michael
Published: February 2019

The acetonitriletriide anion C2N3–, the fully deprotonated form of acetonitrile, is stabilized in a pure alkaline earth metal environment in Sr4N[CN2][C2N]. The heterogeneous reaction of graphite and elemental nitrogen (from decomposed NaN3) with Sr2N at 1020 K yields for the first time a phase that contains the two triatomic anions acetonitriletriide C2N3– and carbodiimide CN22– side by side. Further synthetic routes were likewise successfully tested, including a sodium free approach (Sr2N + C) and the use of NaCN as carbon and nitrogen source. The monoclinic crystal structure is derived from powder and single‐crystal X‐ray diffraction data (P21/c, a = 397.74(1) pm, b = 1411.72(3) pm, c = 692.57(1) pm, β = 103.57(1)°, Z = 2). The existence of both anions in Sr4N[CN2][C2N] is further confirmed by IR and Raman spectroscopy. With its novel 1‐D chain structure of edge‐sharing NSr6 octahedra, the material also enriches the structural variety of ternary alkaline earth metal nitrides.
Local Geometry Symmetry and Electrostatic Distribution Dominated Eight‐Coordinate β‐Diketone DyIII SIMs
Authors: Yao Xu , Yan Pengfei , An Guanghui , Li Yuxin , Li Weizuo , Li Guangming
Published: February 2019

To further explore the correlation among the relaxation dynamics, geometry symmetry and ligand field of DyIII SIMs, three β‐diketone mononuclear DyIII complexes, formulating as [Dy(thd)2(NO3)(TPPO)2] (1), [Dy(tfa)2(NO3)(TPPO)2] (2) and [Dy(thd)3(4‐Py)2] (3) (thd = 2,2,6,6‐tetramethyl‐3,5‐heptanedione, tfa = trifluoroacetylacetonate, Tppo = Triphenylphosphane oxide and 4‐Py = 4‐methylpyridine) have been synthesized. Single‐crystal X‐ray diffractions reveal that complexes 1–3 are all eight‐coordinated mononuclear structures with D2d, C2v and D4d local symmetry, respectively. Magnetic analysis reveals that all complexes 1–3 exhibit field‐induced single‐ion magnets (SIMs) behavior resulted from the mixed eigenstates of ground state doublets. The differences in the results of energy barrier indicate that the local geometry symmetry and electrostatic distribution of DyIII ions dominate the magnetic property. Furthermore, the relationship between the structure and magnetism of eight‐coordinated DyIII ions SIMs with the SAP N2O6 coordination environment was also discussed via correlation between the anisotropy axis and coordinating geometry symmetry.
α‐Fe2O3 Based Carbon Composite as Pure Negative Electrode for Application as Supercapacitor
Authors: Li Jiangfeng , Chen Dandane , Wu Qingsheng
Published: February 2019

Supercapacitors have drawn the great attention of researchers as green energy storage devices. Until now, serious positive electrodes for asymmetric cells have been developed noticeably. Nevertheless, negative electrode materials have been less explored, especially pseudocapacitive materials. In this review, the impact of the morphology and composition of hematite (α‐Fe2O3) based carbon composite as pure negative electrode are discussed. Besides, the specific capacitance, electrochemical stability, power density, and energy density of those materials are covered. The asymmetric supercapacitor using α‐Fe2O3 based carbon composite electrode shows high energy density, which can compete with batteries.
p‐TSA‐Based DESs as “Active Green Solvents” for Microwave Enhanced Cyclization of 2‐Alkynyl‐(hetero)‐arylcarboxylates: an Alternative Access to 6‐Substituted 3,4‐Fused 2‐Pyranones
Authors: Curti Fabiola , Tiecco Matteo , Pirovano Valentina , Germani Raimondo , Caselli Alessandro , Rossi Elisabetta , Abbiati Giorgio
Published: February 2019

In this paper, we describe the use of p‐TSA based Deep Eutectic Solvents (DESs) as alternative environmental‐friendly “active” solvents for the microwave‐mediated synthesis of 6‐substituted 3,4‐fused 2‐pyranones, and in particular isocoumarins, starting from 2‐alkynyl‐(hetero)arylcarboxylates. When the alkyne terminus bears a neutral or an electron‐donating group (EDG), the reactions are fast, clean and highly regioselective, to give the 6‐endo‐dig cyclization products in good to excellent yields. For substrates bearing an electron‐withdrawing group (EWG) on the alkyne end, the regioselectivity can be tuned by adding a small amount of silver(I) triflate as co‐catalyst. DES was demonstrated to be reusable without loss of efficiency in terms of reaction yields. Based on experimental evidence and previous findings, two competitive mechanisms working simultaneously are proposed to explain the outcomes and the regioselectivity issues.
Regioselective C3‐Phosphonation of Free Indoles via Transition‐Metal‐Free Radical/Hydrolysis Cascade
Authors: Guo Shengmei , Jie Kun , Zhang Zhebin , Fu Zhengjiang , Cai Hu
Published: February 2019

The selectivity is of great importance for the preparation of molecules in organic chemistry. Herein, a novel method to enable the highly regioselective C3‐phosphonation of free indoles has been developed. This transformation involves a radical and a hydrolysis procedure, and tolerates a range of functional groups, which gives an efficient route toward the 1H‐indol‐3 – ylphosphonic acid monoesters in one step.
Hydrothermal liquefaction of Malaysia's algal biomass for high‐quality bio‐oil production
Authors: Abdul Latif Nor‐Insyirah Syahira , Ong Mei Yin , Nomanbhay Saifuddin
Published: February 2019

Currently, fossil materials form the majority of our energy and chemical source. Many global concerns force us to rethink about our current dependence on the fossil energy. Limiting the use of these energy sources is a key priority for most countries that pledge to reduce greenhouse gas emissions. The application of biomass, as substitute fossil resources for producing biofuels, plastics and chemicals, is a widely accepted strategy for sustainable development. Aquatic plants including algae possess competitive advantages as biomass resources compared to the terrestrial plants in this current global situation. Bio‐oil production from algal biomass is technically and economically viable, cost competitive, requires no capacious lands and minimal water use and reduces atmospheric carbon dioxide. The aim of this paper is to review the potential of converting algal biomass, as an aquatic plant, into high‐quality crude bio‐oil through applicable processes in Malaysia. In particular, bio‐based materials and fuels from algal biomass are considered as one of the reliable alternatives for clean energy. Currently, pyrolysis and hydrothermal liquefaction (HTL) are two foremost processes for bio‐oil production from biomass. HTL can directly convert high‐moisture algal biomass into bio‐oil, whereas pyrolysis requires feedstock drying to reduce the energy consumption during the process. Microwave‐assisted HTL, which can be conducted in aqueous environment, is suitable for aquatic plants and wet biomass such as algae.
Taxonomic notes on Centaurea pseudoscabiosa (Asteraceae, Cardueae–Centaureinae) from Iran
Authors: Negaresh Kazem
Published: February 2019

Centaurea pseudoscabiosa Boiss. & Buhse subsp. araratica (Azn.) Wagenitz and C. pseudoscabiosa subsp. glehnii (Trautv.) Wagenitz are reported as new to Iran, and both subspecies are also typified here. In addition, the geographic distribution of discussed subspecies is presented and mapped. Finally, a taxonomic key to all subspecies of C. pseudoscabiosa is provided.
Beurteilung des Abriebwiderstands verbesserter Böden im Radversuchsstand
Authors: Becker Andreas , Vrettos Christos
Published: February 2019

Das Befahren unbefestigter Straßen führt in trockenen Perioden zu unerwünschter Staubbildung mit negativen Folgen bzgl. der Verkehrssicherheit. Bei stärkeren Regenereignissen kann eine unzureichende Oberflächenversiegelung zu Erosion und Straßenunebenheiten führen. Eine kostengünstige und bewährte Stabilisierungsmaßnahme ist der Zusatz von Kalkhydrat. Ein natürlich anstehender bindiger Boden wurde durch Kalkzugabe verbessert und hinsichtlich Tragfähigkeit und Quellpotenzial untersucht. Ein neuer, selbst entwickelter Radversuchsstand für terramechanische Anwendungen wurde zur Quantifizierung des erhöhten Abriebwiderstands bei Beanspruchung des Bodens durch ein drehendes Modellrad eingesetzt. Die Studie bestätigt die signifikante Verbesserung infolge der Bindemittelzugabe. Eine Gleichung zur ersten Abschätzung der Radeinsenkung als Funktion der Radübergänge wird aus den Ergebnissen hergeleitet.
Prothrombin Complex Concentrates for Coagulopathy in Liver Disease: Single‐Center, Clinical Experience in 105 Patients
Authors: Drebes Anja , de Vos Marie , Gill Sunita , Fosbury Emma , Mallett Sue , Burroughs Andy , Agarwal Banwari , Patch David , Chowdary Pratima
Published: February 2019

Patients with liver disease frequently develop coagulopathy, and fresh frozen plasma is traditionally used for correction of coagulopathy to manage and prevent bleeding. Prothrombin complex concentrates (PCCs) offer an attractive alternative because they are more readily available and avoid large‐volume transfusion. This retrospective, single‐center study reviewed clinical use of PCC in patients with acute/chronic liver disease. A total of 105 patients with 194 episodes of PCC administration were reviewed. Data pertaining to indication, dosing, effectiveness, and safety were collected. The effect of PCC on coagulation was analyzed in patients for whom coagulation results were available 7 hours before and after PCC. Data on thromboembolic events and mortality within 4 weeks of PCC administration were captured. Most patients (77%) had chronic liver disease; the remainder had acute liver failure. Indications for PCC were preprocedure prophylaxis and treatment for active/recent bleeding in 48% and 52% of 194 treatment episodes, respectively. The median dose of PCC administered was 22 IU/kg (interquartile range, 16‐29 IU/kg). Before PCC administration, 45% of patients had an international normalized ratio (INR) greater than 2.0, and 36% had fibrinogen levels of at least 1.5 g/L. PCC produced statistically significant reductions in prothrombin time and INR (coadministration with fibrinogen or cryoprecipitate: 3.1 versus 1.9; P < 0.001; no coadministration: 2.3 versus 1.8; P < 0.001). Three patients with multiple risk factors developed thrombotic events (hepatic artery thrombosis, incidental bilateral pulmonary embolism, nonocclusive portal vein thrombosis); there were no cardiovascular or cerebrovascular adverse events. Overall, 46 patients died of causes unrelated to PCC treatment. Conclusion: In patients with liver disease, PCC therapy was effective in improving coagulation test results without an excess of thrombotic events. Further assessment of PCC as hemostatic therapy in this setting is required.
Molecular alterations and poziotinib efficacy, a pan‐HER inhibitor, in human epidermal growth factor receptor 2 (HER2)‐positive breast cancers: Combined exploratory biomarker analysis from a phase II clinical trial of poziotinib for refractory HER2‐positive breast cancer patients
Authors: Kim Ji‐Yeon , Lee Eunjin , Park Kyunghee , Jung Hae Hyun , Park Woong‐Yang , Lee Kyung‐Hun , Sohn Joohyuk , Lee Keun Seok , Jung Kyung Hae , Kim Jee Hyun , Lee Ki Hyeong , Im Seock‐Ah , Park Yeon Hee
Published: February 2019

We aimed to investigate the impact of genetic alterations on the efficacy of poziotinib in a phase II clinical trial of patients with heavily treated HER2‐positive metastatic breast cancer (BC). We performed targeted ultra‐deep sequencing with a customized cancer gene panel and RNA expression assay using BC specimens. Of 106 patients, biomarker data were available for 85. Copy number (CN) amplifications of HER2 were observed in 72 patients (85%), and CN >8 in 50 (59%). Single nucleotide variants (SNVs) of HER2 were found in 16 patients (19%). Genetic alterations of PIK3CA pathway were found in 40 patients (47%). Median progression free survival (PFS) of the biomarker analysis group was 3.61 months. In terms of PFS, HER2 with CN >8 prolonged (hazard ratio (HR) 0.61, 95% CI: 0.38, 0.97, p = 0.037) and alteration of PIK3CA pathway shortened the duration of survival (HR 2.25, 95% CI: 1.39, 3.63, p = 0.001). SNVs of HER2 increased survival duration, but the effect was not significant (HR: 0.58, 95% CI: 0.31, 1.08, p = 0.085). In addition, SNVs in the ERBB3 cytoplasmic domain decreased poziotinib response (HR: 4.58, 95% CI: 2.02, 10.37, p < 0.001). In multigene analysis, BC with HER2 CN >8 and intact PIK3CA pathway had significantly longer PFS compared to others (HR: 0.37, 95% CI: 0.21, 0.66, p = 0.001), while SNVs in the ERBB3 cytoplasmic domain predicted poor prognosis (HR: 4.28, 95% CI: 1.71, 10.71, p < 0.001). In conclusion, HER2 CN amplification, PIK3CA pathway alteration, and ERBB3 cytoplasmic mutation showed predictive roles on clinical outcomes of HER2‐positive MBC treated with poziotinib.
1H NMR‐based metabolomics reveal overlapping discriminatory metabolites and metabolic pathway disturbances between colorectal tumor tissues and fecal samples
Authors: Lin Yan , Ma Changchun , Bezabeh Tedros , Wang Zhening , Liang Jiahao , Huang Yao , Zhao Jiayun , Liu Xinmu , Ye Wei , Tang Wan , Ouyang Ting , Wu Renhua
Published: February 2019

Previous studies have compared fecal metabolites from healthy and colorectal cancer (CRC) patients to predict the pro‐CRC signatures. However, the systemic mechanistic link between feces and colonic tissues of CRC patients is still limited. The current study was a paralleled investigation of colonic tumor tissues and their normal adjacent tissues alongside patient‐matched feces by using 1H nuclear magnetic resonance spectroscopy combined with pattern recognition to investigate how fecal metabolic phenotypes are linked to the changes in colorectal tumor profiles. A set of overlapping discriminatory metabolites across feces and tumor tissues of CRC were identified, including elevated levels of lactate, glutamate, alanine, succinate and reduced amounts of butyrate. These changes could indicate the networks for metabolic pathway perturbations in CRC potentially involved in the disruptions of glucose and glycolytic metabolism, TCA cycle, glutaminolysis, and short chain fatty acids metabolism. Furthermore, changes in fecal acetate were positively correlated with alterations of glucose and myo‐inositol in colorectal tumor tissues, implying enhanced energy production for rapid cell proliferation. Compared to other fecal metabolites, acetate demonstrated the highest diagnostic performance for diagnosing CRC, with an AUC of 0.843 in the training set, and a good predictive ability in the validation set. Overall, these associations provide evidence of distinct metabolic signatures and metabolic pathway disturbances between the colonic tissues and feces within the same individual, and changes of fecal metabolic signature could reflect the CRC tissue microenvironment, highlighting the significance of the distinct fecal metabolic profiles as potential novel and noninvasive relevant indicators for CRC detection.
Maternal experience of their infants’ crying in the context of war trauma: Determinants and consequences
Authors: Lahti Katri , Vänskä Mervi , Qouta Samir R. , Diab Safwat Y. , Perko Kaisa , Punamäki Raija‐Leena
Published: February 2019

We examined, first, how prenatal maternal mental health and war trauma predicted mothers’ experience of their infant crying, indicated by emotions, cognitions, and behavior; and second, how these experiences influenced the mother–infant interaction and infant development. Participants were 511 Palestinian mothers from the Gaza Strip, reporting their war trauma, symptoms of posttraumatic stress disorder (PTSD), depression, and perceived stress during pregnancy (Time 1). They reported experiences of infant crying at 4 months (Time 2), and the mother–infant interaction and infant sensorimotor and language development at 12 months of infants’ age (Time 3). Results revealed that maternal mental health problems, but not war trauma, were important to experiences of infant crying. A high level of PTSD symptoms predicted negative emotions evoked by infant crying, and high depressive symptoms predicted low active and positive responses to crying. Unexpectedly, high prenatal perceived stress predicted high active and positive responsiveness. Concerning the consequences, mothers’ sensitive interpretation of infant crying predicted optimal infant sensorimotor development, and mothers’ active and positive responses predicted high emotional availability in mother–infant interaction. Crying is the first communication tool for infants, and mothers’ sensitive responses to crying contribute to infant well‐being. Therefore, reinforcing mother's optimal responses is important when helping war‐affected dyads.
The link between child temperament and low‐income mothers’ and fathers’ parenting
Authors: Padilla Christina M. , Ryan Rebecca M.
Published: February 2019

Numerous studies have shown that children's temperamental characteristics impact the quality and quantity of parent–child interactions. However, these studies have largely focused on middle‐class samples, have not compared multiple domains of parenting across mothers and fathers, and have not considered the possibility of nonlinear associations between temperament and parenting. The present study addresses these gaps by examining the potentially nonlinear role of two temperamental characteristics—negative emotionality and sociability—in predicting the quality and quantity of low‐income mothers’ and fathers’ parenting. Data were drawn from the Early Head Start Research and Evaluation Project, a study of low‐income children and families. Results indicated that whereas parenting quality was somewhat impaired when children were temperamentally vulnerable (low sociability, high negativity), parents increased parenting quantity with the same vulnerable children. There was some evidence that parents were most reactive to children who scored either very high or very low on negative emotionality and sociability in both parenting domains. Patterns also suggest that mothers were more reactive to sociability, and fathers to negative emotionality.
Inhibition of activated factor X; a new pathway in ameliorating carbon tetrachloride–induced liver fibrosis in rats
Authors: Mahmoud Nesreen Ishak , Messiha Basim Anwar Shehata , Abo‐Saif Ali Ahmed , Abdel‐Bakky Mohamed Sadek
Published: February 2019

Activated factor X has a central role in the coagulation activation and also contributes to chronic inflammation and tissue fibrosis. In this study, rivaroxaban, a direct factor X inhibitor, attenuates liver fibrosis induced by carbon tetrachloride (CCl4). Male rats were randomly allocated into three groups: a control group, CCl
4 fibrotic group, and CCl
4+rivaroxaban (5 mg/kg) group. Liver fibrosis was induced by subcutaneous injection of CCl
4 twice a week for 6 weeks. Rivaroxaban significantly restored the biochemical parameter including inflammatory and fibrosis markers with histopathological evidence using routine and Masson trichrome staining. It reduced also the expression of tissue factor, fibrin, transforming growth factor and α‐smooth muscle actin in the liver tissues. This concludes that rivaroxaban attenuates liver injury caused by CCl
4, at least in part by inhibiting coagulation and proinflammatory activation. In conclusion, rivaroxaban may be used for the management of liver fibrosis.
Effects of CPAP on the transcriptional signatures in patients with obstructive sleep apnea via coexpression network analysis
Authors: Peng Juxiang , Song Jukun , Zhou Jing , Yin Xinhai , Song Jinlin
Published: February 2019

A growing number of studies provide epidemiological evidence linking obstructive sleep apnea (OSA) with a number of chronic disorders. Transcriptional analyses have been conducted to analyze the gene expression data. However, the weighted gene coexpression network analysis (WGCNA) method has not been applied to determine the transcriptional consequence of continuous positive airway pressure (CPAP) therapy in patients with severe OSA. The aim of this study was to identify key pathways and genes in patients with OSA that are influenced by CPAP treatment and uncover/unveil potential molecular mechanisms using WGCNA. We analyzed the microarray data of OSA (GSE 49800) listed in the Gene Expression Omnibus database. Coexpression modules were constructed using WGCNA. In addition, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis were also conducted. After the initial data processing, 5101 expressed gene profiles were identified. Next, a weighted gene coexpression network was established and 16 modules of coexpressed genes were identified. The interaction analysis demonstrated a relative independence of gene expression in these modules. The black module, tan module, midnightblue module, pink module, and greenyellow module were significantly associated with the alterations in circulating leukocyte gene expression at baseline and after exposure to CPAP. The five hub genes were considered to be candidate OSA‐related genes after CPAP treatment. Functional enrichment analysis revealed that steroid biosynthesis, amino sugar and nucleotide sugar metabolism, protein processing in the endoplasmic reticulum, and the insulin signaling pathway play critical roles in the development of OSA in circulating leukocyte gene expression at baseline and after exposure to CPAP. Using this new systems biology approach, we identified several genes and pathways that appear to be critical to OSA after CPAP treatment, and these findings provide a better understanding of OSA pathogenesis.
C1qTNF‐related protein‐6 protects against doxorubicin‐induced cardiac injury
Authors: Zheng Wei‐Feng , Zhang Shou‐Yan , Ma Hui‐Fang , Chang Xue‐Wei , Wang Hao
Published: February 2019

The clinical use of doxorubicin (DOX) is limited by its toxic effect. However, there is no specific drug that can prevent DOX‐related cardiac injury. C1qTNF‐related protein‐6 (CTRP6) is a newly identified adiponectin paralog with many protective functions on metabolism and cardiovascular diseases. However, little is known about the effect of CTRP6 on DOX‐induced cardiac injury. The present study aimed to investigate whether CTRP6 could protect against DOX‐related cardiotoxicity. To induce acute cardiotoxicity, the mice were intraperitoneally injected with a single dose of DOX (15 mg/kg). Cardiomyocyte‐specific CTRP6 overexpression was achieved using an adenoassociated virus system at 4 weeks before DOX injection. The data in our study demonstrated that CTRP6 messenger RNA and protein expression were decreased in DOX‐treated hearts. CTRP6 attenuated cardiac atrophy induced by DOX injection and inhibited cardiac apoptosis and improved cardiac function in vivo. CTRP6 also promoted the activation of protein kinase B (AKT/PKB) signaling pathway in DOX‐treated mice. CTRP6 prevented cardiomyocytes from DOX‐induced apoptosis and activated the AKT pathway in vitro. CTRP6 lost its protection against DOX‐induced cardiac injury in mice with AKT inhibition. In conclusion, CTRP6 protected the heart from DOX‐cardiotoxicity and improves cardiac function via activation of the AKT signaling pathway.
Emerging roles of microRNAs in regulating the mTOR signaling pathway during tumorigenesis
Authors: Javid Hossein , Soltani Arash , Mohammadi Fariba , Hashemy Seyed Isaac
Published: February 2019

The mammalian target of rapamycin (mTOR) is a large Ser/Thr protein kinase that belongs to the phosphoinositide 3‐kinase (PI3K) family and mediates various physiological and pathological processes, especially cell proliferation, protein synthesis, autophagy, and cancer development. The mTOR expression is transient and tightly regulated in normal cells, but it is overactivated in cancer cells. Recently, several studies have indicated that microRNAs (miRNAs) play a critical role in the regulation of mTOR and mTOR‐associated processes, some acting as inhibitors and the others as activators. Although it is still in infancy, the strategy of combining both miRNAs and mTOR inhibitors might provide an approach to selectively sensitizing tumor cells to chemotherapy‐induced DNA damage and subsequently attenuating the tumor cell growth and apoptosis.
Computational and mutational analysis of TatD DNase of Bacillus anthracis
Authors: Singh Damini , Rahi Amit , Kumari Romika , Gupta Vatika , Gautam Gunjan , Aggarwal Somya , Rehan Mohd , Bhatnagar Rakesh
Published: February 2019

The role of TatD DNases as DNA repair enzymes or cell death (apoptotic) nucleases is well established in prokaryotes as well as eukaryotes. The current study aims to characterize the TatD nuclease from Bacillus anthracis (Ba TatD) and to explore its key histidine catalytic residues. Ba TatD was found to be a metal‐dependent, nonspecific endonuclease which could efficiently cleave double‐stranded DNA substrates. Moreover, Ba TatD nuclease was observed to be thermostable up to 55°C and act in a wide pH range indicating its industrial applicability. Diethyl pyrocarbonate‐based histidine‐selective alkylation of the Ba TatD resulted in a loss of its nuclease activity suggesting a crucial role of the histidine residues in its activity. The key residues of Ba TatD were predicted using sequence analysis and structure‐based approaches, and then the predicted residues were further tested by mutational analysis. Upon mutational analysis, H128 and H153 have been found to be crucial for Ba TatD activity, though H153 seems to bear an important but a dispensable role for the Ba TatD nuclease. Ba TatD had a uniform expression in the cytosol of B. anthracis, which indicates a significant role of the protein in the pathogen's life cycle. This is the first study to identify and characterize the TatD DNase from B. anthracis and will be helpful in gaining more insights on the role of TatD proteins in Gram‐positive bacteria where it remains unexplored.
On the fringes: How youth experiencing homelessness conceptualize social and economic inequality–A Photovoice study
Authors: Barman‐Adhikari Anamika , DeChants Jonah P. , M. Brydon Daphne , Portillo Andrea , Bender Kimberly
Published: February 2019

This study used Photovoice methods with young adults experiencing homelessness to collaboratively identify issues that are of greatest importance in an open‐ended, exploratory, and inductive manner. Participants selected two concepts to focus their inquiry: freedom and prosperity. Within these concepts, participants discussed nature as a source of inspiration, a desire to better themselves and to change their situations, and passion for contributing to social change by exposing economic inequality and raising awareness about homelessness. These findings demonstrate that young people are keenly aware of the structural and macro‐level factors that have contributed to their risks of social exclusion and marginalization.
Is Bioequivalence Established Based on the Reference‐Scaled Average Bioequivalence Approach Relevant to Chronic Administration of Phenytoin? Perspectives Based on Population Pharmacokinetic Modeling and Simulations
Authors: Kim Hyewon , Fang Lanyan , Yu Jingyu , Meng Zhaoyu , Trame Mirjam N. , Schmidt Stephan , Lesko Lawrence J. , Zhao Liang
Published: February 2019

Phenytoin demonstrates time‐dependent and nonlinear pharmacokinetics (PK) within the therapeutic range of 10 to 20 μg/mL. There are discussions on the relevance of bioequivalence (BE) demonstrated in a single‐dose BE study in healthy subjects to exposure under chronic use conditions in patients, particularly given that phenytoin has a narrow therapeutic index. The objective of this study was to quantitatively evaluate the appropriateness of single‐dose PK BE through simulations for the phenytoin extended‐capsule products. A previously published population PK model was updated to account for the interoccasion variability using the dense PK data of the reference listed drug (Dilantin) from 5 single‐dose, fully replicated BE studies (n = 124). BE studies with alternative designs were simulated using the developed PK model and subsequently analyzed accordingly: Scenario 1, multiple‐dose, 2‐period, crossover BE studies with an average BE approach; Scenario 2, single‐dose, 4‐period, fully replicated BE studies with a reference‐scaled average BE approach as recommended in the product‐specific guidance. In both scenarios, hypothetical phenytoin capsules with different formulation‐related PK parameters, such as relative bioavailability and absorption rates, were included in the simulations. The results showed that the both scenarios provided the same results with respect to BE conclusions.