bluuebunny/crossref_metadata_2025 huggingface dataset:
Ecological Networks and Community Attachment and Support Among Recently Resettled Refugees
Authors: Soller Brian , Goodkind Jessica R. , Greene R. Neil , Browning Christopher R. , Shantzek Cece
Published: March 2018

Interventions aimed at enhancing mental health are increasingly centered around promoting community attachment and support. However, few have examined and tested the specific ecological factors that give rise to these key community processes. Drawing from insights from the ecological network perspective, we tested whether spatial and social overlap in routine activity settings (e.g., work, school, childcare) with fellow ethnic community members is associated with individuals’ attachment to their ethnic communities and access to social resources embedded in their communities. Data on routine activity locations drawn from the Refugee Well‐Being Project (based in a city in the Southwestern United States) were used to reconstruct the ecological networks of recently resettled refugee communities, which were two‐mode networks that comprise individuals and their routine activity locations. Results indicated that respondents’ community attachment and support increased with their ecological network extensity—which taps the extent to which respondents share routine activity locations with other community members. Our study highlights a key ecological process that potentially enhances individuals’ ethnic community attachment that extends beyond residential neighborhoods.
Octacarbonyl Anion Complexes of Group Three Transition Metals [TM(CO)8]− (TM=Sc, Y, La) and the 18‐Electron Rule
Authors: Jin Jiaye , Yang Tao , Xin Ke , Wang Guanjun , Jin Xiaoyang , Zhou Mingfei , Frenking Gernot
Published: March 2018

We report the gas‐phase synthesis of stable 20‐electron carbonyl anion complexes of group 3 transition metals, TM(CO)8− (TM=Sc, Y, La), which are studied by mass‐selected infrared (IR) photodissociation spectroscopy. The experimentally observed species, which are the first octacarbonyl anionic complexes of a TM, are identified by comparison of the measured and calculated IR spectra. Quantum chemical calculations show that the molecules have a cubic (Oh) equilibrium geometry and a singlet (1A1g) electronic ground state. The 20‐electron systems TM(CO)8− are energetically stable toward loss of one CO ligand, yielding the 18‐electron complexes TM(CO)7− in the 1A1 electronic ground state; these exhibit a capped octahedral structure with C3v symmetry. Analysis of the electronic structure of TM(CO)8− reveals that there is one occupied valence molecular orbital with a2u symmetry, which is formed only by ligand orbitals without a contribution from the metal atomic orbitals. The adducts of TM(CO)8− fulfill the 18‐electron rule when only those valence electrons that occupy metal–ligand bonding orbitals are considered.
Transition‐Metal‐Free Decarboxylative Propargylic Substitution/Cyclization with either Azolium Enolates or Acyl Anions
Authors: Lu Shenci , Ong Jun‐Yang , Poh Si Bei , Tsang Terence , Zhao Yu
Published: March 2018

Presented herein is an unprecedented transition‐metal‐free propargylic substitution reaction with either azolium enolates or acyl anions, which are generated from aldehydes under N‐heterocyclic carbene catalysis. This new catalytic activation operates on readily available cyclic propargylic carbamates through decarboxylation, and generates reactive allene intermediates that can undergo divergent cyclization pathways to deliver skeletally diverse polycyclic compounds with high levels of efficiency and excellent enantioselectivities.
Two‐fold Bioorthogonal Derivatization by Different Formylglycine‐Generating Enzymes
Authors: Krüger Tobias , Weiland Stefanie , Falck Georg , Gerlach Marcus , Boschanski Mareile , Alam Sarfaraz , Müller Kristian M. , Dierks Thomas , Sewald Norbert
Published: March 2018

Formylglycine‐generating enzymes are of increasing interest in the field of bioconjugation chemistry. They catalyze the site‐specific oxidation of a cysteine residue to the aldehyde‐containing amino acid Cα‐formylglycine (FGly). This non‐canonical residue can be generated within any desired target protein and can subsequently be used for bioorthogonal conjugation reactions. The prototypic formylglycine‐generating enzyme (FGE) and the iron‐sulfur protein AtsB display slight variations in their recognition sequences. We designed specific tags in peptides and proteins that were selectively converted by the different enzymes. Combination of the different tag motifs within a single peptide or recombinant protein enabled the independent and consecutive introduction of two formylglycine residues and the generation of heterobifunctionalized protein conjugates.
Evolution of mechanical properties of polypropylene separator in liquid electrolytes for lithium‐ion batteries
Authors: Chen Jinhan , Hu Hongjiu , Li Shuang , He Yaolong
Published: March 2018

Knowledge of the mechanical behaviors of polymeric separators immersed in liquid electrolytes is of great significance for predicting the long‐term performance of lithium batteries with high performance and safety. In terms of tensile tests, heating shrinkage, and dynamic mechanical analysis as well as the essential work of fracture method, the study reported here encompasses a systematic investigation of the mechanical properties of a typical commercial polypropylene separator in mixtures of ethylene carbonate and dimethyl carbonate and lithium hexafluorophosphate (LiPF6), comparing with the results in ionic liquid (IL) electrolyte composed of lithium tetrafluoroborate (LiBF4) and 1‐butyl‐3‐methylimidazolium tetrafluoroborate (BMIBF4) and dry condition. It has been found that liquid electrolytes have obvious negative effect on the dimensional stability at elevated temperature and mechanical properties, especially on crack resistance of the polymer separator. LiBF4‐BMIBF4has much smaller damage on the strength, Young's modulus and fracture toughness of separator than the organic solution except the dynamic modulus at high temperature. Notably, the maximum tensile stress, Young's modulus and the reciprocal of relaxation time of the polymer separator are linearly dependent with strain rate under quasi‐static condition, and the relaxation time has clarified the coupling effect mechanism of liquid electrolyte and loading rate. Moreover, the non‐dimensional viscoelastic constitute equation could perfectly track the tensile behavior of wet and dry separators at different strain rate, and a property model could well characterize the temperature‐dependent storage modulus of polymer separators from rubbery to viscous state. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci.2018,135, 46441.
Preventing Other ‘Marawis’ in the Southern Philippines
Authors: Franco Joseph
Published: March 2018

After more than 5 months of intense fighting, the Battle for Marawi has concluded as the largest urban combat scenario in modern Philippine history. Winning a kinetic campaign against violent extremist organisations like the Maute Group is insufficient in itself to prevent the eruption of other ‘Marawis’ in the future. The Duterte Administration should craft a cohesive countering violent extremism strategy. A prospective strategy should recognise the importance of coherent messaging and focus on the non‐ideological drivers of conflict.
Model Predictive Control for Constrained Image‐Based Visual Servoing in Uncalibrated Environments
Authors: Qiu Zhoujingzi , Hu Shiqiang , Liang Xinwu
Published: March 2018

This paper presents a novel approach for image‐based visual servoing (IBVS) of a robotic system by considering the constraints in the case when the camera intrinsic and extrinsic parameters are uncalibrated and the position parameters of the features in 3‐D space are unknown. Based on the model predictive control method, the robotic system's input and output constraints, such as visibility constraints and actuators limitations, can be explicitly taken into account. Most of the constrained IBVS controllers use the traditional image Jacobian matrix, the proposed IBVS scheme is developed by using the depth‐independent interaction matrix. The unknown parameters can appear linearly in the prediction model and they can be estimated by the identification algorithm effectively. In addition, the model predictive control determines the optimal control input and updates the estimated parameters together with the prediction model. The proposed approach can simultaneously handle system constraints, unknown camera parameters and depth parameters. Both the visual positioning and tracking tasks can be achieved desired performances. Simulation results based on a 2‐DOF planar robot manipulator for both the eye‐in‐hand and eye‐to‐hand camera configurations are used to demonstrate the effectiveness of the proposed method.
Ermüdungsfestigkeit zyklisch beanspruchter Stahlbetonbalken ohne Querkraftbewehrung
Authors: Kohl Matthias , Rombach Günter
Published: March 2018

Der rechnerische Querkraftnachweis von Stahlbetontragwerken ohne Schubbewehrung (im Allgemeinen Platten, bspw. Fahrbahnplatten, WEA‐Fundamente) auf Ermüdung nach DIN EN 1992‐1‐1 [1] bzw. DIN EN 1992‐2/NA beruht weitgehend auf empirischen Untersuchungen. Der Ansatz wurde bislang kaum experimentell validiert. Nachfolgend wird über theoretische, experimentelle und numerische Untersuchungen zum Tragverhalten von Stahlbetonbalken ohne Querkraftbewehrung unter dynamischen und statischen Einwirkungen berichtet. Neben der Validierung des Normansatzes mittels 20 Balkenversuchen konnten auch die Tragmechanismen nach Auftreten eines Biegeschubrisses studiert werden.
Smooth individual level covariates adjustment in disease mapping
Authors: Huque Md Hamidul , Anderson Craig , Walton Richard , Woolford Samuel , Ryan Louise
Published: March 2018

Spatial models for disease mapping should ideally account for covariates measured both at individual and area levels. The newly available “indiCAR” model fits the popular conditional autoregresssive (CAR) model by accommodating both individual and group level covariates while adjusting for spatial correlation in the disease rates. This algorithm has been shown to be effective but assumes log‐linear associations between individual level covariates and outcome. In many studies, the relationship between individual level covariates and the outcome may be non‐log‐linear, and methods to track such nonlinearity between individual level covariate and outcome in spatial regression modeling are not well developed. In this paper, we propose a new algorithm, smooth‐indiCAR, to fit an extension to the popular conditional autoregresssive model that can accommodate both linear and nonlinear individual level covariate effects while adjusting for group level covariates and spatial correlation in the disease rates. In this formulation, the effect of a continuous individual level covariate is accommodated via penalized splines. We describe a two‐step estimation procedure to obtain reliable estimates of individual and group level covariate effects where both individual and group level covariate effects are estimated separately. This distributed computing framework enhances its application in the Big Data domain with a large number of individual/group level covariates. We evaluate the performance of smooth‐indiCAR through simulation. Our results indicate that the smooth‐indiCAR method provides reliable estimates of all regression and random effect parameters. We illustrate our proposed methodology with an analysis of data on neutropenia admissions in New South Wales (NSW), Australia.
Dynamic prediction of cumulative incidence functions by direct binomial regression
Authors: Grand Mia K. , de Witte Theo J. M. , Putter Hein
Published: March 2018

In recent years there have been a series of advances in the field of dynamic prediction. Among those is the development of methods for dynamic prediction of the cumulative incidence function in a competing risk setting. These models enable the predictions to be updated as time progresses and more information becomes available, for example when a patient comes back for a follow‐up visit after completing a year of treatment, the risk of death, and adverse events may have changed since treatment initiation. One approach to model the cumulative incidence function in competing risks is by direct binomial regression, where right censoring of the event times is handled by inverse probability of censoring weights. We extend the approach by combining it with landmarking to enable dynamic prediction of the cumulative incidence function. The proposed models are very flexible, as they allow the covariates to have complex time‐varying effects, and we illustrate how to investigate possible time‐varying structures using Wald tests. The models are fitted using generalized estimating equations. The method is applied to bone marrow transplant data and the performance is investigated in a simulation study.
Least median of squares and iteratively re‐weighted least squares as robust linear regression methods for fluorimetric determination of α‐lipoic acid in capsules in ideal and non‐ideal cases of linearity
Authors: Korany Mohamed A. , Gazy Azza A. , Khamis Essam F. , Ragab Marwa A. A. , Kamal Miranda F.
Published: March 2018

This study outlines two robust regression approaches, namely least median of squares (LMS) and iteratively re‐weighted least squares (IRLS) to investigate their application in instrument analysis of nutraceuticals (that is, fluorescence quenching of merbromin reagent upon lipoic acid addition). These robust regression methods were used to calculate calibration data from the fluorescence quenching reaction (∆F and F‐ratio) under ideal or non‐ideal linearity conditions. For each condition, data were treated using three regression fittings: Ordinary Least Squares (OLS), LMS and IRLS. Assessment of linearity, limits of detection (LOD) and quantitation (LOQ), accuracy and precision were carefully studied for each condition. LMS and IRLS regression line fittings showed significant improvement in correlation coefficients and all regression parameters for both methods and both conditions. In the ideal linearity condition, the intercept and slope changed insignificantly, but a dramatic change was observed for the non‐ideal condition and linearity intercept. Under both linearity conditions, LOD and LOQ values after the robust regression line fitting of data were lower than those obtained before data treatment. The results obtained after statistical treatment indicated that the linearity ranges for drug determination could be expanded to lower limits of quantitation by enhancing the regression equation parameters after data treatment. Analysis results for lipoic acid in capsules, using both fluorimetric methods, treated by parametric OLS and after treatment by robust LMS and IRLS were compared for both linearity conditions.
Enhanced spectrofluorimetric determination of two novel combination therapies for the treatment of benign prostatic hyperplasia containing tamsulosin hydrochloride
Authors: El‐Kimary Eman I. , Khamis Essam F. , Belal Saeid F. , Abdel Moneim Mona M.
Published: March 2018

Two novel combination therapies for the treatment of benign prostatic hyperplasia were analyzed using simple and enhanced spectrofluorimetric methods based on derivative and derivative ratio techniques. The two combinations contained tamsulosin hydrochloride (TAM) as a minor component with tolterodine tartrate (TOL) or solifenacin succinate (SOL). The fluorescence of the three drugs under study was measured in methanolic water solution. For the TAM and SOL mixture, successful resolution between both drugs was achieved by derivative manipulation of both ratio and zero‐order emission spectra with good linearity in the ranges of 0.75–3.50 and 2.5–15.0 μg ml−1 for TAM and SOL, respectively. Extensive emission spectral overlap was observed for the TAM and TOL mixture. Therefore, only derivative application of the ratio emission spectra resolved such overlap and quantitated TAM and TOL simultaneously in the ranges 0.75–3.50 and 2.5–20.0 μg ml–1 for TAM and TOL, respectively. Optimization of various experimental parameters that affected the fluorescence intensity of the three drugs was performed. Successful application of all proposed methods was achieved for analysis of the two drugs in each combination therapy in their laboratory‐prepared mixtures and dosage forms with good accuracy and precision.
Increasing the Photoautotrophic Growth Rate of Synechocystis sp. PCC 6803 by Identifying the Limitations of Its Cultivation
Authors: van Alphen Pascal , Abedini Najafabadi Hamed , Branco dos Santos Filipe , Hellingwerf Klaas J.
Published: March 2018

Many conditions have to be optimized in order to be able to grow the cyanobacterium Synechocystis sp. PCC 6803 (Synechocystis) for an extended period of time under physiologically well‐defined and constant conditions. It is still poorly understood what limits growth of this organism in batch and continuous cultures in BG‐11, the standard medium used to grow Synechocystis. Through a series of batch experiments in flasks and continuous mode experiments in advanced photobioreactors, it is shown that the limiting nutrient during batch cultivation is sulfate, the depletion of which leads to ROS formation and rapid bleaching of pigments after entry into stationary phase. In continuous mode, however, the limiting nutrient is iron. Optimizing these growth conditions resulted in a so far highest growth rate of 0.16 h−1 (4.3 h doubling time), which is significantly higher than the textbook value of 0.09 h−1 (8 h doubling time). An improved medium, BG‐11 for prolonged cultivation (BG‐11‐PC) is introduced, that allows for controlled, extended cultivation of Synechocystis, under well‐defined physiological conditions. The data present here have implications for mass‐culturing of cyanobacteria.
Pilot Scale‐up of Poly(3‐hydroxybutyrate‐co‐4‐hydroxybutyrate) Production by Halomonas bluephagenesis via Cell Growth Adapted Optimization Process
Authors: Ye Jianwen , Huang Wuzhe , Wang Dongsheng , Chen Fengyi , Yin Jin , Li Teng , Zhang Haoqian , Chen Guo‐Qiang
Published: March 2018

Poly(3‐hydroxybutyrate‐co‐4‐hydroxybutyrate), P(3HB‐co‐4HB), is one of the most valuable biopolymers because of its flexible mechanical properties. In this study, the goal is to establish a scaled‐up process of low cost P(3HB‐co‐4HB) from a 7.5‐L fermentor to 1‐ and 5‐m3 industrial bioreactors, respectively, using Halomonas bluephagenesis TD40 grown on glucose, γ‐butyrolactone, and waste corn steep liquor (CSL) as substrates, under open non‐sterile and fed‐batch or continuous conditions. The non‐sterile process enables the energy reduction for less steam consumption. Moreover, waste gluconate is successfully utilized to replace glucose as a carbon source for cell growth and PHA accumulation in 7.5‐L fermentor, which opens the possibility of 60% of raw material cost reduction for recycling the waste resources. A mathematical model and rational calculation is established to help guide the feeding strategy and scale‐up, respectively, leading to 100 g L−1 cell dry weight (CDW) containing 60.4% P(3HB‐co‐mol 13.5% 4HB) after 36 h of growth in the 5 m3 vessel. An even higher P(3HB‐co‐4HB) content of 74% is achieved by decreasing the use of waste CSL. A stable and continuous open process for efficient low‐cost production of P(3HB‐co‐4HB) is successfully developed coupling fermentation with the downstream extraction processing.
Analysis of metabolic networks of Streptomyces leeuwenhoekii C34 by means of a genome scale model: Prediction of modifications that enhance the production of specialized metabolites
Authors: Razmilic Valeria , Castro Jean F. , Andrews Barbara , Asenjo Juan A.
Published: March 2018

The first genome scale model (GSM) for Streptomyces leeuwenhoekii C34 was developed to study the biosynthesis pathways of specialized metabolites and to find metabolic engineering targets for enhancing their production. The model, iVR1007, consists of 1,722 reactions, 1,463 metabolites, and 1,007 genes, it includes the biosynthesis pathways of chaxamycins, chaxalactins, desferrioxamines, ectoine, and other specialized metabolites. iVR1007 was validated using experimental information of growth on 166 different sources of carbon, nitrogen and phosphorous, showing an 83.7% accuracy. The model was used to predict metabolic engineering targets for enhancing the biosynthesis of chaxamycins and chaxalactins. Gene knockouts, such as sle03600 (L‐homoserine O‐acetyltransferase), and sle39090 (trehalose‐phosphate synthase), that enhance the production of the specialized metabolites by increasing the pool of precursors were identified. Using the algorithm of flux scanning based on enforced objective flux (FSEOF) implemented in python, 35 and 25 over‐expression targets for increasing the production of chaxamycin A and chaxalactin A, respectively, that were not directly associated with their biosynthesis routes were identified. Nineteen over‐expression targets that were common to the two specialized metabolites studied, like the over‐expression of the acetyl carboxylase complex (sle47660 (accA) and any of the following genes: sle44630 (accA_1) or sle39830 (accA_2) or sle27560 (bccA) or sle59710) were identified. The predicted knockouts and over‐expression targets will be used to perform metabolic engineering of S. leeuwenhoekii C34 and obtain overproducer strains.
Truncation of the processive Cel5A of Thermotoga maritima results in soluble expression and several fold increase in activity
Authors: Basit Abdul , Akhtar Muhammad W.
Published: March 2018

Cel5A of Thermotoga maritima, a 37 kDa cellulase of the family GH5, was expressed in partially soluble state in E. coli. However, the truncated version tCel5A1, produced by removing ten residues from the C‐terminal of Cel5A, was expressed in a completely soluble form. tCel5A1 showed 7.3‐ fold increased specific activity against carboxy methyl cellulose while the increase in activities against regenerated amorphous cellulose and Avicel were 21 and 16 fold, respectively. tCel5A1 is stable at 60 °C for more than 2 hr and it showed temperature and pH optima 70 °C and 6.0, respectively, under the assay conditions used. These characteristics are similar to those of the native enzyme. As expected, CD spectral analysis showed that C‐terminal truncation has little effect on the secondary structure of the molecule. tCel5A1 showed higher binding to pretreated rice straw (84%) as compared to the native form (46%). Molecular modelling analysis of tCel5A1 showed that the removal of C‐terminal residues exposed the active site residues Glu253, Trp286, and Phe292, which are located in the catalytic cavity close to the C‐terminus. Making these residues more accessible to the substrate would result in increased activity. The ratio of 10.01 between the soluble to the insoluble reducing groups produced from RAC on treatment with tCel5A1, and the presence of cellobiose as the major end product in the hydrolysate showed that tCel5A1 is a processive cellulase. Although other processive cellulases belonging to the family GH5, mainly of the fungal origin, have been reported, but tCel5A1, to our knowledge, is the first processive cellulase from an extreme thermophile reported so far.
Anatomical study of the articular branches innervated the hip and knee joint with reference to mechanism of referral pain in hip joint disease patients
Authors: Sakamoto Junya , Manabe Yoshitaka , Oyamada Joichi , Kataoka Hideki , Nakano Jiro , Saiki Kazunobu , Okamoto Keishi , Tsurumoto Toshiyuki , Okita Minoru
Published: March 2018

Introduction: Referred pain in the anterior knee joint is the most common symptom in hip disease patients. The development of referred pain is considered to be related to dichotomizing peripheral sensory fibers. However, no gross anatomical findings identify any dichotomizing fibers innervating both the hip and knee joints. We dissected the femoral and obturator nerves in human cadavers to investigate the distribution of the articular branches in the hip and knee joints. Fourteen embalmed left lower limbs from 14 Japanese adult cadavers (five from females, nine from males, average age 73.8 ± 14.1 years) were observed macroscopically. The articular branches of the femoral and obturator nerves were dissected at the anterior margin of the groin toward the thigh region. After dissections of the articular nerves of the hip joints, the femoral and obturator nerves were exposed from proximally to distally to identify the articular nerves of the knee joints. The branching pattern of the articular branches in the hip and knee joints was recorded. In six of 14 limbs (42.9%), the femoral nerve supplied articular branches to the anteromedial aspect of both the hip and knee joints. These articular branches were derived from the same bundle of femoral nerve. These gross anatomical findings suggested that dichotomizing peripheral sensory fibers innervate the hip and knee joints and these could relate to the referred pain confirmed in the anterior knee joints of patients with hip disease. Clin. Anat. 31:705–709, 2018. © 2018 Wiley Periodicals, Inc.
Internal and external morphology of mandibular molars: An original micro‐CT study and meta‐analysis with review of implications for endodontic therapy
Authors: Tomaszewska Iwona M. , Skinningsrud Bendik , Jarzębska Anna , Pękala Jakub R. , Tarasiuk Jacek , Iwanaga Joe
Published: March 2018

The aim of this radiological micro‐CT study and meta‐analysis was to determine the morphological features of the root canal anatomy of the mandibular molars. The radiological study included micro‐CT scans of 108 mandibular first, 120 mandibular second, and 146 mandibular third molars. For our meta‐analysis, an extensive search was conducted through PubMed, Embase, and Web of Science to identify articles eligible for inclusion. Data extracted included investigative method (cadaveric, intraoperative, or imaging), Vertucci type of canal configuration, presence/number of canals, roots, apical foramina, apical deltas, and intercanal communications. In the mesial roots of mandibular molars, the most frequent Vertucci type of canal configuration was type IV, except for the mandibular third molar where type I was most common. Type I was most common in the distal root. There were usually two canals in the mesial root and one in the distal root. Two was the most common number of roots, and a third root was most prevalent in Asia. One apical foramen was most common in the distal root and two apical foramina in the mesial root. Intercanal communications were most frequent in the mesial root. Knowledge of the complex anatomy of the mandibular molars can make root canal therapy more likely to succeed. We recommend the use of cone‐beam computed tomography before and after endodontic treatment to enable the root anatomy to be accurately described and properly diagnosed, and treatment outcome to be assessed. Clin. Anat. 31:797–811, 2018. © 2018 Wiley Periodicals, Inc.
Impact of pediatric cancer on family relationships
Authors: Erker Craig , Yan Ke , Zhang Liyun , Bingen Kristin , Flynn Kathryn E. , Panepinto Julie
Published: March 2018

Little is known about the impact of cancer on family relationships from the perspective of the pediatric cancer patient and their sibling(s). This study assessed and compared children's experiences of family relationships in patients receiving active cancer therapy, those who have completed therapy, and siblings. A cross‐sectional study of children with cancer and their siblings aged 8–17 years old was conducted. Children completed the PROMIS Pediatric Family Relationships short form and the Depressive Symptoms, Anxiety, and Peer Relationships short forms. The Mann–Whitney test assessed differences in Family Relationships scores between therapy groups, while the Wilcoxon signed‐rank test assessed differences between patients and siblings. An actor–partner interdependence model (APIM) was used to assess how patient and sibling variables were associated with their own and each others’ family relationships. Two hundred and sixty‐five children completed the assessments. Siblings of patients on‐therapy had worse family relationships than patients on‐therapy (P = 0.015). Family relationships of patients off‐therapy did not differ from their siblings or the patients on‐therapy. Family relationships scores did not differ between the sibling cohorts. The APIM found patient family relationships were impaired when their own peer relationships decreased and when either their own or their siblings had increased depressive symptoms. Sibling family relationships were impaired when their own depression increased, and when the patient counterpart was female, younger age, had less depressive symptoms, more anxiety or a diagnosis of leukemia/lymphoma (compared to solid tumor). Based on these findings, increased psychosocial resources for patients and siblings of children undergoing cancer therapy may be warranted.
Prostate‐specific antigen nadir within 12 months as an early surrogate marker of biochemical failure and distant metastasis after low‐dose‐rate brachytherapy or external beam radiotherapy for localized prostate cancer
Authors: Nishimura Shuichi , Ohashi Toshio , Momma Tetsuo , Sakayori Masanori , Eriguchi Takahisa , Tanaka Tomoki , Yamashita Shoji , Kosaka Takeo , Oya Mototsugu , Shigematsu Naoyuki
Published: March 2018

Prostate‐specific antigen nadir (nPSA) after radiotherapy for localized prostate cancer has been investigated as a predictor. However, nPSA usually requires several years, limiting its clinical utility. We investigated the significance of nPSA within 12 months (nPSA12) after low‐dose‐rate prostate brachytherapy (LDR‐PB) or external beam radiotherapy (EBRT) on treatment outcomes. Between 2006 and 2014, 663 patients with prostate cancer were treated with LDR‐PB or EBRT at two institutions. Four hundred and seventy‐four men received LDR‐PB and 189 men received EBRT, without androgen deprivation therapy. The Kaplan–Meier method was used for biochemical failure (BF)‐free survival (BFFS) and distant metastasis (DM)‐free survival (DMFS) analyses, and multivariable Cox regression analysis was performed. The median follow‐up was 61.3 months. The median nPSA12 in the LDR‐PB and EBRT cohorts was 0.7 and 1.0 ng/mL, respectively. The 7‐year BFFS and DMFS rates in LDR‐PB patients with nPSA12 ≤ 0.7 ng/mL were 99.1% and 99.5%, respectively; when nPSA12 was >0.7 ng/mL, they were 90.2% and 94.8%, respectively. In EBRT patients with nPSA12 ≤ 1.0 ng/mL, BFFS and DMFS rates were 85.4% and 98.5%, respectively; when nPSA12 was >1.0 ng/mL, they were 67.1% and 87.2%, respectively. nPSA12 was an independent predictor of BF and DM in both cohorts (LDR‐PB, P = 0.004 and 0.020, respectively; EBRT, P = 0.005 and 0.041, respectively). The nPSA12 after LDR‐PB or EBRT is significantly associated with treatment outcomes of prostate cancer. Higher nPSA12 may identify patients at high risk of relapse who might benefit from salvage treatment.
A novel monoclonal antibody KMP1 has potential antitumor activity of bladder cancer by blocking CD44 in vivo and in vitro
Authors: Chen Yujin , Wang Haifeng , Zuo Yigang , Li Ning , Ding Mingxia , Li Chong
Published: March 2018

Bladder cancer becomes a serious medical and social concern due to its high recurrence and mortality rates. Thus, it is urgent to search a novel prognostic biomarker and targeted therapy with high sensitivity and specificity. In this study, we used the human bladder cancer cell line EJ as an immunogen to generate a novel mouse monoclonal antibody KMP1 that specifically bound to bladder cancer, and then, the antitumor effect of KMP1 against bladder cancer was investigated both in vivo and in vitro. The results showed that expression of the KMP1 epitope is consistent with clinical severity and prognosis of bladder cancer. Furthermore, KMP1 not only significantly inhibited the proliferation, migration, and adhesion of EJ cells in vivo, but also suppressed the xenograft tumor growth in nude mice compared with the control group treated with mIgG. Subsequently, the underlying mechanism of KMP1 against bladder cancer was explored via antigen affinity chromatography and mass spectrometry. CD44 located on the cytomembrane was found as the antigen of KMP1. Using RNA interference technology to knock down CD44 expression, we further identified that KMP1 has the antitumor activity by binding to CD44 and blocking its functions. In conclusion, KMP1 might be valuable for development as a promising specific diagnostic biomarker or targeted agent for bladder cancer.
A phase 4 study of nilotinib in Korean patients with Philadelphia chromosome‐positive chronic myeloid leukemia in chronic phase: ENESTKorea
Authors: Shin Junghoon , Koh Youngil , Yoon Seo Hyun , Cho Joo‐Youn , Kim Dae‐Young , Lee Kyoo‐Hyung , Kim Hyeong‐Joon , Ahn Jae‐Sook , Kim Yeo‐Kyeoung , Park Jinny , Sohn Sang‐Kyun , Moon Joon Ho , Lee Yoo Jin , Yoon Seonghae , Lee Jeong‐Ok , Cheong June‐Won , Kim Kyoung Ha , Kim Sung‐Hyun , Kim Hoon‐Gu , Kim Hawk , Nam Seung‐Hyun , Do Young Rok , Park Sang‐Gon , Park Seong Kyu , Bae Sung Hwa , Song Hun Ho , Shin Dong‐Yeop , Oh Doyeun , Kim Min Kyoung , Jung Chul Won , Park Seonyang , Kim Inho
Published: March 2018

Although nilotinib has improved efficacy compared to imatinib, suboptimal response and intolerable adverse events (AEs) limit its effectiveness in many patients with chronic myeloid leukemia in chronic phase (CML‐CP). We investigated the 2‐year efficacy and safety of nilotinib and their relationships with plasma nilotinib concentrations (PNCs). In this open‐label, multi‐institutional phase 4 study, 110 Philadelphia chromosome‐positive CML‐CP patients were treated with nilotinib at a starting dose of 300 mg twice daily. Molecular responses (MRs) and AEs were monitored for up to 24 months. The 24‐month cumulative MR4.5 rate was evaluated as the primary endpoint. Plasma samples were collected from 94 patients to determine PNCs, and the per‐patient mean was used to categorize them into four mean PNC (MPNC) groups. Cumulative MR rates and safety were compared between groups. With a median follow‐up of 22.2 months, the 24‐month cumulative MR4.5 rate was 56.2% (95% confidence interval, 44.0%–8.3%), and the median time to MR4.5 was 23.3 months. There were no significant differences in the cumulative rates of major molecular response, MR4, and MR4.5 between MPNC groups. One patient died due to acute viral hepatitis, and two developed hematological or cytogenetic relapse, while no progression to accelerated or blast phase was observed. Safety results were consistent with previous studies with no new safety signal identified. Across the MPNC groups, there was no significant linear trend in the frequency of AEs. Nilotinib is highly effective for the treatment of CML‐CP with manageable AEs. The measurement of PNC has no predictive value for patient outcomes and is thus not found to be clinically useful. This study is registered with clinicaltrials.gov, Number NCT03332511.
Induction of Signal Transduction by Using Non‐Channelrhodopsin‐Type Optogenetic Tools
Authors: Ueda Yoshibumi , Sato Moritoshi
Published: March 2018

Signal transductions are the basis for all cellular functions. Previous studies investigating signal transductions mainly relied on pharmacological inhibition, RNA interference, and constitutive active/dominant negative protein expression systems. However, such studies do not allow the modulation of protein activity with high spatial and temporal precision in cells, tissues, and organs in animals. Recently, non‐channelrhodopsin‐type optogenetic tools for regulating signal transduction have emerged. These photoswitches address several disadvantages of previous techniques, and allow us to control a variety of signal transductions such as cell membrane dynamics, calcium signaling, lipid signaling, and apoptosis. In this review we summarize recent advances in the development of such photoswitches and in how these optotools are applied to signaling processes.
Post‐cationic Modification of a Pyrimidine‐Based Conjugated Microporous Polymer for Enhancing the Removal Performance of Anionic Dyes in Water
Authors: Liu Yuchuan , Cui Yuanzheng , Zhang Chenghui , Du Jianfeng , Wang Shun , Bai Yang , Liang Zhiqiang , Song Xiaowei
Published: March 2018

Ionic porous organic polymers have attracted much attention due to their broad applications in catalysis, energy storage/conversion, proton conduction, etc. In this paper, an ionic porous organic polymer, CMP‐PM‐Me, was synthesized through post‐synthetic modification of a pyrimidine‐based conjugated microporous polymer, CMP‐PM, which was constructed by the palladium catalyzed Sonogashira reaction of 1,3,5‐triethynylbenzen and 2,5‐dibromopyrimidine. These two polymers are porous with Brunauer–Emmett–Teller surface areas of 416 and 241 m2 g−1 for CMP‐PM and CMP‐PM‐Me, respectively. Due to the cationic framework, CMP‐PM‐Me exhibits a much faster and more efficient adsorption performance to anionic dyes such as Congo red (CR) and methyl orange (MO) than that of CMP‐PM with a neutral framework. The uptakes for CR are 400.0 mg g−1 for CMP‐PM‐Me and 344.8 mg g−1 for CMP‐PM, respectively. Furthermore, CMP‐PM‐Me could quickly and drastically separate anionic dyes from the binary mixed solution of anionic and nonanionic dyes within a short time. This work not only enriches the family of ionic organic porous polymers and widens their synthetic utility, but also demonstrates their applications in the adsorption and separation of anionic dyes in water.
A Free Silanide from Nucleophilic Substitution at Silicon(II)
Authors: Witteman Léon , Evers Tim , Lutz Martin , Moret Marc‐Etienne
Published: March 2018

A computationally guided synthetic route to a free silanide derived from tris(3‐methylindol‐2‐yl)methane ([(tmim)Si]−) through nucleophilic substitution on the SiII precursor (Idipp)SiCl2 is reported (Idipp=2,3‐dihydro‐1,3‐bis(2,6‐diisopropylphenyl)‐1H‐imidazol‐2‐ylidene). This approach circumvents the need for strained tetrahedral silanes as synthetic intermediates. Computational investigations show that the electron‐donating properties of [(tmim)Si]− are close to those of PMe3. Experimentally, the [(tmim)Si]− anion is shown to undergo clean complexation to the base metal salts CuCl and FeCl2, demonstrating the potential utility as a supporting ligand.
An Isoindigo‐Based “Double‐Cable” Conjugated Polymer for Single‐ Component Polymer Solar Cells
Authors: Yu Changshi , Xu Yunhua , Li Cheng , Feng Guitao , Yang Fan , Li Junyu , Li Weiwei
Published: March 2018

An isoindigo‐based “double‐cable” conjugated polymer bearing perylene bisimide side units was developed via Stille polymerization for application in single‐component polymer solar cells, in which a power conversion efficiency of 1% with broad photo‐response from 300 nm to 800 nm was achieved. There is no evidence of large phase separation confirmed by AFM images and photoluminescence (PL) spectra. The space charge limit current measurements and light intensity dependence measurements indicate that the low electron mobility and the significant recombination of photogenerated charge carriers in active layer mainly account for the low performance of our solar cells. Our results suggest that these “double‐cable” are promising candidates for use in single‐component polymer solar cells with NIR photoresponse.
„The paradox of ion radii“ – experimental establishing of (hydrated) ion radii of different cations observed by the intercalation into Prussian Blue
Authors: Wagner Corina , Blank Martin , Oetken Marco
Published: March 2018

Die oktaedrische Berliner Blau‐Struktur eignet sich gut zur Einlagerung von monovalenten Kationen aus wässrigen Lösungen. Aufgrund der Größe der Oktaederlücken können jedoch nur bestimmte Ionen mit Hydrathülle eingelagert werden. Die Größe der Ionenradien mit Hydrathülle der I. Hauptgruppe können durch das unterschiedliche Einlagerungsverhalten und das gleichzeitige Umfärben von blau zu transparent mit dem elektrochromen Material Berliner Blau eindrucksvoll für die Schule veranschaulicht werden.
Rationale and design of the FELICITAR registry (Frailty Evaluation After List Inclusion, Characteristics and Influence on Transplantation and Results)
Authors: Ayesta Ana , Astiz María Teresa Vidán , Masa María Jesús Valero , Segovia Javier , Cosío María Dolores García , Martínez‐Sellés Manuel
Published: March 2018

Frailty reflects a state of decreased physiological reserve and vulnerability to stressors. Its prevalence among patients with cardiovascular disease is as high as 60%. Frailty is associated with a poor prognosis for patients with heart failure, increasingly frequent hospitalization, and death. The recent published listing criteria for heart transplantation of the International Society for Heart and Lung Transplantation recommend assessing frailty (class IIb recommendation, level of evidence C). However, this recommendation is not based on prospective studies, and frailty scores have only been validated in patients age > 65 years. The aim of the FELICITAR registry (Frailty Evaluation After List Inclusion, Characteristics and Influence on Transplantation and Results) is to assess the impact of frailty on prognosis before and after heart transplantation. A series of 100 patients from 3 Spanish centers will be included as soon as they are added to the national heart transplantation waiting list. Frailty will be evaluated again every 3 months until heart transplantation and at 3, 6, and 12 months thereafter. Depression, cognitive assessment, and quality of life also will be analyzed. The 2 primary endpoints are all‐cause mortality and prevalence of frailty assessed using the Fried frailty index. Results from this study may show that frailty is frequent in patients with advanced heart failure listed for heart transplantation and is associated with a poor prognosis both before and after surgery. The findings may contribute to a better understanding of the characteristics of the optimal candidate for heart transplantation.
Capture of tobacco use among population‐based registries: Findings from 10 National Program of Cancer Registries states
Authors: Siegel David A. , Henley S. Jane , Wike Jennifer M. , Ryerson A. Blythe , Johnson Christopher J. , Rees Judy R. , Pollack Lori A. ,   the Enhancement of NPCR for Comparative Effectiveness Research Team
Published: March 2018

BACKGROUND

Tobacco use data are important when the epidemiology and prognosis of tobacco‐associated cancers are being defined. Central cancer registries in 10 National Program of Cancer Registries states pilot‐tested the collection of standardized tobacco use variables. This study evaluated the capture of tobacco use data and examined smoking prevalence among cancer patients.

METHODS

Participating registries collected data about the use of tobacco—cigarettes, other smoked tobacco, and smokeless tobacco—for cases diagnosed during 2011‐2013. The percentage of cases with known tobacco variable values was calculated, and the prevalence of tobacco use was analyzed by the primary cancer site and state.

RESULTS

Among 1,646,505 incident cancer cases, 51% had known cigarette use data: 18% were current users, 31% were former users, and 51% reported never using. The percentage of cases with a known status for both other smoked tobacco and smokeless tobacco was 43%, with 97% and 98% coded as never users, respectively. The percent known for cigarette use ranged from 27% to 81% by state and improved from 47% in 2011 to 59% in 2013 for all 10 states combined. The percent known for cigarette use and the prevalence of ever smoking cigarettes were highest for laryngeal cancer and tracheal, lung, and bronchus cancer.

CONCLUSIONS

Cancer registrars ascertained cigarette use for slightly more than half of all new cancer cases, but other tobacco‐related fields were less complete. Studies to evaluate the validity of specific tobacco‐related variables and the ability of cancer registries to capture this information from the medical record are needed to gauge the usefulness of collecting these variables through cancer surveillance systems. Cancer 2018;124:2381‐9. © 2018 American Cancer Society.
Erlotinib in the treatment of recurrent or metastatic cutaneous squamous cell carcinoma: A single‐arm phase 2 clinical trial
Authors: Gold Kathryn A. , Kies Merrill S. , William William N. , Johnson Faye M. , Lee J. Jack , Glisson Bonnie S.
Published: March 2018

BACKGROUND

Cutaneous squamous cell carcinoma (CSCC) is a very common malignancy in which most patients present with localized disease. Recurrent and metastatic disease is rare, and there is no standard therapy. These tumors frequently overexpress the epidermal growth factor receptor (EGFR). We conducted a phase 2 trial to determine the response rate to therapy with erlotinib, an EGFR tyrosine kinase inhibitor, in patients with locoregionally recurrent or metastatic CSCC that was not amenable to curative treatment (NCT01198028).

METHODS

Eligible patients had CSCC not amenable to curative intent therapy. Patients who had previously received anti‐EGFR targeted therapy were excluded. All patients received oral therapy with erlotinib 150 mg daily. Response was assessed every 8 weeks, and treatment continued until progression, unacceptable toxicity, or withdrawal of consent. The primary endpoint was overall response rate according to RECIST 1.1 criteria.

RESULTS

A total of 39 patients received treatment during the trial; 29 of these patients were evaluable for response. The overall response rate was 10% (3/29); all responses were partial responses. The disease control rate (partial response + stable disease) was 72% (21/29). The median progression‐free survival was 4.7 months (95% confidence interval, 3.5‐6.2 months); the median overall survival was 13 months (95% confidence interval, 8.4‐20.5 months). No unexpected toxicities were seen.

CONCLUSION

Erlotinib therapy was feasible for most patients with incurable CSCC and was associated with expected toxicities. However, only a modest response rate of 10% was observed. Further study of EGFR tyrosine kinase inhibitors in this patient population is not warranted. Cancer 2018;124:2169‐73. © 2018 American Cancer Society.
Cytologic‐histologic correlation: Where are we now, and where are we going?
Authors: Crothers Barbara A.
Published: March 2018

The author was the chair of a College of American Pathologists working group at the Gynecologic Cytopathology Quality Consensus Conference outlining then current practices in cytology‐histology correlation, and published this work in the Archives of Pathology and Laboratory Medicine. Cancer Cytopathol 2018;126:301‐8. Published 2018. This article is a U.S. Government work and is in the public domain in the USA.
Pharmacokinetics, Safety, and Tolerability of Lamotrigine Chewable/Dispersible Tablet Following Repeat‐Dose Administration in Healthy Chinese Volunteers
Authors: Li Yan , Zhang Fan , Xu Yanmei , Hu Joice , Li Huafang
Published: March 2018

In this open‐label, single‐center study, the pharmacokinetics, safety, and tolerability of lamotrigine chewable/dispersible tablets were assessed in healthy Chinese volunteers. Each volunteer (N = 16) received repeat doses of oral lamotrigine titrated from 25 mg to 50 mg to 100 mg over 42 days and was followed up for 10‐17 days. Safety and tolerability were assessed throughout the study. Lamotrigine pharmacokinetic parameters were estimated using noncompartmental analysis. Overall, 15 (94%) volunteers completed the study. Lamotrigine serum concentrations peaked 2.5 hours postdose, with a mean terminal half‐life of 36.8 hours. The apparent lamotrigine oral clearance was 1577.88 mL/h. The accumulation ratios (day 14 vs day 1) were 2.53 and 2.58 for area under the curve and peak concentration, respectively. Lamotrigine 25 to 100 mg once daily exhibited dose‐proportional pharmacokinetics (based on area under the curve and peak concentration), following repeat dosing. Nine volunteers reported adverse events, 2 experienced oropharyngeal pain, each receiving 25 mg and 50 mg. One volunteer withdrew due to an increase in liver enzymes. No deaths, serious adverse effects, or skin rashes were reported during the study. No new safety concerns were observed. Overall, the pharmacokinetic profiles after repeat doses of lamotrigine chewable/dispersible tablets once daily in a Chinese population were similar to those observed in Western populations.