bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fine tuning breath‐hold‐based cerebrovascular reactivity analysis models
Authors: van Niftrik Christiaan Hendrik Bas , Piccirelli Marco , Bozinov Oliver , Pangalu Athina , Valavanis Antonios , Regli Luca , Fierstra Jorn 
Published: January 2016

AbstractIntroductionWe elaborate on existing analysis methods for breath‐hold (BH)‐derived cerebrovascular reactivity (CVR) measurements and describe novel insights and models toward more exact CVR interpretation.MethodsFive blood‐oxygen‐level‐dependent (BOLD) fMRI datasets of neurovascular patients with unilateral hemispheric hemodynamic impairment were used to test various BH CVR analysis methods. Temporal lag (phase), percent BOLD signal change (CVR), and explained variance (coherence) maps were calculated using three different sine models and two novel “Optimal Signal” model‐free methods based on the unaffected hemisphere and the sagittal sinus fMRI signal time series, respectively.ResultsAll models showed significant differences in CVR and coherence between the affected—hemodynamic impaired—and unaffected hemisphere. Voxel‐wise phase determination significantly increases CVR (0.60 ± 0.18 vs. 0.82 ± 0.27; P < 0.05). Incorporating different durations of breath hold and resting period in one sine model (two‐task) did increase coherence in the unaffected hemisphere, as well as eliminating negative phase commonly obtained by one‐task frequency models. The novel model‐free “optimal signal” methods both explained the BOLD MR data similar to the two task sine model.ConclusionsOur CVR analysis demonstrates an improved CVR and coherence after implementation of voxel‐wise phase and frequency adjustment. The novel “optimal signal” methods provide a robust and feasible alternative to the sine models, as both are model‐free and independent of compliance. Here, the sagittal sinus model may be advantageous, as it is independent of hemispheric CVR impairment.
Late rectal toxicity determined by dose–volume parameters in computed tomography‐based brachytherapy for locally advanced cervical cancer
Authors: Zhou Yong‐Chun , Zhao Li‐Na , Wang Ning , Hu Jing , Sun Xiao‐Huan , Zhang Ying , Li Jian‐Ping , Li Wei‐Wei , Liu Jun‐Yue , Wei Li‐Chun , Shi Mei 
Published: January 2016

AbstractThe aim of this study was to observe the relationship between dose–volume histogram (DVH) parameters and rectal late side effects (LSE) in computed tomography (CT)‐based brachytherapy (BT) for patients with locally advanced cervical cancer. In total, 144 cervical cancer patients received external beam radiotherapy and CT‐based BT. The data from 111 survival cases with pelvic local control (LC) were used to analyze the relationship between DVH parameters and rectal LSE. The total doses, manifesting 2, 1, and 0.1 cm3 (D2cc, D1cc, and D0.1cc) of the rectum, and D90 for high‐risk clinical target volume (HR CTV) were computed and normalized to 2 Gy fractions (EQD2) using a linear‐quadratic model. The rectal LSE were evaluated by the late effects in normal tissues‐subjective, objective, management, and analytic (LENT‐SOMA) scale. A dose–response relationship was evaluated by probit analyses. For all patients, the total rate of rectal LSE was 56%, and the rate of ≥Grade 2 LSE was 27.4%. For the 111 survival cases with pelvic LC, the total mean for D2cc was 71.23 ± 5.54 Gy for the rectum, and the D2cc, D1cc, and D0.1cc values for Grades 2 and 3 were higher than those for Grades 0 and 1. In addition, the number of complications increased, and the complications became more severe as the dose increased, with a dose of 73.5 Gy resulting in a 10% probability of ≥Grade 3 LSE. In conclusion, DVH parameters could predict the incidence and grades of rectal LSE in CT‐based BT. D2cc showed an excellent predictive value, and 73.5 Gy for D2cc of the rectum might be considered as an alternative dose limit.
Preliminary treatment results of proton beam therapy with chemoradiotherapy for stage I–III esophageal cancer
Authors: Takada Akinori , Nakamura Tatsuya , Takayama Kanako , Makita Chiyoko , Suzuki Motohisa , Azami Yusuke , Kato Takahiro , Tsukiyama Iwao , Hareyama Masato , Kikuchi Yasuhiro , Daimon Takashi , Toyomasu Yutaka , Ii Noriko , Nomoto Yoshihito , Sakuma Hajime , Fuwa Nobukazu 
Published: January 2016

AbstractThe effect of proton beam therapy (PBT) on various cancers is controversial. We aimed to evaluate the efficacy and safety of PBT with alternating chemoradiotherapy (ACRT) for patients with stage I–III esophageal cancer. Two cycles of systemic chemotherapy with a continuous infusion of 5‐fluorouracil (5‐FU) on days 1–5 and a 5h infusion of nedaplatin (NDP) on day 6 were accompanied by thoracic irradiation using X‐ray therapy and PBT. During the first half of the treatment, X‐rays were delivered to the prophylactic area. During the second half of the treatment, proton beams were used to irradiate the involved field. To reduce the dose of cardiac irradiation, proton beams were delivered with posterior and posterior oblique angles. Between January 2009 and December 2012, 47 patients were enrolled in this study. The median follow‐up duration was 29 months for all patients and 40 months for survivors. The 3 year overall survival rate, progression‐free survival rate, and local control rate were 59.2%, 56.3%, and 69.8%, respectively. With respect to grade 3–4 late toxicities, there were no pleural or pericardial effusions, but two patients (4.3%) had esophageal stenosis, one patient (2.1%) had fistula, and two patients (4.3%) developed radiation pneumonitis. PBT with ACRT might have the potential to reduce the risk of cardiac damage and might become one of the primary methods of esophageal cancer treatment.
PEPCOL: a GERCOR randomized phase II study of nanoliposomal irinotecan PEP02 (MM‐398) or irinotecan with leucovorin/5‐fluorouracil as second‐line therapy in metastatic colorectal cancer
Authors: Chibaudel Benoist , Maindrault‐Gœbel Frédérique , Bachet Jean‐Baptiste , Louvet Christophe , Khalil Ahmed , Dupuis Olivier , Hammel Pascal , Garcia Marie‐Line , Bennamoun Mostefa , Brusquant David , Tournigand Christophe , André Thierry , Arbaud Claire , Larsen Annette K , Wang Yi‐Wen , Yeh C. Grace , Bonnetain Franck , de Gramont Aimery 
Published: January 2016

AbstractA multicenter, open‐label, noncomparative, randomized phase II study (PEPCOL) was conducted to evaluate the efficacy and safety of the irinotecan or PEP02 (MM‐398, nanoliposomal irinotecan) with leucovorin (LV)/5‐fluorouracil (5‐FU) combination as second‐line treatment in patients with metastatic colorectal cancer (mCRC). Patients with unresectable mCRC who had failed one prior oxaliplatin‐based first‐line therapy were randomized toirinotecan with LV/5‐FU (FOLFIRI) or PEP02 with LV/5‐FU (FUPEP; PEP02 80 mg/m2 with LV 400 mg/m2 on day 1 and 5‐FU 2400 mg/m2 on days 1–2). Bevacizumab (5 mg/kg, biweekly) was allowed in both arms. The primary endpoint was 2‐month response rate (RR). Fifty‐five patients were randomized (FOLFIRI, n = 27; FUPEP, n = 28). In the intent‐to‐treat population (n = 55), 2‐month RR response rate was observed in two (7.4%) and three (10.7%) patients in the FOLFIRI and FUPEP arms, respectively. The most common grade 3–4 adverse events reported in the respective FOLFIRI and FUPEP arms were diarrhea (33% vs. 21%), neutropenia (30% vs. 11%), mucositis (11% vs. 11%), and grade 2 alopecia (26% vs. 25%). FUPEP has activity and acceptable safety profile in oxaliplatin‐pretreated mCRC patients.
Feedstock Characterization and Suitability Assessment for Dry Anaerobic Batch Digestion
Authors: Wedwitschka Harald , Jenson Earl , Liebetrau Jan 
Published: January 2016

AbstractSubstrate characterization experiments were carried out on different feedstocks and structure materials considered appropriate for use in dry anaerobic batch digestion systems. Physical material characteristics tested were bulk and saturated bulk density, compressed density, permeability, compactibility, water holding capacity, maximum water content, and volatile solid content. Oedometer tests were conducted on prepared feedstock/structure material mixtures targeting a high permeability under compression. Porous materials such as straw and woodchips were tested to determine if they enhance material mixture properties to yield superior permeability and allow percolation.
Back‐Illuminated Si‐Based Photoanode with Nickel Cobalt Oxide Catalytic Protection Layer
Authors: Bae Dowon , Mei Bastian , Frydendal Rasmus , Pedersen Thomas , Seger Brian , Hansen Ole , Vesborg Peter C. K. , Chorkendorff Ib 
Published: January 2016

AbstractSi is an excellent photo‐absorber for use in dual‐band‐gap photoelectrochemical water splitting. We investigate photoanodes with n+pp+‐Si configuration under back‐side illumination, which is suited to work in a tandem device stack. A co‐sputtered NiCoOx film coupled to the Si was used as a protective catalyst for the water oxidation reaction in 1 m KOH. The sample showed a high photocurrent (21 mA cm−2) under red‐light illumination (38.6 mW cm−2). Long‐term stability testing showed a gradual decrease of activity in the beginning, and then the activity increased, yielding a cathodic shift of the onset voltage (>50 mV), likely owing to the divergent response of Ni and Co to the Fe present in KOH. Once the activity of the sample stabilized, no further degradation was observed for the following 6 days, indicating that the demonstrated back‐illuminated photoanode configuration can be considered a promising architecture for use as a bottom cell of the tandem water‐splitting device under alkaline conditions.
Emergence of the First Catalytic Oligonucleotides in a Formamide‐Based Origin Scenario
Authors: Šponer Judit E. , Šponer Jiří , Nováková Olga , Brabec Viktor , Šedo Ondrej , Zdráhal Zbyněk , Costanzo Giovanna , Pino Samanta , Saladino Raffaele , Di Mauro Ernesto 
Published: January 2016

Abstract50 years after the historical Miller–Urey experiment, the formamide‐based scenario is perhaps the most powerful concurrent hypothesis for the origin of life on our planet besides the traditional HCN‐based concept. The information accumulated during the last 15 years in this topic is astonishingly growing and nowadays the formamide‐based model represents one of the most complete and coherent pathways leading from simple prebiotic precursors up to the first catalytically active RNA molecules. In this work, we overview the major events of this long pathway that have emerged from recent experimental and theoretical studies, mainly concentrating on the mechanistic, methodological, and structural aspects of this research.
Tuning the Electronic Coupling and Electron Transfer in Mo2 Donor–Acceptor Systems by Variation of the Bridge Conformation
Authors: Kang Mei Ting , Meng Miao , Tan Ying Ning , Cheng Tao , Liu Chun Y. 
Published: January 2016

AbstractAssembling two quadruply bonded dimolybdenum units [Mo2(DAniF)3]+ (DAniF=N,N′‐di(p‐anisyl)formamidinate) with 1,4‐naphthalenedicarboxylate and its thiolated derivatives produced three complexes [{Mo2(DAniF)3}2(μ‐1,4‐O2CC10H6CO2)], [{Mo2(DAniF)3}2(μ‐1,4‐OSCC10H6COS)], and [{Mo2(DAniF)3}2(μ‐1,4‐S2CC10H6CS2)]. In the X‐ray structures, the naphthalene bridge deviates from the plane defined by the two Mo−Mo bond vectors with the torsion angle increasing as the chelating atoms of the bridging ligand vary from O to S. The mixed‐valent species exhibit intervalence transition absorption bands with high energy and very low intensity. In comparison with the data for the phenylene analogues, the optically determined electronic coupling matrix elements (Hab=258–345 cm−1) are lowered by a factor of two or more, and the electron‐transfer rate constants (ket≈1011 s−1) are reduced by about one order of magnitude. These results show that, when the electron‐transporting ability of the bridge and electron‐donating (electron‐accepting) ability of the donor (acceptor) are both variable, the former plays a dominant role in controlling the intramolecular electron transfer. DFT calculations revealed that increasing the torsion angle enlarges the HOMO–LUMO energy gap by elevating the (bridging) ligand‐based LUMO energy. Therefore, our experimental results and theoretical analyses verify the superexchange mechanism for electronic coupling and electron transfer.
Templated Formation of Discrete RNA and DNA:RNA Hybrid G‐Quadruplexes and Their Interactions with Targeting Ligands
Authors: Bonnat Laureen , Dejeu Jérôme , Bonnet Hugues , Génnaro Béatrice , Jarjayes Olivier , Thomas Fabrice , Lavergne Thomas , Defrancq Eric 
Published: January 2016

AbstractG‐rich RNA and DNA oligonucleotides derived from the human telomeric sequence were assembled onto addressable cyclopeptide platforms through oxime ligations and copper‐catalyzed azide‐alkyne cycloaddition (CuAAc) reactions. The resulting conjugates were able to fold into highly stable RNA and DNA:RNA hybrid G‐quadruplex (G4) architectures as demonstrated by UV, circular dichroism (CD), and NMR spectroscopic analysis. Whereas rationally designed parallel RNA and DNA:RNA hybrid G4 topologies could be obtained, we could not force the formation of an antiparallel RNA G4 structure, thus supporting the idea that this topology is strongly disfavored. The binding affinities of four representative G4 ligands toward the discrete RNA and DNA:RNA hybrid G4 topologies were compared to the one obtained with the corresponding DNA G4 structure. Surface plasmon resonance (SPR) binding analysis suggests that the accessibility to G4 recognition elements is different among the three structures and supports the idea that G4 ligands might be shaped to achieve structure selectivity in a biological context.
Flow Synthesis in Hot Water: Synthesis of the Atypical Antipsychotic Iloperidone
Authors: Hartwig Jan , Kirschning Andreas 
Published: January 2016

AbstractInductively heated steel reactors continuously perform organic transformations in water under high temperature conditions, utilizing the unique physiochemical properties of water at subcritical conditions. We demonstrated the power of this set‐up in the continuous synthesis of the atypical antipsychotic drug iloperidone, in which we performed four out of five steps under aqueous conditions.
Mechanochemical Encapsulation of Fullerenes in Peptidic Containers Prepared by Dynamic Chiral Self‐Sorting and Self‐Assembly
Authors: Szymański Marek , Wierzbicki Michał , Gilski Mirosław , Jędrzejewska Hanna , Sztylko Marcin , Cmoch Piotr , Shkurenko Aleksander , Jaskólski Mariusz , Szumna Agnieszka 
Published: January 2016

AbstractMolecular capsules composed of amino acid or peptide derivatives connected to resorcin[4]arene scaffolds through acylhydrazone linkers have been synthesized using dynamic covalent chemistry (DCC) and hydrogen‐bond‐based self‐assembly. The dynamic character of the linkers and the preference of the peptides towards self‐assembly into β‐barrel‐type motifs lead to the spontaneous amplification of formation of homochiral capsules from mixtures of different substrates. The capsules have cavities of around 800 Å3 and exhibit good kinetic stability. Although they retain their dynamic character, which allows processes such as chiral self‐sorting and chiral self‐assembly to operate with high fidelity, guest complexation is hindered in solution. However, the quantitative complexation of even very large guests, such as fullerene C60 or C70, is possible through the utilization of reversible covalent bonds or the application of mechanochemical methods. The NMR spectra show the influence of the chiral environment on the symmetry of the fullerene molecules, which results in the differentiation of diastereotopic carbon atoms for C70, and the X‐ray structures provide unique information on the modes of peptide–fullerene interactions.
Cobalt(III)‐Mediated Permanent and Stable Immobilization of Histidine‐Tagged Proteins on NTA‐Functionalized Surfaces
Authors: Wegner Seraphine V. , Schenk Franziska C. , Spatz Joachim P. 
Published: January 2016

AbstractWe present the cobalt(III)‐mediated interaction between polyhistidine (His)‐tagged proteins and nitrilotriacetic acid (NTA)‐modified surfaces as a general approach for a permanent, oriented, and specific protein immobilization. In this approach, we first form the well‐established Co2+‐mediated interaction between NTA and His‐tagged proteins and subsequently oxidize the Co2+ center in the complex to Co3+. Unlike conventionally used Ni2+‐ or Co2+‐mediated immobilization, the resulting Co3+‐mediated immobilization is resistant toward strong ligands, such as imidazole and ethylenediaminetetraacetic acid (EDTA), and washing off over time because of the high thermodynamic and kinetic stability of the Co3+ complex. This immobilization method is compatible with a wide variety of surface coatings, including silane self‐assembled monolayers (SAMs) on glass, thiol SAMs on gold surfaces, and supported lipid bilayers. Furthermore, once the cobalt center has been oxidized, it becomes inert toward reducing agents, specific and unspecific interactions, so that it can be used to orthogonally functionalize surfaces with multiple proteins. Overall, the large number of available His‐tagged proteins and materials with NTA groups make the Co3+‐mediated interaction an attractive and widely applicable platform for protein immobilization.
Biomass‐Derived Porous Carbon with Micropores and Small Mesopores for High‐Performance Lithium–Sulfur Batteries
Authors: Yang Kai , Gao Qiuming , Tan Yanli , Tian Weiqian , Qian Weiwei , Zhu Lihua , Yang Chunxiao 
Published: January 2016

AbstractBiomass‐derived porous carbon BPC‐700, incorporating micropores and small mesopores, was prepared through pyrolysis of banana peel followed by activation with KOH. A high specific BET surface area (2741 m2 g−1), large specific pore volume (1.23 cm3 g−1), and well‐controlled pore size distribution (0.6–5.0 nm) were obtained and up to 65 wt % sulfur content could be loaded into the pores of the BPC‐700 sample. When the resultant C/S composite, BPC‐700‐S65, was used as the cathode of a Li–S battery, a large initial discharge capacity (ca. 1200 mAh g−1) was obtained, indicating a good sulfur utilization rate. An excellent discharge capacity (590 mAh g−1) was also achieved for BPC‐700‐S65 at the high current rate of 4 C (12.72 mA cm−2), showing its extremely high rate capability. A reversible capacity of about 570 mAh g−1 was achieved for BPC‐700‐S65 after 500 cycles at 1 C (3.18 mA cm−2), indicating an outstanding cycling stability.
A Simple and Non‐Destructive Method for Assessing the Incorporation of Bipyridine Dicarboxylates as Linkers within Metal–Organic Frameworks
Authors: Hendon Christopher H. , Bonnefoy Jonathan , Quadrelli Elsje Alessandra , Canivet Jerome , Chambers Matthew B. , Rousse Gwenaelle , Walsh Aron , Fontecave Marc , Mellot‐Draznieks Caroline 
Published: January 2016

AbstractAs a novel avenue for applications, metal–organic frameworks (MOFs) are increasingly used for heterogenizing catalytic molecular species as linkers into their crystalline framework. These multifunctional compounds can be accessed with mixed linkers synthesis or postsynthetic‐exchange strategies. Major limitations still reside in their challenging characterization; in particular, to provide evidence of the genuine incorporation of the functionalized linkers into the framework and their quantification. Herein, we demonstrate that a combination of computational chemistry, spectroscopy and X‐ray diffraction allows access to a non‐destructive analysis of mixed‐linker UiO‐67‐type materials featuring biphenyl‐ and bipyridine‐dicarboxylates. Our UV/Vis‐based methodology has been further applied to characterize a series of Rh‐functionalized UiO‐67‐type catalysts. The proposed approach allows a recurrent key issue in the characterization of similar supported organometallic systems to be solved.
Fluorescence imaging to localize head and neck squamous cell carcinoma for enhanced pathological assessment
Authors: Warram Jason M , de Boer Esther , van Dam Gooitzen M , Moore Lindsay S , Bevans Stephanie L , Walsh Erika M , Young Erik S , Carroll William R , Stevens Todd M , Rosenthal Eben L 
Published: January 2016

AbstractAccurately identifying close or positive margins in real‐time permits re‐excision during surgical procedures. Intraoperative assessment of margins via gross examination and frozen section is a widely used tool to assist the surgeon in achieving complete resection. While this methodology permits diagnosis of freshly resected tissue, the process is fraught with misinterpretation and sampling errors. During fluorescence‐guided surgery, an exogenous fluorescent agent specific for the target disease is imaged in order to navigate the surgical excision. As this technique quickly advances into the clinic, we hypothesize that the disease‐specific fluorescence inherently contained within the resected tissues can be used to guide histopathological assessment. To evaluate the feasibility of fluorescence‐guided pathology, we evaluated head and neck squamous cell carcinoma tumour specimens and margins resected from animals and patients after systemic injection of cetuximab‐IRDye800CW. In a preclinical model of luciferase‐positive tumour resection using bioluminescence as the gold standard, fluorescence assessment determined by closed‐field fluorescence imaging of fresh resected margins accurately predicted the presence of disease in 33/39 positive margins yielding an overall sensitivity of 85%, specificity of 95%, positive predictive value (PPV) of 94%, and a negative predictive value (NPV) of 87%, which was superior to both surgical assessment (54%, 61%, 57%, and 58%) and pathological assessment (49%, 95%, 91%, and 66%), respectively. When the power of the technique was evaluated using human‐derived tumour tissues, as little as 0.5mg (1mm3) of tumour tissue was identified (tumour‐to‐background‐ratio:5.2). When the sensitivity/specificity of fluorescence‐guided pathology was determined using traditional histological assessment as the gold standard in human tissues obtained during fluorescence‐guided surgery, the technique was highly accurate with a sensitivity of 91%, specificity of 85%, PPV of 81%, and NPV of 93% for 90 human‐derived samples. This approach can be used as a companion to the pathologist, eliminating confounding factors while impacting surgical intervention and patient management.
Synthesis and Biological Assessment of Racemic Benzochromenopyrimidinimines as Antioxidant, Cholinesterase, and Aβ1−42 Aggregation Inhibitors for Alzheimer's Disease Therapy
Authors: Dgachi Youssef , Ismaili Lhassane , Knez Damijan , Benchekroun Mohamed , Martin Hélène , Szałaj Natalia , Wehle Sarah , Bautista‐Aguilera Oscar M. , Luzet Vincent , Bonnet Alexandre , Malawska Barbara , Gobec Stanislav , Chioua Mourad , Decker Michael , Chabchoub Fakher , Marco‐Contelles José 
Published: January 2016

AbstractGiven the complex nature of Alzheimer′s disease (AD), compounds that are able to simultaneously address two or more AD‐associated targets show greater promise for development into drugs for AD therapy. Herein we report an efficient two‐step synthesis and biological evaluation of new racemic benzochromene derivatives as antioxidants, inhibitors of cholinesterase and β‐amyloid (Aβ1−42) aggregation. Based on the results of the primary screening, we identified 15‐(3‐methoxyphenyl)‐9,11,12,15‐tetrahydro‐10H,14H‐benzo[5,6]chromeno[2,3‐d]pyrido[1,2‐a]pyrimidin‐14‐imine (3 e) and 16‐(3‐methoxyphenyl)‐9,10,11,12,13,16‐hexahydro‐15H‐benzo[5′,6′]chromeno[2′,3′:4,5]pyrimido[1,2‐a]azepin‐15‐imine (3 f) as new potential multitarget‐directed ligands for AD therapy. Further in‐depth biological analysis showed that compound 3 f is a good human acetylcholinesterase inhibitor [IC50=(0.36±0.02) μm], has strong antioxidant activity (3.61 μmol Trolox equivalents), and moderate Aβ1−42 antiaggregating power (40.3 %).