bluuebunny/crossref_metadata_2025_split huggingface dataset:
Patient-level costs in margin re-excision for breast-conserving surgery
Authors: Grant Y , Al-Khudairi R , St John E , Barschkett M , Cunningham D , Al-Mufti R , Hogben K , Thiruchelvam P , Hadjiminas D J , Darzi A , Carter A W , Leff D R 
Published: December 2018

Abstract

Background
High rates of reoperation following breast-conserving surgery (BCS) for positive margins are associated with costs to healthcare providers. The aim was to assess the quality of evidence on reported re-excision costs and compare the direct patient-level costs between patients undergoing successful BCS versus reoperations after BCS.

Methods
The study used data from women who had BCS with or without reoperation at a single institution between April 2015 and March 2016. A systematic review of health economic analysis in BCS was conducted and scored using the Quality of Health Economic Studies (QHES) instrument. Financial data were retrieved using the Patient-Level Information and Costing Systems (PLICS) for patients. Exchange rates used were: US $1 = £0·75, £1 = €1·14 and US $1 = €0·85.

Results
The median QHES score was 47 (i.q.r. 32·5–79). Only two of nine studies scored in the upper QHES quartile (score at least 75). Costs of initial lumpectomy and reoperation were in the range US $1234–11786 and $655–9136 respectively. Over a 12-month interval, 153 patients had definitive BCS and 59 patients underwent reoperation. The median cost of reoperations after BCS (59 patients) was £4511 (range 1752–18 019), representing an additional £2136 per patient compared with BCS without reoperation (P &lt; 0·001).

Conclusion
The systematic review demonstrated variation in methodological approach to cost estimates and a paucity of high-quality cost estimate studies for reoperations. Extrapolating local PLICS data to a national level suggests that getting BCS right first time could result in substantial savings.
An HPLC method for the determination of adenosine diphosphate: An important marker of hexokinase activity in metabolic diseases
Authors: Brito Santos Rodrigo , Pereira da Silva Railmara , Akihiro Melo Otsuka Felipe , de Jesus Trindade Danielle , Costa Santos Aline , Reis Matos Humberto 
Published: December 2018

AbstractHexokinases play a critical role in the cellular uptake and utilization of glucose. As such, they are of fundamental importance to all cells. By catalyzing glucose to produce glucose‐6‐phosphate, hexokinases control the first irreversible step of glucose metabolism and initiate all major pathways of glucose consumption. Our objective was to develop and validate highly sensitive and selective high‐performance liquid chromatography with photodiode array detector (HPLC‐PDA) assays allowing the determination of adenosine diphosphate, which was used for the determination of hexokinase activity. Samples were analyzed by HPLC‐PDA using a C18 analytical column (250 × 4.6 mm) for chromatographic separation. Optimal detection was achieved based on isocratic elution with a mobile phase consisting of a mixture of sodium phosphate monobasic buffer and methanol. This method met all of the requirements of specificity, sensitivity, linearity, precision, accuracy and stability generally accepted in bioanalytical chemistry and was successfully applied to a study of hexokinase activity in an alloxan‐induced diabetic rat model. Determination of hexokinase activity will permit characterization of cellular metabolic state in many diseases, such as cancer and diabetes.
Preliminary evidence from a prospective DTI study suggests a posterior‐to‐anterior pattern of recovery in college athletes with sports‐related concussion
Authors: Cubon Valerie A. , Murugavel Murali , Holmes Katharine W. , Dettwiler Annegret 
Published: December 2018

AbstractObjectivesWe compared the integrity of white matter (WM) microstructure to the course of recovery in athletes who sustained one sports‐related concussion (SRC), assessing individual longitudinal changes in WM fiber tracts following SRC using pre‐ and post‐injury measurements.Materials and MethodsBaseline diffusion tensor imaging (DTI) scans and neuropsychological tests were collected on 53 varsity contact‐sport college athletes. Participants (n = 13) who subsequently sustained an SRC underwent DTI scans and neuropsychological testing at 2 days, 2 weeks, and 2 months following injury.ResultsRelying on tract‐based spatial statistics (TBSS) analyses, we found that radial diffusivity (RD) and mean diffusivity (MD) were significantly increased at 2 days post‐injury compared to the same‐subject baseline (corrected p < 0.02). These alterations were visible in anterior/posterior WM regions spanning both hemispheres, demonstrating a diffuse pattern of injury after concussion. Implicated WM fiber tracts at 2 days include the following: right superior/inferior longitudinal fasciculus; right/left inferior fronto‐occipital fasciculus; right corticospinal tract; right acoustic radiation; right/left anterior thalamic radiations; right/left uncinate fasciculus; and forceps major/minor. At 2 weeks post‐injury, persistently elevated RD and MD were observed solely in prefrontal portions of WM fiber tracts (using same‐subject contrasts). No significant differences were found for FA in any of the post‐injury comparisons to baseline. Plots of individual subject RD and MD in prefrontal WM demonstrated homogenous increases from baseline to just after SRC; thereafter, trajectories became more variable. Most subjects’ diffusivity values remained elevated at 2 months post‐injury relative to their own baseline. Over the 2‐month period after SRC, recovery of WM fiber tracts appeared to follow a posterior‐to‐anterior trend, paralleling the posterior–anterior pattern of WM maturation previously identified in the normal population.ConclusionThese results suggest greater vulnerability of prefrontal regions to SRC, underline the importance of an individualized approach to concussion management, and show promise for using RD and MD for imaging‐based diagnosis of SRC.
Synthesis, Characterization and in vitro Studies of a Cathepsin B‐Cleavable Prodrug of the VEGFR Inhibitor Sunitinib
Authors: Karnthaler‐Benbakka Claudia , Koblmüller Bettina , Mathuber Marlene , Holste Katharina , Berger Walter , Heffeter Petra , Kowol Christian R. , Keppler Bernhard K. 
Published: December 2018

AbstractSince several decades, the prodrug concept has raised considerable interest in cancer research due to its potential to overcome common problems associated with chemotherapy. However, for small‐molecule tyrosine kinase inhibitors, which also cause severe side effects, hardly any strategies to generate prodrugs for therapeutic improvement have been reported so far. Here, we present the synthesis and biological investigation of a cathepsin B‐cleavable prodrug of the VEGFR inhibitor sunitinib. Cell viability assays and Western blot analyses revealed, that, in contrast to the non‐cathepsin B‐cleavable reference compound, the prodrug shows activity comparable to the original drug sunitinib in the highly cathepsin B‐expressing cell lines Caki‐1 and RU‐MH. Moreover, a cathepsin B cleavage assay confirmed the desired enzymatic activation of the prodrug. Together, the obtained data show that the concept of cathepsin B‐cleavable prodrugs can be transferred to the class of targeted therapeutics, allowing the development of optimized tyrosine kinase inhibitors for the treatment of cancer.
Investigation of a KcsA Cytoplasmic pH Gate in Lipoprotein Nanodiscs
Authors: Qasim Arwa , Sher Inbal , Hirschhorn Orel , Shaked Hadassa , Qasem Zena , Ruthstein Sharon , Chill Jordan H. 
Published: December 2018

AbstractThe bacterial potassium channel KcsA is gated by pH, opening for conduction under acidic conditions. Molecular determinants responsible for this effect have been identified at the extracellular selectivity filter, at the membrane–cytoplasm interface (TM2 gate), and in the cytoplasmic C‐terminal domain (CTD), an amphiphilic four‐helix bundle mediated by hydrophobic and electrostatic interactions. Here we have employed NMR and EPR to provide a structural view of the pH‐induced open‐to‐closed CTD transition. KcsA was embedded in lipoprotein nanodiscs (LPNs), selectively methyl‐protonated at Leu/Val residues to allow observation of both states by NMR, and spin‐labeled for the purposes of EPR studies. We observed a pHinduced structural change between an associated structured CTD at neutral pH and a dissociated flexible CTD at acidic pH, with a transition in the 5.0–5.5 range, consistent with a stabilization of the CTD by channel architecture. A double mutant constitutively open at the TM2 gate exhibited reduced stability of associated CTD, as indicated by weaker spin–spin interactions, a shift to higher transition pH values, and a tenfold reduction in the population of the associated “closed” channels. We extended these findings for isolated CTD‐derived peptides to full‐length KcsA and have established a contribution of the CTD to KcsA pH‐controlled gating, which exhibits a strong correlation with the state of the proximal TM2 gate.
A Substantial Structural Conversion of the Native Monomer Leads to in‐Register Parallel Amyloid Fibril Formation in Light‐Chain Amyloidosis
Authors: Lecoq Lauriane , Wiegand Thomas , Rodriguez‐Alvarez Francisco J. , Cadalbert Riccardo , Herrera Guillermo A. , del Pozo‐Yauner Luis , Meier Beat H. , Böckmann Anja 
Published: December 2018

AbstractAmyloid light‐chain (AL) amyloidosis is a rare disease in which plasma‐cell‐produced monoclonal immunoglobulin light chains misfold and become deposited as fibrils in the extracellular matrix. λ6 subgroup light chains are particularly fibrillogenic, and around 25 % of amyloid‐associated λ6 light chains exist as the allotypic G24R variant that renders the protein less stable. The molecular details of this process, as well as the structures of the fibrils, are unknown. We have used solid‐state NMR to investigate different fibril polymorphs. The secondary structures derived from NMR predominantly show β‐strands, including in former turn or helical regions, and provide a molecular basis for previously identified fibrillogenic hotspots. We have determined, by using differentially 15N:13C‐labeled samples, that the β‐strands are stacked in‐register parallel in the fibrils. This supramolecular arrangement shows that the native globular folds rearrange substantially upon fibrillization, and rules out the previously hypothesized fibril formation from native monomers.
The CORE‐10 in screening for current mental health problems and severe mental illness in prisoners
Authors: O'Connor Gwen , Morris Reg 
Published: December 2018

AbstractBackgroundFew mental health screening tools are validated for prisoners. Existing tools do not guide referral between primary and secondary care pathways.AimsThis study aimed to assess performance of the CORE‐10 in screening any current mental health problem and current severe mental illness (SMI) in prisoners.MethodCORE‐10 ratings were compared with mini international neuropsychiatric interview (MINI) version 6.0 ratings and current practice outcomes for 150 male prisoners. Receiver operating curve (ROC) analyses were used to estimate the likelihood with which CORE‐10 ratings matched MINI ratings, yielding “area under the curve” statistics.ResultsROC analyses suggested a strong relationship between CORE‐10 screen scores and the more detailed assessment both in identifying any problem (AUC 0.85) and severe mental illness (AUC 0.76). Sensitivity was 0.88 and 0.83, and specificity was 0.64 and 0.61, respectively. Retest reliability was moderate (ICC = 0.83). The CORE‐10 identified many cases of “any problem” and of severe illness also identified by the MINI who had not been referred to clinical services in routine practice.ConclusionsThis study provides evidence for the potential of the CORE‐10 for improving appropriate referrals for prisoners to mental health services.
Safety and efficacy of a novel abluminal groove‐filled biodegradable polymer sirolimus‐eluting stent for the treatment of de novo coronary lesions: Final five‐year results of the patient‐level pooled analysis from the TARGET I and TARGET II trials
Authors: Li Chongjian , Guan Changdong , Zhang Ruiyan , Yang Yuejin , Ma Changsheng , Li Hui , Chen Shaoliang , Han Yaling , Xu Bo , Gao Runlin ,   for the TARGET Investigators
Published: December 2018

AbstractObjectivesThe study reports the final 5‐year safety and effectiveness outcomes of the novel abluminal groove‐filled biodegradable polymer‐coated FIREHAWK sirolimus‐eluting stent in a large patient cohort.BackgroundThe TARGET clinical program was conducted to evaluate the performance of the FIREHAWK stent, and this objective performance criterion study pooled long‐term safety and efficacy data from three TARGET trials for greater statistical power to analyze low‐frequency events.MethodsPatient‐level pooled data from 1,007 individuals in the TARGET I randomized controlled trial (n = 227), TARGET I long lesion cohort (n = 50), and TARGET II registry (n = 730) were prospectively collected and analyzed. The primary endpoint, target lesion failure (TLF), was defined as a composite of cardiac death, target vessel myocardial infarction (TV‐MI), and ischemia‐driven indicated target lesion revascularization (ID‐TLR) at 5 years. All patients were exclusively treated with the FIREHAWK stent and had annual follow‐up visits for up to 5 years.ResultsAmong 947 patients (94.0%) who completed the 5‐year clinical follow‐up, the 5‐year TLF event rate was 8.1%; the events included 18 cardiac deaths, 36 TV‐MIs, and 33 ID‐TLRs. Only four (0.4%) very late probable or definite stent thrombosis events were observed beyond 1 year after stent implantation. In the subgroup analysis, lesion length ≥ 30 mm was associated with higher long‐term TLF incidence, while the use of a predilation‐sizing‐postdilation technique showed no significant effect on long‐term outcomes.ConclusionsFive‐year results demonstrate the continuing safety and efficacy of the FIREHAWK Stent, with relatively lower incidence of thrombotic events.
Base‐Catalyzed Ethanolysis of Waste Cooking Oil in a Micro/Millireactor System: Flow and Reaction Analysis
Authors: Borovinskaya Ekaterina S. , Sabaditsch Daniel , Reschetilowski Wladimir 
Published: December 2018

AbstractAn important way for the production of biodiesel is the base‐catalyzed transesterification of oil or fat with monohydric alcohols. Flow and reaction analysis with respect to the applicability of a micro/millireactor setup to two‐phase ethanolysis of waste cooking oil is described. The flow in the micro/millireactor system was examined on the example of a soybean oil/ethanol mixture and compared with a T‐mixer. Parallel and slug flow were observed in different reactor sections of the micro/milli‐reactor system and evaluated concerning their efficiency. A method for determination of the viscosity of the mixture was conducted and validated. Certain pretreatments were investigated with regard to the suitability of the waste cooking oil for ethanolysis. Relations between biodiesel yields and some oil properties like chain length and acid number were found.
Electrochemical Synthesis and Thermodynamic Properties of Pr‐Ni Intermetallic Compounds in a LiCl‐KCl‐NiCl2‐PrCl3 Melt
Authors: Yin Taiqi , Xue Yun , Yan Yongde , Zheng Yanghai , Song Yali , Wang Guiling , Zhang Milin , Qiu Min , Hu Donghui 
Published: December 2018

AbstractIn this report, the electrochemical behaviors of Pr(III) and Ni(II) ions on a W electrode were investigated in LiCl‐KCl eutectic by cyclic voltammetry (CV), square wave voltammetry (SWV), chronopotentiometry (CP) and open‐circuit chronopotentiometry (OCP) techniques. From the results of electrochemical methods, different signals corresponding to seven kinds of intermetallic compounds in the phase diagram of Pr−Ni were observed. The thermodynamic properties of intermetallic compounds in the temperature range of 823–923 K were investigated by open‐circuit chronopotentiometry. With the evaluated apparent standard potentials of Pr−Ni intermetallic compounds, the Gibbs energies, enthalpies and entropies of formation were also calculated. The co‐reduction products by galvanostatic and potentiostatic electrolysis were characterized based on X‐ray diffraction (XRD) and scanning electron microscopy (SEM) coupled with energy dispersive X‐ray spectroscopy (EDS). The shape of the alloy obviously changes from granular to bulk, and the alloy phase changes from Pr‐rich to Ni‐rich. The co‐reduction products of PrNi5, PrNi2 and PrNi were identified.
Network‐Like Ni1−xMox Nanosheets: Multi‐Functional Electrodes for Overall Water Splitting and Supercapacitor
Authors: Tong Rui , Sun Zhi , Wang Xina , Wang Shuangpeng , Pan Hui 
Published: December 2018

AbstractExploring efficient, abundant, cheap and stable materials for the electrolysis of water and supercapacitor is a challenging task. Here, Ni1−xMox nanosheets are obtained on carbon cloth (CC), which can be multi‐functional electrodes for electrochemical applications. Impressively, we find that the electrochemical abilities can be optimized by constructing network‐like nanosheets and tuning the ratio of Ni and Mo in the alloy. To acquire a current density of 10 mA cm−2 (j10), Ni0.75Mo0.25/CC shows the lowest overpotentials (79 mV for hydrogen evolution reaction (HER) and 330 mV for oxygen evolution reaction (OER)) in 1 M KOH. Using Ni0.75Mo0.25/CC as both positive and negative poles, the cell only requires a potential of 1.74 V to reach j10 and shows long‐term durability. We further show that Ni0.75Mo0.25 electrode exhibits a superior specific capacitance (422 F g−1 at 1 A g−1) and high capacitance retention (108.2 % after 1000 cycles) in 1 M KOH. The super‐electrochemical performances of Ni0.75Mo0.25/CC is attributed to its high electronic conductivity, rich active sites, and large surface area. We believe that the Ni0.75Mo0.25/CC electrode with extraordinary electrochemical performances is a hopeful material for practical applications in both electrocatalysis and supercapacitors (SC).
Temperature‐Responsive Electrocatalysis Based on Poly(N‐Isopropylacrylamide)‐Modified Graphene Oxide (PNIPAm‐GO)
Authors: Zhang Hairan , Zhang Qiuyue , Zhang Ling , Pei Tingting , Li Erni , Wang Huiting , Zhang Qian , Xia Lixin 
Published: December 2018

AbstractPoly(N‐isopropylacrylamide)‐modified graphene oxide (PNIPAm‐GO), which is a type of thermally responsive GO, was designed and synthesized through a covalent “grafting‐from” strategy. The as‐prepared modified nanosheets integrated the individual advantages of two components, such as the thermal sensitivity of the PNIPAm terminal as well as the conductivity and the open 2D structure of the GO substrate. PNIPAm‐GO was able to perform the reversible regulation of hydrophilicity/hydrophobicity in aqueous solution upon variations in the temperature. Such a unique property might also lead to the utilization of PNIPAm‐GO as an intelligent electrode material to achieve a switchable electrochemical response toward a [Fe(CN)6]3−/4− probe. The PNIPAm‐GO modified glassy carbon electrode (PNIPAm‐GO/GC electrode) was able to exhibit better electrochemical performance in an ON/OFF switching effect than the PNIPAm‐modified glassy carbon electrode (PNIPAm/GC electrode) without GO owing to the intrinsic properties and large surface area of the introduced GO. Moreover, it was found that the PNIPAm‐GO/GC electrode also displayed excellent thermally responsive electrocatalysis toward the detection of 1,4‐dihydro‐β‐nicotinamide adenine dinucleotide (NADH) and dopamine (DA), which resulted in two different catalytic statuses on the same electrode. This kind of switchable catalytic performance of the PNIPAm‐GO/GC electrode might greatly enhance the flexibility of its application, and thus it is expected to have wide potential for applications in the fields of biosensors and biocatalysis.
Ligands Based on Phosphine‐Stabilized Aluminum(I), Boron(I), and Carbon(0)
Authors: Vondung Lisa , Jerabek Paul , Langer Robert 
Published: December 2018

AbstractA systematic quantum chemical study of the bonding in d6‐transition‐metal complexes, containing phosphine‐stabilized, main‐group‐element fragments, (R3P)2E, as ligands (E=AlH, BH, CH+, C), is reported. By using energy decomposition analysis, it is demonstrated that a strong M−E bond is accompanied by weak P−E bonds, and vice versa. Although the Al−M bond is, for example, found to be very strong, the weak Al−P bond suggests that the corresponding metal complexes will not be stable towards phosphine dissociation. The interaction energies for the boron(I)‐based ligand are lower, but still higher than those for two‐carbon‐based ligands. For neutral ligands, electrostatic interactions are the dominating contributions to metal–ligand bonding, whereas for the cationic ligand a significant destabilization, with weak orbital and even weaker electrostatic metal–ligand interactions, is observed. Finally, for iron(II) complexes, it is demonstrated that different reactivity patterns are expected for the four donor groups: the experimentally observed reversible E−H reductive elimination of the borylene‐based ligand (E=BH) exhibits significantly higher barriers for the protonated carbodiphosphorane (CDP) ligand (E=CH) and would proceed through different intermediates and transition states. For aluminum, such reaction pathways are not feasible (E=AlH). Moreover, it is demonstrated that the metal hydrido complexes with CDP ligands might not be stable towards reduction and isomerization to a protonated CDP ligand and a reduced metal center.
Unexpected Zwitterionic Allenyls from Silylenes and a Fischer Alkynylcarbene: A Remarkable Silylene‐Promoted Rearrangement
Authors: Cabeza Javier A. , García‐Álvarez Pablo , Gómez‐Gallego Mar , González‐Álvarez Laura , Merinero Alba D. , Sierra Miguel A. 
Published: December 2018

AbstractThe silylenes Si(tBu2bzam)R (tBu2bzam=N,N′‐bis(tertbutyl)benzamidinate; R=mesityl, CH2SiMe3) attack the Ccarbene atom of the Fischer alkynyl(ethoxy)carbene complex [W(CO)5{C(OEt)C2Ph}] to give, after a striking rearrangement, zwitterionic σ‐allenyl complexes in which the original carbene C atom forms part of the allene C3 fragment and also of a Si‐C‐N‐C‐N five‐membered ring after insertion into a Si−N bond of the original amidinatosilylene. These remarkable allenyl products, which contain two stereogenic groups, are selectively formed as single diastereomers.
Organocatalytic alkylation of carbohydrate‐containing aldehydes with dihydroquinoline N,O‐acetals: Absolute configuration of 1,2‐dihydroquinolines
Authors: Menichetti Andrea , Berti Francesco , Guazzelli Lorenzo , Favero Lucilla , Di Pietro Sebastiano , Pescitelli Gennaro , Pineschi Mauro 
Published: December 2018

AbstractThe direct catalytic α‐amidoalkylation of dihydroquinolines with aldehydes bearing oxygen functionalities at different positions in a Mannich‐type reaction has been studied. β‐Alkoxy‐aldehyde 1d gave high enantioselectivity, albeit with an inherently poor diastereoselectivity, while the use of α‐alkoxy aldehydes 1c was detrimental also to enantioselectivity. Mannich‐type reactions have been studied for the first time using new chiral carbohydrate‐derived aldehydes 1a,b showing a reactivity markedly influenced by the presence of water. The chiral glycidic backbone showed a slight but significant influence on the overall stereochemical outcome only when present in α‐position of the aldehyde. The absolute stereochemistry of the products was studied by electronic circular dichroism (ECD) spectra and compared with theoretical calculations. ECD analysis easily provides the absolute configuration of 1,2‐dihydroquinoline derivatives such as quinoline‐1(2H)‐carboxylates.