bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combinatorial pathway engineering using type I‐E CRISPR interference
Authors: Tarasava Katia , Liu Rongming , Garst Andrew , Gill Ryan T. 
Published: March 2018

ABSTRACTOptimization of metabolic flux is a difficult and time‐consuming process that often involves changing the expression levels of multiple genes simultaneously. While some pathways have a known rate limiting step, more complex metabolic networks can require a trial‐and‐error approach of tuning the expression of multiple genes to achieve a desired distribution of metabolic resources. Here we present an efficient method for generating expression diversity on a combinatorial scale using CRISPR interference. We use a modified native Escherichia coli Type I‐E CRISPR‐Cas system and an iterative cloning strategy for construction of guide RNA arrays. This approach allowed us to build a combinatorial gene expression library three orders of magnitude larger than previous studies. In less than 1 month, we generated ∼12,000 combinatorial gene expression variants that target six different genes and screened these variants for increased malonyl‐CoA flux and 3‐hydroxypropionate (3HP) production. We were able to identify a set of variants that exhibited a significant increase in malonyl‐CoA flux and up to a 98% increase in 3HP production. This approach provides a fast and easy‐to‐implement strategy for engineering metabolic pathway flux for development of industrially relevant strains, as well as investigation of fundamental biological questions.
A validated LC–MS/MS method for the simultaneous determination of thalidomide and its two metabolites in human plasma: Application to a pharmacokinetic assay
Authors: Jiang Fulin , Peng Xiang , Cai Dake , Wen Dingsheng , Liu Yao , Zhi Min , Chen Jiangying , Hu Pinjin , Wang Xueding , Gao Yujie , Huang Min , Gao Xiang , Zhong Guoping 
Published: March 2018

AbstractAn accurate and sensitive LC–MS/MS method for determining thalidomide, 5‐hydroxy thalidomide and 5′‐hydroxy thalidomide in human plasma was developed and validated using umbelliferone as an internal standard. The analytes were extracted from plasma (100 μL) by liquid–liquid extraction with ethyl acetate and then separated on a BETASIL C18 column (4.6 × 150 mm, 5 μm) with mobile phase composed of methanol–water containing 0.1% formic acid (70:30, v/v) in isocratic mode at a flow rate of 0.5 mL/min. The detection was performed using an API triple quadrupole mass spectrometer in atmospheric pressure chemical ionization mode. The precursor‐to‐product ion transitions m/z 259.1 → 186.1 for thalidomide, m/z 273.2 → 161.3 for 5‐hydroxy thalidomide, m/z 273.2 → 146.1 for 5′‐hydroxy thalidomide and m/z 163.1 → 107.1 for umbelliferone (internal standard, IS) were used for quantification. The calibration curves were obtained in the concentrations of 10.0–2000.0 ng/mL for thalidomide, 0.2–50.0 ng/mL for 5‐hydroxy thalidomide and 1.0–200.0 ng/mL for 5′‐hydroxy thalidomide. The method was validated with respect to linear, within‐ and between‐batch precision and accuracy, extraction recovery, matrix effect and stability. Then it was successfully applied to estimate the concentration of thalidomide, 5‐hydroxy thalidomide and 5′‐hydroxy thalidomide in plasma samples collected from Crohn's disease patients after a single oral administration of thalidomide 100 mg.
Ibrutinib versus rituximab in relapsed or refractory chronic lymphocytic leukemia or small lymphocytic lymphoma: a randomized, open‐label phase 3 study
Authors: Huang Xiaojun , Qiu Lugui , Jin Jie , Zhou Daobin , Chen Xiequn , Hou Ming , Hu Jianda , Hu Yu , Ke Xiaoyan , Li Junmin , Liang Yingmin , Liu Ting , Lv Yue , Ren Hanyun , Sun Aining , Wang Jianmin , Zhao Chunting , Salman Mariya , Sun Steven , Howes Angela , Wang Jingzhao , Wu Peng , Li Jianyong 
Published: March 2018

AbstractIn the Asia‐Pacific region, treatment options are limited for patients with relapsed/refractory chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). Rituximab is widely used in this setting when purine analog‐based therapies are not appropriate. We evaluated the efficacy and safety of ibrutinib compared with rituximab in a randomized, open‐label phase 3 study in predominantly Asian patients with relapsed/refractory CLL/SLL. Patients (N = 160) were randomly assigned 2:1 to receive 420 mg ibrutinib (n = 106) until disease progression (PD) or unacceptable toxicity or up to six cycles of rituximab (n = 54). The primary endpoint was investigator‐assessed progression‐free survival (PFS); key secondary endpoints were overall response rate (ORR), overall survival (OS), and safety. Rituximab‐treated patients could crossover to receive ibrutinib after confirmed PD. At data cutoff, median treatment duration was 16.4 months for ibrutinib and 4.6 months for rituximab. Ibrutinib significantly improved PFS (hazard ratio [HR] = 0.180, 95% confidence interval [CI]: 0.105–0.308). ORR was significantly higher (P < 0.0001) with ibrutinib (53.8%) than with rituximab (7.4%). At a median follow‐up of 17.8 months, ibrutinib improved OS compared with rituximab (HR = 0.446; 95% CI: 0.221–0.900; P = 0.0206). Overall incidence of adverse events (AEs) was similar between treatments and was not exposure‐adjusted. With ibrutinib, most common AEs were diarrhea and platelet count decreased; with rituximab, most common AEs were neutrophil count decreased and platelet count decreased. Grade ≥3 AEs were reported in 82.7% of ibrutinib‐treated patients and 59.6% of rituximab‐treated patients. Ibrutinib improved PFS, ORR, and OS compared with rituximab and displayed a manageable safety profile in Asian patients with relapsed/refractory CLL/SLL.
Chemotherapy and terminal skeletal muscle differentiation in WT1‐mutant Wilms tumors
Authors: Royer‐Pokora Brigitte , Beier Manfred , Brandt Artur , Duhme Constanze , Busch Maike , de Torres Carmen , Royer Hans‐Dieter , Mora Jaume 
Published: March 2018

AbstractWilms tumors (WT) with WT1 mutations do not respond well to preoperative chemotherapy by volume reduction, suggesting resistance to chemotherapy. The histologic pattern of this tumor subtype indicates an intrinsic mesenchymal differentiation potential. Currently, it is unknown whether cytotoxic treatments can induce a terminal differentiation state as a direct comparison of untreated and chemotherapy‐treated tumor samples has not been reported so far. We conducted gene expression profiling of 11 chemotherapy and seven untreated WT1‐mutant Wilms tumors and analyzed up‐ and down‐regulated genes with bioinformatic methods. Cell culture experiments were performed from primary Wilms tumors and genetic alterations in WT1 and CTNNB1 analyzed. Chemotherapy induced MYF6 165‐fold and several MYL and MYH genes more than 20‐fold and repressed many genes from cell cycle process networks. Viable tumor cells could be cultivated when patients received less than 8 weeks of chemotherapy but not in two cases with longer treatments. In one case, viable cells could be extracted from a lung metastasis occurring after 6 months of intensive chemotherapy and radiation. Comparison of primary tumor and metastasis cells from the same patient revealed up‐regulation of RELN and TBX2, TBX4 and TBX5 genes and down‐regulation of several HOXD genes. Our analyses demonstrate that >8 weeks of chemotherapy can induce terminal myogenic differentiation in WT1‐mutant tumors, but this is not associated with volume reduction. The time needed for all tumor cells to achieve the terminal differentiation state needs to be evaluated. In contrast, prolonged treatments can result in genetic alterations leading to resistance.
National cancer database analysis of outcomes in pediatric glioblastoma
Authors: Liu Meng , Thakkar Jigisha P. , Garcia Catherine R. , Dolecek Therese A. , Wagner Lars M. , Dressler Emily Van Meter , Villano John L. 
Published: March 2018

AbstractGlioblastoma in children is an aggressive disease with no defined standard therapy. We evaluated hospital‐based demographic and survival patterns obtained through the National Cancer Database to better characterize children with glioblastoma. Our study identified 1173 patients from 0 to 19 years of age between 1998 and 2011. Comparisons were made among demographics, clinical characteristics, treatment, and survival variables. Fifty‐four percent of patients were over 10 years of age. Approximately 80% of patients underwent either partial or complete resection. Adjuvant therapy was used variably, and its use increased with patient age. Forty‐eight percent of patients received the combination of surgery, radiation, and chemotherapy, and 4% did not receive any treatment. As expected, patients ≤5 years of age had better 5‐year survival than those ages 6–10 (P = 0.01) or 11–19 years (P = 0.0077). Other factors associated with poor survival included black race and central tumor location. Better outcomes were associated with treatment that included surgery, radiotherapy, and chemotherapy compared to any other treatment combinations. Radiotherapy had no impact on survival in the 0 to 10‐year‐old age group, but was associated with improved survival for patients 11–19 years. We report an extensive demographic and survival analysis of pediatric glioblastoma. The observed differences likely reflect variances in tumor biology and likelihood of treatment receipt. Improved survival was associated with the use of surgery, radiotherapy, and chemotherapy. Radiation therapy was not associated with survival in patients younger than 10 years of age.
Comparison of Polyphenol Profile and Antimutagenic and Antioxidant Activities in Two Species Used as Source of Solidaginis herba – Goldenrod
Authors: Woźniak Dorota , Ślusarczyk Sylwester , Domaradzki Krzysztof , Dryś Andrzej , Matkowski Adam 
Published: March 2018

European Pharmacopoeia accepts two equivalent species Solidago canadensis L. and S. gigantea Aiton as goldenrod (Solidaginis herba). We compared phytochemical profile of both species from invasive populations in Poland. Further, we compared in vitro antimutagenic and antioxidant activities of solvent extracts from aerial (AP) and underground parts (UP). In S. gigantea, flavonoid profile was dominated by quercetin glycosides, with quercitrin as the major compound. In S. canadensis, quercetin and kaempferol rutinosides were two major constituents. Caffeoylquinic acids (CQAs) were less diverse with 5‐CQA as a main compound. In UP, over 20 putative diterpenoids were detected, mostly unidentified. Several CQAs were present in higher amounts than in AP. Antioxidant and antimutagenic activities were different between species and organs, with the strongest inhibition of lipid peroxidation by Et2O and AcOEt fractions from AP of both species (IC50 13.33 – 16.89 μg/mL) and BuOH fraction from S. gigantea UP (IC50 = 13.32 μg/mL). Chemical mutagenesis was completely inhibited by non‐polar fractions, but oxidative mutagenesis was inhibited up to 35% only by S. canadensis. No clear relationship was found between chemical profiles and antimutagenic activity. In conclusion, both species have diverse activity and their phytochemical profiles should be considered in quality evaluation. UP of these weeds can also provide potential chemopreventive substances for further studies.
Chloro‐Functionalized Photo‐crosslinking BODIPY for Glutathione Sensing and Subcellular Trafficking
Authors: Murale Dhiraj P. , Hong Seong Cheol , Haque Md Mamunul , Lee Jun‐Seok 
Published: March 2018

AbstractGlutathione (GSH) is one of major antioxidants inside cells that regulates oxidoreduction homeostasis. Recently, there have been extensive efforts to visualize GSH in live cells, but most of the probes available today are simple detection sensors and do not provide details of cellular localization. A new fluorescent probe (pcBD2‐Cl), which is cell permeable and selectively reacts with GSH in situ, has been developed. The in situ GSH‐labeled probe (pcBD2–GSH) exhibited quenches fluorescence, but subsequent binding to cellular abundant glutathione S‐transferase (GST) recovers the fluorescence intensity, which makes it possible to image the GSH–GST complex in live cells. Interactions between probe and GST were confirmed by means of photo‐crosslinking under intact live‐cell conditions. Interestingly, isomers of chloro‐functionalized 4,4‐difluoro‐4‐bora‐3a,4a‐diaza‐s‐indacene (BODIPY) compounds behaved very distinctively inside the cells. Following co‐staining imaging with MitoTracker and mitochondria fractionation upon lipopolysaccharide‐mediated reactive oxygen species induction experiments showed that pcBD2–GSH accumulated in mitochondria. This is the first example of a live‐cell imaging probe to visualize translocation of GSH from the cytosol to mitochondria.
Long‐term outcomes of patients with diabetes mellitus undergoing percutaneous intervention for popliteal and infrapopliteal peripheral arterial disease
Authors: Neupane Saroj , Edla Sushruth , Maidona Eesha , Sweet Matthew C. , Szpunar Susan , Davis Thomas , LaLonde Thomas A. , Mehta Rajendra H. , Rosman Howard S. , Yamasaki Hiroshi 
Published: March 2018

AbstractObjectivesTo evaluate the association of diabetes mellitus (DM) with clinical and angiographic characteristics and outcomes of patients with popliteal and infrapopliteal peripheral arterial disease (PAD) undergoing peripheral vascular intervention (PVI).BackgroundClinical features and outcomes in patients with DM and popliteal or infrapopliteal PAD undergoing PVI are not well described.MethodsUsing the data from the laser in popliteal and infrapopliteal stenosis study, we retrospectively examined the association of diabetes with clinical and angiographic characteristics and risk adjusted short‐ and intermediate term outcomes (all cause death, major adverse events (MAE) [composite of death, ipsilateral major amputation, or repeat revascularization]) in patients with popliteal and infrapopliteal PAD undergoing PVI for critical limb ischemia treated either with laser‐assisted balloon angioplasty or balloon angioplasty alone.ResultsOf 714 patients, 418 had DM (58.5%). Patients with DM were younger with higher prevalence of history of coronary artery disease, heart failure, end‐stage renal disease, and prior contralateral limb amputation compared to those without DM. At 5 years, mean event free survival for all cause mortality (39.9 vs. 45.5 months; P = 0.001), MAE (29.3 vs. 36.8 months; P < 0.001), ipsilateral major amputation (55.3 vs. 57.4 months; P = 0.001), and repeat revascularization (42.0 vs. 45.8 months; P = 0.03) were significantly lower in DM patients. On multivariate analysis, DM was associated with significantly higher all cause mortality (HR = 1.83, 95% CI 1.33–2.52), MAE (HR = 1.73, 95% CI 1.35–2.23), and ipsilateral major amputation (HR = 5.52, 95% CI 1.82–16.71).ConclusionsAmong patients with popliteal and infrapopliteal PAD undergoing PVI, DM was associated with higher mortality, major amputations and MAE that was independent of baseline comorbidities. Our data suggested the need for future studies evaluating existing and/or novel therapies to improve the poor long‐term outcomes in diabetic patients with popliteal and infrapopliteal PAD.
A case of methicillin‐resistant Staphylococcus aureus wound infection: phylogenetic analysis to establish if nosocomial or community acquired
Authors: Cancilleri Francesco , Ciccozzi Massimo , Fogolari Marta , Cella Eleonora , De Florio Lucia , Berton Alessandra , Salvatore Giuseppe , Dicuonzo Giordano , Spoto Silvia , Denaro Vincenzo , Angeletti Silvia 
Published: March 2018

Key Clinical MessageMethicillin‐resistant Staphylococcus aureus (MRSA) infection is rapidly increasing in both hospital and community settings. A 71‐year‐old man admitted at the Department of Orthopaedics and Trauma Surgery, University Campus Bio‐Medico of Rome, with MRSA wound infection consequent to orthopedic surgery was studied and the MRSA transmission evaluated by phylogenetic analysis.
Gaucher disease and chronic myeloid leukemia: first reported patient receiving enzyme replacement and tyrosine kinase inhibitor therapies simultaneously
Authors: Noya MSoledad , Andrade‐Campos Marcio , Irun Pilar , López de Frutos Laura , López‐Fernandez MFernanda , Giraldo Pilar 
Published: March 2018

Key Clinical MessageReport a female diagnosed as type 1 Gaucher disease after a femoral pathologic fracture when she was 55 years old. Enzyme replacement therapy was started, and she achieved therapeutic goals. In 2015, a Ph’ CML with numerous pseudo‐Gaucher cells in bone marrow appears. BCR/ABL was not present at GD diagnosis.
Unusual manifestation of vitamin A deficiency presenting with generalized xerosis without night blindness
Authors: Phanachet Pariya , Shantavasinkul Prapimporn Chattranukulchai , Chantrathammachart Pichika , Rattanakaemakorn Ploysyne , Jayanama Kulapong , Komindr Surat , Warodomwichit Daruneewan 
Published: March 2018

Key Clinical MessageVitamin A deficiency from malabsorption syndromes, including bariatric surgery, has become an emerging problem in developed countries. Early detection and prompt treatment lead to rapid and complete recovery. Nevertheless, it may result in irreversible blindness or death if left untreated. Health care personnel should be aware of this condition.
Global Average Hydroxyl Radical Yield throughout the Lifetime of Cavitation Bubbles
Authors: Tao Yuequn , Cai Jun , Huai Xiulan , Liu Bin 
Published: March 2018

AbstractAn improved model to predict OH• yield in hydrodynamic cavitation for wastewater treatment is developed. Relaxing the chemical equilibrium assumption, the model can estimate the global average OH• yield during the whole oscillation cycle of all bubbles by considering radicals diffusion, cavitation event rate, and bubble radius distribution. Reliability of the model is verified by comparing with experimental data from literature in terms of geometric and operating parameters. The results show that the maximum OH• yield is achieved at optimal upstream pressure of 3.6 × 105 Pa, while increasing downstream pressure always enhances OH• yield. Decreasing the hole and pipe diameters benefits the OH• yield. Finally, a relevant correlation is developed for the design of cavitation reactors.
Biodiesel Production from Rubber Seed Oil by Transesterification Using a Co‐solvent of Fatty Acid Methyl Esters
Authors: Le Hanh Ngoc Thi , Imamura Kiyoshi , Watanabe Norie , Furuta Masakazu , Takenaka Norimichi , Boi Luu Van , Maeda Yasuaki 
Published: March 2018

AbstractRubber seed oil (RSO) is a high‐potential feedstock for the production of biodiesel fuel (BDF) in Asia. Transesterification using fatty acid methyl esters (FAMEs) as co‐solvents was developed for BDF production from RSO with high content of free fatty acids (FFAs). The homogeneous system (FAMEs/triglyceride/methanol) was attained when the FAME content was more than 30 wt %. After esterification of RSO, the crude RSO obtained was transesterified with FAMEs as a co‐solvent. The quality of BDF with high FAME content satisfied the criteria of the EN 14214/JIS K2390 standards. These results suggest that FAMEs converted from FFAs can be applied as a co‐solvent and, thus, reused for BDF production.
MoS2‐Nanosheet‐Decorated Carbon Nanofiber Composites Enable High‐Performance Cathode Materials for Mg Batteries
Authors: Tan Yi‐Hong , Zhou Fei , Huang Zhi‐Hong , Yao Wei‐Tang , Zhang Tian‐Wen , Yao Hong‐Bin , Lu Lei‐Lei , Yu Shu‐Hong 
Published: March 2018

AbstractThe front cover artwork is provided by Yi‐Hong Tan and Dr. Hong‐Bin Yao, Department of Chemistry, University of Science and Technology of China. The image shows that developing low‐cost and high‐energy‐density batteries is important for powering our city. The MoS2 nanosheets are good electrode materials for Li/Mg‐ion batteries. Read the full text of the Communication at 10.1002/celc.201701347.
Synthesis and Identification of Aryl and Alkyl Gem‐Dilithium Phosphido‐Boranes: A Boost to the Chemistry of Phosphandiides
Authors: Guang Jie , Duwald Romain , Maddaluno Jacques , Oulyadi Hassan , Lakhdar Sami , Gaumont Annie‐Claude , Harrison‐Marchand Anne 
Published: March 2018

AbstractThe synthesis and identification of unprecedented gem‐dianionic phosphorus compounds, that is, gem‐dilithium phosphido‐boranes Li2[RP⋅BH3], with R=Ph or Cy, are reported in THF solution. These were obtained by double deprotonation of the corresponding primary phosphine‐borane precursors RPH2⋅BH3. Their in‐depth structural study, based on multinuclear (1H, 6Li, 7Li, 11B, 13C, 31P) mono‐ and bi‐dimensional NMR analyses, indicates a strong influence of the phosphorus substituent on the structure of the gem‐dianionic phosphorus structure; a monomeric arrangement was obtained when R=phenyl, whereas a cyclic oligomer was observed for R=cyclohexyl. These compounds represent a new type of useful reagent, and their access paves the way for the concept of “RP synthons” (i.e., RP2− phosphandiides), likely to be the most flexible precursors of a variety of phosphorus targets.
A 1,5‐Naphthyridine‐Fused Porphyrin Dimer: Intense NIR Absorption and Facile Redox Interconversion with Its Reduced Congener
Authors: Fujimoto Keisuke , Osuka Atsuhiro 
Published: March 2018

AbstractPtII‐catalyzed cyclization of β‐to‐β ethynylene‐bridged meso‐amino NiII porphyrin dimer 4 followed by oxidation with PbO2 afforded 1,5‐naphthyridine‐fused porphyrin dimer 5 in good yield. This dimer possesses a redox‐active 1,4‐diazabutadiene linkage that is interconvertible with its reduced 1,2‐diaminoethene linkage upon treatments with NaBH4 or PbO2. The dimer 5 exhibits an intense NIR absorption and a narrow HOMO–LUMO gap with a remarkably low reduction potential mainly due to effective bonding interactions in the LUMO through the 1,4‐diazabutadiene linkage. In contrast, the reduced dimer 7 is fairly electron‐rich with high HOMO energy and shows a relatively large HOMO–LUMO gap compared to that of 5.
Two Discrete RuCp* (Cp*=Pentamethylcyclopentadienyl) Binding Modes of N‐Confused Porphyrins: Peripheral π Complex and Sitting Atop Ruthenocenophane Complex by Skeletal Transformation
Authors: Yamamoto Takaaki , Mitsuno Koki , Mori Shigeki , Itoyama Shuhei , Shiota Yoshihito , Yoshizawa Kazunari , Ishida Masatoshi , Furuta Hiroyuki 
Published: March 2018

AbstractComplexation of a RuCp* cation with N‐confused tetraarylporphyrins (NCPs) forms directly bound ruthenium(II) pentamethylcyclopentadienyl (Cp*) π‐complex on a specific meso‐aryl group (e.g., phenyl) neighboring peripheral imino nitrogen of NCPs in high yields. In contrast, in the case of NCPs bearing bulky meso‐substituents (e.g., 3,5‐di‐tert‐butylphenyl), new ruthenocenophane‐like complex embedded on an N‐confused calix[4]phyrin was formed through multiple C−H bond activation of methyl groups of Cp* ligand. The mechanistic insight into the formation of the ruthenocenophane was derived from DFT calculations.
Rhodium(I)‐Catalyzed Ring‐Closing Reaction of Allene–Alkene–Alkynes: One‐Step Construction of Tricyclo[6.4.0.02,6] and Bicyclo[6.3.0] Skeletons from Linear Carbon Chains
Authors: Kawaguchi Yasuaki , Nagata Asami , Kurokawa Kei , Yokosawa Haruna , Mukai Chisato 
Published: March 2018

AbstractTreatment of dodecatrienyne derivatives with [RhCl(CO)2]2 in refluxing toluene effected the cycloisomerization to produce tricyclo[6.4.0.02,6]dodecadienes. The one‐carbon shortened undecatrienyne derivatives, however, afforded bicyclo[6.3.0]undecatriene derivatives instead of tricyclic compounds, the latter of which are well known as a basic skeleton of naturally occurring octanoids. On the basis of two experiments with deuterated substrates, a plausible reaction mechanism for the construction of these products was proposed.