bluuebunny/crossref_metadata_2025 huggingface dataset:
Sexual Dimorphism of Digit‐Length Ratio in a Viviparous Lizard: Influence of Age, but not Preservation State or Sex of Interuterine Twin
Authors: Woodhead Nikita , Hare Kelly M. , Cree Alison
Published: March 2018

The existence of sex differences in digit‐length ratio (especially between the second and fourth digits, 2D:4D) is well established for humans from fetal life onwards, and has been linked with later performance. In rodents, the ratio is affected prenatally by exposure to androgens and estrogens, with some research suggesting an influence from sex of the neighbouring intrauterine fetus. However, the ubiquity and ontogenetic development of sexual dimorphism in digit ratios is not well established among wild amniotes. We report the first digit ratios for a gekkotan lizard, representing a speciose lineage in which viviparity has evolved independently from mammals and other reptiles. For the gecko Woodworthia “Otago/Southland”, in which up to two embryos develop in separate uteri, we found: (1) significant sexual dimorphism in adults in 2D:3D of the right hindlimb only (larger in males), but not in 2D:4D for any limb; (2) no dimorphism in ratios for young juveniles, with no influence of sex of the interuterine twin, and no relationship with sprint speed; (3) in preserved tissues of the same juveniles, no sexual dimorphism in ratios, but a change in relative lengths of some digits with preservation. The ontogenetic pattern might be explained by altered sex–steroid exposure at the transition to adulthood rather than during prenatal development. Our results support a phylogenetic hypothesis that sauropsids (birds and reptiles) differ from mammals in the direction of sex difference, if present. Experiments are needed to establish the roles of androgens and estrogens in establishing these sex differences in lizards. Anat Rec, 301:1169–1178, 2018. © 2018 Wiley Periodicals, Inc.
Fungal biofilm inhibition by piperazine‐sulphonamide linked Schiff bases: Design, synthesis, and biological evaluation
Authors: Patil Rajendra H. , Kalam Khan Firoz A. , Jadhav Kaivalya , Damale Manoj , Akber Ansari Siddique , Alkahtani Hamad M. , Ali Khan Azmat , Shinde Shantanu D. , Patil Rajesh , Sangshetti Jaiprakash N.
Published: March 2018

We report the synthesis of some new piperazine‐sulphonamide linked Schiff bases as fungal biofilm inhibitors with antibacterial and antifungal potential. The biofilm inhibition result of Candida albicans proposed that the compounds 6b (IC50 = 32.1 μM) and 6j (IC50 = 31.4 μM) showed higher inhibitory activity than the standard fluconazole (IC50 = 40 μM). Compound 6d (MIC = 26.1 μg/mL) with a chloro group at the para position was found to be the most active antibacterial agent of the series against Bacillus subtilis when compared with the standard ciprofloxacin (MIC = 50 μg/mL). Compound 6j (MIC = 39.6 μg/mL) with an OH group at the ortho position showed more potent antifungal activity as compared to that of the standard fluconazole (IC50 = 50 μM) against C. albicans. Thus, the synthesized compounds 6a–k were found to be potent biofilm inhibitors as well as active antibacterial and antifungal agents. The molecular docking study of the synthesized compounds against the secreted aspartyl protease (SAP5) enzyme of C. albicans exhibited good binding properties. The in silico ADME properties of the synthesized compounds were also analyzed and showed their potential to be developed as potential oral drug candidates.
Modulation of Inflammatory Arthritis in Mice by Gut Microbiota Through Mucosal Inflammation and Autoantibody Generation
Authors: Jubair Widian K. , Hendrickson Jason D. , Severs Erin L. , Schulz Hanna M. , Adhikari Sumitra , Ir Diana , Pagan Jose D. , Anthony Robert M. , Robertson Charles E. , Frank Daniel N. , Banda Nirmal K. , Kuhn Kristine A.
Published: March 2018

Objective

Observations of microbial dysbiosis in patients with rheumatoid arthritis (RA) have raised interest in studying microbial–mucosal interactions as a potential trigger of RA. Using the murine collagen‐induced arthritis (CIA) model, we undertook this study to test our hypothesis that microbiota modulate immune responses leading to autoimmune arthritis.

Methods

CIA was induced by immunization of mice with type II collagen (CII) in adjuvant on days 0 and 21, with arthritis appearing on days 23 and 24. Intestinal microbiota were profiled by 16S ribosomal RNA sequencing every 7 days during the course of CIA, and intestinal mucosal changes were evaluated on days 14 and 35. Then, microbiota were depleted either early (7 days before immunization) or late (day 21 after immunization) by administration of broad‐spectrum antibiotics. Disease severity, autoantibody and systemic cytokine production, and intestinal mucosal responses were monitored in the setting of microbial reduction.

Results

Significant dysbiosis and mucosal inflammation occurred early in CIA, prior to visible arthritis, and continued to evolve during the course of disease. Depletion of the microbiota prior to the induction of CIA resulted in an ~40% reduction in disease severity and in significantly reduced levels of serum inflammatory cytokines and anti‐CII antibodies. In intestinal tissue, production of interleukin‐17A (IL‐17A) and IL‐22 was delayed. Unexpectedly, microbial depletion during the late phase of CIA resulted in a >50% decrease in disease severity. Anti‐CII antibodies were mildly reduced but were significantly impaired in their ability to activate complement, likely due to altered glycosylation profiles.

Conclusion

These data support a model in which intestinal dysbiosis triggers mucosal immune responses that stimulate T and B cells that are key for the development of inflammatory arthritis.
Mixtures of Berkson and classical covariate measurement error in the linear mixed model: Bias analysis and application to a study on ultrafine particles
Authors: Deffner Veronika , Küchenhoff Helmut , Breitner Susanne , Schneider Alexandra , Cyrys Josef , Peters Annette
Published: March 2018

The ultrafine particle measurements in the Augsburger Umweltstudie, a panel study conducted in Augsburg, Germany, exhibit measurement error from various sources. Measurements of mobile devices show classical possibly individual–specific measurement error; Berkson–type error, which may also vary individually, occurs, if measurements of fixed monitoring stations are used. The combination of fixed site and individual exposure measurements results in a mixture of the two error types. We extended existing bias analysis approaches to linear mixed models with a complex error structure including individual–specific error components, autocorrelated errors, and a mixture of classical and Berkson error. Theoretical considerations and simulation results show, that autocorrelation may severely change the attenuation of the effect estimations. Furthermore, unbalanced designs and the inclusion of confounding variables influence the degree of attenuation. Bias correction with the method of moments using data with mixture measurement error partially yielded better results compared to the usage of incomplete data with classical error. Confidence intervals (CIs) based on the delta method achieved better coverage probabilities than those based on Bootstrap samples. Moreover, we present the application of these new methods to heart rate measurements within the Augsburger Umweltstudie: the corrected effect estimates were slightly higher than their naive equivalents. The substantial measurement error of ultrafine particle measurements has little impact on the results. The developed methodology is generally applicable to longitudinal data with measurement error.
Incorporating historical information in biosimilar trials: Challenges and a hybrid Bayesian‐frequentist approach
Authors: Mielke Johanna , Schmidli Heinz , Jones Byron
Published: March 2018

For the approval of biosimilars, it is, in most cases, necessary to conduct large Phase III clinical trials in patients to convince the regulatory authorities that the product is comparable in terms of efficacy and safety to the originator product. As the originator product has already been studied in several trials beforehand, it seems natural to include this historical information into the showing of equivalent efficacy. Since all studies for the regulatory approval of biosimilars are confirmatory studies, it is required that the statistical approach has reasonable frequentist properties, most importantly, that the Type I error rate is controlled—at least in all scenarios that are realistic in practice. However, it is well known that the incorporation of historical information can lead to an inflation of the Type I error rate in the case of a conflict between the distribution of the historical data and the distribution of the trial data. We illustrate this issue and confirm, using the Bayesian robustified meta‐analytic‐predictive (MAP) approach as an example, that simultaneously controlling the Type I error rate over the complete parameter space and gaining power in comparison to a standard frequentist approach that only considers the data in the new study, is not possible. We propose a hybrid Bayesian‐frequentist approach for binary endpoints that controls the Type I error rate in the neighborhood of the center of the prior distribution, while improving the power. We study the properties of this approach in an extensive simulation study and provide a real‐world example.
Development of N‐acetylneuraminic acid responsive biosensors based on the transcriptional regulator NanR
Authors: Peters Gert , De Paepe Brecht , De Wannemaeker Lien , Duchi Dries , Maertens Jo , Lammertyn Jeroen , De Mey Marjan
Published: March 2018

Transcriptional biosensors have various applications in metabolic engineering, including dynamic pathway control and high‐throughput screening of combinatorial strain libraries. Previously, various biosensors have been created from naturally occurring transcription factors (TFs), largely relying on native sequences without the possibility to modularly optimize their response curve. The lack of design and engineering techniques thus greatly hinders the development of custom biosensors. In view of the intended application this is detrimental. In contrast, a bottom‐up approach to design tailor‐made biosensors was pursued here. Novel biosensors were created that respond to N‐acetylneuraminic acid (Neu5Ac), an important sugar moiety with various biological functions, by employing native and engineered promoters that interact with the TF NanR. This bottom‐up approach, whereby various tuned modules, e.g., the ribosome binding site (RBS) controlling NanR translation can be combined, enabled the reliable engineering of various response curve characteristics. The latter was validated by testing these biosensors in combination with various Neu5Ac‐producing pathways, which allowed to produce up to 1.4 ± 0.4 g/L extracellular Neu5Ac. In this way, the repertoire of biosensors was expanded with seven novel functional Neu5Ac‐responsive biosensors.
Industrial bioprocessing perspectives on managing therapeutic protein charge variant profiles
Authors: Chung Stanley , Tian Jun , Tan Zhijun , Chen Jie , Lee Jongchan , Borys Michael , Li Zheng Jian
Published: March 2018

Controlling the charge profile of therapeutic protein is a critical challenge in the current quality‐by‐design (QbD) paradigm, throughout all phases of biologics process development (PD): cell line development, upstream cell culture, recovery process, downstream purification, and analytical characterization. Charge variant profiles may influence efficacy and/or lead to unintended side‐effects. Thus, maintaining a consistent charge profile is of tremendous importance, and increasingly, researchers have focused efforts toward developing strategies to mitigate variability during cell culture and to improve separation and detection of charge variants. Current understanding of factors affecting charge variant formation during manufacturing remains inadequate, and sometimes, even substantial commitment of resources may still not fully achieve the desired or consistent profiles. As such, this review attempts to provide a comprehensive resource for the biologics community by summarizing the impact of charge variants and CQA management, analytical methods for charge variant detection, as well as strategies in downstream and upstream PD for controlling charge variant profiles.
Combinatorial pathway engineering using type I‐E CRISPR interference
Authors: Tarasava Katia , Liu Rongming , Garst Andrew , Gill Ryan T.
Published: March 2018

Optimization 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

An 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

In 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

Wilms 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

Glioblastoma 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.
Volatile Constituents fromBaccharisspp. L. (Asteraceae): Chemical Support for the Conservation of Threatened Species in Uruguay
Authors: Minteguiaga Manuel , González Andrés , Cassel Eduardo , Umpierrez Noelia , Fariña Laura , Dellacassa Eduardo
Published: March 2018

Chemical bioprospecting is an important tool for generating knowledge regarding local human‐threatened floras and for conservation management. ForBaccharisL. (Asteraceae), several volatile components have been reported for Brazil, Argentina, Bolivia, and Chile as a result of bioprospection, but not for Uruguayan flora, which is composed of more than 50 native species. In this work, through collection of aerial parts of different species and volatile simultaneous‐distillation extraction and gas chromatography‐mass spectrometry analyses, twelve native species ofBacchariswere studied (B.articulata,B.cultrata,B.genistifolia,B.gibertii,B.gnaphalioides,B.ochracea,B.phyteumoides,B.punctulata,B.crispa,B.dracunculifolia,B.linearifoliasubsp.linearifolia, andB.spicata). A detailed analysis of the male and female volatile composition was conducted for the last four species. The profiles ofB.cultrata,B.genistifolia,B.gibertii, andB.gnaphalioidesare reported for the first time. Because half of the species analyzed in this work are in Uruguay and are threatened or potentially threatened by human economic activities, the importance of their conservation as natural, sustainable resources is highlighted.
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

Glutathione (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

Objectives

To 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).

Background

Clinical features and outcomes in patients with DM and popliteal or infrapopliteal PAD undergoing PVI are not well described.

Methods

Using 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.

Results

Of 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).

Conclusions

Among 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 Message

Methicillin‐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 Message

Report 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 Message

Vitamin 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

An 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

Rubber 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

The 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

The 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

PtII‐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

Complexation 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

Treatment 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.
Partial Isobutane Oxidation to tert‐Butyl Hydroperoxide in a Micro Reactor – Comparison of DTBP and Aqueous TBHP as Initiator
Authors: Willms Thomas , Kryk Holger , Hampel Uwe
Published: March 2018

The oxidation of isobutane has been investigated for the first time in a micro reactor for a wide range of process conditions comparing the product ratios obtained with di‐tert‐butyl peroxide (DTBP) and tert‐butyl hydroperoxide (TBHP) as initiator. DTBP led to nearly the double conversion compared to the same concentration of TBHP, but the selectivity of TBHP using TBHP as initiator was higher. Using aqueous TBHP, the conversions reached up to 6 % in case of supercritical conditions but stayed below 2 % in case of two‐phase flow experiments. With TBHP in decane as initiator a high conversion was reached but nearly no TBHP was formed. It seems that the silicon layer of the micro reactor was not stable under such experimental conditions. In the present work, for the first time a conversion level near to that of the industrial batch process has been reached in a micro reactor for the isobutane oxidation.
The Relevance of XBRL Voluntary Disclosure for Stock Market Valuation: The Role of Corporate Governance
Authors: Cormier Denis , Dufour Dominique , Luu Philippe , Teller Pierre , Teller Robert
Published: March 2018

The aim of this paper is to investigate the relevance for stock market pricing of accounting earnings of voluntary disclosures in XBRL files considering the quality of corporate governance. Results are the following. It appears that XBRL extensions attract financial analysts. Good governance is positively associated with voluntary XBRL extensions. We observe that XBRL extensions enhance the positive relationship between accounting earnings and stock price. However, this positive association is reduced for firms with good governance, suggesting a substitution effect between XBRL extensions and corporate governance. Finally, it appears that XBRL extensions would strategically be related to earnings quality. This research highlights the importance to consider governance when assessing the value relevance of XBRL disclosures for stock market pricing.
Behaviour‐Based and Outcome‐Based Control Systems: A Meta‐Analytic Study
Authors: de Oliveira Santini Fernando , Vieira Valter Afonso , Ladeira Wagner Junior , Sampaio Claudio Hoffmann
Published: March 2018

Sales control systems are instruments used by firms to improve performance and other organizational outcomes. To understand their antecedents and consequences, this paper conducts a meta‐analysis based on 104 studies. The results showed significant relationships between behaviour‐ and outcome‐based control systems and the complexity of the products, bonuses, financial performance, sales innovation, organizational support and satisfaction with supervisors. The outcomes revealed that behaviour‐based control systems were the most effective mechanism in turbulent markets and for determining financial performance. However, outcome‐based control systems were the most efficient instrument for complex products.
Posttraumatic stress disorder and mortality in VA patients with implantable cardioverter‐defibrillators
Authors: Ofman Peter , Hoffmeister Peter , Kaloupek Danny G. , Gagnon David R. , Peralta Adelqui , Djousse Luc , Gaziano J. Michael , Rahilly‐Tierney Catherine R.
Published: March 2018

Background

The association between posttraumatic stress disorder (PTSD) and mortality in patients undergoing implantable cardioverter‐defibrillator (ICD) placement has not been evaluated in US veterans.

Hypothesis

PTSD in veterans with ICD is associated with increased mortality.

Methods

We studied a retrospective cohort of 25 678 veterans who underwent ICD implantation between September 30, 2002, and December 31, 2011. Of these subjects, 3280 carried the diagnosis of PTSD prior to ICD implantation. Primary outcome was all‐cause mortality between date of ICD implantation and end of follow‐up (September 30, 2013). We used Cox proportional hazard models to compute multivariable adjusted hazard ratios with corresponding 95% confidence intervals for the relation between PTSD diagnosis and death following ICD placement.

Results

During a mean follow‐up of 4.21 ± 2.62 years, 11 015 deaths were reported. The crude incidence rate of death was 87.8 and 103.9/1000 person‐years for people with and without PTSD, respectively. We did not find an association between presence of PTSD before or after ICD implantation and incident death when adjusted for multiple risk factors (hazard ratio: 1.003, 95% confidence interval: 0.948–1.061). In secondary analysis, no statistically significant association was found.

Conclusions

In this retrospective cohort study among more than 25 000 veterans undergoing ICD implantation, almost 13% had a diagnosis of PTSD. Subjects with PTSD were significantly younger, yet they had a higher incidence of coronary heart disease, major cardiac comorbidities, cancer, and mental health conditions. We found no association between presence of PTSD before or after ICD implantation and incident death when adjusting for all covariates.
Association between transthoracic impedance and electrical cardioversion success with biphasic defibrillators: An analysis of 1055 shocks for atrial fibrillation and flutter
Authors: Sadek Mouhannad M. , Chaugai Varsha , Cleland Mark J. , Zakutney Timothy J. , Birnie David H. , Ramirez F. Daniel
Published: March 2018

Background

The relevance of transthoracic impedance (TTI) to electrical cardioversion (ECV) success for atrial tachyarrhythmias when using biphasic waveform defibrillators is unknown.

Hypothesis

TTI is predictive of ECV success with contemporary defibrillators.

Methods

De‐identified data stored in biphasic defibrillator memory cards from ECV attempts for atrial fibrillation (AF) or atrial flutter (AFL) over a 2‐year period at our center were evaluated. ECV success, defined as arrhythmia termination and ≥ 1 sinus beat, was adjudicated by 2 blinded cardiac electrophysiologists. The association between TTI and ECV success was assessed via Cochrane‐Armitage trend and Spearman rank correlation tests, as well as simple and multivariable logistic regression. The influence of TTI on the number of shocks and on cumulative energy delivered per patient was also examined.

Results

703 patients (593 with AF, 110 with AFL) receiving 1055 shocks were included. Last shock success was achieved in 88.0% and 98.2% of patients with AF and AFL, respectively. In patients with AF, TTI was positively associated with last shock failure (Ptrend =0.019), the need for multiple shocks (Ptrend <0.001), and cumulative energy delivered (ρ = 0.348; P < 0.001). After adjusting for first shock energy, 10‐Ω increments in TTI were associated with odds ratios of 1.36 (95% CI: 1.24–1.49) and 1.22 (95% CI: 1.09–1.37) for first and last shock failure, respectively (P < 0.001 for both).

Conclusions

Although contemporary defibrillators are designed to compensate for TTI, this variable continues to be associated with ECV failure in patients with AF. Strategies to lower TTI during ECV for AF may improve procedural success.
Rationale, design, and preliminary results of the Quebec Warfarin Cohort Study
Authors: Perreault Sylvie , Shahabi Payman , Côté Robert , Dumas Stéphanie , Rouleau‐Mailloux Étienne , Feroz Zada Yassamin , Provost Sylvie , Mongrain Ian , Dorais Marc , Huynh Thao , Kouz Simon , Diaz Ariel , Blostein Mark , de Denus Simon , Turgeon Jacques , Ginsberg Jeffrey , Lelorier Jacques , Lalonde Lyne , Busque Lambert , Kassis Jeannine , Talajic Mario , Tardif Jean‐Claude , Dubé Marie‐Pierre
Published: March 2018

Over‐ and undercoagulation with warfarin are associated with hemorrhagic and thromboembolic events, respectively. Genetic and clinical factors affect warfarin response, and the causes of this variability remain unclear. We present descriptive statistics and test for predictors of poor anticoagulation control. The Quebec Warfarin Cohort (QWC) comprises 1059 new warfarin users, with prospective follow‐up using telephone questionnaires every 3 months for 1 year, and using healthcare administrative databases (RAMQ and Med‐Echo) for 5 years prior to cohort entry and up to 10 years following active patient participation. Genetic material was collected, and genotyping of CYP2C9 and VKORC1 genes was conducted. Measured outcomes included the percentage of time patients spent within therapeutic range, anticoagulation control, warfarin dose, bleeding, and thromboembolic events. We report baseline characteristics and outcomes after 1 year of follow‐up. Poor anticoagulation control was defined as time in therapeutic range <60% in the 3‐ to 12‐month interval. Participants had a mean age of 71 years, and 62% were men. The most common indication for warfarin was atrial fibrillation (87%). Mean time in therapeutic range was 56% (±25%) in the 3 months following warfarin initiation, and 70% (±21%) in the 3‐ to 12‐month interval. During follow‐up, the rate of stroke or systemic embolism was 1.8 events per 100 person‐years; for major bleeding events, 3.3 events per 100 person‐years. Independent predictors of poor anticoagulation control were chronic kidney disease, heart failure, dyslipidemia, and age. The QWC represents a good research cohort to investigate clinical and genetic factors in a warfarin‐anticoagulated population.