bluuebunny/crossref_metadata_2025_split huggingface dataset:
A simple method for correcting for the Will Rogers phenomenon with biometrical applications
Authors: Stander Mark , Stander Julian 
Published: January 2020

AbstractIn its basic form, the Will Rogers phenomenon takes place when an increase in the average value of each of two sets is achieved by moving an element from one set to another. This leads to the conclusion that there has been an improvement, when in fact essentially nothing has changed. Extended versions of this phenomenon can occur in epidemiological studies, rendering their results unreliable. After describing epidemiological and clinical studies that have been affected by the Will Rogers phenomenon, this paper presents a simple method to correct for it. The method involves introducing a transition matrix between the two sets and taking probability weighted expectations. Two real‐world biometrical examples, based on migration economics and breast cancer epidemiology, are given and improvements against a naïve analysis are demonstrated. In the cancer epidemiology example, we take account of estimation uncertainty. We also discuss briefly some limitations associated with our method.
Population size estimation with interval censored counts and external information: Prevalence of multiple sclerosis in Rome
Authors: Farcomeni Alessio 
Published: January 2020

AbstractWe discuss Bayesian log‐linear models for incomplete contingency tables with both missing and interval censored cells, with the aim of obtaining reliable population size estimates. We also discuss use of external information on the censoring probability, which may substantially reduce uncertainty. We show in simulation that information on lower bounds and external information can each improve the mean squared error of population size estimates, even when the external information is not completely accurate. We conclude with an original example on estimation of prevalence of multiple sclerosis in the metropolitan area of Rome, where five out of six lists have interval censored counts. External information comes from mortality rates of multiple sclerosis patients.
First‐derivative synchronous spectrofluorimetric method for estimation of losartan potassium and atorvastatin in their pure forms and in tablets
Authors: Attaa Bakr Norhane , Saad Samar , Elshabrawy Yasser , Eid Manal 
Published: January 2020

AbstractLosartan potassium (LOS) and atorvastatin (ATR) are used in combination for long‐term treatment of stroke and for treatment of hypertension with high‐level cholesterol. Both drugs were simultaneously determined and validated using a novel, easy, fast, and economical first‐derivative synchronous fluorescence spectroscopic method. Methanol was used as the solvent for both drugs at a Δλ 80 nm and with a scanning rate of 600 nm/min. Peaks were determined as at 288.1 nm and 263.6 nm for LOS and ATR, respectively. The proposed method was validated according to International Conference on Harmonization guidelines and, subsequently, the developed method was applicable to the analysis of the two compounds in their different formulations without interference from each other. Amplitude–concentration plots were rectilinear over the concentration ranges 1.0–10.0 μg/ml and 0.5–5.0 μg/ml for LOS and ATR, respectively. Detection limits were found to be 0.096 μg/ml and 0.030 μg/ml and quantitation limits were 0.291 μg/ml and 0.093 μg/ml for LOS and ATR, respectively. The proposed method was successfully applied to the analysis of both compounds in synthetic mixtures and in laboratory‐prepared tablets. These results were in accordance with the results acquired using the comparison method, high‐performance liquid chromatography.
Microalgal swimming signatures and neutral lipids production across growth phases
Authors: You Jiaqi , Mallery Kevin , Mashek Douglas G. , Sanders Mark , Hong Jiarong , Hondzo Miki 
Published: January 2020

AbstractMicroalgae have been shown as a potential bioresource for food, biofuel, and pharmaceutical products. During the growth phases with corresponding environmental conditions, microalgae accumulate different amounts of various metabolites. We quantified the neutral lipids accumulation and analyzed the swimming signatures (speed and trajectories) of the motile green alga, Dunaliella primolecta, during the lag–exponential–stationary growth cycle at different nutrient concentrations. We discovered significant changes in the neutral lipid content and swimming signatures of microalgae across growth phases. The timing of the maximum swimming speed coincided with the maximum neutral lipid content and both maxima occurred under nutrient stress at the stationary growth phase. Furthermore, the swimming trajectories suggested statistically significant changes in swimming modes at the stationary growth phase when the maximum intracellular neutral lipid content was observed. Our results provide the potential exploitation of microalgal swimming signatures as possible indicators of the cultivation conditions and the timing of microalgal harvest to maximize the lipid yield for biofuel production. The findings can also be implemented to explore the production of food and antibiotics from other microalgal metabolites with low energy costs.
Harnessing mesenchymal stem cell secretome: Effect of extracellular matrices on proangiogenic signaling
Authors: Sears Victoria , Ghosh Gargi 
Published: January 2020

AbstractThe low engraftment and retention rate of mesenchymal stem cells (MSCs) at the target site indicates that the potential benefits of MSC‐based therapies can be attributed to their paracrine signaling. In this study, the extracellular matrices (ECMs) deposited by bone marrow‐derived human MSCs in the presence and absence of ascorbic acid was characterized. MSCs were seeded on top of decellularized ECM (dECM) and the concentrations of proangiogenic and antiangiogenic molecules released in culture (conditioned) media was compared. Effects of ECM derived from MSCs with different passage numbers on MSC secretome was also investigated. Our study revealed that the expression of proangiogenesis‐related factors were upregulated when MSCs were harvested on dECMs, irrespective of media supplementation, as compared with those cultured on tissue culture plates. In addition, dECM generated in the presence of ascorbic acid promoted the expression of proangiogenic molecules as compared with dECM‐derived in absence of media supplementation. Further, it was observed that the effectiveness of dECM to stimulate proangiogenic signaling of MSCs was reduced as cell passage number was increased from P3 to P5. The proliferation as well as capillary morphogenesis of human umbilical vein endothelial cells (HUVECs) in the presence of conditioned media were enhanced compared with the normal HUVECs culture media. These data indicate that the secretory signatures of MSCs and consequently, the therapeutic efficacy of MSCs can be regulated by presentation of dECM composition and variation of its composition.
High‐level heterologous production of propionate in engineered Escherichia coli
Authors: Miscevic Dragan , Mao Ju‐Yi , Moo‐Young Murray , Chou Chih‐Hsiung Perry 
Published: January 2020

AbstractA propanologenic (i.e., 1‐propanol‐producing) bacterium Escherichia coli strain was previously derived by activating the genomic sleeping beauty mutase (Sbm) operon. The activated Sbm pathway branches out of the tricarboxylic acid (TCA) cycle at the succinyl‐CoA node to form propionyl‐CoA and its derived metabolites of 1‐propanol and propionate. In this study, we targeted several TCA cycle genes encoding enzymes near the succinyl‐CoA node for genetic manipulation to identify the individual contribution of the carbon flux into the Sbm pathway from the three TCA metabolic routes, that is, oxidative TCA cycle, reductive TCA branch, and glyoxylate shunt. For the control strain CPC‐Sbm, in which propionate biosynthesis occurred under relatively anaerobic conditions, the carbon flux into the Sbm pathway was primarily derived from the reductive TCA branch, and both succinate availability and the SucCD‐mediated interconversion of succinate/succinyl‐CoA were critical for such carbon flux redirection. Although the oxidative TCA cycle normally had a minimal contribution to the carbon flux redirection, the glyoxylate shunt could be an alternative and effective carbon flux contributor under aerobic conditions. With mechanistic understanding of such carbon flux redirection, metabolic strategies based on blocking the oxidative TCA cycle (via ∆sdhA mutation) and deregulating the glyoxylate shunt (via ∆iclR mutation) were developed to enhance the carbon flux redirection and therefore propionate biosynthesis, achieving a high propionate titer of 30.9 g/L with an overall propionate yield of 49.7% upon fed‐batch cultivation of the double mutant strain CPC‐Sbm∆sdhA∆iclR under aerobic conditions. The results also suggest that the Sbm pathway could be metabolically active under both aerobic and anaerobic conditions.
Influence of cytoskeleton organization on recombinant protein expression by CHO cells
Authors: Pourcel Lucille , Buron Flavien , Arib Ghislaine , Le Fourn Valérie , Regamey Alexandre , Bodenmann Iris , Girod Pierre‐Alain , Mermod Nicolas 
Published: January 2020

AbstractIn this study, we assessed the importance of cytoskeleton organization in the mammalian cells used to produce therapeutic proteins. Two cytoskeletal genes, Actin alpha cardiac muscle 1 (ACTC1) and a guanosine triphosphate GTPase‐activating protein (TAGAP), were found to be upregulated in highly productive therapeutic protein‐expressing Chinese hamster ovary (CHO) cells selected by the deprivation of vitamin B5. We report here that the overexpression of the ACTC1 protein was able to improve significantly recombinant therapeutic production, as well as to decrease the levels of toxic lactate metabolic by‐products. ACTC1 overexpression was accompanied by altered as well as decreased polymerized actin, which was associated with high protein production by CHO cell cultured in suspension. We suggest that the depolymerization of actin and the possible modulation of integrin signaling, as well as changes in basal metabolism, may be driving the increase of protein secretion by CHO cells.
Reduced scale model qualification of 5‐L and 250‐ml bioreactors using multivariant visualization and Bayesian inferential methods
Authors: Banton Dwaine , Canova Christopher , Clark Kevin , Naguib Sara , Schaefer Eugene 
Published: January 2020

AbstractA novel method for the qualification of reduced scale models (RSMs) was illustrated using data from both a 250‐ml advanced microscale bioreactor (ambr) and a 5‐L bioreactor RSM for a 2,000‐L manufacturing scale process using a CHO cell line to produce a recombinant monoclonal antibody. The example study showed how the method was used to identify process performance attributes and product quality attributes that capture important aspects of the RSM qualification process. The method uses two novel statistical approaches: multivariate dimension reduction and data visualization techniques, via partial least squares discriminant analysis (PLS‐DA), and Bayesian multivariate linear modeling for inferential analysis. Bayesian multivariate linear modeling allows for individual probability distributions of the differences of the mean of each attribute for each scale, as well as joint probability statements on the differences of the means for multiple attributes. Depending on the results of this inferential procedure, PLS‐DA is used to identify the process performance outputs at the different scales which have the greatest negative impact on the multivariate Bayesian joint probabilities. Experience with that particular process can then be leveraged to adjust operating conditions to minimize these differences, and then equivalence can be reassessed using the multivariate linear model.
Tissue scaffolds functionalized with therapeutic elastin‐like biopolymer particles
Authors: Bulutoglu Beyza , Devalliere Julie , Deng Sarah L. , Acun Aylin , Kelangi Sarah S. , Uygun Basak E. , Yarmush Martin L. 
Published: January 2020

AbstractTissue engineering scaffolds are intended to provide mechanical and biological support for cells to migrate, engraft and ultimately regenerate the tissue. Development of scaffolds with sustained delivery of growth factors and chemokines would enhance the therapeutic benefits, especially in wound healing. In this study, we incorporated our previously designed therapeutic particles, composed of fusion of elastin‐like peptides (ELPs) as the drug delivery platform to keratinocyte growth factor (KGF), into a tissue scaffold, alloderm. The results demonstrated that sustained KGF–ELP release was achieved and the bioactivity of the released therapeutic particles was shown via cell proliferation assay, as well as a mouse pouch model in vivo, where higher cellular infiltration and vascularization were observed in scaffolds functionalized with KGF–ELPs.
A randomized trial of nurse‐administered behavioral interventions to manage anticipatory nausea and vomiting in chemotherapy
Authors: Hunter Jonathan J. , Maunder Robert G. , Sui Dawen , Esplen Mary Jane , Chaoul Alejandro , Fisch Michael J. , Bassett Roland L. , Harden‐Harrison Marlys M. , Lagrone Lore , Wong Lucas , Baez‐Diaz Luis , Cohen Lorenzo 
Published: January 2020

AbstractPurposeChemotherapy side effects diminish quality of life and can lead to treatment delay. Nausea and vomiting can occur prior to chemotherapy because of classical conditioning. We studied the effects of 20‐minute behavioral interventions, administered by oncology nurses, of higher intensity (mindfulness relaxation—MR) or lower intensity (relaxing music—RM), on anticipatory nausea and vomiting (ANV).Patients and methodsPatients undergoing chemotherapy for solid tumors were randomized to MR (N = 160), RM (N = 159), or standard care SC (N = 155). Subjects were mostly female (91.8%) and white (86.1%) with breast cancer (85%). Most patients had early stage disease (Stage I: 26%; II: 52.9%; III: 19%; IV: 0.1%). Anticipatory nausea and vomiting were assessed at the midpoint and end of the chemotherapy course using the Morrow Assessment of Nausea and Emesis (MANE).ResultsCompared to SC, there was reduced anticipatory nausea at the midpoint of chemotherapy in those receiving MR (OR 0.44, 95% CI 0.20‐0.93) and RM (OR 0.40, 95% CI 0.20‐0.93), controlling for age, sex, cancer stage, and emetogenic level of chemotherapy. There was no difference between treatment groups in anticipatory nausea at the end of chemotherapy or in anticipatory vomiting and postchemotherapy nausea and vomiting at either time point.ConclusionA brief nurse‐delivered behavioral intervention can reduce midpoint ANV associated with chemotherapy.
Extending the Salinilactone Family
Authors: Schlawis Christian , Harig Tim , Ehlers Stephanie , Guillen‐Matus Dulce G. , Creamer Kaitlin E. , Jensen Paul R. , Schulz Stefan 
Published: January 2020

AbstractFive new members of the salinilactone family, salinilactones D–H, are reported. These bicyclic lactones are produced by Salinispora bacteria and display extended or shortened alkyl side chains relative to the recently reported salinilactones A–C. They were identified by GC/MS, gas chromatographic retention index, and comparison with synthetic samples. We further investigated the occurrence of salinilactones across six newly proposed Salinispora species to gain insight into how compound production varies among taxa. The growth‐inhibiting effect of this compound family on multiple biological systems including non‐Salinispora actinomycetes was analyzed. Additionally, we found strong evidence for significant cytotoxicity of the title compounds.
Platelet function testing guided antiplatelet therapy reduces cardiovascular events in Chinese patients with ST‐segment elevation myocardial infarction undergoing percutaneous coronary intervention: The PATROL study
Authors: You Jieyun , Li Hongda , Guo Wei , Li Jiming , Gao Liming , Wang Yunkai , Geng Liang , Wang Xingxu , Wan Qing , Zhang Qi 
Published: January 2020

AbstractBackgroundDual antiplatelet therapy (DAPT) with aspirin and a P2Y12 receptor inhibitor has become the standard of care to reduce thrombotic events in patients with acute coronary syndrome or after percutaneous coronary intervention (PCI). The role of routine platelet function testing (PFT) in patients treated with DAPT after PCI remains controversial and evidence of PFT‐guided antiplatelet therapy for patients with ST‐segment elevation myocardial infarction (STEMI) undergoing primary PCI is limited.MethodsWe analyzed 1,353 consecutive STEMI patients undergoing primary PCI. PFT was performed 72 hr postprocedure using a vasodilator‐stimulated phosphoprotein assay. The primary endpoint of major adverse cardio‐cerebral events (MACCEs) was defined as a composite of all‐cause death, cardiac death, nonfatal myocardial infarction, target vessel revascularization, and ischemic stroke. Patients with high platelet reactivity (HPR) were randomized to receive an intensified antiplatelet strategy by switching from clopidogrel to ticagrelor (HPR switch group) or to continue on clopidogrel (HPR nonswitch group). One‐year clinical outcomes were compared among the groups.ResultsThe baseline clinical characteristics were comparable across all groups (all p > .05). At the 1‐year clinical follow‐up, the primary endpoint of MACCE was significantly higher in the HPR nonswitch group than in the non‐HPR and HPR switch groups (19.49% vs. 10.20% or 8.57%, p < .05), which was mainly caused by higher mortality (14.87% vs. 4.51% or 5.71%, p < .05). Major bleeding events were comparable across the groups.ConclusionsIn STEMI patients with HPR, identified by vasodilator stimulated phosphoprotein (VASP)‐determined PFT, switching clopidogrel to ticagrelor could significantly improve 1‐year clinical outcomes without increasing the risk of bleeding.
FeCoNi Ternary Spinel Oxides Nanosheets as High Performance Water Oxidation Electrocatalyst
Authors: Kong Qingquan , Bai Weijing , Bai Fangzheng , An Xuguang , Feng Wei , Zhou Fengling , Chen Qiuyue , Wang Qingyuan , Sun Chenghua 
Published: January 2020

AbstractFeCoNi spinel oxides nanosheets array directly supported on the Ni foam substrate were prepared via a facile wet chemical method with 2‐methylimidazole as a structure directing agent and subsequently annealing. The as‐prepared 0.1Fe−CoNiO/NF offers high intrinsic catalytic activity, high surface area and good conductivity, resulting in enhanced activity for the oxygen evolution reaction (OER) in the alkaline solution. It demonstrates an ultralow overpotentials of 240 mV at 10 mA cm−2 and a small Tafel slope of 36.8 mV dec−1, with attractive durability during long‐term operation in 1 M KOH solution.
Anion Recognition by Neutral Chalcogen Bonding Receptors: Experimental and Theoretical Investigations
Authors: Navarro‐García Encarnación , Galmés Bartomeu , Velasco María D. , Frontera Antonio , Caballero Antonio 
Published: January 2020

AbstractThe utilization of neutral receptors for the molecular recognition of anions based on chalcogen bonding (ChB) is an undeveloped area of host‐guest chemistry. In this manuscript, the synthesis of two new families of sulfur, selenium, and tellurium‐based ChB binding motifs are reported. The stability of the thiophene, selenophene, and tellurophene binding motifs has enabled the determination of the association constants for ChB halide anion binding in the polar aprotic solvent THF by1H,77Se, and125Te NMR experiments. Two different aromatic cores are used and one or two Ch‐binding motifs are incorporated with the purpose of encapsulating the anion, offering up to two concurrent chalcogen bonds. Theoretical calculations and NMR experiments reveal that, for S and Se receptors, hydrogen‐bonding interactions involving the acidic H atom adjacent to the chalcogen atom are energetically favored over the ChB interaction. However, for the tellurophene binding motif, the σ‐hole interaction is competitive and more favored than the hydrogen bond.
Chemiluminescent Carbapenem‐Based Molecular Probe for Detection of Carbapenemase Activity in Live Bacteria
Authors: Das Sayantan , Ihssen Julian , Wick Lukas , Spitz Urs , Shabat Doron 
Published: January 2020

AbstractCarbapenemase‐producing organisms (CPOs) pose a severe threat to antibacterial treatment due to the acquisition of antibiotic resistance. This resistance can be largely attributed to the antibiotic‐hydrolyzing enzymes that the bacteria produce. Current carbapenem “wonder drugs”, such as doripenem, ertapenem, meropenem, imipenem, and so on, are resistant to regular β‐lactamases, but susceptible to carbapenemases. Even worse, extended exposure of bacteria to these drugs accelerates the spread of resistance genes. In order to preserve the clinical efficacy of antibacterial treatment, carbapenem drugs should be carefully regulated and deployed only in cases of a CPO infection. Early diagnosis is therefore of paramount importance. Herein, we report the design, synthesis, and activity of the first carbapenemase‐sensitive chemiluminescent probe, CPCL, which may be used to monitor CPO activity. The design of our probe enables enzymatic cleavage of the carbapenem core, which is followed by a facile 1,8‐elimination process and the emission of green light through rapid chemical excitation. We have demonstrated the ability of the probe to detect a number of clinically relevant carbapenemases and the successful identification of CPO present in bacterial cultures, such as those used for clinical diagnosis. We believe that our use of “turn‐on” chemiluminescence activation will find significant application in future diagnostic assays and improve antibacterial treatment.
Reassessment of an Innovative Insulin Analogue Excludes Protracted Action yet Highlights the Distinction between External and Internal Diselenide Bridges
Authors: Dhayalan Balamurugan , Chen Yen‐Shan , Phillips Nelson B. , Swain Mamuni , Rege Nischay K. , Mirsalehi Ali , Jarosinski Mark , Ismail‐Beigi Faramarz , Metanis Norman , Weiss Michael A. 
Published: January 2020

AbstractLong‐acting insulin analogues represent the most prescribed class of therapeutic proteins. An innovative design strategy was recently proposed: diselenide substitution of an external disulfide bridge. This approach exploited the distinctive physicochemical properties of selenocysteine (U). Relative to wild type (WT), Se‐insulin[C7UA, C7UB] was reported to be protected from proteolysis by insulin‐degrading enzyme (IDE), predicting prolonged activity. Because of this strategy's novelty and potential clinical importance, we sought to validate these findings and test their therapeutic utility in an animal model of diabetes mellitus. Surprisingly, the analogue did not exhibit enhanced stability, and its susceptibility to cleavage by either IDE or a canonical serine protease (glutamyl endopeptidase Glu‐C) was similar to WT. Moreover, the analogue's pharmacodynamic profile in rats was not prolonged relative to a rapid‐acting clinical analogue (insulin lispro). Although [C7UA, C7UB] does not confer protracted action, nonetheless its comparison to internal diselenide bridges promises to provide broad biophysical insight.