bluuebunny/crossref_metadata_2025_split huggingface dataset:
Osteoclast‐Derived Autotaxin, a Distinguishing Factor for Inflammatory Bone Loss
Authors: Flammier Sacha , Peyruchaud Olivier , Bourguillault Fanny , Duboeuf François , Davignon Jean‐Luc , Norman Derek D. , Isaac Sylvie , Marotte Hubert , Tigyi Gabor , Machuca‐Gayet Irma , Coury Fabienne 
Published: June 2019

ObjectiveThe severity of rheumatoid arthritis (RA) correlates directly with bone erosions arising from osteoclast (OC) hyperactivity. Despite the fact that inflammation may be controlled in patients with RA, those in a state of sustained clinical remission or low disease activity may continue to accrue erosions, which supports the need for treatments that would be suitable for long‐lasting inhibition of OC activity without altering the physiologic function of OCs in bone remodeling. Autotaxin (ATX) contributes to inflammation, but its role in bone erosion is unknown.MethodsATX was targeted by inhibitory treatment with pharmacologic drugs and also by conditional inactivation of the ATX gene Ennp2 in murine OCs (ΔATXCtsk). Arthritic and erosive diseases were studied in human tumor necrosis factor–transgenic (hTNF+/−) mice and mice with K/BxN serum transfer–induced arthritis. Systemic bone loss was also analyzed in mice with lipopolysaccharide (LPS)–induced inflammation and estrogen deprivation. Joint inflammation and bone erosion were assessed by histology and micro–computed tomography. The role of ATX in RA was also examined in OC differentiation and activity assays.ResultsOCs present at sites of inflammation overexpressed ATX. Pharmacologic inhibition of ATX in hTNF+/− mice, as compared to vehicle‐treated controls, significantly mitigated focal bone erosion (36% decrease; P < 0.05) and systemic bone loss (43% decrease; P < 0.05), without affecting synovial inflammation. OC‐derived ATX was revealed to be instrumental in OC bone resorptive activity and was up‐regulated by the inflammation elicited in the presence of TNF or LPS. Specific loss of ATX in OCs from mice subjected to ovariectomy significantly protected against the systemic bone loss and erosion that had been induced with LPS and K/BxN serum treatments (30% reversal of systemic bone loss [P < 0.01]; 55% reversal of erosion [P < 0.001]), without conferring bone‐protective properties.ConclusionOur results identify ATX as a novel OC factor that specifically controls inflammation‐induced bone erosions and systemic bone loss. Therefore, ATX inhibition offers a novel therapeutic approach for potentially preventing bone erosion in patients with RA.
Associations of Gout and Baseline Serum Urate Level With Cardiovascular Outcomes: Analysis of the Coronary Disease Cohort Study
Authors: Stamp Lisa K. , Frampton Christopher , Drake Jill , Doughty Robert N. , Troughton Richard W. , Richards A. Mark 
Published: June 2019

ObjectiveTo determine whether gout and serum urate (SU) levels are associated with increased risk of death, time to first readmission for any cardiovascular event, or incident heart failure in individuals with cardiovascular disease.MethodsIndividuals presenting with an acute coronary syndrome (ACS) were enrolled in the Coronary Disease Cohort Study. Clinical data were collected from the medical records at the index hospital admission, and clinical, echocardiographic, and biochemical data were collected postdischarge. Gout was defined by self‐report, use of urate‐lowering therapy, or use of colchicine with evidence of gout on review of the medical record. The primary end points were all‐cause mortality, time to readmission for a cardiac ischemic event, and time to readmission for heart failure.ResultsData from 1,514 participants were available. During the follow‐up period, 53 of 160 participants with gout (33.1%) and 298 of 1,354 participants without gout (22.0%) died. After adjustment for other factors known to be associated with mortality, there was no gout‐specific increase in risk of mortality (adjusted hazard ratio 0.98 [95% confidence interval 0.69–1.38]). Time to readmission for heart failure was significantly briefer in those with, compared to those without, gout (adjusted hazard ratio 1.42 [95% confidence interval 1.02–1.97]). Irrespective of whether a participant had gout or not, as SU level increased, there was an increased risk of death and readmission for either a cardiovascular event or heart failure.ConclusionSurvival post‐ACS is similar with and without the presence of gout. People with gout are at an increased risk of readmission for heart failure and have longer hospital stays. Risk of these events increases in parallel with increases in SU levels.
Selective Synthesis of Discrete Mono‐, Interlocked‐, and Borromean Ring Ensembles Based on a π‐Electron‐Deficient Ligand
Authors: Feng Hui‐Jun , Gao Wen‐Xi , Lin Yue‐Jian , Jin Guo‐Xin 
Published: June 2019

AbstractHerein, we present a new synthetic approach to achieve selective supramolecular transformations and construct different interlocked metallacycles featuring a π‐electron‐deficient thiazolo[5,4‐d]thiazole‐derived ligand. We demonstrate that the formation of mono‐rings, interlocked rings ([2]catenanes) and Borromean rings can be controlled by adjusting the length of the binuclear half‐sandwich RhIII and IrIII building blocks. Furthermore, a concentration effect or D‐A stacking interaction between the pyrene guest and the thiazolo[5,4‐d]thiazole‐based ligand promotes a unique and reversible conversion between catenane structures and metalla‐rectangles. The synthetic results are supported by single‐crystal X‐ray diffraction analysis.
Identification of a potent indigoid persister antimicrobial by screening dormant cells
Authors: Song Sooyeon , Gong Ting , Yamasaki Ryota , Kim Jun‐Seob , Wood Thomas K. 
Published: June 2019

AbstractThe subpopulation of bacterial cells that survive myriad stress conditions (e.g., nutrient deprivation and antimicrobials) by ceasing metabolism, revive by activating ribosomes. These resuscitated cells can reconstitute infections; hence, it is imperative to discover compounds which eradicate persister cells. By screening 10,000 compounds directly for persister cell killing, we identified 5‐nitro‐3‐phenyl‐1H‐indol‐2‐yl‐methylamine hydrochloride (NPIMA) kills Escherichia coli persister cells more effectively than the best indigoid found to date, 5‐iodoindole, and better than the DNA‐crosslinker cisplatin. In addition, NPIMA eradicated Pseudomonas aeruginosa persister cells in a manner comparable to cisplatin. NPIMA also eradicated Staphylococcus aureus persister cells but was less effective than cisplatin. Critically, NPIMA kills Gram‐positive and Gram‐negative bacteria by damaging membranes and causing lysis as demonstrated by microscopy and release of extracellular DNA and protein. Furthermore, NPIMA was effective in reducing P. aeruginosa and S. aureus cell numbers in a wound model, and no resistance was found after 1 week. Hence, we identified a potent indigoid that kills persister cells by damaging their membranes.
Neural correlates of appreciating natural landscape and landscape garden: Evidence from an fMRI study
Authors: Zhang Wei , He Xianyou , Liu Sizhe , Li Ting , Li Jinhui , Tang Xiaoxiang , Lai Shuxian 
Published: June 2019

AbstractIntroductionRambling natural landscapes or landscape gardens may invoke positive emotions. However, the manner in which people experience landscape gardens and the cortical differences in the appreciation of the naturalness and artificiality of landscapes remain unknown.MethodsThis study scanned participants with functional magnetic resonance imaging while they viewed photographs of natural landscapes and landscape gardens and performed scene type judgment task.ResultsAs predicted, we identified brain regions that were associated with perceptual process, cognitive process, and rewarding experience when appreciating natural landscapes and landscape gardens without color preference. Meanwhile, the contrast between the appreciation of landscape gardens and natural landscapes was characterized by stronger activations of the inferior occipital lobe, the left superior parietal lobule (SPL), the right fusiform gyrus, the right cuneus, and the right hippocampus.ConclusionsResponses in these regions indicate that the appreciation of landscape gardens and natural landscapes relies on common cortical regions, and suggest the possibility that the inferior occipital lobe, the SPL, the fusiform gyrus, and the cuneus may be specifically associated with the appreciation of landscape gardens.
Impact of alternative irrigation practices on rice quality
Authors: Graham‐Acquaah Seth , Siebenmorgen Terry J. , Reba Michele L. , Massey Joseph H. , Mauromoustakos Andy , Adviento‐Borbe Arlene , January Robin , Burgos Redentor , Baltz‐Gray Joanne 
Published: June 2019

AbstractBackground and objectivesCurrent global concerns about water scarcity present a need to investigate more water‐efficient rice production methods. Alternate wetting and drying (AWD) is fast emerging as a water‐saving irrigation practice, but its effects on rice quality are largely unknown. To ascertain the impact of water‐saving irrigation practices on rice quality, three irrigation treatments, namely continuous flooding with cascade delivery (four fields); continuous flooding with multiple‐inlet delivery (four fields); and AWD with multiple‐inlet delivery (four fields), were established on 12 production‐sized (16.2 ha) fields in 2017.FindingsResults of rice quality evaluations showed that irrigation treatment had a significant (p < 0.05) effect on chalkiness. Samples harvested from the AWD fields had slightly greater mean chalkiness (5.6%) than samples harvested from the two continuously flooded fields (5.1–5.2%). Milling yields were not affected (p > 0.05) by irrigation treatments. The average milled rice and head rice yields across irrigation treatments were 73% and 59%, respectively. Regarding pasting properties, while peak and breakdown viscosities were not affected (p > 0.05) by the irrigation treatments, setback viscosity (SB), which is often linked with cooked rice texture, was impacted. Among the irrigation treatments, mean SB was least for the AWD treatment (146 cP), while the mean SB for the continuously flooded fields was similar at 168–169 cP.ConclusionsIn summary, the use of AWD with multiple‐inlet delivery did not impact milling yields of rice relative to the conventional practices of continuous flooding. However, rice harvested from the AWD treatment fields had slightly greater chalkiness and lesser SB.Significance and noveltyThis study addresses a gap in literature concerning the impact of emerging water‐saving irrigation techniques, especially AWD as it involves subjecting rice to a certain level of water stress, on rice grain quality characteristics.
Unilateral segmental Darier's disease associated with neuropsychiatric disorders
Authors: Horton Luke , Mehregan Darius 
Published: June 2019

AbstractUnilateral segmental Darier's disease (DD) is a rare variant of DD that presents with erythematic lesions in a unilateral distribution without other associated features of DD. Although diagnosis is challenging, unilateral segmental DD should be considered for an acantholytic dermatosis in a unilateral distribution and a history of neuropsychiatric disorders.
Metal‐Free Hybrid of Nitrogen‐Doped Nanocarbon@Carbon Networks for Highly Efficient Oxygen Reduction Electrocatalyst
Authors: Shi Qing , Ma Yu , Qin Lin , Tang Bin , Yang Weiyou , Liu Qiao 
Published: June 2019

AbstractFurther improving the oxygen reduction reaction (ORR) catalytic activity of carbon catalysts is highly challenging and remains a key issue to push forward their commercial progress as Pt alternatives in fuel cells and metal‐air batteries. Herein, a facile and economic strategy was proposed to maximize the active sites exposed in porous carbon catalysts by growing dense N‐doped carbon nanonodules firmly located within carbon fiber networks (NCN@CF) via the in situ polymerization of dopamine on bacterial cellulose fibers and a subsequent carbonization process. This metal‐free hybrid catalyst exhibits enhanced ORR activity and better stabilities against long duration and the methanol crossover effect than the commercial Pt/C catalyst in 0.1 M KOH. Notably, when the NCN@CF hybrid was used as an air electrode catalyst in a Zn‐air battery, the as‐fabricated battery presented a larger peak power density of 168 mW cm−2, higher specific capacity of 720.5 mA h g−1 and energy density of 900.0 Wh kg−1 compared to those based on commercial Pt/C and most N‐doped carbon catalysts ever reported, evidencing its highly promising use as a Pt‐alternative catalyst for the ORR.
Flow‐Assisted Self‐Organization of Hybrid Membranes
Authors: Wang Qingpu , Steinbock Oliver 
Published: June 2019

AbstractMicrofluidic flows are a powerful tool to drive reactions far from equilibrium and, thus, induce chemical selforganization. Studies of membrane formation in microfluidic devices have been limited to non‐redox and purely inorganic reactions. Here, the formation of hybrid membranes at the interface of AgNO3 and 3,3′,5,5′‐tetramethylbenzidine solutions, which are steadily co‐injected into a microfluidic device, is reported. The membrane thickening occurs in both directions and reveals oscillatory dynamics. The hybrid membrane mainly consists of hair‐like Ag microstructures, Ag nanowires, and unbranched TMB–TMB2+ microfibers. Branched dendrite‐like fibers form on the TMB side when the flow is stopped. These components were characterized with techniques including micro‐Raman and energy dispersive X‐ray spectroscopy as well as scanning electron microscopy. The effects of initial concentration ratios on the membrane thickening speed and its opaqueness were also studied.
Asymmetric Synthesis of β2‐Aryl Amino Acids through Pd‐Catalyzed Enantiospecific and Regioselective Ring‐Opening Suzuki–Miyaura Arylation of Aziridine‐2‐carboxylates
Authors: Takeda Youhei , Matsuno Tetsuya , Sharma Akhilesh K. , Sameera W. M. C. , Minakata Satoshi 
Published: June 2019

AbstractA Pd‐catalyzed enantiospecific and regioselective ring‐opening Suzuki–Miyaura arylation of aziridine‐2‐carboxylates was developed. The cross‐coupling allows for the asymmetric preparation of enantioenriched β2‐aryl amino acids, starting from commercially available enantiopure d‐ and l‐serine esters. The mechanism and selectivity of the reaction was rationalized based on computational models.
Transition‐Metal‐Free Aryl–Aryl Cross‐Coupling: C−H Arylation of 2‐Naphthols with Diaryliodonium Salts
Authors: Ghosh Manoj K. , Rzymkowski Jan , Kalek Marcin 
Published: June 2019

AbstractTransition‐metal‐free regioselecitive C−H arylation of 2‐naphthols with diaryliodonium salts has been developed. The reaction proceeds under very simple experimental conditions and affords a range of products with various substitution patterns. The method allows for the incorporation of electron‐deficient aryls, which complements well currently existing metal‐free aryl–aryl cross‐couplings of phenols that have been so far restricted to the introduction of electron‐rich aryl moieties. The mechanism of the reaction was studied by means of DFT calculations, demonstrating that the C−C bond formation occurs via a dearomatization of 2‐naphthol substrate, followed by a subsequent rearomatization by tautomerization. The computations show that the use of a low polarity solvent and an insoluble inorganic base is key to securing the high selectivity of the C−C coupling over a competing C−O arylation pathway, by preventing the incipient deprotonation of 2‐naphthol.
Combining 1,3‐Ditriazolylbenzene and Quinoline to Discover a New G‐Quadruplex‐Interactive Small Molecule Active against Cancer Stem‐Like Cells
Authors: Mendes Eduarda , Cadoni Enrico , Carneiro Filipa , Afonso Marta B. , Brito Hugo , Lavrado João , dos Santos Daniel J. V. A. , Vítor Jorge B. , Neidle Stephen , Rodrigues Cecília M. P. , Paulo Alexandra 
Published: June 2019

AbstractQuadruplex nucleic acids are promising targets for cancer therapy. In this study we used a fragment‐based approach to create new flexible G‐quadruplex (G4) DNA‐interactive small molecules with good calculated oral drug‐like properties, based on quinoline and triazole heterocycles. G4 melting temperature and polymerase chain reaction (PCR)‐stop assays showed that two of these compounds are selective G4 ligands, as they were able to induce and stabilize G4s in a dose‐ and DNA sequence‐dependent manner. Molecular docking studies have suggested plausible quadruplex binding to both the G‐quartet and groove, with the quinoline module playing the major role. Compounds were screened for cytotoxicity against four cancer cell lines, where 4,4′‐(4,4′‐(1,3‐phenylene)bis(1H‐1,2,3‐triazole‐4,1‐diyl))bis(1‐methylquinolin‐1‐ium) (1 d) showed the greater activity. Importantly, dose–response curves show that 1 d is cytotoxic in the human colon cancer HT‐29 cell line enriched in cancer stem‐like cells, a subpopulation of cells implicated in chemoresistance. Overall, this study identified a new small molecule as a promising lead for the development of drugs targeting G4 in cancer stem cells.
Nivolumab in patients with advanced hepatocellular carcinoma and Child‐Pugh class B cirrhosis: Safety and clinical outcomes in a retrospective case series
Authors: Kambhampati Thiruvengadam Swetha , Bauer Kelly E. , Bracci Paige M. , Keenan Bridget P. , Behr Spencer C. , Gordan John D. , Kelley Robin K. 
Published: June 2019

BackgroundNivolumab demonstrated durable responses and safety in patients with hepatocellular carcinoma (HCC) with Child‐Pugh class A cirrhosis in the CheckMate 040 trial, with rates of hepatotoxicity that were similar to those of non‐HCC populations. To the authors' knowledge, the safety and efficacy of nivolumab has not been established in patients with Child‐Pugh class B (CPB) cirrhosis, a population with limited therapeutic options and a poor prognosis.MethodsThe authors conducted a retrospective case series of patients with advanced HCC and CPB cirrhosis who were treated with nivolumab and enrolled in the University of California at San Francisco Hepatobiliary Tissue Bank and Registry. Safety endpoints included rates of grade ≥3 adverse events (AEs) (graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events [version 4.03]) and serious AEs, immune‐related AEs (irAE), steroid requirement, and discontinuation. Efficacy endpoints included time on treatment, the objective response rate according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, overall survival, and progression‐free survival.ResultsA total of 18 patients were included, with 72% of them (13 of 18 patients) previously treated with sorafenib. The majority of patients (94%; 17 of 18 patients) experienced a grade ≥3 AE, with treatment‐related grade ≥3 AEs reported in 28% of patients (5 of 18 patients). irAEs were reported to occur in approximately 50% of patients (9 of 18 patients), and 28% (5 of 18 patients) required steroids. Treatment‐related AEs required discontinuation in 4 patients (22%). The median time on treatment was 2.3 months (95% CI, 1.9 months to upper bound not estimable). The objective response rate was 17% (3 of 18 patients), including 2 partial responses and 1 complete response. The median overall survival from the time of nivolumab initiation was 5.9 months (95% CI, 3 months to upper bound not estimable), with a median progression‐free survival of 1.6 months (95% CI, 1.4‐3.5 months).ConclusionsPatients with CPB HCC experienced high rates of AEs, although the frequency of irAEs was similar to that of patients with Child‐Pugh class A HCC in the CheckMate 040 trial. A subset of patients experienced prolonged tumor responses. Nivolumab warrants further study in patients with CPB HCC.
Diagnostic predictive value of the Bladder EpiCheck test in the follow‐up of patients with non–muscle‐invasive bladder cancer
Authors: Trenti Emanuela , D'Elia Carolina , Mian Christine , Schwienbacher Christine , Hanspeter Esther , Pycha Alexander , Kafka Mona , Degener Stephan , Danuser Hansjörg , Roth Stephan , Pycha Armin 
Published: June 2019

BackgroundThe objective of this study was to evaluate the diagnostic accuracy of the Bladder EpiCheck test in the follow‐up of patients with non–muscle‐invasive bladder cancer (NMIBC) and to compare it with the accuracy of urinary cytology, cystoscopy, and/or histology.MethodsIn total, 243 patients were enrolled in the current study. Patients were evaluated by voided urine cytology, by the Bladder EpiCheck test, and by white‐light cystoscopy.ResultsOverall sensitivity was 33.3% for cytology, 62.3% for Bladder EpiCheck, and 66.7% for the 2 tests combined. The sensitivity of cytology increased from 7.7% in low‐grade (LG) tumors to 66.6% in high‐grade (HG) tumors; whereas, for the Bladder EpiCheck test, the sensitivity was 46.1% in LG tumors and 83.3% in HG tumors. Combined cytology and Bladder EpiCheck testing yielded an overall sensitivity of 56.4% for LG tumors and 90% for HG tumors. Overall specificity was 98.6% for cytology, 86.3% for Bladder EpiCheck, and 85.6% for the 2 tests combined. The positive predictive value was 92% for cytology and 68.2% for Bladder EpiCheck. For the 2 tests combined, it was 68.6%. The negative predictive value was similar for the 2 tests: 75.8% for cytology, 82.9% for Bladder EpiCheck, and 84.5% for the 2 tests combined.ConclusionsThe sensitivity of the Bladder EpiCheck test was significantly higher than that of cytology. The test performed very well in terms of specificity but could not reach the high value of cytology. The positive predictive value was higher for Bladder EpiCheck, whereas the negative predictive value was approximately the same for both tests.
Can Cyanuric Acid and 2,4,6‐Triaminopyrimidine Containing Ribonucleosides be Components of Prebiotic RNA? Insights from QM Calculations and MD Simulations
Authors: Kaur Sarabjeet , Sharma Purshotam , Wetmore Stacey D. 
Published: June 2019

AbstractThe front cover artwork is provided by the groups of Dr. Purshotam Sharma (Panjab University) and Prof. Stacey Wetmore (University of Lethbridge). The image highlights the plausible relevance of cyanuric acid and 2,4,6‐triaminopyrimidine as nucleobases of prebiotic RNA assemblies. Read the full text of the Article at 10.1002/cphc.201900237.