bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of Dose‐Intense Ifosfamide, with and Without Edatrexate, in Adults with Sarcoma
Authors: Casper Ephraim S. , Schwartz Gary M. , Leung Denis , Sugarman Alison , Bertino Joseph R. 
Published: July 2002

Purpose. To define the maximally tolerated dose (MTD) of ifosfamide
when given with G‐CSF on an every other week schedule, and to define the MTD of
edatrexate that can be given every two weeks with an intense schedule of ifosfamide.Patients and Methods. Forty‐one patients with metastatic or unresectable,
locally advanced sarcoma participated in this 2‐step phase I trial.The starting dose of
ifosfamide was 10 gm/m2
given by continuous intravenous infusion over 4 days every
2 weeks.When the MTD was defined, edatrexate, beginning at a dose of 40 mg/m2
intravenously every 2 weeks was added in subsequent cohorts of patients.Results. Myelosuppression was the most prominent toxicity.
Fatigue, nausea, and vomiting were observed in the majority of patients. Ifosfamide
12 gm/m2 given every 2 weeks approached or exceeded the MTD. Edatrexate 100 mg/m2
could be given safety as an intravenous bolus with ifosfamide 10 gm/m2 every 2 weeks.
Therapeutic responses were observed in patients with measurable disease.Conclusions. This study demonstrates the feasibility of administering
a dose‐intense schedule of ifosfamide alone or ifosfamide with edatrexate that might be
applied in the adjuvant or neo‐adjuvant setting.
New scoring schemes for protein fold recognition based on Voronoi contacts.
Authors: Zimmer R , W√∂hler M , Thiele R 
Published: July 2002

Abstract
MOTIVATION: The genome projects produce a wealth of protein sequences. Theoretical methods to predict possible structures and functions are needed for screening purposes, large-scale comparisons and in-depth analysis to identify worthwhile targets for further experimental research. Sequence-structure alignment is a basic tool for the identification of model folds for protein sequences and the construction of crude structural models. Empirical contact potentials (potentials of mean force) are used to optimize and evaluate such alignments. RESULTS: We propose new scoring schemes based on a contact definition derived from Voronoi decompositions of the three-dimensional coordinates of protein structures. We demonstrate that Voronoi potentials are superior to pure distance-based contact potentials with respect to recognition rate and significance for native folds. Moreover, the scoring scheme has the potential to provide a reasonable balance of detail and ion such that it is also useful for the recognition of distantly related (both homologous and non-homologous) proteins. This is demonstrated here on a set of structural alignments showing much better correspondence of native and model scores for the Voronoi potentials as compared to conventional distance-based potentials. AVAILABILITY: The potentials are made available via the program system ToPLign (URL: http://cartan.gmd.de/ToPLign.html). CONTACT: Ralf.Zimmer,Ralf.Thiele@gmd.de
Clinical effectiveness of levofloxacin in patients with acute purulent exacerbations of chronic bronchitis: the relationship with in-vitro activity
Authors: Davies B. I. , Maesen F. P. V. 
Published: July 2002

Abstract
The objective of this randomized, double-blind study was to compare the clinical efficacy of levofloxacin at two different dosages with that of cefuroxime axetil in patients with acute purulent exacerbations of chronic bronchitis and, in particular, to assess the impact of the susceptibility to levofloxacin on the clinical findings. In total, 124 evaluable patients were treated for 7 days with oral levofloxacin 250 mg or 500 mg od, or cefuroxime axetil 250 mg bd. Sputum cultures were monitored pre-treatment, and at 1 and 7 days after the end of treatment. The susceptibility of Streptococcus pneumoniae isolates was tested by agar dilution in Columbia blood agar and by disc diffusion, but all other isolates were tested solely by the disc diffusion method. A greater number of infections were eradicated by levofloxacin than by cefuroxime axetil: infections were eradicated in 68% of patients receiving the 500 mg dosage and in 63% of those taking 250 mg levofloxacin, whereas the eradication rate with the comparator drug was much lower (48%). Against all pre-treatment S. pneumoniae isolates ( n = 39), the MICs of levofloxacin were between 0.25 and 2 mg/L (geometric mean 0.95 mg/L), similar to those of the post-treatment strains ( n = 32; mean 1.11 mg/L). All except one of the S. pneumoniae isolates were susceptible to penicillin G (MIC ≤ 0.06 mg/L), and the remaining isolate was inhibited by 0.5 mg/L of penicillin G, but was fully susceptible to levofloxacin. Some pre-treatment strains of Pseudomonas aeruginosa were resistant to levofloxacin, but many more resistant strains were encountered afterwards. All strains of Moraxella catarrhalis and Haemophilus influenzae were highly susceptible to levofloxacin in the disc diffusion tests. All the antimicrobial agents used in the study were well tolerated: only two patients discontinued treatment because of adverse drug effects. The results of this study indicated that, although there were some failures in patients with S. pneumoniae and P. aeruginosa infections, resistance to levofloxacin did not emerge rapidly among strains of S. pneumoniae during therapy with levofloxacin, and that natural resistance among pneumococci, H. influenzae and M. catarrhalis was rare.
Analysis of the 5S RNA Pool in Arabidopsis thaliana: RNAs Are Heterogeneous and Only Two of the Genomic 5S Loci Produce Mature 5S RNA
Authors: Cloix Catherine , Tutois Sylvie , Yukawa Yasushi , Mathieu Olivier , Cuvillier Claudine , Espagnol Marie-Claude , Picard Georges , Tourmente Sylvette 
Published: July 2002

One major 5S RNA, 120 bases long, was revealed by an analysis of mature 5S RNA from tissues, developmental stages, and polysomes inArabidopsis thaliana. Minor 5S RNA were also found, varying from the major one by one or two base substitutions; 5S rDNA units from each 5S array of the Arabidopsis genome were isolated by PCR using CIC yeast artificial chromosomes (YACs) mapped on the different loci. By using a comparison of the 5S DNA and RNA sequences, we could show that both major and minor 5S transcripts come from only two of the genomic 5S loci: chromosome 4 and chromosome 5 major block. Other 5S loci are either not transcribed or produce rapidly degraded 5S transcripts. Analysis of the 5′- and 3′-DNA flanking sequence has permitted the definition of specific signatures for each 5S rDNA array.[EMBL accession nos: AF330825-AF331032;AF335777-AF335873.]
Structures of an unliganded neurophysin and its vasopressin complex: Implications for binding and allosteric mechanisms
Authors: Wu Chia Kuei , Hu Bing , Rose John P. , Liu Zhi‐Jie , Nguyen Tam L. , Zheng Changsheng , Breslow Esther , Wang Bi‐Cheng 
Published: July 2002

AbstractThe structures of des 1–6 bovine neurophysin‐II in the unliganded state and as its complex with lysine vasopressin were determined crystallographically at resolutions of 2.4 Å and 2.3 Å, respectively. The structure of the protein component of the vasopressin complex was, with some local differences, similar to that determined earlier of the full‐length protein complexed with oxytocin, but relatively large differences, probably intrinsic to the hormones, were observed between the structures of bound oxytocin and bound vasopressin at Gln 4. The structure of the unliganded protein is the first structure of an unliganded neurophysin. Comparison with the liganded state indicated significant binding‐induced conformational changes that were the largest in the loop region comprising residues 50–58 and in the 7–10 region. A subtle binding‐induced tightening of the subunit interface of the dimer also was shown, consistent with a role for interface changes in neurophysin allosteric mechanism, but one that is probably not predominant. Interface changes are suggested to be communicated from the binding site through the strands of β‐sheet that connect these two regions, in part with mediation by Gly 23. Comparison of unliganded and liganded states additionally reveals that the binding site for the hormone α‐amino group is largely preformed and accessible in the unliganded state, suggesting that it represents the initial site of hormone protein recognition. The potential molecular basis for its thermodynamic contribution to binding is discussed.
Phenotypic differences between Edwardsiella piscicida and Edwardsiella anguillarum isolates in Japan
Authors: Sugiura Hidehiro , Fukunishi Kosuke , Kawakami Hidemasa , Imajoh Masayuki 
Published: August 2022

Abstract

Objective
Edwardsiella tarda has been regarded as the causative agent of edwardsiellosis in cultured marine and freshwater fish species in Japan. Our previous study genetically classified an E. tarda-like isolate from diseased Olive Flounder Paralichthys olivaceus as E. piscicida and that from diseased Red Seabream Pagrus major as E. anguillarum. This study aimed to understand the phenotypic differences between E. piscicida and E. anguillarum.

Methods
Fourteen E. piscicida and seven E. anguillarum isolates were used in this study. The colonies of each isolate were grown on brain–heart infusion agar plates and then subjected to DNA extraction. The extracted DNA was amplified using PCR. carbohydrate fermentation of the isolates was examined using API 50 CH test kits. Moreover, the growth of the two species was examined in defined media. Also, free amino acids in Olive Flounder and Red Seabream sera were detected and quantified via high-performance liquid chromatography–mass spectrometry. Statistical differences in the concentrations of free amino acids were analyzed using Welch's t-tests.

Result
The API 50 CH test revealed that L-arabinose and D-mannitol were fermented by E. anguillarum isolates but not E. piscicida isolates. Furthermore, the growth of E. piscicida and E. anguillarum was reduced in the defined medium without methionine and iron sulfate. The growth of E. piscicida was reduced in the defined medium without phenylalanine, tyrosine, alanine, or nicotinic acid, whereas the growth of E. anguillarum was reduced in the defined medium without serine, cysteine, leucine, threonine, or isoleucine. Tyrosine and alanine were present in higher concentrations in the Olive Flounder serum, whereas threonine and isoleucine were present in higher concentrations in the Red Seabream serum, suggesting favorable growth conditions for E. piscicida and E. anguillarum.

Conclusion
This study characterizes a minimal defined medium that can be used for developing vaccines against E. piscicida and E. anguillarum.
Stably Immobilizing Sub‐3 nm High‐Entropy Pt Alloy Nanocrystals in Porous Carbon as Durable Oxygen Reduction Electrocatalyst
Authors: Zhang Wenjing , Feng Xin , Mao Zhan Xin , Li Jing , Wei Zidong 
Published: August 2022

AbstractImmobilizing ultrafine high‐entropy Pt alloy nanocrystals (HENs) in porous carbon (PC) with strong interface interaction, which is crucial to efficient and durable oxygen reduction reaction (ORR), remains a challenge. In this study, an anchoring‐carbonization strategy for strongly bonding sub‐3 nm HENs in ordered mesoporous carbon is reported. When heating the orderly assembled composites containing hydrophobic organometallic precursors, structure directing agent F127, and hydrophilic resol, F127 is first removed at moderate temperature region, leading to reduced metallic species directly anchored on partially carbonized resol framework. Then along further temperature increase, in situ carbonization of resol around the HENs, enables more effective plane bonding rather than a single point contact of HENs with carbon. It not only enhances the anchor strength, but also inhibits migration and size growth of HENs along the subsequent high‐temperature carbonization. As a result, senary, septenary, octonary, and denary Pt‐based HENs with average nanocrystal sizes of 2.2, 2.6, 2.9, and 2.8 nm, respectively, are successfully imbedded into porous carbon. In electrocatalytic ORR, porous carbon‐supported senary Pt‐based HENs (6‐HENs/PC) exhibit superior activity and durability, representing a promising electrocatalyst. This strategy allows for the preparation of a range of ultrafine HENs strongly loaded on porous carbon for wide applications.
Efficient and Stable 3D/2D Perovskite Solar Cells through Vertical Heterostructures with (BA)4AgBiBr8 Nanosheets
Authors: Zhao Dan , Gao Danpeng , Wu Xin , Li Bo , Zhang Shoufeng , Li Zhen , Wang Qi , Wu Zongxiao , Zhang Chunlei , Choy Wallace C. H. , Zhong Xiaoyan , He Qiyuan , Zhu Zonglong 
Published: August 2022

AbstractPerovskite solar cells (PVSCs) have drawn great attention due to their high processability and superior photovoltaic properties. However, their further development is often hindered by severe nonradiative recombination at interfaces that decreases power conversion efficiency (PCE). To this end, a facile strategy to construct a 3D/2D vertical heterostructure to reduce the energy loss in PVSCs is developed. The heterostructure is contrived through the van der Waals integration of 2D perovskite ((BA)4AgBiBr8) nanosheets onto the surface of 3D‐FAPbI3‐based perovskites. The large bandgap of (BA)4AgBiBr8 enables the formation of type‐I heterojunction with 3D‐FAPbI3‐based perovskites, which serves as a barrier to suppress the trap‐assisted recombination at the interface. As a result, a satisfying PCE of 24.48% is achieved with an improved open‐circuit voltage (VOC) from 1.13 to 1.17 V. Moreover, the 2D perovskite nanosheets can effectively mitigate the iodide ion diffusion from perovskite to the metal electrode, hence enhancing the device stability. 3D/2D architectured devices retain ≈90% of their initial PCE under continuous illumination or heating after 1000 h, which are superior to 3D‐based devices. This work provides an effective and controllable strategy to construct 3D/2D vertical heterostructure to simultaneously boost the efficiency and stability of PVSCs.
Sequential Drug Release Achieved with Dual‐Compartment Microcontainers: Toward Combination Therapy
Authors: Christfort Juliane Fjelrad , Milián‐Guimerá Carmen , Kamguyan Khorshid , Hansen Morten Borre , Hagner Nielsen Line , Thamdrup Lasse Højlund Eklund , Zór Kinga , Boisen Anja 
Published: August 2022

AbstractCombination drug therapy is commonly used to treat cancer, diabetes, cardiovascular conditions, and infections. However, these therapies face challenges associated with patient compliance and toxicology. Over the past decades, microdevices have emerged as a promising candidate for oral delivery allowing for targeted drug delivery with a tunable drug release. In the present work, engineered and monodisperse dual‐compartment microdevices are developed to achieve a physical separation of two drugs followed by a sequential release in the gastrointestinal tract. As proof‐of‐concept, the compartments are sealed with two pH‐sensitive polymers of different thicknesses to control the sequential release of propranolol and furosemide. In vitro release studies and in vivo absorption studies in rats confirm a sequential drug release from the two compartments. Unlike other proposed approaches, it is highly advantageous that the drugs can be loaded directly as powders, and that their release can be tuned via optimized coatings to achieve the desired release and absorption profiles. Conclusively, this study lays a strong foundation for the future use of microdevices to enable co‐delivery of drugs followed by a sequential release in close proximity in the gastrointestinal tract.
Automated Recognition of Plasmodium falciparum Parasites from Portable Blood Levitation Imaging
Authors: Deshmukh Shreya S. , Byaruhanga Oswald , Tumwebaze Patrick , Akin Demir , Greenhouse Bryan , Egan Elizabeth S. , Demirci Utkan 
Published: August 2022

AbstractIn many malaria‐endemic regions, current detection tools are inadequate in diagnostic accuracy and accessibility. To meet the need for direct, phenotypic, and automated malaria parasite detection in field settings, a portable platform to process, image, and analyze whole blood to detect Plasmodium falciparum parasites, is developed. The liberated parasites from lysed red blood cells suspended in a magnetic field are accurately detected using this cellphone‐interfaced, battery‐operated imaging platform. A validation study is conducted at Ugandan clinics, processing 45 malaria‐negative and 36 malaria‐positive clinical samples without external infrastructure. Texture and morphology features are extracted from the sample images, and a random forest classifier is trained to assess infection status, achieving 100% sensitivity and 91% specificity against gold‐standard measurements (microscopy and polymerase chain reaction), and limit of detection of 31 parasites per µL. This rapid and user‐friendly platform enables portable parasite detection and can support malaria diagnostics, surveillance, and research in resource‐constrained environments.
Catalytic Disproportionation for Suppressing Polysulfide Shuttle in Li–S Pouch Cells: Beyond Adsorption Interactions
Authors: Lin Yilong , Zhou Yecheng , Huang Sheng , Xiao Min , Han Dongmei , Qin Jiaxiang , Wang Shuanjin , Meng Yuezhong 
Published: August 2022

AbstractAddressing the lithium polysulfide shuttle is critical for the high‐energy‐density lithium–sulfur pouch cells in practical applications, especially under high sulfur loading and lean electrolyte conditions. In contrast to previously reported heterogeneous adsorption catalysis within cathode or separator with slow catalytic kinetics and limited adsorption area, herein, lithium difluorophosphate (LiPO2F2) is demonstrated as a homogeneous catalyst in electrolyte which mitigates polysulfide diffusion. The Li–S pouch cell with LiPO2F2 in the electrolyte has record‐breaking shelving stability of two months, significantly improved capacity retention from 37.0% to 81.4% after long cycling, and electrical‐car‐level energy density over 400 Wh kg−1. A minimal amount of 1 wt% LiPO2F2 tends to facilitate lithium polysulfide disproportionation on the S/C cathode instead of in the electrolyte, which initiates the fast transformation of soluble lithium polysulfide to insoluble solid S8 and Li2S2/Li2S. The reliable mechanism of polysulfide disproportionation via biradicals is further proposed by both density functional theory calculation and experiments. To best of the authors’ knowledge, this is the first report on mechanism of polysulfide disproportionation via biradical intermediates. It is believed that this new insight into homogeneous catalytic mechanisms in electrolytes may pave the way for the commercialization of high‐energy‐density Li–S batteries.
Biomass‐derived Sugar Ionic Liquid as a Sustainable Organocatalyst: An Efficient Synthesis of Functionalized Dihydropyrano Coumarins
Authors: Garg Pooja , Reddy Sabbasani Rajasekhara 
Published: August 2022

AbstractMulti‐component reaction approach was utilized in the synthesis of dihydropyrano coumarins under mild reaction conditions. Biomass derived carbohydrate was used as sugar source for the formation of D‐ribose based sugar ionic liquid. The developed catalyst catalyzed efficient synthesis of these hetero atom functionalized compounds. A wide range of substrates were prepared with substituted aliphatic or aromatic aldehydes. Substitution in phenyl ring did not affect the rate of reaction much. All compounds were obtained in good to excellent yield up to 76–92%. The recyclablity of the catalyst was also examined.
Accessing hearing‐health services for deaf and hard‐of‐hearing children during the COVID‐19 pandemic: Parent and child perspectives
Authors: Mardinli Ahmed , Weerasuriya Rona , Gillespie Alanna , Smith Libby , Sung Valerie 
Published: August 2022

AbstractTo describe hearing‐health service use, especially use of telehealth, during the early stages of the COVID‐19 pandemic in deaf/hard‐of‐hearing children. In 2020, the Victorian Childhood Hearing Longitudinal Databank surveyed 497 (61.6%) families of deaf/hard‐of‐hearing children aged 0.4–19.6 years, with 449 (90.3%) providing quantitative data and 336 (67.6%) providing free‐text comments about COVID‐19's impact on service use and access. We summarised quantitative data using descriptive statistics and analysed free‐text responses using inductive and deductive reasoning. Of the 1152 services families used during the pandemic, 711 (62%) were accessed via telehealth. Parents reported several challenges and facilitators of service access during the pandemic, particularly regarding telehealth. Parents reported that their child found telehealth appointments more difficult (347/665, 52.1%) and of worse quality (363/649, 55.9%) compared to in‐person. These difficulties were more evident in pre‐school than school‐age children. Consideration of these factors when implementing telehealth practice beyond the pandemic would improve family experiences, ensuring quality of care.
Modular Construction of Heterobiaryl Atropisomers and Axially Chiral Styrenes via All‐Carbon Tetrasubstituted VQMs
Authors: Gou Bo‐Bo , Tang Yue , Lin Yan‐Hong , Yu Le , Jian Qing‐Song , Sun Huai‐Ri , Chen Jie , Zhou Ling 
Published: August 2022

AbstractHere we report a new type of chiral all‐carbon tetrasubstituted VQMs generated via chiral phosphoric acids catalyzed nucleophilic addition of 2‐alkynylnaphthols too‐quinone methides or imines, which can be captured intramolecularly as a result of cycloaddition reaction. A new class of naphthyl‐2H‐chromenes bearing axially and centrally chiral elements and axially chiral quinone‐naphthols were prepared efficiently with good to excellent yields, diastereoselectivities and enantioselectivities. Noteworthy, the enantioselective cycloaddition of alkynylnaphthols witho‐quinone methides proceeded via a [2+2] cycloaddition, followed by a retro‐4π‐electrocyclization and a 6π re‐cyclization. While the cycloaddition of alkynylnaphthols with imines proceeded via a sequential [2+4] cycloaddition and an auto oxidation reaction. Moreover, the obtained axially chiral naphthols can be converted into valuable phosphine ligands and other functional molecules.
Identification of a Novel Pseudo‐Natural Product Type IV IDO1 Inhibitor Chemotype
Authors: Davies Caitlin , Dötsch Lara , Ciulla Maria Gessica , Hennes Elisabeth , Yoshida Kei , Gasper Raphael , Scheel Rebecca , Sievers Sonja , Strohmann Carsten , Kumar Kamal , Ziegler Slava , Waldmann Herbert 
Published: August 2022

AbstractNatural product (NP)‐inspired design principles provide invaluable guidance for bioactive compound discovery. Pseudo‐natural products (PNPs) are de novo combinations of NP fragments to target biologically relevant chemical space not covered by NPs. We describe the design and synthesis of apoxidoles, a novel pseudo‐NP class, whereby indole‐ and tetrahydropyridine fragments are linked in monopodal connectivity not found in nature. Apoxidoles are efficiently accessible by an enantioselective [4+2] annulation reaction. Biological evaluation revealed that apoxidoles define a new potent type IV inhibitor chemotype of indoleamine 2,3‐dioxygenase 1 (IDO1), a heme‐containing enzyme considered a target for the treatment of neurodegeneration, autoimmunity and cancer. Apoxidoles target apo‐IDO1, prevent heme binding and induce unique amino acid positioning as revealed by crystal structure analysis. Novel type IV apo‐IDO1 inhibitors are in high demand, and apoxidoles may provide new opportunities for chemical biology and medicinal chemistry research.