bluuebunny/crossref_metadata_2025_split huggingface dataset:
Garenoxacin (BMS-284756) and Moxifloxacin in Experimental Meningitis Caused by Vancomycin-Tolerant Pneumococci
Authors: Rodriguez-Cerrato Violeta , McCoig Cindy C. , Saavedra Jesus , Barton Tess , Michelow Ian C. , Hardy Robert D. , Bowlware Karen , Iglehart Janie , Katz Kathy , McCracken George H. 
Published: December 2002

ABSTRACT

The emergence of multidrug-resistant strains of
Streptococcus pneumoniae
drives the development and evaluation of new antipneumococcal agents, especially for the treatment of bacterial meningitis. The aims of the present study were to assess the antibacterial effectiveness of two new quinolones, garenoxacin (BMS; BMS-284756) and moxifloxacin (MOX) in experimental meningitis caused by a vancomycin (VAN)-tolerant
S. pneumoniae
strain and to compare the results with those obtained by therapy with VAN and ceftriaxone (CRO) in combination. Meningitis was induced in young male New Zealand White rabbits by intracisternal inoculation of a VAN-tolerant pneumococcal strain (strain Tupelo) from a child with meningitis. Sixteen hours after inoculation, therapy was given by intravenous administration of BMS at 20 mg/kg of body weight, followed 5 h later by administration at a dosage of 10 mg/kg (
n
= 9 animals) or MOX as two doses of 20 mg/kg every 5 h (
n
= 8 animals). For comparison, we studied the following groups: (i) animals treated with VAN (20 mg/kg every 5 h, three doses) and CRO (125 mg/kg, one dose) (
n
= 9), (ii) animals infected with a VAN-tolerant strain but not treated (
n
= 8), (iii) animals infected with a VAN-tolerant pneumococcus isolated from the nasopharynx of a carrier and treated with BMS (
n
= 8), and (iv) animals infected with a cephalosporin-resistant type 6B
S. pneumoniae
strain and treated with BMS (
n
= 6). The MICs of penicillin, CRO, VAN, BMS, and MOX for the Tupelo strain were 2, 1, 0.5, 0.06, and 0.03 μg/ml, respectively. The rates of killing of strain Tupelo (the change in the log
10
number of CFU per milliliter per hour) in cerebrospinal fluid at 5 h were −0.70 ± 0.35, −0.61 ± 0.44, and −0.49 ± 0.36 for BMS, MOX, and VAN-CRO, respectively. Therapy with BMS and MOX was as effective as therapy with VAN-CRO against VAN-tolerant pneumococcal meningitis in rabbits.
Combination of Drug Level Measurement and Parasite Genotyping Data for Improved Assessment of Amodiaquine and Sulfadoxine-Pyrimethamine Efficacies in Treating
Plasmodium falciparum
Malaria in Gabonese Children
Authors: Aubouy Agnès , Bakary Mohamed , Keundjian Annick , Mbomat Bernard , Makita Jean Ruffin , Migot-Nabias Florence , Cot Michel , Le Bras Jacques , Deloron Philippe 
Published: December 2002

ABSTRACT

Many African countries currently use a sulfadoxine-pyrimethamine combination (SP) or amodiaquine (AQ) to treat uncomplicated
Plasmodium falciparum
malaria. Both drugs represent the last inexpensive alternatives to chloroquine. However, resistant
P. falciparum
populations are largely reported in Africa, and it is compulsory to know the present situation of resistance. The in vivo World Health Organization standard 28-day test was used to assess the efficacy of AQ and SP to treat uncomplicated
falciparum
malaria in Gabonese children under 10 years of age. To document treatment failures, molecular genotyping to distinguish therapeutic failures from reinfections and drug dosages were undertaken. A total of 118 and 114 children were given AQ or SP, respectively, and were monitored. SP was more effective than AQ, with 14.0 and 34.7% of therapeutic failures, respectively. Three days after initiation of treatment, the mean level of monodesethylamodiaquine (MdAQ) in plasma was 149 ng/ml in children treated with amodiaquine. In those treated with SP, mean levels of sulfadoxine and pyrimethamine in plasma were 100 μg/ml and 212 ng/ml, respectively. Levels of the three drugs were higher in patients successfully treated with AQ (MdAQ plasma levels) or SP (sulfadoxine and pyrimethamine plasma levels). Blood concentration higher than breakpoints of 135 ng/ml for MdAQ, 100 μg/ml for sulfadoxine, and 175 ng/ml for pyrimethamine were associated with treatment success (odds ratio: 4.5, 9.8, and 11.8, respectively; all
P
values were <0.009). Genotyping of merozoite surface proteins 1 and 2 demonstrated a mean of 4.0 genotypes per person before treatment. At reappearance of parasitemia, both recrudescent parasites (represented by common bands in both samples) and newly inoculated parasites (represented by bands that were absent before treatment) were present in the blood of most (51.1%) children. Only 3 (6.4%) therapeutic failures were the result not of treatment inefficacy but of new infection. In areas where levels of drug resistance and complexity of infections are high, drug dosage and parasite genotyping may be of limited interest in improving the precision of drug efficacy measurement. Their use should be weighted according to logistical constraints.
Genetic and Functional Analysis of the Chromosome-Encoded Carbapenem-Hydrolyzing Oxacillinase OXA-40 ofAcinetobacter baumannii
Authors: Héritier Claire , Poirel Laurent , Aubert Daniel , Nordmann Patrice 
Published: December 2002

ABSTRACTClinical isolateAcinetobacter baumanniiCLA-1 was resistant to a series of antibiotic molecules, including carbapenems. Cloning and expression of the β-lactamase gene content of this isolate inEscherichia coliDH10B identified a chromosome-encoded oxacillinase, OXA-40, that differed by one or two amino acid changes from OXA-24, -25, and -26 and an AmpC-type cephalosporinase. The OXA-40 β-lactamase had a mainly narrow-spectrum hydrolytic profile, but it included ceftazidime and imipenem. Its activity was resistant to inhibition by clavulanic acid, tazobactam, sulbactam, and, like most of the other carbapenem-hydrolyzing oxacillinases, NaCl. OXA-40 had an FGN triad replacing a YGN motif at class D β-lactamase (DBL) positions 144 to 146. Site-directed DNA mutagenesis leading to a Phe-to-Tyr change at DBL position 144 in OXA-40 gave a mutant enzyme with increased hydrolytic activity against most β-lactams, including imipenem. Conversely, with a gene encoding the narrow-spectrum oxacillinase OXA-1 as the template, a nucleotide substitution leading to a Tyr-to-Phe change in the YGN motif of OXA-1 gave a mutant enzyme with decreased hydrolytic activity without an increase in carbapenem-hydrolyzing activity. Thus, the Phe residue in the FGN motif was not associated with carbapenem-hydrolyzing activity by itself but instead was associated with weak overall hydrolytic activity. Finally, this Phe residue in OXA-40 explained resistance to inhibition by NaCl whereas a Tyr residue in motif YGN was related to susceptibility to NaCl.
In Vitro Activities of Daptomycin, Vancomycin, Quinupristin- Dalfopristin, Linezolid, and Five Other Antimicrobials against 307 Gram-Positive Anaerobic and 31
Corynebacterium
Clinical Isolates
Authors: Goldstein Ellie J. C. , Citron Diane M. , Merriam C. Vreni , Warren Yumi A. , Tyrrell Kerrin L. , Fernandez Helen T. 
Published: December 2002

ABSTRACT

The activities of daptomycin, a cyclic lipopeptide, and eight other agents were determined against 338 strains of gram-positive anaerobic bacteria and corynebacteria by the NCCLS reference agar dilution method with supplemented brucella agar for the anaerobes and Mueller-Hinton agar for the corynebacteria. The daptomycin MICs determined on Ca
2+
-supplemented (50 mg/liter) brucella agar plates were one- to fourfold lower than those determined in unsupplemented media. Daptomycin was highly active (MICs, ≤2 μg/ml) against many strains including 36 of 37 peptostreptococci, 37 of 48 isolates of the
Eubacterium
group, and all strains of
Propionibacterium
spp.,
Clostridium perfringens
,
Clostridium difficile
, and other
Clostridium
spp. It was fourfold or greater more active than vancomycin against
Clostridium innocuum
and 16 of 34 strains of vancomycin-resistant lactobacilli. Three strains of
C. difficile
for which quinupristin-dalfopristin and linezolid MICs were >8 μg/ml were inhibited by <1 μg of daptomycin per ml. Daptomycin MICs were ≥4 μg/ml for most strains of
Clostridium clostridioforme
,
Clostridium paraputrificum
,
Clostridium tertium
, and
Clostridium ramosum
; the isolates were generally more resistant to other antimicrobials. Daptomycin was two- to fourfold less active against
Actinomyces
spp. than vancomycin, quinupristin-dalfopristin, or linezolid. Twenty-nine of 31 strains of
Corynebacterium
spp., including
Corynebacterium jeikeium
,
Corynebacterium amycolatum
, and
Corynebacterium pseudodiphtheriticum
, were inhibited by ≤0.25 μg of daptomycin per ml. For two strains of “
Corynebacterium aquaticum
,” 8 μg of daptomycin per ml was required for inhibition. Daptomycin demonstrated very good activities against a broad range of gram-positive organisms including vancomycin-resistant
C. innocuum
and lactobacillus strains and quinupristin-dalfopristin- and linezolid-resistant
C. difficile
strains.
In Vitro Activities of Linezolid against Clinical Isolates of
Mycobacterium tuberculosis
That Are Susceptible or Resistant to First-Line Antituberculous Drugs
Authors: Alcalá Luis , Ruiz-Serrano María Jesús , Pérez-Fernández Turégano Cristina , García de Viedma Darío , Díaz-Infantes Marisol , Marín-Arriaza Mercedes , Bouza Emilio 
Published: December 2002

ABSTRACT

We evaluated 117 isolates of
Mycobacterium tuberculosis
for susceptibility to linezolid by the proportion and E-test methods. Linezolid showed high in vitro activity, with all the strains inhibited by ≤1 μg of the drug per ml. E-test MICs were at least 4 dilutions lower than their equivalents by the standard proportion method.
Activation and Deactivation of a Broad-Spectrum Antiviral Drug by a Single Enzyme: Adenosine Deaminase Catalyzes Two Consecutive Deamination Reactions
Authors: Wu Jim Zhen , Walker Heli , Lau Johnson Y. N. , Hong Zhi 
Published: December 2002

ABSTRACT
Ribavirin is an approved broad-spectrum antiviral drug. A liver-targeting prodrug of ribavirin, viramidine, is in clinical trial in an attempt to provide a better therapeutic index. The conversion of viramidine to ribavirin, and of ribavirin to an inactive metabolite through adenosine deaminase, is reported. Kinetic analysis indicates that adenosine deaminase is likely involved in activation of viramidine in vivo, and the process is highly pH sensitive. The differential activities of two consecutive deamination reactions are kinetically studied and interpreted based on adenosine deaminase structural information. A comprehensive understanding of the viramidine and ribavirin deamination mechanism should help in designing better nucleoside therapeutics in the future.
Clinical
Trichophyton rubrum
Strain Exhibiting Primary Resistance to Terbinafine
Authors: Mukherjee Pranab K. , Leidich Steven D. , Isham Nancy , Leitner Ingrid , Ryder Neil S. , Ghannoum Mahmoud A. 
Published: December 2002

ABSTRACT

The in vitro antifungal susceptibilities of six clinical
Trichophyton rubrum
isolates obtained sequentially from a single onychomycosis patient who failed oral terbinafine therapy (250 mg/day for 24 weeks) were determined by broth microdilution and macrodilution methodologies. Strain relatedness was examined by random amplified polymorphic DNA (RAPD) analyses. Data obtained from both broth micro- and macrodilution assays were in agreement and revealed that the six clinical isolates had greatly reduced susceptibilities to terbinafine. The MICs of terbinafine for these strains were >4 μg/ml, whereas they were <0.0002 μg/ml for the susceptible reference strains. Consistent with these findings, the minimum fungicidal concentrations (MFCs) of terbinafine for all six strains were >128 μg/ml, whereas they were 0.0002 μg/ml for the reference strain. The MIC of terbinafine for the baseline strain (cultured at the initial screening visit and before therapy was started) was already 4,000-fold higher than normal, suggesting that this is a case of primary resistance to terbinafine. The results obtained by the broth macrodilution procedure revealed that the terbinafine MICs and MFCs for sequential isolates apparently increased during the course of therapy. RAPD analyses did not reveal any differences between the isolates. The terbinafine-resistant isolates exhibited normal susceptibilities to clinically available antimycotics including itraconazole, fluconazole, and griseofulvin. However, these isolates were fully cross resistant to several other known squalene epoxidase inhibitors, including naftifine, butenafine, tolnaftate, and tolciclate, suggesting a target-specific mechanism of resistance. This is the first confirmed report of terbinafine resistance in dermatophytes.
The impact of roster changes on absenteeism and incident frequency in an Australian coal mine
Authors: Baker A , Heiler K , Ferguson S A 
Published: December 2002

Background:The occupational health and safety implications associated with compressed and extended work periods have not been fully explored in the mining sector.Aims:To examine the impact on employee health and safety of changes to the roster system in an Australian coal mine.Methods:Absenteeism and incident frequency rate data were collected over a 33 month period that covered three different roster schedules. Period 1 covered the original 8-hour/7-day roster. Period 2 covered a 12-month period under a 12-hour/7-day schedule, and period 3 covered a 12-month period during which a roster that scheduled shifts only on weekdays, with uncapped overtime on weekends and days off (12-hour/5-day) was in place. Data were collected and analysed from the maintenance, mining, and coal preparation plant (CPP) sectors.Results:The only significant change in absenteeism rates was an increase in the maintenance sector in the third data collection period. Absenteeism rates in the mining and CPP sectors were not different between data collection periods. The increase in the maintenance sector may be owing to: (1) a greater requirement for maintenance employees to perform overtime as a result of the roster change compared to other employee groups; or (2) greater monotony associated with extended work periods for maintenance employees compared to others. After the first roster change, accident incident frequency decreased in the CPP sector but not in the other sectors. There was no effect on incident frequency after the second roster change in any sector.Conclusions:The current study did not find significant negative effects of a 12-hour pattern, when compared to an 8-hour system. However, when unregulated and excessive overtime was introduced as part of the 12-hour/5-day roster, absenteeism rates were increased in the maintenance sector. The combination of excessive work hours and lack of consultation with employees regarding the second change may have contributed to the overall negative effects.
Metabolic responses in the gills of Yellowtail Lambari Astyanax lacustris under low- and high-temperature thermal stress
Authors: Schleger Ieda Cristina , Pereira Diego Mauro Carneiro , Resende Anna Carolina , Romão Silvia , Herrerias Tatiana , Neundorf Ananda Karla Alves , Souza Maria Rosa Dmengeon Pedreiro , Donatti Lucélia 
Published: January 2024

Abstract

Objective
Ectothermic fish are directly affected by temperature changes in the environment. The aim of this study was to evaluate the metabolic responses in the gills of Yellowtail Lambari Astyanax lacustris under thermal stress.

Methods
To this end, we used spectrophotometry to evaluate the biomarkers of carbohydrate and protein metabolism, antioxidant defense, and oxidative damage in fish subjected to low (15°C) and high (31°C) temperatures, with control groups held at 23°C, for 2, 6, 12, 24, 48, and 96 h.

Result
The results showed that cold thermal stress did not change the energy demand, and the antioxidant defense was reduced; therefore, the gills were vulnerable to the action of reactive oxygen species (ROS), presenting increased protein carbonylation at 12 h. With heat thermal stress, a higher energy demand was observed, which was verified by an increase in aerobic metabolism by glycolysis and the citric acid cycle. High-temperature stress also increased the antioxidant defenses, as verified by the increased activities of glutathione peroxidase, glutathione reductase, and glutathione S-transferase. However, the antioxidant defense system could not protect tissues from the action of ROS, as protein carbonylation increased at 6 and 24 h, indicating oxidative stress.

Conclusion
The results showed that (1) temperature variations caused metabolic adjustments in the gills of Yellowtail Lambari, (2) the adaptive responses were different for winter and summer temperatures, and (3) Yellowtail Lambari recovered homeostasis when subjected to thermal stress, even with the occurrence of oxidative stress.
DNA‐Programmed (De)Hybridization of Near‐Infrared Photosensitized UCNP‐QDs‐GNPs Nanoprobes for MicroRNA Imaging and Image‐Guided Cancer Therapy
Authors: Sun Jie , Geng Jiangtao , Tang Ben Zhong , He Xuewen 
Published: January 2024

AbstractAccurate and sensitive analysis of cancer‐associated microRNAs in living tissue is of great significance for the early diagnosis and treatment of cancer. Herein, a hierarchical nanoprobe denoted as UCNP‐QDs‐GNPs is delicately designed, where a near‐infrared (NIR) absorptive upconversion nanoparticle (UCNP) serves as the core, broad‐absorptive and bright emissive quantum dots (QDs) and emission‐quencher gold nanoparticles (GNPs) surround as satellites for microRNA imaging and image‐guided cancer therapy. Through the programmed assembly of heterobivalent DNA‐conjugated QDs with DNA‐modified GNPs and UCNPs, the well‐defined nanostructured UCNP‐QDs‐GNPs are generated with quenched fluorescence. Upon encountering the microRNA‐21 target, GNPs underwent catalytic disassembly, resulting in the concurrent recovery and amplification of fluorescence from QDs and UCNPs, which enabled sensitive imaging and quantification of microRNA‐21 within living cells. Furthermore, dithiol‐constituted aggregation‐induced emission (AIE) photosensitizers bonded on the surface of QDs, are effectively photosensitized by the QDs. The NIR excitation harvested by UCNPs is therefore efficiently transferred to QDs and subsequently converged on the AIE photosensitizers, boosting photodynamic activity for image‐guided therapy in deep‐seated tumors. The DNA‐programmed (de)hybridization strategy, facilitating the conversion of NIR excitation into imaging signals and photodynamic activity, offers a promising avenue for the early theranostics of malignancies.
Microinstrumentation for Brain Organoids
Authors: Patel Devan , Shetty Saniya , Acha Chris , Pantoja Itzy E. Morales , Zhao Alice , George Derosh , Gracias David H. 
Published: January 2024

AbstractBrain organoids are three‐dimensional aggregates of self‐organized differentiated stem cells that mimic the structure and function of human brain regions. Organoids bridge the gaps between conventional drug screening models such as planar mammalian cell culture, animal studies, and clinical trials. They can revolutionize the fields of developmental biology, neuroscience, toxicology, and computer engineering. Conventional microinstrumentation for conventional cellular engineering, such as planar microfluidic chips; microelectrode arrays (MEAs); and optical, magnetic, and acoustic techniques, has limitations when applied to three‐dimensional (3D) organoids, primarily due to their limits with inherently two‐dimensional geometry and interfacing. Hence, there is an urgent need to develop new instrumentation compatible with live cell culture techniques and with scalable 3D formats relevant to organoids. This review discusses conventional planar approaches and emerging 3D microinstrumentation necessary for advanced organoid–machine interfaces. Specifically, this article surveys recently developed microinstrumentation, including 3D printed and curved microfluidics, 3D and fast‐scan optical techniques, buckling and self‐folding MEAs, 3D interfaces for electrochemical measurements, and 3D spatially controllable magnetic and acoustic technologies relevant to two‐way information transfer with brain organoids. This article highlights key challenges that must be addressed for robust organoid culture and reliable 3D spatiotemporal information transfer.
Extracellular Matrix‐Trapped Bioinspired Lipoprotein Prolongs Tumor Retention to Potentiate Antitumor Immunity
Authors: Wu Yao , Li Yongping , Hu Zixin , Li Yuan , Zhang Shixuan , Bao Xinyue , Zhou Yu , Gao Yuan , Li Yaping , Zhang Zhiwen 
Published: January 2024

AbstractThe immunomodulatory effects of many therapeutic agents are significantly challenged by their insufficient delivery efficiency and short retention time in tumors. Regarding the distinctively upregulated fibronectin (FN1) and tenascin C (TNC) in tumor stroma, herein a protease‐activated FN1 and/or TNC binding peptide (FTF) is designed and an extracellular matrix (ECM)‐trapped bioinspired lipoprotein (BL) (FTF‐BL‐CP) is proposed that can be preferentially captured by the TNC and/or FN1 for tumor retention, and then be responsively dissociated from the matrix to potentiate the antitumor immunity. The FTF‐BL‐CP treatment produces a 6.96‐, 9.24‐, 6.72‐, 7.32‐, and 6.73‐fold increase of CD3+CD8+ T cells and their interferon‐γ‐, granzyme B‐, perforin‐, and Ki67‐expressing subtypes versus the negative control, thereby profoundly eliciting the antitumor immunity. In orthotopic and lung metastatic breast cancer models, FTF‐BL‐CP produces notable therapeutic benefits of retarding tumor growth, extending survivals, and inhibiting lung metastasis. Therefore, this ECM‐trapping strategy provides an encouraging possibility of prolonging tumor retention to potentiate the antitumor immunity for anticancer immunotherapy.
Light‐Driven Sign Inversion of Circularly Polarized Luminescence Enabled by Dichroism Modulation in Cholesteric Liquid Crystals
Authors: Li Yang , Chen Yihan , Luo Jiaxin , Quan Yiwu , Cheng Yixiang 
Published: January 2024

AbstractStimuli‐responsive circularly polarized luminescence (CPL) materials show great promise in applying information encryption and anticounterfeiting. Herein, light‐driven CPL sign inversion is achieved by combining a photoresponsive achiral negative dichroic dye (KG) and a static achiral positive dichroic dye (NR) as dopants at the 0.5:0.5 weight ratio into the cholesteric liquid crystal (CLC) host. The side chains of KG undergo trans/cis isomerization after 365 nm UV light irradiation, leading to the dichroism (SF) decrease. The |glum| value of CLC doping with KG (CLC‐KG) weakens from 0.67 to 0.28 in response to the order degree change. Taking advantage of its unique CPL response property, the light‐driven CPL sign inversion is achieved (from −0.20/0.14 to 0.02/−0.04) by incorporating NR (0.5:0.5) into the CLC‐KG with helical superstructure static. Based on the synergistic use of circular polarization and responsiveness state as cryptographic primitives, the multidimensional information encryption CLC system can be realized.