bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical safety and efficacy of novel antifungal, fosmanogepix, for the treatment of candidaemia: results from a Phase 2 trial
Authors: Pappas Peter G , Vazquez Jose A , Oren Ilana , Rahav Galia , Aoun Mickael , Bulpa Pierre , Ben-Ami Ronen , Ferrer Ricard , Mccarty Todd , Thompson George R , Schlamm Haran , Bien Paul A , Barbat Sara H , Wedel Pamela , Oborska Iwona , Tawadrous Margaret , Hodges Michael R 
Published: August 2023

Abstract

Background
Fosmanogepix is a first-in-class antifungal targeting the fungal enzyme Gwt1, with broad-spectrum activity against yeasts and moulds, including multidrug-resistant fungi, formulated for intravenous (IV) and oral administration.

Methods
This global, multicenter, non-comparative study evaluated the safety and efficacy of fosmanogepix for first-line treatment of candidaemia in non-neutropenic adults. Participants with candidaemia, defined as a positive blood culture for Candida spp. within 96 h prior to study entry, with ≤2 days of prior systemic antifungals, were eligible. Participants received fosmanogepix for 14 days: 1000 mg IV twice daily on Day 1, followed by maintenance 600 mg IV once daily, and optional switch to 700 mg orally once daily from Day 4. Eligible participants who received at least one dose of fosmanogepix and had confirmed diagnosis of candidaemia (&lt;96 h of treatment start) composed the modified intent-to-treat (mITT) population. Primary efficacy endpoint was treatment success at the end of study treatment (EOST) as determined by the Data Review Committee. Success was defined as clearance of Candida from blood cultures with no additional antifungal treatment and survival at the EOST.

Results
Treatment success was 80% (16/20, mITT; EOST) and Day 30 survival was 85% (17/20; 3 deaths unrelated to fosmanogepix). Ten of 21 (48%) were switched to oral fosmanogepix. Fosmanogepix was well tolerated with no treatment-related serious adverse events/discontinuations. Fosmanogepix had potent in vitro activity against baseline isolates of Candida spp. (MICrange: CLSI, 0.002–0.03 mg/L).

Conclusions
Results from this single-arm Phase 2 trial suggest that fosmanogepix may be a safe, well-tolerated, and efficacious treatment for non-neutropenic patients with candidaemia, including those with renal impairment.
Pharmacokinetics and optimized dosing of dispersible and non-dispersible levofloxacin formulations in young children
Authors: van der Laan Louvina E , Hesseling Anneke C , Schaaf H Simon , Palmer Megan , Draper Heather R , Wiesner Lubbe , Denti Paolo , Garcia-Prats Anthony J 
Published: August 2023

Abstract

Background
Levofloxacin is used for treatment and prevention of rifampicin-resistant (RR)-TB in children. Recent data showed higher exposures with 100 mg dispersible compared with non-dispersible tablet formulations with potentially important dosing implications in children. We aimed to verify and better characterize this finding.

Methods
We conducted a crossover pharmacokinetic trial in children aged ≤5 years receiving levofloxacin RR-TB preventive therapy. Pharmacokinetic sampling was done after 15–20 mg/kg doses of levofloxacin with 100 mg dispersible and crushed 250 mg non-dispersible levofloxacin formulations. A population pharmacokinetic model was developed.

Results
Twenty-five children were included, median (IQR) weight and age 12.2 (10.7–15.0) kg and 2.56 (1.58–4.03) years, respectively. A two-compartment model with first-order elimination and transit compartment absorption best described levofloxacin pharmacokinetics. Allometric scaling adjusted for body size, and maturation of clearance with age was characterized. Typical clearance in a 12 kg child was estimated at 4.17 L/h. Non-dispersible tablets had 21.5% reduced bioavailability compared with the dispersible formulation, with no significant differences in other absorption parameters.
Dosing simulations showed that current recommended dosing for both formulations result in median exposures below adult-equivalent exposures at a 750 mg daily dose, mainly in children &gt;6 months. Higher levofloxacin doses of 16–30 mg/kg for dispersible and 20–38 mg/kg for crushed non-dispersible tablets may be required in children &gt;6 months.

Conclusions
The dispersible paediatric levofloxacin formulation has improved bioavailability compared with the crushed non-dispersible adult formulation, but exposures remain below those in adults. We propose optimized age- and weight-based dosing for levofloxacin, which require further evaluation.
Treatment outcomes with benzylpenicillin and non-benzylpenicillin antibiotics, and the performance of the penicillin zone-edge test versus molecular detection of blaZ in penicillin-susceptible Staphylococcus aureus (PSSA) bacteraemia
Authors: Mok Hoi Tong , Teng Christine B , Bergin Sarah , Hon Pei Yun , Lye David C , De Partha P , Vasoo Shawn 
Published: August 2023

Abstract

Objectives
The blaZ gene encodes penicillinase, which inactivates penicillin. As there were reports on suboptimal sensitivity for the penicillin zone-edge test, a phenotypic method for blaZ detection, we investigated treatment outcomes in patients with penicillin-susceptible Staphylococcus aureus (PSSA) bacteraemia (phenotypically negative for penicillinase), subjecting isolates to molecular testing for blaZ retrospectively.

Patients and methods
A retrospective cohort study was conducted on 121 patients with a first episode of PSSA bacteraemia from 1 January 2012 to 31 October 2015 at Tan Tock Seng Hospital (TTSH), Singapore. Patients were grouped into IV benzylpenicillin and non-benzylpenicillin groups. The primary outcome was overall treatment failure, defined as either 30 day all-cause mortality and/or 90 day relapse. The penicillin (P10) zone-edge test was repeated on archived PSSA isolates, concurrently with penicillin MIC determination via gradient diffusion and PCR for blaZ.

Results
Among 121 patients, 57 patients (47.1%) received IV benzylpenicillin as the predominant antibiotic. There was no significant difference in overall treatment failure between treatment with the benzylpenicillin [7/57 (12.3%)] versus non-benzylpenicillin groups [12/64 (18.8%)] (P = 0.33) or cloxacillin/cefazolin [6/37 (16.2%)] (P = 0.59). For 112 PSSA isolates available for testing, repeat penicillin zone-edge testing was negative for penicillinase production, corroborating previous results. A single PSSA isolate with a negative penicillin zone-edge test was found to be positive for blaZ.

Conclusions
We found no differences in overall treatment failure between patients with PSSA bacteraemia treated with benzylpenicillin, anti-staphylococcal β-lactams cefazolin/cloxacillin and other antimicrobials, when using the penicillin zone-edge test as the phenotypic method for blaZ screening.
Encapsulation of Pseudomonas aeruginosa strain KBN12 decolourizes and bioremediates brilliant blue dye mediated toxicity in mung bean (Vigna radiata L.)
Authors: Chandwani Sapna , Gajera Aashruti , Riddhi Modi , Gamit Harshida A , Amaresan Natarajan 
Published: August 2023

Abstract

Aim
The aim of this study was to explore the decolourization and bioremediation ability of non-encapsulated and encapsulated Pseudomonas aeruginosa (strain KBN 12) against the azo dye brilliant blue (BB).

Methods and results
Six efficient BB dye-decolourizing bacteria were isolated from textile dye effluent. The most efficient free cells of P. aeruginosa KBN 12 along with the optimized conditions such as carbon source (maltose: 5 g L−1), and nitrogen source (ammonium chloride: 4 g L−1) at pH 6 at 37°C decolourized 72.69% of BB dye aerobically after 9 days of incubation under static conditions. Encapsulated (calcium alginate) P. aeruginosa KBN 12 decolourized 87.67% of BB dye aerobically after 9 days of incubation under the same optimized conditions. Fourier-transform infrared spectroscopy (FTIR) and gas chromatography (GC) analysis of the chemical structure of BB dye after decolourization found changes in functional and chemical groups. Phytotoxicity and soil respiration enzyme assays revealed that the decolourized dye or dye products were less toxic than the pure BB dye.

Conclusion
The encapsulation of P. aeruginosa KBN 12 proved to be an effective method for BB dye decolourization or remediation.
Main Pathogens Causing Infections and Antibiotic Resistance Profile in Major Burns in Brazil Comparing Two Periods: 2015/2016 and 2019/2020
Authors: Rissetto Nicoli Gueno , de Oliveira Julia Werner , Nisihara Renato 
Published: August 2023

Abstract
Sepsis is the main cause of death in major burns. In this retrospective study conducted in a reference hospital in Brazil, the main agents causing infection and the resistance profile to antibiotics were identified. In addition, the epidemiological profile, length of hospital stay, type of burn, and total body surface area (TBSA) in major burns were collected from medical records, comparing the years 2015/2016 and 2019/2020. In both time periods, there was a predominance of males with a mean age of 43 years. Burns with less than 30% of TBSA predominated. There was a significant increase in positive cultures (P = .00026), from 58.7% to 80%, and an increase in skin punch culture collection from 25.6% to 43.9% in the years 2019/2020. The predominant etiological agent was Pseudomonas aeruginosa, followed by Acinetobacter baumannii resistant to carbapenems, and Staphylococcus aureus in both evaluated periods. The percentage of deaths was higher in 2019/2020 (26.2% vs. 14.6%; P = .026). The length of hospital stay was shorter in the latter period (P = .0081). Sepsis was the cause of death in 81.2% of cases in 2015/2020 and 78.3% in 2019/2020. Among the deaths, P. aeruginosa was the main agent identified. There was no change in the main pathogens and bacterial antibiotic resistance between the 2 time periods.
Global Burn Prevention: Ukraine
Authors: Dabek Robert J , Decik Myroslava , Driscoll Daniel N , Fuzaylov Gennadiy 
Published: August 2023

Abstract
Burn injury accounts for a large proportion of surgically treatable disease. It is estimated that over 180 000 flame burn deaths occur annually across the globe, with roughly 95% occurring in low- or middle-income countries (LMIC). Within these countries, children account for a disproportionately high number of burn injuries. As such, the WHO has identified burn prevention as a topic of interest, with an increased need in LMIC. Here, we describe the creation and implementation of a burn prevention program in Ukraine. We instituted a 5-step burn prevention initiative consisting of; data gathering, program design, implementation, outcome evaluation, program maintenance, and expansion. The burn prevention initiative has been adopted nationally leading to policy change. Active education and an information campaign were used to target pediatric scald injuries and improve first-aid care. The authors have successfully implemented a targeted multifaceted, national, burn prevention program within Ukraine. The described approach may be used as a guide and adapted to create similar prevention programs within other countries or regions. At this time, the Russo-Ukrainian War has caused an abrupt hold on our role in the prevention program and left the healthcare system in havoc. Moving forward, our team is prepared to re-evaluate the impact of the war on social life and the medical system and aid in redesigning the prevention program when appropriate.
Variation and taphonomic implications of composition in modern and fossil malacostracan cuticles (Decapoda: Malacostraca)
Authors: Plotnick Roy E , McCarroll Steve 
Published: August 2023

Abstract
The crustacean fossil record is dominated by mineralized forms. These fossils, in turn, are mainly decapod chelae or parts of chelae. Studies of the composition of modern crustacean cuticles have likewise been dominated by decapods. We summarize major element chemical analyses (Ca, Mg, Na, P) using SEM-EDS of modern crustacean exoskeletons from Bermuda, Georgia (USA), and Lake Tanganyika (Burundi). Although most specimens were brachyuran and anomuran crabs, material also included examples of stomatopods, isopods, caridean shrimps, and achelatans. Transects were made of sections of the carapace, palm of the propodus, and tips of either the dactyl or propodus. Multiple transects were made of the Bermudan land crab Gecarcinus lateralis. Additional studies were made of brachyuran fossil crabs from Texas and South Dakota and of brachyuran crabs having undergone ten months of burial in marine sediments. Overall, the tips of the chela were the thickest and most heavily mineralized regions and had the lowest phosphorus content. In nearly all cases, they also had the lowest ratios of Mg to Ca. One notable exception was Gecarcinus, where the denticles had elevated Mg:Ca values. Anomura and Brachyura had markedly different composition from Stomatopoda and possibly Isopoda, suggestive of independent evolutionary origins of biomineralization within the Crustacea. There were also significant differences in composition between brachyuran crabs from Georgia and Bermuda, perhaps due to differences in water temperature. The fossil crustaceans had much more phosphate in their cuticles, likely as a result of diagenetic processes. Composition should be a first order control on the fossil record of crustaceans. Future studies need to expand the taxonomic and geographic ranges of material examined, determine whether there are environmental controls on composition, and explore the relevant diagenetic processes.
Exploring a Right to Submit Environmental Information Under International Environmental Law
Authors: Whittaker Sean 
Published: August 2023

Abstract
Discussions on how the public engages with environmental information within environmental governance matters are primarily centred around the supply of environmental information to the public by the state. However, this focus downplays the importance of environmental information held by members of the public and the difficulties that individuals can experience when submitting such information to the state outside formal environmental decision-making procedures. This article examines the benefits of guaranteeing a general right to submit environmental information before considering the extent to which environmental law, specifically the Aarhus Convention, supports the creation of such a right. The article then concludes by constructing a hypothetical regime to implement the proposed right, identifying how the proposed right can be balanced against the needs of the state and points of divergence between this hypothetical regime and the current environmental information regime set out in the Aarhus Convention.
Dynamical characterization of the 6/1 mean motion resonance between Quaoar’s ring and Weywot
Authors: Rodríguez Adrián , Morgado B E , Callegari Jr. N 
Published: August 2023

ABSTRACT
Recently, it has been reported the discovery of a dense ring around the trans-Neptunian object 50000 Quaoar. The ring particles seem to be very close to the 6/1 mean motion resonance with Weywot, the only known satellite in the system. In this work, we investigate the dynamical environment in the close vicinity of the 6/1 orbital resonance in the context of the restricted three-body problem. We aim to analyse whether, in view of observational constraints, the ring could be effectively evolving in resonant motion with the satellite. Through the technique of dynamical maps we identify and characterize the 6/1 mean motion resonance, finding that the main location of the resonance deviates by only 29 km from the central part of the ring. This difference lies within the 3σ confidence level, considering the uncertainties in the observational parameters. We also show that the Weywot’s eccentricity plays a significant role in the dynamical structure of the 6/1 resonance. The results show that the resonance width is smaller than the estimated ring’s width. Under assumption of a ring with eccentricity smaller than 0.05, clumping of test particles appears at the position of the different resonant multiplets, considering the nominal value of Weywot’s eccentricity. This is in agreement with observations, which indicate that the estimated resonance width (≤10 km) is comparable with the narrow and dense arc of material within Quaoar’s ring. Our results may be an indicative that the 6/1 resonance plays a key role in confining the arc ring.
Study of structural parameters and systemic proper motion of Sextans dwarf spheroidal galaxy with Subaru Hyper Suprime-Cam data
Authors: Tokiwa Akira , Takada Masahiro , Qiu Tian , Yasuda Naoki , Komiyama Yutaka , Chiba Masashi , Hayashi Kohei 
Published: August 2023

ABSTRACTWe use the Subaru Hyper Suprime-Cam (HSC) data to study structural parameters and systemic proper motion of the Sextans dwarf spheroidal galaxy at the heliocentric distance of 86 kpc, which is one of the most important targets for studies of dark matter nature and galaxy formation physics. Thanks to the superb image quality and wide area coverage, the HSC data enable a secure selection of member star candidates based on the colour–magnitude cut, yielding about 10 000 member candidates at magnitudes down to i ∼ 24. We use a likelihood analysis of the two-dimensional distribution of stars to estimate the structural parameters of Sextans taking into account the contamination of foreground halo stars in the Milky Way, and find that the member star distribution is well fitted by an elliptical King profile with ellipticity ϵ ≃ 0.25 and the core and tidal radii of Rc = (368.4 ± 8.5) pc and Rt = (2.54 ± 0.046) kpc, respectively. Then using the two HSC data sets of 2.66 yr time baseline on average, we find the systemic proper motions of Sextans to be (μα, μδ) = (−0.448 ± 0.075, 0.058 ± 0.078) mas yr−1, which are consistent with some of the previous works using the Gaia data of relatively bright member stars in Sextans. Thus, our results give a demonstration that ground-based, large-aperture telescope data that cover a wide solid angle of the sky and have a long time baseline, such as the upcoming data from Legacy Survey of Space and Time (LSST), can be used to study systemic proper motions of dwarf galaxies.
Modelling the expected very high energy γ-ray emission from accreting neutron stars in X-ray binaries
Authors: Ducci L , Romano P , Vercellone S , Santangelo A 
Published: August 2023

ABSTRACT
The detection of γ-ray emission from accreting pulsars in X-ray binaries (XRBs) has long been sought after. For some high-mass X-ray binaries (HMXBs), marginal detections have recently been reported. Regardless of whether these will be confirmed or not, future telescopes operating in the γ-ray band could offer the sensitivity needed to achieve solid detections and possibly spectra. In view of future observational advances, we explored the expected emission above 10 GeV from XRBs, based on the Cheng & Ruderman model, where γ-ray photons are produced by the decay of π0 originated by protons accelerated in the magnetosphere of an accreting pulsar fed by an accretion disc. We improved this model by considering, through Monte Carlo simulations, the development of cascades inside of and outside the accretion disc, taking into account pair and photon production processes that involve interaction with nuclei, X-ray photons from the accretion disc, and the magnetic field. We produced grids of solutions for different input parameter values of the X-ray luminosity (Lx), magnetic field strength (B), and for different properties of the region where acceleration occurs. We found that the γ-ray luminosity spans more than five orders of magnitude, with a maximum of ∼1035 erg s−1. The γ-ray spectra show a large variety of shapes: some have most of the emission below ∼100 GeV, others are harder (emission up to 10–100 TeV). We compared our results with Fermi/LAT and VERITAS detections and upper limits of two HMXBs: A0535+26 and GRO J1008−57. More consequential comparisons will be possible when more sensitive instruments will be operational in the coming years.
On the conditions for warping and breaking protoplanetary discs
Authors: Young Alison K , Stevenson Struan , Nixon C J , Rice Ken 
Published: August 2023

ABSTRACT
Recent observations demonstrate that misalignments and other out-of-plane structures are common in protoplanetary discs. Many of these have been linked to a central host binary with an orbit that is inclined with respect to the disc. We present simulations of misaligned circumbinary discs with a range of parameters to gain a better understanding of the link between those parameters and the disc morphology in the wave-like regime of warp propagation that is appropriate to protoplanetary discs. The simulations confirm that disc tearing is possible in protoplanetary discs as long as the mass ratio, μ, and disc–binary inclination angle, i, are not too small. For the simulations presented here, this corresponds to μ &gt; 0.1 and i ≳ 40°. For highly eccentric binaries, tearing can occur for discs with smaller misalignment. Existing theoretical predictions provide an estimate of the radial extent of the disc in which we can expect breaking to occur. However, there does not seem to be a simple relationship between the disc properties and the radius within the circumbinary disc at which the breaks appear, and furthermore the radius at which the disc breaks can change as a function of time in each case. We discuss the implications of our results for interpreting observations and suggest some considerations for modelling misaligned discs in the future.
Characterizing fragmentation and sub-Jovian clump properties in magnetized young protoplanetary discs
Authors: Kubli Noah , Mayer Lucio , Deng Hongping 
Published: August 2023

ABSTRACT
We study the initial development, structure, and evolution of protoplanetary clumps formed in three-dimensional resistive magnetohydrodynamic (MHD) simulations of self-gravitating discs. The magnetic field grows by means of the recently identified gravitational instability dynamo. Clumps are identified and their evolution is tracked finely both backward and forward in time. Their properties and evolutionary path is compared with clumps in companion simulations without magnetic fields. We find that magnetic and rotational energy are important in the clumps’ outer regions, while in the cores, despite appreciable magnetic field amplification, thermal pressure is most important in counteracting gravity. Turbulent kinetic energy is of a smaller scale than magnetic energy in the clumps. Compared with non-magnetized clumps, rotation is less prominent, which results in lower angular momentum in much better agreement with observations. In order to understand the very low sub-Jovian masses of clumps forming in MHD simulations, we revisit the perturbation theory of magnetized sheets finding support for a previously proposed magnetic destabilization in low-shear regions. This can help explaining why fragmentation ensues on a scale more than an order of magnitude smaller than that of the Toomre mass. The smaller fragmentation scale and the high magnetic pressure in clumps’ envelopes explain why clumps in magnetized discs are typically in the super-Earth to Neptune mass regime rather than super-Jupiter as in conventional disc instability. Our findings put forward a viable alternative to core accretion to explain widespread formation of intermediate-mass planets.