bluuebunny/crossref_metadata_2025_split huggingface dataset:
A population pharmacokinetic model for posaconazole intravenous solution and oral powder for suspension formulations in pediatric patients with neutropenia
Authors: Winchell Gregory , de Greef Rik , Ouerdani Aziz , Fauchet Floris , Wrishko Rebecca E. , Mangin Eric , Bruno Christopher , Waskin Hetty 
Published: February 2024

ABSTRACT

The objective of this study was to support posaconazole dose regimens in pediatric patients aged ≥2 years, using a population pharmacokinetic (PK) approach with data from a phase 1b study (NCT02452034). A one-compartment model with first-order absorption was fit to pharmacokinetic data from 144 participants aged 2 to 17 years, who were administered posaconazole as intravenous (IV) and powder for oral suspension (PFS) formulations, or IV only, at dosing regimens of 3.5, 4.5, and 6 mg/kg. The influence of demographic and clinical factors on pharmacokinetic parameters was evaluated using a stepwise forward inclusion/backward exclusion procedure. The final model simulated posaconazole exposure in patients aged 2 to <7 and 7 to 17 years at dosing regimens of 4.5, 6, and 7.5 mg/kg. Plasma concentration data following IV and PFS administration were well-described by a one-compartment model with first-order absorption and estimated bioavailability, where clearance and volume were subject to allometric scaling by body weight. The 6-mg/kg dosing regimen achieved the pharmacokinetic target (90% of the pediatric population having an average steady-state plasma concentration of ≥500 and <2,000 ng/mL) for both age groups, regardless of whether patients received IV and PFS or IV only. In a virtual adolescent population (body weight >40 kg), the 300 mg/day posaconazole tablet was also predicted to achieve the pharmacokinetic target and remain within a safe range of exposure. These data informed a weight-based nomogram for PFS dosing to maximize the number of pediatric patients achieving the pharmacokinetic target across weight bands, while also maintaining a favorable benefit/risk profile.
Bactericidal and sterilizing activity of novel regimens combining bedaquiline or TBAJ-587 with GSK2556286 and TBA-7371 in a mouse model of tuberculosis
Authors: Li Si-Yang , Tyagi Sandeep , Soni Heena , Betoudji Fabrice , Converse Paul J. , Mdluli Khisimuzi , Upton Anna M. , Fotouhi Nader , Barros-Aguirre David , Ballell Lluís , Jimenez-Navarro Elena , Nuermberger Eric L. 
Published: February 2024

ABSTRACT

The combination of bedaquiline, pretomanid, and linezolid (BPaL) has become a preferred regimen for treating multidrug- and extensively drug-resistant tuberculosis (TB). However, treatment-limiting toxicities of linezolid and reports of emerging bedaquiline and pretomanid resistance necessitate efforts to develop new short-course oral regimens. We recently found that the addition of GSK2556286 increases the bactericidal and sterilizing activity of BPa-containing regimens in a well-established BALB/c mouse model of tuberculosis. Here, we used this model to evaluate the potential of new regimens combining bedaquiline or the more potent diarylquinoline TBAJ-587 with GSK2556286 and the DprE1 inhibitor TBA-7371, all of which are currently in early-phase clinical trials. We found the combination of bedaquiline, GSK2556286, and TBA-7371 to be more active than the first-line regimen and nearly as effective as BPaL in terms of bactericidal and sterilizing activity. In addition, we found that GSK2556286 and TBA-7371 were as effective as pretomanid and the novel oxazolidinone TBI-223 when either drug pair was combined with TBAJ-587 and that the addition of GSK2556286 increased the bactericidal activity of the TBAJ-587, pretomanid, and TBI-223 combination. We conclude that GSK2556286 and TBA-7371 have the potential to replace pretomanid, an oxazolidinone, or both components, in combination with bedaquiline or TBAJ-587.
Genome sequence of
Arthrobacter globiformis
phage MaGuCo
Authors: Diggins Amanda E. , Gubitose Mary G. , Hinrichsen Elijah G. , Jones Patrick T. , Kearns Brian S. , Lord Caitlynn E. , Parsons Mary T. , Pitt Rachel A. , Woods Isabella A. , Zarakotas Teagan R. , Wilkes Beth M. 
Published: February 2024

ABSTRACT

MaGuCo is a temperate phage isolated from soil collected in Alton, NH, USA, using
Arthrobacter globiformis
. Its genome is 43,924 base pairs long and contains 63 protein-encoding genes, 44 of which were assigned putative functions. MaCuGo is assigned to cluster AZ2 based on gene content similarity to actinobacteriophages.
Multidrug resistance plasmids commonly reprogram the expression of metabolic genes in
Escherichia coli
Authors: Hall Rebecca J. , Snaith Ann E. , Thomas Matthew J. N. , Brockhurst Michael A. , McNally Alan 
Published: February 2024

ABSTRACT

Multidrug-resistant
Escherichia coli
is a leading cause of global mortality. Transfer of plasmids carrying genes encoding beta-lactamases, carbapenamases, and colistin resistance between lineages is driving the rising rates of hard-to-treat nosocomial and community infections. Multidrug resistance (MDR) plasmid acquisition commonly causes transcriptional disruption, and while a number of studies have shown strain-specific fitness and transcriptional effects of an MDR plasmid across diverse bacterial lineages, fewer studies have compared the impacts of different MDR plasmids in a common bacterial host. As such, our ability to predict which MDR plasmids are the most likely to be maintained and spread in bacterial populations is limited. Here, we introduced eight diverse MDR plasmids encoding resistances against a range of clinically important antibiotics into
E. coli
K-12 MG1655 and measured their fitness costs and transcriptional impacts. The scale of the transcriptional responses varied substantially between plasmids, ranging from >650 to <20 chromosomal genes being differentially expressed. However, the scale of regulatory disruption did not correlate significantly with the magnitude of the plasmid fitness cost, which also varied between plasmids. The identities of differentially expressed genes differed between transconjugants, although the expression of certain metabolic genes and functions were convergently affected by multiple plasmids, including the downregulation of genes involved in L-methionine transport and metabolism. Our data show the complexity of the interaction between host genetic background and plasmid genetic background in determining the impact of MDR plasmid acquisition on
E. coli
.

IMPORTANCE
The increase in infections that are resistant to multiple classes of antibiotics, including those isolates that carry carbapenamases, beta-lactamases, and colistin resistance genes, is of global concern. Many of these resistances are spread by conjugative plasmids. Understanding more about how an isolate responds to an incoming plasmid that encodes antibiotic resistance will provide information that could be used to predict the emergence of MDR lineages. Here, the identification of metabolic networks as being particularly sensitive to incoming plasmids suggests the possible targets for reducing plasmid transfer.
Functional characterization of RhuB as a second TonB2-dependent hemin receptor in
Riemerella anatipestifer
CH-1
Authors: Wang Mengying , Wang Siyi , Wang Mingshu , Zhu Dekang , Jia Renyong , Chen Shun , Zhao Xinxin , Yang Qiao , Wu Ying , Zhang Shaqiu , Huang Juan , Liu Mafeng , Cheng Anchun 
Published: February 2024

ABSTRACT

In the previous study, it was shown that
Riemerella anatipestifer
(
R. anatipestifer
, RA), a pathogen in ducks and some other birds, encodes a hemin uptake system. The
R. anatipestifer
hemin uptake receptor RhuR is a TonB2-dependent hemin transporter. However, it remains unclear whether
R. anatipestifer
encodes additional TonB-dependent hemin transporters. Herein, we demonstrated that
R. anatipestifer
hemin uptake receptor B (RhuB) of
R. anatipestifer
CH-1 (RA CH-1) was negatively regulated by iron and mediated by the Fur protein, and knocking out
rhuB
damaged the ability of RA CH-1 to utilize iron from duck hemoglobin (Hb) but not that from duck serum. Moreover, the ability to use iron from Hb was restored by the expression
rhuB in trans
. Furthermore, the RhuB of RA CH-1 is a membrane protein, and recombinant RhuB could bind hemin at a 1:1 molar ratio
in vitro
. Compared to that of Δ
tonB1
Δ
rhuR
, the ability of Δ
tonB1
Δ
rhuR
Δ
rhuB
to utilize hemin was impaired; meanwhile, compared to that of Δ
tonB2
Δ
rhuR
, the hemin utilization ability of Δ
tonB2
Δ
rhuR
Δ
rhuB
was not affected, indicating that RhuB is a TonB2-dependent receptor. Compared to Δ
rhuB
,
ΔrhuBΔrhuA
did not affect hemin utilization. However, compared to Δ
rhuA
,
ΔrhuBΔrhuA
had reduced ability to utilize hemin, suggesting that RhuA relies on RhuB for its activity. Finally, the deletion of
rhuB
did not affect the virulence of RA CH-1. These results suggested that RhuB encodes a TonB2-dependent hemin receptor. The characterization of the second TonB-dependent receptor in
R. anatipestifer
enriches our understanding of the hemin uptake system of this bacterium.

IMPORTANCE

Iron is essential for the survival of most bacteria, and hemin of hemoglobin can serve as an important iron source. In our previous studies, we showed that
R. anatipestifer
CH-1 encodes a TonB2-dependent hemin receptor RhuR, which is involved in hemin uptake. The deletion of
rhuR
did not abolish hemin utilization by RA CH-1. We hypothesized that additional hemin uptake systems exist in this bacterium. In this study, we identified the second TonB2-dependent hemin receptor RhuB in RA CH-1 through hemin utilization, protein localization, and hemin-binding experiments. The duck infection model showed that the deletion of
rhuB
did not affect the virulence of RA CH-1. This study is not only important for further understanding the hemin utilization mechanism of
R. anatipestifer
, but also for enriching the hemin uptake transporters of gram-negative bacteria.
Detection of
Salmonella enterica
and
Listeria monocytogenes
in alternative irrigation water by culture and qPCR-based methods in the Mid-Atlantic U.S.
Authors: Acheamfour Chanelle L. , Parveen Salina , Gutierrez Alan , Handy Eric T. , Behal Sara , Kim Donghyun , Kim Seongyun , East Cheryl , Xiong Ray , Haymaker Joseph R. , Micallef Shirley A. , Rosenberg Goldstein Rachel E. , Kniel Kalmia E. , Sapkota Amy R. , Hashem Fawzy , Sharma Manan 
Published: February 2024

ABSTRACT

Alternative irrigation waters (rivers, ponds, and reclaimed water) can harbor bacterial foodborne pathogens like
Salmonella enterica
and
Listeria monocytogenes
, potentially contaminating fruit and vegetable commodities. Detecting foodborne pathogens using qPCR-based methods may accelerate testing methods and procedures compared to culture-based methods. This study compared detection
of S. enterica and L. monocytogenes
by qPCR (real-time PCR) and culture methods in irrigation waters to determine the influence of water type (river, pond, and reclaimed water), season (winter, spring, summer, and fall), or volume (0.1, 1, and 10 L) on sensitivity, accuracy, specificity, and positive (PPV), and negative (NPV) predictive values of these methods. Water samples were collected by filtration through modified Moore swabs (MMS) over a 2-year period at 11 sites in the Mid-Atlantic U.S. on a bi-weekly or monthly schedule. For qPCR, bacterial DNA from culture-enriched samples (
n
= 1,990) was analyzed by multiplex qPCR specific for
S. enterica
and
L. monocytogenes
. For culture detection, enriched samples were selectively enriched, isolated, and PCR confirmed. PPVs for qPCR detection of
S. enterica
and
L. monocytogenes
were 68% and 67%, respectively. The NPV were 87% (
S. enterica
) and 85% (
L. monocytogenes
). Higher levels of qPCR/culture agreement were observed in spring and summer compared to fall and winter for
S. enterica
; for
L. monocytogenes
, lower levels of agreement were observed in winter compared to spring, summer, and fall. Reclaimed and pond water supported higher levels of qPCR/culture agreement compared to river water for both
S. enterica
and
L. monocytogenes
, indicating that water type may influence the agreement of these results.

IMPORTANCE

Detecting foodborne pathogens in irrigation water can inform interventions and management strategies to reduce risk of contamination and illness associated with fresh and fresh-cut fruits and vegetables. The use of non-culture methods like qPCR has the potential to accelerate the testing process. Results indicated that pond and reclaimed water showed higher levels of agreement between culture and qPCR methods than river water, perhaps due to specific physiochemical characteristics of the water. These findings also show that season and sample volume affect the agreement of qPCR and culture results. Overall, qPCR methods could be more confidently utilized to determine the absence of
Salmonella enterica
and
Listeria monocytogenes
in irrigation water samples examined in this study.
The Polarization Jet/SAID and Plasma Irregularities of Different Scales
Authors: Sinevich A. A. , Chernyshov A. A. , Chugunin D. V. , Miloch W. J. , Mogilevsky M. M. 
Published: February 2024

Abstract
Results are presented from a study of the internal small-scale structure of the polarization jet/SAID using data from different satellites. The minimum size of irregularities and the typical internal composition of a stratified subauroral ion drift (SSAID) are confirmed. A two-peak structure is found that contains two large strata of the polarization jet/SAID. A shift in latitude is shown for the strata of electron density and temperature, relative to each other.
Unintentional injury deaths associated with sport and recreation in Québec, Canada, 2006–2019
Authors: Richard Philippe , Lahiri-Rousseau Judith , Phimmasone Jonathan , Belley-Ranger Emilie , Sylvain-Morneau Jérémie , Gagne Mathieu , Perron Paul-André , Goulet Claude 
Published: February 2024

ObjectivesThis study examined trends in the frequencies and rates of deaths associated with unintentional injuries in sport and recreation in Québec, Canada, for the period January 2006–December 2019.MethodsIn this descriptive retrospective study, data were extracted from the database of the Bureau du coroner du Québec. Incidence rates were calculated using participation data from the Étude des blessures subies au cours de la pratique d’activités récréatives et sportives au Québec (ÉBARS) and Canadian census population data. Poisson regression was used to investigate changes in death rates over the 14-year period by estimating incidence rate ratios.ResultsThere were 1937 unintentional injury deaths and the population-based death rate was 1.72 per 100 000 person-years. The participation-based rate was 1.40 per 100 000 participant-years, considering the 24 matching activities in both ÉBARS’ editions. Using both population-based and participation-based denominators, separate analyses consistently showed declining death rates in non-motorised navigation and cycling. Deaths related to all-terrain vehicles, snowmobiles, swimming, cycling, motorised navigation and non-motorised navigation activities accounted for 80.2% of all deaths. Drowning was documented as a cause of death in 39.3% of all fatalities. Males represented 86.8% of all deaths, with males aged 18–24 years and 65 and over having the highest rates.ConclusionThe death rates of unintentional injury deaths associated with non-motorised navigation and cycling declined, from January 2006 to December 2019. The characteristics and mechanisms of drowning deaths and fatalities that occurred in activities associated with higher death frequencies and rates need to be further investigated.
Sex Differences in Coronary Inflammation and Atherosclerosis Phenotypes in Response to Imaging Marker of Stress-Related Neural Activity
Authors: Dai Neng , Tang Xianglin , Weng Xinyu , Cai Haidong , Zhuang Jianhui , Yang Guangjie , Zhou Fan , Wu Ping , Liu Bao , Duan Shaofeng , Yu Yongfu , Guo Weifeng , Ju Zhiguo , Zhang Longjiang , Wang Zhenguang , Wang Yuetao , Lu Bin , Shi Hongcheng , Qian Juying , Ge Junbo 
Published: February 2024

BACKGROUND:
Sex-specific differences in coronary phenotypes in response to stress have not been elucidated. This study investigated the sex-specific differences in the coronary computed tomography angiography-assessed coronary response to mental stress.

METHODS:

This retrospective study included patients with coronary artery disease and without cancer who underwent resting
18
F-fluorodexoyglucose positron emission tomography/computed tomography and coronary computed tomography angiography within 3 months.
18
F-flourodeoxyglucose resting amygdalar uptake, an imaging biomarker of stress-related neural activity, coronary inflammation (fat attenuation index), and high-risk plaque characteristics were assessed by coronary computed tomography angiography. Their correlation and prognostic values were assessed according to sex.

RESULTS:

A total of 364 participants (27.7% women and 72.3% men) were enrolled. Among those with heightened stress-related neural activity, women were more likely to have a higher fat attenuation index (43.0% versus 24.0%;
P
=0.004), while men had a higher frequency of high-risk plaques (53.7% versus 39.3%;
P
=0.036). High amygdalar
18
F-flourodeoxyglucose uptake (B-coefficient [SE], 3.62 [0.21];
P
<0.001) was selected as the strongest predictor of fat attenuation index in a fully adjusted linear regression model in women, and the first-order interaction term consisting of sex and stress-related neural activity was significant (
P
<0.001). Those with enhanced imaging biomarkers of stress-related neural activity showed increased risk of major adverse cardiovascular event both in women (24.5% versus 5.1%; adjusted hazard ratio, 3.62 [95% CI, 1.14–17.14];
P
=0.039) and men (17.2% versus 6.9%; adjusted hazard ratio, 2.72 [95% CI, 1.10–6.69];
P
=0.030).

CONCLUSIONS:
Imaging-assessed stress-related neural activity carried prognostic values irrespective of sex; however, a sex-specific mechanism linking psychological stress to coronary plaque phenotypes existed in the current hypothesis-generating study.

REGISTRATION:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT05545618.
The past, present, and future of the brain imaging data structure (BIDS)
Authors: Poldrack Russell A. , Markiewicz Christopher J. , Appelhoff Stefan , Ashar Yoni K. , Auer Tibor , Baillet Sylvain , Bansal Shashank , Beltrachini Leandro , Benar Christian G. , Bertazzoli Giacomo , Bhogawar Suyash , Blair Ross W. , Bortoletto Marta , Boudreau Mathieu , Brooks Teon L. , Calhoun Vince D. , Castelli Filippo Maria , Clement Patricia , Cohen Alexander L. , Cohen-Adad Julien , D’Ambrosio Sasha , de Hollander Gilles , de la Iglesia-Vayá María , de la Vega Alejandro , Delorme Arnaud , Devinsky Orrin , Draschkow Dejan , Duff Eugene Paul , DuPre Elizabeth , Earl Eric , Esteban Oscar , Feingold Franklin W. , Flandin Guillaume , Galassi Anthony , Gallitto Giuseppe , Ganz Melanie , Gau Rémi , Gholam James , Ghosh Satrajit S. , Giacomel Alessio , Gillman Ashley G. , Gleeson Padraig , Gramfort Alexandre , Guay Samuel , Guidali Giacomo , Halchenko Yaroslav O. , Handwerker Daniel A. , Hardcastle Nell , Herholz Peer , Hermes Dora , Honey Christopher J. , Innis Robert B. , Ioanas Horea-Ioan , Jahn Andrew , Karakuzu Agah , Keator David B. , Kiar Gregory , Kincses Balint , Laird Angela R. , Lau Jonathan C. , Lazari Alberto , Legarreta Jon Haitz , Li Adam , Li Xiangrui , Love Bradley C. , Lu Hanzhang , Marcantoni Eleonora , Maumet Camille , Mazzamuto Giacomo , Meisler Steven L. , Mikkelsen Mark , Mutsaerts Henk , Nichols Thomas E. , Nikolaidis Aki , Nilsonne Gustav , Niso Guiomar , Norgaard Martin , Okell Thomas W. , Oostenveld Robert , Ort Eduard , Park Patrick J. , Pawlik Mateusz , Pernet Cyril R. , Pestilli Franco , Petr Jan , Phillips Christophe , Poline Jean-Baptiste , Pollonini Luca , Raamana Pradeep Reddy , Ritter Petra , Rizzo Gaia , Robbins Kay A. , Rockhill Alexander P. , Rogers Christine , Rokem Ariel , Rorden Chris , Routier Alexandre , Saborit-Torres Jose Manuel , Salo Taylor , Schirner Michael , Smith Robert E. , Spisak Tamas , Sprenger Julia , Swann Nicole C. , Szinte Martin , Takerkart Sylvain , Thirion Bertrand , Thomas Adam G. , Torabian Sajjad , Varoquaux Gael , Voytek Bradley , Welzel Julius , Wilson Martin , Yarkoni Tal , Gorgolewski Krzysztof J. 
Published: February 2024

Abstract
The Brain Imaging Data Structure (BIDS) is a community-driven standard for the organization of data and metadata from a growing range of neuroscience modalities. This paper is meant as a history of how the standard has developed and grown over time. We outline the principles behind the project, the mechanisms by which it has been extended, and some of the challenges being addressed as it evolves. We also discuss the lessons learned through the project, with the aim of enabling researchers in other domains to learn from the success of BIDS.
“Now I Get It!”: Eureka Experiences During the Acquisition of Mathematical Concepts
Authors: Barot Charlotte , Chevalier Louise , Martin Lucie , Izard Véronique 
Published: February 2024

Abstract
Many famous scientists have reported anecdotes where a new understanding occurred to them suddenly, in an unexpected flash. Do people generally experience such “Eureka” moments when learning science concepts? And if so, do these episodes truly vehicle sudden insights, or is this impression illusory? To address these questions, we developed a paradigm where participants were taught the mathematical concept of geodesic, which generalizes the common notion of straight line to straight trajectories drawn on curved surfaces. After studying lessons introducing this concept on the sphere, participants (N = 56) were tested on their understanding of geodesics on the sphere and on other surfaces. Our findings indicate that Eureka experiences are common when learning mathematics, with reports by 34 (61%) participants. Moreover, Eureka experiences proved an accurate description of participants’ learning, in two respects. First, Eureka experiences were associated with learning and generalization: the participants who reported experiencing Eurekas performed better at identifying counterintuitive geodesics on new surfaces. Second, and in line with the firstperson experience of a sudden insight, our findings suggest that the learning mechanisms responsible for Eureka experiences are inaccessible to reflective introspection. Specifically, reports of Eureka experiences and of participants’ confidence in their own understanding were associated with different profiles of performance, indicating that the mechanisms bringing about Eureka experiences and those informing reflective confidence were at least partially dissociated. Learning mathematical concepts thus appears to involve mechanisms that operate unconsciously, except when a key computational step is reached and a sudden insight breaks into consciousness.