bluuebunny/crossref_metadata_2025_split huggingface dataset:
Catabolism of germinant amino acids is required to prevent premature spore germination in
Bacillus subtilis
Authors: Kasu Iqra R. , Reyes-Matte Octavio , Bonive-Boscan Alejandro , Derman Alan I. , Lopez-Garrido Javier 
Published: April 2024

ABSTRACT

Spores of
Bacillus subtilis
germinate in response to specific germinant molecules that are recognized by receptors in the spore envelope. Germinants signal to the dormant spore that the environment can support vegetative growth, so many germinants, such as alanine and valine, are also essential metabolites. As such, they are also required to build the spore. Here we show that these germinants cause premature germination if they are still present at the latter stages of spore formation and beyond, but that
B. subtilis
metabolism is configured to prevent this: alanine and valine are catabolized and cleared from wild-type cultures even when alternative carbon and nitrogen sources are present. Alanine and valine accumulate in the spent media of mutants that are unable to catabolize these amino acids, and premature germination is pervasive. Premature germination does not occur if the germinant receptor that responds to alanine and valine is eliminated, or if wild-type strains that are able to catabolize and clear alanine and valine are also present in coculture. Our findings demonstrate that spore-forming bacteria must fine-tune the concentration of any metabolite that can also function as a germinant to a level that is high enough to allow for spore development to proceed, but not so high as to promote premature germination. These results indicate that germinant selection and metabolism are tightly linked, and suggest that germinant receptors evolve in tandem with the catabolic priorities of the spore-forming bacterium.

IMPORTANCE
Many bacterial species produce dormant cells called endospores, which are not killed by antibiotics or common disinfection practices. Endospores pose critical challenges in the food industry, where endospore contaminations cause food spoilage, and in hospitals, where infections by pathogenic endospore formers threaten the life of millions every year. Endospores lose their resistance properties and can be killed easily when they germinate and exit dormancy. We have discovered that the enzymes that break down the amino acids alanine and valine are critical for the production of stable endospores. If these enzymes are absent, endospores germinate as they are formed or shortly thereafter in response to alanine, which can initiate the germination of many different species' endospores, or to valine. By blocking the activity of alanine dehydrogenase, the enzyme that breaks down alanine and is not present in mammals, it may be possible to inactivate endospores by triggering premature and unproductive germination.
Draft genome sequence of the deep-subsurface
Ciceribacter
sp. strain T2.26MG-112.2, a second Rhizobiaceae isolated from the Iberian Pyrite Belt at 492.6 mbs
Authors: Martínez José M. , García R. , Leandro T. , Amils R. 
Published: April 2024

ABSTRACT

T2.26MG-112.2 is a
Ciceribacter
strain that has been isolated from the deep subsurface of the Iberian Pyrite Belt. We report its draft genome consisting of a chromosome of ≈4.9 Mb and a plasmid of 357 kb. The annotation reveals 4,824 coding sequences, 48 tRNA genes, and 1 rRNA operon.
Oxytetracycline hyper-production through targeted genome reduction of
Streptomyces rimosus
Authors: Pšeničnik Alen , Slemc Lucija , Avbelj Martina , Tome Miha , Šala Martin , Herron Paul , Shmatkov Maksym , Petek Marko , Baebler Špela , Mrak Peter , Hranueli Daslav , Starčević Antonio , Hunter Iain S. , Petković Hrvoje 
Published: April 2024

ABSTRACT

Most biosynthetic gene clusters (BGC) encoding the synthesis of important microbial secondary metabolites, such as antibiotics, are either silent or poorly expressed; therefore, to ensure a strong pipeline of novel antibiotics, there is a need to develop rapid and efficient strain development approaches. This study uses comparative genome analysis to instruct rational strain improvement, using
Streptomyces rimosus
, the producer of the important antibiotic oxytetracycline (OTC) as a model system. Sequencing of the genomes of two industrial strains M4018 and R6-500, developed independently from a common ancestor, identified large DNA rearrangements located at the chromosome end. We evaluated the effect of these genome deletions on the parental
S. rimosus
Type Strain (ATCC 10970) genome where introduction of a 145 kb deletion close to the OTC BGC in the Type Strain resulted in massive OTC overproduction, achieving titers that were equivalent to M4018 and R6-500. Transcriptome data supported the hypothesis that the reason for such an increase in OTC biosynthesis was due to enhanced transcription of the OTC BGC and not due to enhanced substrate supply. We also observed changes in the expression of other cryptic BGCs; some metabolites, undetectable in ATCC 10970, were now produced at high titers. This study demonstrated for the first time that the main force behind BGC overexpression is genome rearrangement. This new approach demonstrates great potential to activate cryptic gene clusters of yet unexplored natural products of medical and industrial value.

IMPORTANCE

There is a critical need to develop novel antibiotics to combat antimicrobial resistance.
Streptomyces
species are very rich source of antibiotics, typically encoding 20–60 biosynthetic gene clusters (BGCs). However, under laboratory conditions, most are either silent or poorly expressed so that their products are only detectable at nanogram quantities, which hampers drug development efforts. To address this subject, we used comparative genome analysis of industrial
Streptomyces rimosus
strains producing high titers of a broad spectrum antibiotic oxytetracycline (OTC), developed during decades of industrial strain improvement. Interestingly, large-scale chromosomal deletions were observed. Based on this information, we carried out targeted genome deletions in the native strain
S. rimosus
ATCC 10970, and we show that a targeted deletion in the vicinity of the OTC BGC significantly induced expression of the OTC BGC, as well as some other silent BGCs, thus suggesting that this approach may be a useful way to identify new natural products.
Pilot study exploring the presence of leadership curricula in undergraduate medical education
Authors: Korndorffer Melanie , Dewsnap Michael A , Barry Erin S , Grunberg Neil , Musick David W , Quinn Joann Farrell 
Published: April 2024

IntroductionThe physician’s role in the healthcare delivery system extends beyond patient care to include numerous critical leadership roles in healthcare. In addition to treating patients, physicians manage multidisciplinary teams and influence policies to optimise public health. Yet, leadership education is not currently emphasised as part of undergraduate medical education. The purpose of this pilot study was to survey US allopathic medical schools about their current leadership curricula for medical students, including aspects that promote or inhibit effective curricular implementation.MethodsA survey was developed and administered to representatives at US allopathic medical schools regarding the presence and nature of leadership curricula for medical students currently in place, as well as barriers to effective implementation.ResultsA total of 41 of 144 medical schools (28%) responded to the survey. Of the schools that responded, 25 schools reported the presence of a leadership curriculum. Primary competencies and goals were similar among these institutions, but the structure of the curriculum and how it is being implemented varied. The study did not identify consistent methods of assessing student leadership competencies. Themes of improved communication and integration within the curriculum emerged as actions promoting successful implementation. Financial restraints and buy-in among stakeholder groups (eg, faculty, staff and students) were mentioned most frequently as barriers to the effective implementation of leadership curricula.ConclusionsAlthough leadership education within undergraduate medical education is emphasised by a variety of groups, including the Association of American Medical Colleges, medical schools do not appear to universally address this topic. The Liaison Committee on Medical Education, the primary accrediting body for medical schools, does not currently require leadership education as a core topic for accreditation. To provide effective education on leadership to medical students, administrative bodies could improve their support for this topic by considering the factors identified that both hinder and promote implementation.
Blood Pressure Lowering in Patients With Central Hypertension: A randomized Clinical Trial
Authors: Sharman James E. , Otahal Petr , Stowasser Michael , Stanton Tony , Reid Christopher M. , Nolan Mark , Roberts-Thomson Philip , Negishi Kazuaki , Greenough Robert , Stewart Simon , Marwick Thomas H. , Abhayaratna Walter P. 
Published: April 2024

BACKGROUND:
Cuff blood pressure (BP) is recommended for guiding hypertension management. However, central BP has been proposed as a superior clinical measurement. This study aimed to determine whether controlling hypertension as measured by central BP was beneficial in reducing left ventricular mass index beyond control of standard cuff hypertension.

METHODS:
This multicenter, open-label, blinded-end point trial was conducted in individuals treated for uncomplicated hypertension with controlled cuff BP (<140/90 mm Hg) but elevated central BP (≥0.5 SD above age- and sex-specific normal values). Participants were randomized to 24-months intervention with spironolactone 25 mg/day (n=148) or usual care control (n=153). The primary outcome was change in left ventricular mass index measured by cardiac MRI. Cuff and central BPs were measured by clinic, 7-day home and 24-hour ambulatory BPs.

RESULTS:

At 24-months, there was a greater reduction in left ventricular mass index (−3.2 [95% CI, −5.0 to −1.3] g/m
2
;
P
=0.001) with intervention compared with control. Cuff and central BPs were lowered by a similar magnitude across all BP measurement modes (eg, clinic cuff systolic BP, −6.16 [−9.60 to −2.72] mm Hg and clinic central systolic BP, −4.96 [−8.06 to −1.86] mm Hg;
P
≥0.48 all). Secondary analyses found that changes in left ventricular mass index correlated to changes in BP, with the magnitude of effect nearly identical for BP measured by cuff (eg, 24-hour systolic BP, β, 0.17 [0.02–0.31] g/m
2
) or centrally (24-hour systolic BP, β, 0.16 [0.01–0.32] g/m
2
).

CONCLUSIONS:
Among individuals with central hypertension, spironolactone had beneficial effects in reducing LV mass. Secondary analyses showed that changes in LV mass were equally well associated with lower measured standard cuff BP and central BP.

REGISTRATION:

URL:
https://www.anzctr.org.au/
; Unique identifier: ACTRN12613000053729
Sublimation of Snow
Authors: Lundquist Jessica D. , Vano Julie , Gutmann Ethan , Hogan Daniel , Schwat Eli , Haugeneder Michael , Mateo Emilio , Oncley Steve , Roden Chris , Osenga Elise , Carver Liz 
Published: April 2024

Abstract
Snow is a vital part of water resources, and sublimation may remove 10%–90% of snowfall from the system. To improve our understanding of the physics that govern sublimation rates, as well as how those rates might change with the climate, we deployed an array of four towers with over 100 instruments from NCAR’s Integrated Surface Flux System from November 2022 to June 2023 in the East River watershed, Colorado, in conjunction with the U.S. Department of Energy’s Surface Atmosphere Integrated Field Laboratory (SAIL) and the National Oceanic and Atmospheric Administration (NOAA)’s Study of Precipitation, the Lower Atmosphere and Surface for Hydrometeorology (SPLASH) campaigns. Mass balance observations, snow pits, particle flux sensors, and terrestrial lidar scans of the evolving snowfield demonstrated how blowing snow influences sublimation rates, which we quantified with latent heat fluxes measured by eddy-covariance systems at heights 1–20 m above the snow surface. Detailed temperature profiles at finer resolutions highlighted the role of the stable boundary layer. Four-stream radiometers indicated the important role of changing albedo in the energy balance and its relationship to water vapor losses. Collectively, these observations span scales from seconds to seasons, from boundary layer turbulence to valley circulation to mesoscale meteorology. We describe the field campaign, highlights in the observations, and outreach and education products we are creating to facilitate cross-disciplinary dialogue and convey relevant findings to those seeking to better understand Colorado River snow and streamflow.
The Impact on Simulated Bow Echoes of Changing Grid Spacing from 3 km to 1 km in the WRF Model
Authors: Dodson Dylan J. , Gallus William A. 
Published: April 2024

Abstract
Ten bow echo events were simulated using the Weather Research and Forecasting (WRF) Model with 3- and 1-km horizontal grid spacing with both the Morrison and Thompson microphysics schemes to determine the impact of refined grid spacing on this often poorly simulated mode of convection. Simulated and observed composite reflectivities were used to classify convective mode. Skill scores were computed to quantify model performance at predicting all modes, and a new bow echo score was created to evaluate specifically the accuracy of bow echo forecasts. The full morphology score for runs using the Thompson scheme was noticeably improved by refined grid spacing, while the skill of Morrison runs did not change appreciably. However, bow echo scores for runs using both schemes improved when grid spacing was refined, with Thompson runs improving most significantly. Additionally, near storm environments were analyzed to understand why the simulated bow echoes changed as grid spacing was changed. A relationship existed between bow echo production and cold pool strength, as well as with the magnitude of microphysical cooling rates. More numerous updrafts were present in 1-km runs, leading to longer intense lines of convection which were more likely to evolve into longer-lived bow echoes in more cases. Large-scale features, such as a low-level jet orientation more perpendicular to the convective line and surface boundaries, often had to be present for bow echoes to occur in the 3-km runs.
Exploring the Potential of Using a Text-Based Game to Inform Simulation Models of Risky Migration Decisions
Authors: Modirrousta-Galian Ariana , Prike Toby , Higham Philip A. , Hinsch Martin , Nurse Sarah , Belabbas Souhila , Bijak Jakub 
Published: April 2024

Background In this paper, we explore the potential of games to collect empirical data for informing agent-based simulation models of migration. To examine the usefulness of game-based approaches, we conducted a simple, yet carefully designed psychological experiment. Methods In a preregistered study, we used a novel, immersive experimental setting to investigate the risky migration decisions made by migrants and non-migrants. Participants (284 migrants and 284 non-migrants) played a choice-based interactive fiction game—a fully text-based game where players progress by selecting from a list of possible actions—that involved making three risky migration decisions. In one condition, participants were shown a non-linear progress bar and explicit acknowledgements of the choices they made to promote perceived agency: the feeling that one’s actions have a non-trivial impact on the game. In the other condition, the progress bar was linear, and the explicit acknowledgements were omitted. Results Our experimental manipulation was successful; participants in the former condition self-reported higher perceived agency than participants in the latter condition, as did migrants compared to non-migrants. Nevertheless, condition and migrant status did not meaningfully affect the risky migration decisions participants made in the game. Conclusion These findings indicate that the results of generic studies on risky migration decisions conducted on non-migrants can potentially inform simulation models of migration. However, these findings were obtained from a single experiment, and thus warrant replication and further research before definitive conclusions can be drawn. Furthermore, a simple text-based game may be too superficial to allow deep insights into the idiosyncrasies of migration decision-making. This suggests a possible trade-off between clear interpretability of the results and the usefulness for informing simulation models of complex social processes, such as migration.
Immunogenicity profile of rurioctocog alfa pegol in previously treated patients with severe congenital hemophilia A
Authors: Horling Frank M. , Reipert Birgit M. , Allacher Peter , Engl Werner , Pan Luying , Tangada Srilatha 
Published: April 2024

Abstract
Rurioctocog alfa pegol is an extended–half-life full-length recombinant factor VIII (FVIII) bound to 20-kDa polyethylene glycol (PEG) that has been shown to be well tolerated and efficacious in the treatment and prevention of bleeding events in previously treated patients with severe hemophilia A. Here, we present a comprehensive analysis of immunogenicity data collected during 6 clinical studies of rurioctocog alfa pegol, including a total of 360 unique previously treated patients with severe hemophilia A. The analysis included treatment-emerging FVIII-neutralizing antibodies (FVIII inhibitors); preexisting and treatment-emerging antibodies binding to FVIII, PEG-FVIII, or PEG; and treatment-emerging antibodies binding to Chinese hamster ovary host cell proteins. Moreover, the potential association between the presence of these binding antibodies and adverse events (AEs) observed in patients was investigated, and the potential impact of these antibodies on the incremental recovery of rurioctocog alfa pegol in patients was analyzed. Overall, the data indicate that rurioctocog alfa pegol is not associated with any unexpected immunogenicity characteristics. Of 360 patients, 1 patient developed a transient FVIII inhibitor with a titer of 0.6 Bethesda units per mL, which was not associated with any serious AEs. Antibodies binding to FVIII, PEG-FVIII, or PEG were not detected at the time when the inhibitor was present. Moreover, 54 of 360 patients either entered the clinical studies with preexisting binding antibodies or developed these antibodies after exposure to rurioctocog alfa pegol. These antibodies were transient in most patients and did not show any causal relationship to either AEs or spontaneous bleeding episodes.
Single intravenous dose ondansetron induces QT prolongation in adult emergency department patients: a prospective observational study
Authors: Rezaei Zadeh Rukerd Mohammad , Shahrbabaki Fatemeh Rafiei , Movahedi Mitra , Honarmand Amin , Pourzand Pouria , Mirafzal Amirhossein 
Published: April 2024

Abstract
Background
Ondansetron is one of the most commonly used drugs in the emergency department (ED) for treating nausea and vomiting, particularly in intravenous (IV) form. Nevertheless, it has been shown to prolong QT interval and increase the risk of ventricular dysrhythmias. This study evaluated the associations between single IV ondansetron dosage and subsequent QTc prolongation in the ED.

Methods
In this prospective observational study, a total number of 106 patients presenting to the ED in a 3-month period with nausea and vomiting treated with IV ondansetron were enrolled. QT and QTc intervals were measured at baseline (QT0 and QTc0), and 60 min (QT60 and QTc60) following a single-dose administration of ondansetron at 4 or 8 mg doses. To evaluate the predictive ability of these variables, we employed receiver operating characteristic (ROC) curve analyses.

Results
The predictive models for QTc prolongation 1-hour post-ondansetron administration showed the following: at baseline, the area under curve of 0.70 for QT, 0.71 for QTc, and 0.64 for dosage. Conversely, a QTc0 = 375 msec indicated a QTc60 > 480 msec with a specificity of 97%. Additionally, a QTc0 of 400 msec had a sensitivity of 100% in predicting a QTc60 < 480 msec, while a QTc0 > 460 msec predicted a QTc60 > 480 msec with a specificity of 98%. Moreover, 8 mg doses were associated with higher rates of QTc60 prolongation, while 4 mg doses favored maintaining QTc60 within normal limits.

Conclusions
Our study demonstrates the predictive capacity of QT0, QTc0, and ondansetron dosage in forecasting QTc60 prolongation (> 480 msec) post-ondansetron administration. These findings advocate for their incorporation into clinical protocols to enhance safety monitoring in adult ED patients.
Oil-based extraction as an efficient method for the quantification of microplastics in environmental samples
Authors: Lekše Nina , Žgajnar Gotvajn Andreja , Zupančič Marija , Griessler Bulc Tjaša 
Published: April 2024

Abstract
Background
Wastewater treatment plant outlets are a major source of microplastics, with more than 90% retained in sewage sludge. No standardised method for the extraction, quantification, and characterisation of microplastics in sewage sludge or soil exists, and direct comparison of studies is often impossible. Our aim was to validate oil extraction efficiency with and without pre-treatment with Fenton’s reagent of selected microplastics in various types of environmental samples (sewage sludge and organic-rich substrates).

Results
Oxidation with Fenton’s reagent removed up to 90% of organic material, which improves the recovery rate and made quantification and characterisation easier and more reliable, regardless of type, shape, size, or density of the selected microplastic particles used in this study. Pre-treatment, as a pre-step of the oil extraction method, was shown to be important in reducing organic matter in all environmental samples, including sewage sludge and organic-rich substrates. It also improved the reliability of the selected method, shortened its duration, and, by reducing organic matter, made extracted microplastics more visible. The recovery rate was better for particles 1–5 mm and lower for particles 0.1 < 1 mm.

Conclusions
By achieving up to a 100% recovery rate for certain types of microplastics (polypropylene and polystyrene), the selected method proved to be a promising extraction method. It was also shown to be efficient in the organic-rich substrates, for which the characterisation of microplastic particles was done by Fourier transform infrared spectroscopy. The most commonly detected types of microplastics in organic-rich substrates were polyethylene, polypropylene, polystyrene and polyester.