bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intranasal administration of octavalent next-generation influenza vaccine elicits protective immune responses against seasonal and pre-pandemic viruses
Authors: Uno Naoko , Ebensen Thomas , Guzman Carlos A. , Ross Ted M. 
Published: August 2024

ABSTRACT

Development of next-generation influenza virus vaccines is crucial to improve protection against circulating and emerging viruses. Current vaccine formulations have to be updated annually due to mutations in seasonal strains and do not offer protection against strains with pandemic potential. Computationally optimized broadly reactive antigen (COBRA) methodology has been utilized by our group to generate broadly reactive immunogens for individual influenza subtypes, which elicit protective immune responses against a broad range of strains over numerous seasons. Octavalent mixtures of COBRA hemagglutinin (HA) (H1, H2, H3, H5, H7, and influenza B virus) plus neuraminidase (NA) (N1 and N2) recombinant proteins mixed with c-di-AMP adjuvant were administered intranasally to naive or pre-immune ferrets in prime-boost fashion. Four weeks after final vaccination, collected sera were analyzed for breadth of antibody response, and the animals were challenged with seasonal or pre-pandemic strains. The octavalent COBRA vaccine elicited antibodies that recognized a broad panel of strains representing different subtypes, and these vaccinated animals were protected against influenza virus challenges. Overall, this study demonstrated that the mixture of eight COBRA HA/NA proteins mixed with an intranasal adjuvant is a promising candidate for a universal influenza vaccine.

IMPORTANCE
Influenza is a respiratory virus which infects around a billion people globally every year, with millions experiencing severe illness. Commercial vaccine efficacy varies year to year and can be low due to mismatch of circulating virus strains. Thus, the formulation of current vaccines has to be adapted accordingly every year. The development of a broadly reactive influenza vaccine would lessen the global economic and public health burden caused by the different types of influenza viruses. The significance of our research is producing a promising universal vaccine candidate which provides protection against a wider range of virus strains over a wider range of time.
Impact of organic compounds on the stability of influenza A virus in deposited 1-μL droplets
Authors: Schaub Aline , David Shannon C. , Glas Irina , Klein Liviana K. , Violaki Kalliopi , Terrettaz Céline , Motos Ghislain , Bluvshtein Nir , Luo Beiping , Pohl Marie , Hugentobler Walter , Nenes Athanasios , Krieger Ulrich K. , Peter Thomas , Stertz Silke , Kohn Tamar 
Published: August 2024

ABSTRACT

The composition of respiratory fluids influences the stability of viruses in exhaled aerosol particles and droplets, though the role of respiratory organics in modulating virus stability remains poorly understood. This study investigates the effect of organic compounds on the stability of influenza A virus (IAV) in deposited droplets. We compare the infectivity loss of IAV at different relative humidities (RHs) over the course of 1 h in 1-µL droplets consisting of phosphate-buffered saline (without organics), synthetic lung fluid, or nasal mucus (both containing organics). We show that IAV stability increases with increasing organic:salt ratios. Among the various organic species, proteins are identified as the most protective component, with smaller proteins stabilizing IAV more efficiently at the same mass concentration. Organics act by both increasing the efflorescence RH and shortening the drying period until efflorescence at a given RH. This research advances our mechanistic understanding of how organics stabilize exhaled viruses and thus influence their inactivation in respiratory droplets.

IMPORTANCE
This study investigates how the composition of respiratory fluids affects the stability of viruses in exhaled droplets. Understanding virus stability in droplets is important as it impacts how viruses spread and how we can combat them. We focus on influenza A virus (IAV) and investigate how different organic compounds found in lung fluid and nasal mucus protect the virus from inactivation. We demonstrate that the ratio of organics to salt in the fluid is an indicator of IAV stability. Among organics, small proteins are particularly effective at protecting IAV. Their effect is in part explained by the proteins’ influence on the crystallization of salts in the droplets, thereby shielding the viruses from prolonged exposure to harmful salt concentrations. Understanding these mechanisms helps us grasp how viruses sustain their infectivity over time in respiratory droplets, contributing to efforts in controlling infectious diseases.
Essential genes for
Haemophilus parainfluenzae
survival and biofilm growth
Authors: de Palma Thais H. , Powers Chris , McPartland Morgan J. , Mark Welch Jessica , Ramsey Matthew 
Published: August 2024

ABSTRACT

Haemophilus parainfluenzae
(
Hp
) is a Gram-negative, highly prevalent, and abundant commensal in the human oral cavity, and an infrequent extraoral opportunistic pathogen.
Hp
occupies multiple niches in the oral cavity, including the supragingival plaque biofilm. Little is known about how
Hp
interacts with its neighbors in healthy biofilms nor its mechanisms of pathogenesis as an opportunistic pathogen. To address this, we identified the essential genome and conditionally essential genes in
in vitro
biofilms aerobically and anaerobically. Using transposon insertion sequencing (TnSeq) with a highly saturated
mariner
transposon library in two strains, the ATCC33392 type-strain (
Hp
392) and oral isolate EL1 (
Hp
EL1), we show that the essential genomes of
Hp
392 and
Hp
EL1 are composed of 395 (20%) and 384 (19%) genes, respectively. The core essential genome, consisting of 341 (17%) essential genes conserved between both strains, was composed of genes associated with genetic information processing, carbohydrate, protein, and energy metabolism. We also identified conditionally essential genes for aerobic and anaerobic biofilm growth, which were associated with carbohydrate and energy metabolism in both strains. RNAseq analysis determined that most genes upregulated during anaerobic growth are not essential for
Hp
392 anaerobic survival. The completion of this library and analysis under these conditions gives us a foundational insight into the basic biology of
H. parainfluenzae
in differing oxygen conditions, similar to its
in vivo
habitat. This library presents a valuable tool for investigation into conditionally essential genes for an organism that lives in close contact with many microbial species in the human oral habitat.

IMPORTANCE

Haemophilus parainfluenzae
is a highly abundant human commensal microbe, present in most healthy individuals where it colonizes the mouth.
H. parainfluenzae
correlates with good oral health and may play a role in preservation of healthy host status. Also,
H. parainfluenzae
can cause opportunistic infections outside of the oral cavity. To date, little is known about how
H. parainfluenzae
colonizes the human host, despite being such a frequent and abundant part of our human microbiome. Here, we demonstrate the creation and use of a powerful tool, a TnSeq library, used to identify genes necessary for both the outright growth of this organism and also genes conditionally essential for growth in varying oxygen status which it can encounter in the human host. This tool and these data serve as a foundation for further study of this relatively unknown organism that may play a role in preserving human health.
Rescue of morphological defects in
Streptomyces venezuelae
by the alkaline volatile compound trimethylamine
Authors: Zhu Yanping , Zeng Yanhong , Liu Meng , Lu Ting , Pang Xiuhua 
Published: August 2024

ABSTRACT

Microorganisms can produce a vast diversity of volatile organic compounds of different chemical classes that are capable of mediating intra- and inter-kingdom interactions. In this study, we showed that the soil-dwelling bacterium
Streptomyces venezuelae
can produce alkaline volatiles under multiple growth conditions, which we discovered through investigation of the
S. venezuelae
mutant strain MU-1. Strain MU-1 has a defective morphology and exhibits a bald phenotype due to the lack of aerial mycelia and spores, as confirmed by scanning electron microscopy. Using physical barriers to separate the strains on culture plates, we determined that volatile compounds produced by wild-type
S. venezuelae
could rescue the phenotype of strain MU-1, and pH analysis of the growth medium indicated that these volatile compounds were alkaline. Ultra-high-performance liquid chromatography, combined with mass spectrometry analysis, showed that wild-type
S. venezuelae
produced abundant levels of the alkaline volatile trimethylamine (TMA) and the oxide form TMAO; however, the levels of these compounds were much lower in strain MU-1. Notably, exposure to TMA alone could rescue the phenotype of this mutant strain, restoring the production of aerial mycelia and spores. We also showed that the rescue effect by alkaline volatiles is mostly species-specific, suggesting that the volatiles may aid particular mutants or other less-fit variants of closely related species to resume normal physiological status and to compete more effectively in complex communities such as soil. Our study reveals a new and intriguing role for bacterial volatiles, including volatiles that may have toxic effects on other species.

IMPORTANCE

Bacterial volatiles have a wide range of biological roles at intra- or inter-kingdom levels. The impact of volatiles has mainly been observed between producing bacteria and recipient bacteria, mostly of different species. In this study, we report that the wild-type, soil-dwelling bacterium
Streptomyces venezuelae
, which forms aerial hypha and spores as part of its normal developmental cycle, also produces the alkaline volatile compound trimethylamine (TMA) under multiple growth conditions. We showed that the environmental dispersion of TMA produced by
S. venezuelae
promotes the growth and differentiation of growth-deficient mutants of the same species or other slowly growing
Streptomyces
bacteria, and thus aids in their survival and their ability to compete in complex environmental communities such as soil. Our novel findings suggest a potentially profound biological role for volatile compounds in the growth and survival of communities of volatile-producing
Streptomyces
species.
Stratigraphic record of tectonic and climatic impact on orogenic growth: An example from the Hexi Corridor Basin, NE Tibetan Plateau
Authors: Pan Baotian , Zhang Jian , Geng Haopeng , Saylor Joel , Cheng Feng , Chen Dianbao , Li Lin , Xu Ziyi , Jian Liwei , Nie Junsheng 
Published: August 2024

Abstract
The locus of shortening, accretion, and erosion are key components in modulating the rate, pattern, and magnitude of orogenic wedge growth, but separating their respective roles in the evolution of wedge taper is often difficult because of the absence of exhumation and uplift data from the mountains. However, such information can be preserved in the adjacent basins, and a combination of sediment provenance and accumulation rate records may be able to distinguish tectonic versus climatically caused orogenic wedge evolution. Here we present a joint sediment accumulation rate (SAR) and provenance analysis based on zircon U-Pb ages and heavy mineral composition of a drill core from the foreland of the Qilian Shan (i.e., Hexi Corridor Basin, NE Tibetan Plateau) with the aim to reveal the evolution of the Qilian orogenic wedge and its relationship to tectonics and climate. The provenance data show a gradual increase in sediment attributable to the Yumu Shan in the toe of the orogenic wedge and associated decrease in contribution from the high-elevation hinterland Zoulang Nan Shan source between 7 Ma and 3 Ma, followed by a reverse of these trends from 3 Ma to the modern. The increased contribution from the toe of the orogenic wedge (Yumu Shan) is accompanied by an increase in SAR, and we interpret this joint signal as the result of in-sequence thrusting, which caused flexural subsidence and created more deposition space in the bounding foreland. The increased contribution from the hinterland from 3.0 Ma to 1.8 Ma, accompanied with the decreased SAR, is attributed to the onset of Northern Hemisphere glaciation, which increased glacial erosion of the high-elevation hinterland areas and caused erosional unloading of the orogenic wedge, leading to flexural uplift in the foreland and reduced SAR. After 1.8 Ma, continued increase in the contribution from the hinterland accompanied with the SAR increase is less straightforward to interpret. We suspect that glacial erosion might have activated fault movements in the hinterland area, and tectonic-caused rock uplift was faster than glacial erosion. Therefore, high sediment flux from the hinterland was maintained but flexural subsidence accelerated. Our results demonstrate that both tectonics and climate have shaped regional landscape evolution and emphasize the role of glacial erosion in accounting for orogenic wedge evolution at ca. 3 Ma.
Prognostic value of the 5-SENSE Score to predict focality of the seizure-onset zone as assessed by stereoelectroencephalography: a prospective international multicentre validation study
Authors: Astner-Rohracher Alexandra , Ho Alyssa , Archer John , Bartolomei Fabrice , Brazdil Milan , Cacic Hribljan Melita , Castellano James , Dolezalova Irena , Fabricius Martin Ejler , Garcés-Sanchez Mercedes , Hammam Kahina , Ikeda Akio , Ikeda Kristin , Kahane Philippe , Kalamangalam Giridhar , Kalss Gudrun , Khweileh Mays , Kobayashi Katsuya , Kwan Patrick , Laing Joshua Andrew , Leitinger Markus , Lhatoo Samden , Makhalova Julia , McGonigal Aileen , Mindruta Iona , Mizera Mary Margaret , Neal Andrew , Oane Irina , Parikh Prachi , Perucca Piero , Pizzo Francesca , Rocamora Rodrigo , Ryvlin Philippe , San Antonio Arce Victoria , Schuele Stephan , Schulze-Bonhage Andreas , Suller Marti Ana , Urban Alexandra , Villanueva Vincente , Vilella Bertran Laura , Whatley Benjamin , Beniczky Sandor , Trinka Eugen , Zimmermann Georg , Frauscher Birgit 
Published: August 2024

IntroductionEpilepsy surgery is the only curative treatment for patients with drug-resistant focal epilepsy. Stereoelectroencephalography (SEEG) is the gold standard to delineate the seizure-onset zone (SOZ). However, up to 40% of patients are subsequently not operated as no focal non-eloquent SOZ can be identified. The 5-SENSE Score is a 5-point score to predict whether a focal SOZ is likely to be identified by SEEG. This study aims to validate the 5-SENSE Score, improve score performance by incorporating auxiliary diagnostic methods and evaluate its concordance with expert decisions.Methods and analysisNon-interventional, observational, multicentre, prospective study including 200 patients with drug-resistant epilepsy aged ≥15 years undergoing SEEG for identification of a focal SOZ and 200 controls at 22 epilepsy surgery centres worldwide. The primary objective is to assess the diagnostic accuracy and generalisability of the 5-SENSE in predicting focality in SEEG in a prospective cohort. Secondary objectives are to optimise score performance by incorporating auxiliary diagnostic methods and to analyse concordance of the 5-SENSE Score with the expert decisions made in the multidisciplinary team discussion.Ethics and disseminationProspective multicentre validation of the 5-SENSE score may lead to its implementation into clinical practice to assist clinicians in the difficult decision of whether to proceed with implantation. This study will be conducted in accordance with the Tri-Council Policy Statement: Ethical Conduct for Research Involving Humans (2014). We plan to publish the study results in a peer-reviewed full-length original article and present its findings at scientific conferences.Trial registration numberNCT06138808.
Baseline tumour vessel perfusion as a non-invasive predictive biomarker for immune checkpoint therapy in non-small-cell lung cancer
Authors: Liu Zhenhua , Ma Ke , Jia Qingzhu , Yang Yunpeng , Fan Peng , Wang Ying , Wang Junhui , Sun Jiya , Sun Liansai , Shi Hongtai , Sun Liang , Zhu Bo , Xu Wei , Zhang Li , Jain Rakesh K. , Qin Songbing , Huang Yuhui 
Published: August 2024

ObjectiveCurrent biomarkers for predicting immunotherapy response in non-small-cell lung cancer (NSCLC) are derived from invasive procedures with limited predictive accuracy. Thus, identifying a non-invasive predictive biomarker would improve patient stratification and precision immunotherapy.Methods and analysisIn this retrospective multicohort study, the discovery cohort included 205 NSCLC patients screened from ORIENT-11 and an external validation (EV) cohort included 99 real-world NSCLC patients. The ‘onion-mode segmentation’ method was developed to extract ‘onion-mode perfusion’ (OMP) from contrast-enhanced CT images. The predictive performance of OMP or its combination with the PD-L1 Tumour Proportion Score (TPS) was evaluated by the area under the curve (AUC).ResultsHigh baseline OMP was associated with significantly longer survival and predicted patient response to combination anti-PD-(L)1 therapy in the discovery and EV cohorts. OMP complemented the PD-L1 TPS with superior predictive sensitivity (p=0.02). In the PD-L1 TPS<50% subgroup, OMP achieved an AUC of 0.77 for the estimation of treatment response (95% CI 0.66 to 0.86, p<0.0001). A simple bivariate model of OMP/PD-L1 robustly predicted therapeutic response in both the discovery (AUC 0.82, 95% CI 0.74 to 0.88, p<0.0001) and EV (AUC 0.80, 95% CI 0.67 to 0.89, p<0.0001) cohorts.ConclusionOMP, derived from routine CT examination, could serve as a non-invasive and cost-effective biomarker to predict NSCLC patient response to immune checkpoint inhibitor-based therapy. OMP could be used alone or in combination with other biomarkers to improve precision immunotherapy.
Barriers and facilitators when seeking healthcare for septic children in Ghana: a single-centre qualitative study of patient caregivers and emergency department clinicians
Authors: Denny Vanessa C. , Appiah John Adabie , Nadkarni Vinay M. , Dassah Ebenezer , Gyimah Mensah Ebenezer , Kwabena Adjei Timothy , Amisah Justicia , Nettey Gustav , Owusu Larko , Woods-Hill Charlotte Z. , Wolfe Heather A. , James Ebor Jacob G. , Ruhama Acheampong Princess 
Published: August 2024

Background/purposeSepsis is a leading cause of morbidity, mortality and healthcare utilisation for children worldwide, particularly in resource-limited regions. In Kumasi, Ghana, organ system failure and mortality in children who present to the emergency department (ED) with symptoms of sepsis are often due to late presentation and lack of recognition and implementation of time-critical evidence-based interventions. The purpose of this study was to assess the barriers and facilitators for families in seeking healthcare for their septic children; and to understand the barriers and facilitators for ED providers in Kumasi to recognise and implement sepsis bundle interventions.DesignSingle-centre qualitative interviews of 39 caregivers and 35 ED providers in a teaching hospital in Kumasi, Ghana.ResultsThematic analysis of data from caregivers about barriers included: fear of hospital, finances, transportation, delay from referring hospital, cultural/spiritual differences, limited autonomy and concerns with privacy and confidentiality. Negative impacts on family life included financial strain and neglect of other children. ED providers reported barriers included: lack of training, poor work environment and accessibility of equipment. Facilitators from caregivers and providers included some support from the National Health Insurance. Caregivers reported having positive experiences with frontline clinicians, which encouraged them to return to seek health services.ImplicationsQualitative structured interviews identified facilitator and critical barrier themes about seeking healthcare, and sepsis identification/management in the paediatric population arriving for care in our centre in Kumasi, Ghana. This study highlights significant deficiencies in healthcare systems that make sepsis management challenging in these settings.
Exact dynamical black hole solutions in five or higher dimensions
Authors: Fahim Bardia H. , Ghezelbash A. M. 
Published: August 2024

AbstractWe construct new classes of the dynamical black hole solutions in five or higher dimensional Einstein–Maxwell theory, coupled to a dilaton field, in the presence of an arbitrary cosmological constant. The dilaton field interacts non-trivially with the Maxwell field, as well as the cosmological constant, with two arbitrary coupling constants. The solutions are non-stationary, and almost conformally regular everywhere. To construct the solutions, we use the four-dimensional Bianchi type IX geometry, as the base space. We find three different classes of solutions, based on the values of the coupling constants. We notice that our solutions could be asymptotically de-Sitter, anti-de-Sitter or flat. We find the relevant quantities of the solutions, and discuss the properties of the solutions.
Complete de-wetting of lipid membranes on silicon carbide
Authors: Ryskulov Ruslan , Pedrueza-Villalmanzo Esteban , Tatli Yagiz Alp , Gözen Irep , Jesorka Aldo 
Published: August 2024

AbstractWe report temperature-induced complete de-wetting of phospholipid membranes from thermally evaporated silicon carbide (SiC) substrates, which occurs in the form of fractal patterns. Excess membrane material released as a result of de-wetting, transforms into fluid-filled membrane pockets, or leads to vesicle formation. The membrane pockets are composed of a double lipid membrane. These double bilayer superstructures, i.e. isolated membrane-enclosed fluid volumes, bring the internal contents into direct contact with the surface. This membrane morphology can be viewed as an alternative prebiotic assembly mechanism with possible implications for protocell development, where physicochemical surface interactions with internal primitive cell contents are greatly facilitated.