bluuebunny/crossref_metadata_2025_split huggingface dataset:
Performance of Wearable Pulse Oximetry During Controlled Hypoxia Induction
Authors: Jiang Yihang , Spies Connor , Roghanizad Ali R. , Bhosai Satasuk Joy , Snyder Laurie , Burke Ashley , MacLeod David , Dunn Jessilyn 
Published: July 2024

AbstractOxygen saturation is a crucial metric used for monitoring patients with lung disease or other conditions who are at risk of hypoxemia. Recently, consumer wearable devices began incorporating oxygen saturation measurement tools, widening their use among individuals with lung disease. However, their performance has not been well characterized, particularly during blood oxygen desaturation, due to limitations in collecting comparison arterial blood gas measurements during exercise-induced hypoxemia. To address this knowledge gap, we performed a controlled oxygen desaturation study in nine healthy participants to mimic exercise-induced hypoxemia, reducing the blood oxygen saturation levels from 100% to 60% using a gas delivery system. We conducted a comparative analysis of the displayed oxygen saturation readings of both the Masimo MightySat Rx finger pulse oximeter and Apple Watch Series 7 with arterial blood oxygen saturation readings obtained from arterial blood gas samples. Both the Masimo MightySat Rx pulse oximeter and the Apple Watch Series 7 tended to overestimate the oxygen saturation. The Masimo pulse oximeter readings were more likely to fall within the acceptable error range than the Apple Watch (49.03% compared to 32.14%). Notably, both devices have limitations under low oxygen saturation levels (<88%) with an error of 1.96% and 4.99% for the Masimo and Apple Watch, respectively. Among the oxygen desaturation measurements at a desaturation rate larger than two percent per minute, a rate which is clinically correlated to sleep apnea, both devices increased their error slightly by 0.29% and 1.80% respectively for the Masimo and Apple Watch. However, no statistically significant increase was found.Author SummaryBlood oxygen saturation (SpO2) is an important measurement for monitoring patients with acute and chronic conditions that are associated with hypoxemia, including chronic obstructive pulmonary disease (COPD), heart failure, and sleep apnea. While smartwatches may provide a novel method for continuous and unobtrusive SpO2monitoring, it is necessary to understand their accuracy and limitations to ensure that they are used in a fit-for-purpose manner, especially under conditions of low oxygen saturation.
Lower levels of household transmission of SARS-CoV-2 VOC Omicron compared to Wild-type: an interplay between transmissibility and immune status
Authors: Winkel AMAM , Kozanli E , Haverkort ME , Euser SM , Sluiter-Post JGC , Mariman R , Vogelzang A. , de Bakker J. , Lap C.R. , van Houten MA , Eggink D , van Lelyveld SFL 
Published: July 2024

AbstractBackgroundKnowledge of SARS-CoV-2 household transmission dynamics guides infection control and vaccination measures. This household cohort study prospectively assessed the impact of both the Omicron BA.2 variant and immunity on household transmission using dense saliva sampling and sequence analysis.MethodsHouseholds consisting of a PCR-confirmed index and at least two household members were enrolled in March and April 2022 during the Omicron BA.2 wave in the Netherlands. SARS-CoV-2 PCR was performed on ten consecutive saliva samples. Serum-antibodies were measured at baseline and day 42. Whole genome sequencing was performed for phylogenetic analysis, followed by sensitivity analysis, to correct for multiple household introductions and index definition. Results were compared with the identical, early-pandemic and pre- immunisation predecessor study.ResultsSixty-seven households were included, consisting of 241 individuals (median age 33.0 years). Maximum household Secondary Attack Rate (SAR) was 59.7%, per-person SAR 41.5%. Underage indexes were more likely to transmit. Transmission was negatively affected by household members’ immunity. Phylogenetic analysis showed multiple introductions in four households. Sensitivity analysis resulted in a minimal household SAR of 51.0% and per-person SAR of 28.5%.ConclusionsThe Omicron BA.2 variant is highly transmissible within households. Nevertheless, transmission rates are lower than our pre-immunisation reported ancestral rates: household SAR decreased from 88.2% to 59.7%, per-person SAR from 64.3% to 41.5%, implying immunity reduces transmission, even for a more transmittable variant. Regardless of immune status, children have a crucial role in Omicron household transmission. Intensive sampling and phylogenetic analysis are essential to correctly calculate transmission rate, especially in times of minimal behavioural restrictions.
A multiscale model of the action of a capsid assembly modulator for the treatment of chronic hepatitis B
Authors: Iyaniwura Sarafa A. , Cassidy Tyler , Ribeiro Ruy M. , Perelson Alan S. 
Published: July 2024

AbstractChronic hepatitis B virus (HBV) infection is strongly associated with increased risk of liver cancer and cirrhosis. While existing treatments effectively inhibit the HBV life cycle, viral rebound occurs rapidly following treatment interruption. Consequently, functional cure rates of chronic HBV infection remain low and there is increased interest in a novel treatment modality, capsid assembly modulators (CAMs). Here, we develop a multiscale mathematical model of CAM treatment in chronic HBV infection. By fitting the model to participant data from a phase I trial of the first-generation CAM vebicorvir, we estimate the drug’s dose-dependent effectiveness and identify the physiological mechanisms that drive the observed biphasic decline in HBV DNA and RNA, and mechanistic differences between HBeAg-positive and negative infection. Finally, we demonstrate analytically and numerically that HBV RNA is more sensitive than HBV DNA to increases in CAM effectiveness.Author summaryCapsid assembly modulators (CAMs) are a novel class of anti-hepatitis B virus (HBV) treatments in clinical trials. These CAMs have a distinct mechanism of action from nucleos(t)ide analogues and thus represent an attractive option for the treatment of chronic HBV infection. We developed a multiscale model of the intracellular HBV lifecycle and extracellular dynamics using a time-since-infection structured partial differential equation. We fit the model to participant data from a recent phase I trial, performed a detailed parameter sensitivity analysis, identified key mechanisms driving viral response to first-generation CAM treatment, and demonstrated that HBV RNA is more sensitive than HBV DNA to changes in CAM efficacy, highlighting the potential role of HBV RNA as a biomarker for CAM effectiveness.
The stress-protectant molecule trehalose mediates fluconazole tolerance inCandida glabrata
Authors: Zhu Qingjuan , Wijnants Stefanie , Feil Regina , Vergauwen Rudy , Lunn John E. , Ende Mieke Van , Van Dijck Patrick 
Published: July 2024

AbstractThe incidence of non-albicans Candidainfections has witnessed a substantial rise in recent decades.Candida glabrata (Nakaseomyces glabratus), an opportunistic human fungal pathogen, is accountable for both superficial mucosal and life-threatening bloodstream infections, particularly in immunocompromised individuals. Distinguished by its remarkable resilience to environmental stressors,C. glabrataexhibits intrinsic tolerance to azoles and a high propensity to swiftly develop azole resistance during treatment. The molecular mechanism for the high tolerance is not fully understood. In this work we investigated the possible role of trehalose in this tolerance. We generated mutants in theC. glabrata TPS1,TPS2, andNTH1genes, encoding trehalose 6-phosphate synthase (Tps1), trehalose 6-phosphate phosphatase (Tps2), and neutral trehalase (Nth1), respectively. As expected, thetps1Δstrain cannot grow on glucose. Thetps2Δ strain demonstrated diminished trehalose accumulation and very high levels of trehalose 6-phosphate (T6P), the biosynthetic intermediate, in comparison to the WT strain. Whereas these higher T6P levels did not affect growth, the lower trehalose levels clearly resulted in lower environmental stress tolerance and a lower susceptibility to fluconazole. More interestingly, thetps2Δstrain completely lost tolerance to fluconazole, characterized by the absence of slow growth at supra-MIC concentrations of this drug. All these phenotypes are reversed in thenth1Δ strain, which accumulates high levels of trehalose. Our findings underscore the role of trehalose in enabling tolerance towards fluconazole inC. glabrata. We further show that the change in tolerance is a result of the effect that trehalose has on the sterol pattern in the cell, showing that accumulation of ‘toxic’ sterols correlate with absence of tolerance.Author summaryC. glabratais a yeast of significant medical importance, known for causing nosocomial outbreaks of invasive candidiasis. Its propensity to develop resistance to antifungal medications, notably azoles such as fluconazole, raises considerable concern. An underlying reason for the rapid development of resistance is its intrinsic tolerance to this drug. The underlying molecular mechanism of tolerance to fluconazole is heavily studied but not understood. This study sheds light on the involvement of trehalose in modulating tolerance to fluconazole. We have elucidated that trehalose serves not only as a protective agent against various stresses but also as a mediator of fluconazole resistance and tolerance. To start elucidating how this may work, we provide data that trehalose (or the enzymes affecting the amount of trehalose in the cell) alters the ergosterol type and level in the cells, thereby affecting tolerance.
Competition and interdependence define multifaceted interactions of symbioticNostocsp. andAgrobacteriumsp. under inorganic carbon limitation
Authors: Teikari Jonna E. , Russo David A. , Heuser Markus , Baumann Otto , Zedler Julie A. Z. , Liaimer Anton , Dittmann Elke 
Published: July 2024

SummaryCyanobacteria of theNostocgenus are capable of forming symbiotic relationships with plants, thus transitioning to a heterotrophic lifestyle in return for providing bioavailable nitrogen to the host. The diazotrophic photoautotrophs also serve as a hub for specialized heterotrophic bacterial communities whose physiological contributions are poorly understood. By comparing the axenic strainNostoc punctiformePCC 73102 and the related strainsNostocsp. KVJ2 and KVJ3, which still maintain their heterotrophic microbiome, we were able to demonstrate an almost obligate dependence of the cyanobacteria on the heterotrophic partners under carbon-limiting conditions. Detailed analysis of the intimate bilateral relationship betweenN. punctiformeand the isolateAgrobacterium tumefaciensHet4 using shotgun proteomics and microscopy uncovered a complex partnership characterized, among other traits, by competition for iron and facilitation for carbon. Although competitive interactions withA. tumefaciensHet4 compromise nitrogen fixation and stimulate the degradation of cyanophycin, mutualistic dependency prevails under inorganic carbon limitation. Both the absence of the high affinity bicarbonate uptake transporter SbtA and the prevalent extracarboxysomal localization of the carbon-fixing enzyme RubisCO, as detected by immunofluorescence microscopy, suggest that a weak carbon concentrating mechanism inN. punctiformeenforces a dependence on heterotrophic bacteria. Further, immunofluorescence, electron microscopic and proteomic analyses reveal a pronounced extracellular recycling of proteins under N- and C-limiting conditions. Our study shows that the pivotal influence of heterotrophic bacteria on symbioticNostocstrains should be considered when analyzing these cyanobacteria, especially in the free-living state. This work also sheds new light on howNostocbenefits from the organic carbon provided by plant hosts.
Comprehensive Biosynthetic Analysis of Human Microbiome Reveals Diverse Protective Ribosomal Peptides
Authors: Zhang Jian , Zhang Dengwei , Xu Yi , Zhang Junliang , Liu Runze , Gao Ying , Shi Yuqi , Cai Peiyan , Zhong Zheng , He Beibei , Li Xuechen , Zhou Hongwei , Chen Muxuan , Li Yong-Xin 
Published: July 2024

AbstractThe human microbiome holds tremendous potential for generating specialized peptides, specifically ribosomally synthesized and post-translationally modified peptides (RiPPs), significantly affecting human health by mediating interactions with other microbes and the human host. However, the capacity of our microbiome to produce these peptides and their links with human health are poorly understood. This study systematically analyzes 306,481 human microbiota-associated genomes, uncovering a broad array of yet-to-be-discovered RiPPs. These RiPPs are distributed across various body sites but show a specific enrichment in the gut and oral microbiome. Big data omics analysis reveals that numerous RiPP families are inversely related to various diseases, suggesting their potential protective effects on health. For a proof of principle study, guided by biosynthetic prediction, nine autoinducing peptides (AIPs) were chemically synthesized forin vitroandex vivoassay. Our findings revealed that five AIPs effectively inhibited the biofilm formation of disease-associated pathogens, with one demonstrating significant anti-inflammatory capabilities. Furthermore, whenex vivotesting gut bacteria from mice with inflammatory bowel disease, we observed that two AIPs could regulate the microbial community and reduce harmful species. These findings highlight the vast potential of human microbial RiPPs in regulating microbial communities and maintaining human health, emphasizing their potential for therapeutic development.
Chemical inactivation of two non-enveloped viruses follows distinct molecular pathways
Authors: Narula Pankhuri , Lokshman Milan Kumar , Pathak Sandip B. , Mukherjee Sayandip , Banerjee Manidipa 
Published: July 2024

AbstractNon-enveloped viruses, which lack a lipid envelope, typically display higher resistance to disinfectants, soaps and sanitizers compared to enveloped viruses. The capsids of these viruses are highly stable and symmetric protein shells that resist inactivation by commonly employed virucidal agents. This group of viruses include highly transmissible human pathogens such as Rotavirus, Poliovirus, Foot and Mouth Disease Virus, Norovirus and Adenovirus; thus, devising appropriate strategies for chemical disinfection is essential. We tested a mild combination of a denaturant, alcohol, and organic acid on two representative non-enveloped viruses – Human Adenovirus 5 (HAdV5) and Feline Calicivirus (FCV)– and evaluated the molecular pathway of capsid neutralization using biophysical methods. The transition temperatures signifying conformational shifts in the capsid were established in the presence and absence of chemical treatment using Differential Scanning Calorimetry (DSC), while the corresponding morphological alterations were visualized and correlated using Transmission Electron Microscopy (TEM). We found that while chemical treatment of purified HAdV5 particles resulted in increased thermal instability, followed by large scale particle aggregation; similar treatment of FCV particles resulted in complete collapse of the capsids. The distinct effects of the chemical treatment on the morphology of HAdV5 and FCV suggests that non-enveloped viruses with icosahedral geometry can follow different molecular pathways to inactivation. Further, while individual components of the chemical formulation caused significant damage to the capsids, a synergistic action of the whole formulation was evident against both non-enveloped viruses tested. Molecular level understanding of inactivation pathways may result in the design and development of effective mass-market formulations for rapid neutralization of non-enveloped viruses.Highlightsformulation consisting of 3.2% citric acid, 1% urea in 70% ethanol, pH4 effectively inactivates HAdV5 and FCV.inactivation pathways with complete formulation, are different for the two viruses.effect of whole formulation is more effective compared to individual components.
Global Prevalence ofCryptosporidiumInfections in Cattle andC. parvum genotypedistribution: A Meta-Analysis
Authors: Buchanan Rachel , Matechou Eleni , Katzer Frank , Tsaousis Anastasios D. , Farré Marta 
Published: July 2024

AbstractBackgroundThe protozoan parasiteCryptosporidiumis the causative agent of a severe diarrhoeal disease, called cryptosporidiosis.Cryptosporidiumspecies are capable of infecting a wide range of hosts including humans and livestock. In cattle, cryptosporidiosis is now one of the most important causes of neonatal scour globally, either as a sole agent or co-infecting with other pathogens. Cryptosporidiosis is considered globally endemic, with a prevalence ofCryptosporidiumin stool samples from 13% to 93% in European cattle. This disease has a significant economic burden, with costs associated with veterinary diagnosis, medication, increased labour, animal rearing and supplemental nutrition as well as being associated with reduced long-term growth rate in calves, causing huge economic losses in livestock industry. Moreover, cattle act as a zoonotic reservoir forCryptosporidium parvum, a species that is capable of infecting humans as well. As such, monitoring the prevalence ofCryptosporidiumin cattle is important due to the public health risk and financial burden the clinical disease causes.MethodsPublications reporting on the prevalence ofCryptosporidiumin cattle were collected from PubMed and Google Scholar. Information regarding the species ofCryptosporidiumin positive samples, the genotype ofC. parvumfound in samples, and the diarrhoeic status of the cattle was collected where available. A total of 279 publications were collected for this meta-analysis from six continents and 65 countries to provide an estimation for global bovineCryptosporidiumprevalence.ResultsA 25.5% global prevalence ofCryptosporidiuminfection was reported, withC. parvumbeing the most frequently identified species, particularly the IIa subfamily. Diarrhoea was reported in 14,141 cattle samples, of which 36.0% tested positive forCryptosporidium. Regarding symptoms, we found that in countries reporting over 50% of diarrhoeic positive cattle,C. parvumwas the most common species.ConclusionsContinued monitoring and reporting ofCryptosporidiumin cattle are crucial for both public health and economic reasons. Consequently, efforts should focus on underreported regions and the development of control measures to reduce prevalence and limit zoonotic transmission.
Acinetobacter baumanniiDacC influences cell shape, biofilm formation and physiological fitness by manifesting DD-carboxypeptidase, and β-lactamase dual-enzyme activities
Authors: Pal Shilpa , Jain Diamond , Biswal Sarmistha , Rastogi Sumit Kumar , Kumar Gaurav , Ghosh Anindya S 
Published: July 2024

AbstractWith the growing threat of drug-resistantAcinetobacter baumannii, there is an urgent need to comprehensively understand the physiology of this nosocomial pathogen. As penicillin-binding proteins are attractive targets for antibacterial therapy, herein we have tried to explore the physiological roles of two putative DD-carboxypeptidases, viz.,dacCanddacDinA. baumannii. Surprisingly, the deletion ofdacCresulted in a reduced growth rate, loss of rod-shaped morphology, reduction in biofilm-forming ability, and enhanced susceptibility towards β-lactams, whereas, the deletion ofdacDhad no such effect. Interestingly, ectopic expression ofdacCrestored the lost phenotypes. The double deletion mutant in which bothdacCanddacDwere absent showed properties similar to thedacCsingle knockout. On the other hand, cell-shape reverting efficiency in septuple PBP deletedE. coliandin vitroenzyme kinetics assessments reveal thatdacDis a stronger DD-CPase as compared todacC. The expression ofdacCwas in the log phase whereasdacDexpression takes place in the stationary phase. In summary, we conclude thatdacCencodes a dual enzyme, possessing activities of DD-CPase and β-lactamase, which significantly affects the physiology ofA. baumanniiin various ways whereasdacDencodes a strong DD-CPase and plays a role in cell morphology, though it exerts negligible impact on other physiological aspects like intrinsic antibiotic resistance or biofilm formation.Graphical Abstract
Stabilised D2R G-protein coupled receptor oligomers identify multi-state β-arrestin complexes
Authors: Sharrocks Katie L. , Fanelli Francesca , Lui Yewei , Milner Annabelle J. , Yining Wu , Byrne Bernadette , Hanyaloglu Aylin C. 
Published: July 2024

AbstractThe G-protein coupled receptor (GPCR) superfamily directs central roles in many physiological and pathophysiological processes via diverse and complex mechanisms. GPCRs can exhibit signal pleiotropy via formation of di/oligomers both with themselves and other GPCRs. A deeper understanding of the molecular basis and functional role of oligomerization would facilitate rational design of activity-selective ligands. A structural model of the D2 dopamine receptor (D2R) homomer identified distinct combinations of substitutions likely to stabilise protomer interactions. Molecular modelling of β-arrestin-2 (βarr2) bound to predicted dimer models suggests a 2:2 receptor:βarr2 stoichiometry, with the dimer favouring βarr2 over Gαi coupling. A combination of biochemical, biophysical and super-resolution, single molecule imaging approaches demonstrated that the D2R mutant homomers exhibited greater stability. The mutant D2R homomers also exhibited bias towards recruitment of the GPCR adaptor protein βarr2 with either faster or ligand-independent βarr2 recruitment, increased internalization and reprogrammed ERK signaling compared to D2R WT. Through GPCR dimer-stabilisation, we demonstrate that D2R di/oligomerization has a role in βarr2-biased signaling.
Coherent control of multiphoton ionization of lithium atoms by a bichromatic laser field
Authors: Mežinska S. , Dorn A. , Pfeifer T. , Bartschat K. 
Published: July 2024

We demonstrate a left-right asymmetry control of the photoelectron angular distribution in multiphoton ionization of Li atoms by a bichromatic laser field. By delaying the fundamental (780 nm) and its second harmonic relative to each other in steps of 130 attoseconds, we can vary the relative phase between the two laser fields with subwavelength accuracy and thereby steer the ejected electrons. Good agreement is found between the measurements and calculations at the appropriate intensities of the two harmonics.

Published by the American Physical Society
2024