bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of the distance of spread through air spaces in non-small cell lung cancer
Authors: Hashinokuchi Asato , Akamine Takaki , Toyokawa Gouji , Matsudo Kyoto , Nagano Taichi , Kinoshita Fumihiko , Kohno Mikihiro , Tomonaga Takumi , Kohashi Kenichi , Shimokawa Mototsugu , Oda Yoshinao , Takenaka Tomoyoshi , Yoshizumi Tomoharu
Published: December 2024

OBJECTIVES

Spread through air spaces (STAS) is considered a poor prognostic factor in patients with resected non-small lung cell cancer; however, the clinical significance of STAS extent remains unclear. We hypothesized that the further the tumour cells spread from the tumour edge, the worse the prognosis becomes.

METHODS

This study retrospectively reviewed the data of 642 patients with completely resected pathological stage I–III non-small lung cell cancer between 2008 and 2018. The maximum spread distance (MSD) from the tumour edge to the farthest STAS was quantitatively evaluated, and STAS was categorized as limited (MSD ≤1000 μm) or extended (MSD >1000 μm), based on the median MSD. Recurrence-free survival (RFS) and overall survival (OS) were compared among patients stratified by STAS classification.

RESULTS

Patients were classified into STAS-negative (n = 382, 59.6%), limited STAS (n = 130, 20.2%) and extended STAS (n = 130, 20.2%) groups. Extended STAS was associated with a high maximum standardized uptake value, advanced pathological stage and vascular invasion compared with limited STAS. The extended STAS group demonstrated significantly shorter RFS and OS than both the limited STAS and STAS-negative groups (both P < 0.001 for RFS; P = 0.007 and P < 0.001 for OS, respectively). Multivariable analysis showed that extended STAS was an independent prognostic factor for both RFS and OS (P < 0.001, P < 0.001, respectively).

CONCLUSIONS

The distance from tumour edge to STAS affects prognosis in patients with completely resected non-small lung cell cancer.

Clinical registration number

IRB approval number: 2019-232
Does Public Opinion on Foreign Policy Affect Elite Preferences? Evidence from the 2022 US Sanctions against Russia
Authors: Peez Anton , Bethke Felix S
Published: December 2024

Does public opinion on international affairs affect elites’ policy preferences? Most research assumes that it does, but this key assumption is difficult to test empirically given limited research access to elite decision-makers. We examine elite responsiveness to public opinion on sanctioning Russia during the 2022 Russian invasion of Ukraine. We fielded a preregistered experiment within the 2022 TRIP survey of US foreign policy practitioners, offering a rare opportunity for a fairly large elite survey experiment ($N = 253$). We used contemporary public polling highly supportive of increasing sanctions as an information treatment. Our research design, involving a salient issue and real-world treatment, substantially expands on previous work. Exposure to the treatment raises elite support for increasing sanctions from 68.0 percent to 76.3 percent (+8.3 pp.). While meaningful, this effect is smaller than those identified elsewhere. We argue that this difference is driven by pretreatment dynamics related to issue salience and ceiling effects and is therefore all the more notable. We provide evidence for substantial treatment effect heterogeneity depending on subject-matter expertise, degree of involvement in political decision-making, and gender, but not party identification. While our results support previous research, they highlight issues of external validity and the context-dependence of elite responsiveness.
Changes in metabolite profiles in solid fermentation of glutamate waste treatment solution by Aspergillus niger and Candida tropicalis
Authors: He Dan , Zhang Ying , Liu Jinxu , Wang Xiao , Hu Yunlong , Xu Weihui , Chen Wenjing , Fan Zhenyu , Wang Zhigang
Published: December 2024

Aims

Glutamate wastewater poses a great environmental challenge to the monosodium glutamate production industry. However, its treatment solution is rich in crude protein, which has the potential to be developed as a new protein source for animal feed.

Methods and results

Given that the fermentation process generates functionally different metabolites, this study innovatively utilized two strains of feed microorganisms, Aspergillus niger and Candida tropicalis, to perform solid-state fermentation of glutamate wastewater treatment solution. The aim was to investigate and analyse the metabolite profiles during fermentation. The significant differences in metabolite profiles between the samples were determined using correlation analysis, principal component analysis, orthogonal partial least-squares discriminant analysis, variable importance in projection analysis, Kyoto Encyclopaedia of Genomes, and Human Metabolome Data Bank analysis. These variations were mainly manifested in essential feed components, such as amino acids, peptides, and their analogues. These included Ile–Pro–Asn, Pro–Gly–Val, alanylvaline, histidylisoleucine, Lys–Leu–Tyr, Ile–Arg, glycyl–leucine, leucyl–lysine, N-palmitoyl histidine, alanylisoleucine, l-glutamate, N-methylisoleucine, Isoleucylproline, dl-m-tyrosine, Isoleucyl–threonine, phenylalanine amide, carboxyethyllysine, N6-acetyl-l-lysine, citrulline, N-alpha-acetyl-l-lysine, N(6)-methyllysine, and l-aspartate-semialdehyde.

Conclusions

This study investigates the metabolite profiles of glutamate wastewater treatment solutions after co-fermentation with A. niger and C. tropicalis using solid-state fermentation. These findings provide a new strategy for efficiently utilizing glutamate wastewater treatment solutions.
Perturbations in the gut microbiome of C57BL/6 mice by the sobriety aid Antabuse® (disulfiram)
Authors: Evans Sarah E , Valentine Meagan E , Gallimore Fallon , Meka Yogesh , Koehler Samuel I , Yu Hongwei D , Valentovic Monica A , Long Timothy E
Published: December 2024

Aims

Disulfiram (Antabuse®) is an oral alcohol sobriety medication that exhibits antimicrobial activity against Gram-positive facultative anaerobes. The aims of this study were to measure the antimicrobial activity against anaerobic bacteria of the gut human microbiome and establish the extent that disulfiram alters the microbial composition of the ileum, cecum, and feces using C57BL/6 mice.

Methods and results

Antimicrobial susceptibility testing by the microdilution method revealed that disulfiram inhibits the in vitro growth of gut anaerobic species of Bacteroides, Clostridium, Peptostreptococcus, and Porphyromonas. Differential sequencing of 16S rRNA isolated from the ileum, cecum, and feces contents of treated vs. untreated mice showed that disulfiram enriches the Gram-negative enteric population. In female mice, the enrichment was greatest in the ileum, whereas the feces composition in male mice was the most heavily altered.

Conclusions

Daily administration of oral disulfiram depletes the enteric Gram-positive anaerobe population as predicted by the minimum inhibitory concentration data for isolates from the human gut microbiota.
Lessons learned on information retrieval in electronic health records: a comparison of embedding models and pooling strategies
Authors: Myers Skatje , Miller Timothy A , Gao Yanjun , Churpek Matthew M , Mayampurath Anoop , Dligach Dmitriy , Afshar Majid
Published: December 2024

Objectives

Applying large language models (LLMs) to the clinical domain is challenging due to the context-heavy nature of processing medical records. Retrieval-augmented generation (RAG) offers a solution by facilitating reasoning over large text sources. However, there are many parameters to optimize in just the retrieval system alone. This paper presents an ablation study exploring how different embedding models and pooling methods affect information retrieval for the clinical domain.

Materials and Methods

Evaluating on 3 retrieval tasks on 2 electronic health record (EHR) data sources, we compared 7 models, including medical- and general-domain models, specialized encoder embedding models, and off-the-shelf decoder LLMs. We also examine the choice of embedding pooling strategy for each model, independently on the query and the text to retrieve.

Results

We found that the choice of embedding model significantly impacts retrieval performance, with BGE, a comparatively small general-domain model, consistently outperforming all others, including medical-specific models. However, our findings also revealed substantial variability across datasets and query text phrasings. We also determined the best pooling methods for each of these models to guide future design of retrieval systems.

Discussion

The choice of embedding model, pooling strategy, and query formulation can significantly impact retrieval performance and the performance of these models on other public benchmarks does not necessarily transfer to new domains. The high variability in performance across different query phrasings suggests that the choice of query may need to be tuned and validated for each task, or even for each institution’s EHR.

Conclusion

This study provides empirical evidence to guide the selection of models and pooling strategies for RAG frameworks in healthcare applications. Further studies such as this one are vital for guiding empirically-grounded development of retrieval frameworks, such as in the context of RAG, for the clinical domain.
Polyamines protect porcine sperm from lipopolysaccharide-induced mitochondrial dysfunction and apoptosis via casein kinase 2 activation
Authors: Li Rongnan , Wu Xiaodong , Cheng Jia , Zhu Zhendong , Guo Ming , Hou Guochao , Li Tianjiao , Zheng Yi , Ma Haidong , Lu Hongzhao , Chen Xiaoxu , Zhang Tao , Zeng Wenxian
Published: December 2024

Bacterial contamination is an inevitable issue during the processing of semen preservation in pigs. As a prototypical endotoxin from Gram-negative bacteria in semen, lipopolysaccharide (LPS) undermines sperm function during liquid preservation. Spermine and spermidine could protect cells against LPS-induced injury, and the content of spermine and spermidine in seminal plasma is positively correlated with sperm quality. Thus, the present study aimed to clarify whether addition of spermine or spermidine is beneficial to porcine semen preservation and able to prevent LPS-induced sperm damage. The supplementation of spermine and spermidine in the diluent resulted in higher sperm motility, viability, acrosome integrity, and mitochondrial membrane potential (ΔΨm) after preservation in vitro at 17 °C for 7 d (P < 0.05). LPS-induced sperm quality deterioration, ΔΨm decline, cellular adenosine-triphosphate depletion, mitochondrial ultrastructure abnormality, mitochondrial permeability transition pore opening, phosphatidylserine (PS) translocation, and caspase-3 activation (P < 0.05). Interestingly, spermine and spermidine alleviated the LPS-induced changes of the aforementioned parameters and mitigated the decrease in the microtubule-associated protein light chain 3-II (LC3-II) to LC3-I ratio. Meanwhile, the α and β subunits of casein kinase 2 (CK2) were detected at the connecting piece and the tail. Significantly, addition of 4,5,6,7-tetrabromobenzotriazole, a specific CK2 inhibitor, counteracted the beneficial effects of spermine and spermidine on sperm quality, mitochondrial activity, and apoptosis. Together, these results suggest that spermine and spermidine improve sperm quality and the efficiency of liquid preservation of porcine semen. Furthermore, spermine and spermidine alleviate LPS-induced sperm mitochondrial dysfunction and apoptosis in a CK2-dependent manner.
Observational study of the efficacy and safety of first-line osimertinib and later treatments for uncommon epidermal growth factor receptor-activating mutation-positive advanced non-small cell lung cancer
Authors: Hirata Tsuyoshi , Watanabe Kageaki , Hosomi Yukio , Yoh Kiyotaka , Usui Kazuhiro , Kishi Kazuma , Naka Go , Tamano Shu , Uemura Kohei , Kunitoh Hideo
Published: December 2024

Introduction

Osimertinib, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, is a first-line therapy for advanced or metastatic non-small cell lung cancer (NSCLC) with EGFR mutations, including both sensitizing and T790M resistance mutations. Its real-world efficacy against uncommon EGFR mutations remains under-researched.

Methods

The REIWA study, a multicentric, prospective, observational study conducted in Japan from September 2018 to August 2020, enrolled patients with advanced or recurrent EGFR mutation-positive NSCLC receiving osimertinib. Data on clinical outcomes, safety, disease progression, and subsequent treatments were collected for patients with uncommon EGFR mutations.

Results

Of 583 patients receiving osimertinib, 39 (6.7%) had an uncommon EGFR mutation. The present study included 32 of these patients after excluding seven patients with an exon 20 insertion mutation. The overall objective response rate was 53.1% [95% confidence interval (CI): 36.4–69.1], and the disease control rate was 78.1% (95% CI: 61.0–89.3). The median progression-free survival was 9.4 months (95% CI: 5.0–20.0), and the median overall survival (OS) was 21.8 (95% CI: 14.4–NA) months. Notably, patients with an exon21 L861Q mutation had a significantly longer OS than those with an exon18 G719X mutation, the respective values being 37.8 and 9.7 months (hazard ratio: 0.29; 95% CI: 0.10–0.85; P = 0.02). The rate of grade 3 or worse adverse events was 10.3%. Seven out of 32 (21.9%) patients showed progression involving only the central nervous system.

Conclusions

Osimertinib demonstrated efficacy and tolerability in the clinical setting in patients with uncommon EGFR mutation-positive NSCLC.
Dynamic modelling of sparse longitudinal data and functional snippets with stochastic differential equations
Authors: Zhou Yidong , Müller Hans-Georg
Published: December 2024

Sparse functional/longitudinal data have attracted widespread interest due to the prevalence of such data in social and life sciences. A prominent scenario where such data are routinely encountered are accelerated longitudinal studies, where subjects are enrolled in the study at a random time and are only tracked for a short amount of time relative to the domain of interest. The statistical analysis of such functional snippets is challenging since information for far-off-diagonal regions of the covariance structure is missing. Our main methodological contribution is to address this challenge by bypassing covariance estimation and instead modelling the underlying process as the solution of a data-adaptive stochastic differential equation. Taking advantage of the interface between Gaussian functional data and stochastic differential equations makes it possible to efficiently reconstruct the target process by estimating its dynamic distribution. The proposed approach allows one to consistently recover forward sample paths from functional snippets at the subject level. We establish the existence and uniqueness of the solution to the proposed data-driven stochastic differential equation and derive rates of convergence for the corresponding estimators. The finite sample performance is demonstrated with simulation studies and functional snippets arising from a growth study and spinal bone mineral density data.
Incidental finding of duplication of vas deferens in inguinal hernia: a case report of rare anomaly
Authors: Shrestha Bibek , Yadav Krishna , Kandel Grishma , Yadav Pratibha , Subedi Sachet
Published: December 2024

Duplication of the vas deferens is a rare congenital anomaly, with an incidence of ~0.05% in the general population. It is typically discovered incidentally during surgeries involving the spermatic cord, such as inguinal hernia repair. This case report presents a 33-year-old male who underwent left inguinal hernioplasty, during which duplication of the vas deferens was incidentally identified. The patient had presented with left-sided inguinal swelling, painful testis, and a small left testis. Preoperative ultrasound suggested an inguinal hernia, but the vas deferens anomaly was only detected intraoperatively. The patient successfully underwent hernioplasty without postoperative complications. This case emphasizes the importance of recognizing rare anatomical variations like vas deferens duplication to prevent surgical complications.
Synergy of sodium dodecyl sulfate and citric acid in removing bacterial biofilms in hydroponic farming facilities
Authors: Zhu Junhan , Huang Jim Junhui , Tham Cliff , Zhou Weibiao , Li Dan
Published: December 2024

This research explored various concentrations of sodium dodecyl sulfate (SDS) and citric acid (CA), both individually and in combination, to assess their effectiveness against Salmonella biofilms in hydroponic agriculture systems. Results demonstrated that a combined sanitizer of 0.1% SDS (1.0 ± 0.1 log reduction when used alone) and 1% CA (1.4 ± 0.3 log reduction when used alone) was highly effective in eliminating Salmonella biofilms from polyvinyl chloride pipes in hydroponic systems, reducing biofilm levels to below detectable limits (>5.6 log reduction when used in combination). Confocal laser scanning microscopy showed significantly greater proportions of damaged/dead cells in the 0.1% SDS- and 1% CA-treated samples (82.6 ± 2.6%) than in the single treatment with 0.1% SDS (26.1 ± 3.0%) and 1% CA (31.6 ± 2.5%) (P < 0.05). Fourier transform infrared spectroscopy together with analysis of proteins and polysaccharides in the extracellular polymeric substances of the biofilm matrices showed that the treatment not only affected bacterial viability but also significantly reduced the biomass of the biofilm. In summary, this research provides a foundation for the development of improved cleaning protocols in hydroponic systems, promoting safer and more sustainable farming practices.
COMAP Galactic science I: observations of spinning dust emission at 30 GHz in dark clouds surrounding the λ-Orionis H ii region
Authors: Harper Stuart E , Dickinson Clive , Cleary Kieran A , Hensley Brandon S , Hoerning Gabriel A , Paladini Roberta , Rennie Thomas J , Cepeda-Arroita R , Dunne Delaney A , Eriksen Hans Kristian , Gundersen Joshua Ott , Ihle Håvard T , Lunde Jonas G S , Ricci Roberto , Stil Jeroen , Stutzer Nils-Ole , Taylor A R , Wehus Ingunn Kathrine
Published: December 2024

Anomalous microwave emission (AME) is a major component of Galactic emission in the frequency band 10–60 GHz and is commonly modelled as rapidly rotating spinning dust grains. The photodissociation region (PDR) at the boundary of the $\lambda$-Orionis H ii region has been identified by several recent analyses as one of the brightest spinning dust-emitting sources in the sky. We investigate the Barnard 30 dark cloud, a dark cloud embedded within the $\lambda$-Orionis PDR. We use total-power observations of Barnard 30 from the CO Mapping Array Project (COMAP) pathfinder instrument at 26–34GHz with a resolution of 4.5 arcmin alongside existing data from Planck, WISE, IRAS, ACT, and the 1.447 GHz GALFACTS survey. We use aperture photometry and template fitting to measure the spectral energy distribution of Barnard 30. We find that the spinning dust is the dominant emission component in the 26–34GHz range at the $6\, \sigma$ level ($S_{30\, \mathrm{GHz}} = 3.35\pm 0.56$ Jy). From correlating COMAP data with dust templates we find no evidence that polycyclic aromatic hydrocarbons are the preferred carrier for the spinning dust emission, suggesting that the spinning dust carriers are due to a mixed population of very small grains. Finally, we find evidence for variations in spinning dust emissivity and peak frequency within Barnard 30, and that these variations are possibly driven by changes in dust grain population and the total radiation field. Confirming the origin of the variations in the spinning dust spectrum will require both future COMAP observations at 15 GHz combined with spectroscopic mid-infrared data of Barnard 30.
A study of the transition to a turbulent shock using a coarse-graining approach to ion phase-space transport
Authors: Trotta D , Valentini F , Burgess D , Servidio S
Published: December 2024

Shocks and turbulence are ubiquitous phenomena, responsible for particle acceleration to very high energies in a large collection of astrophysical systems. Using self-consistent, hybrid-kinetic simulations with and without pre-existing turbulence, we study the transition of a shock from ‘laminar’ to turbulent. We show that the changes in upstream proton transport behaviour are crucial to understand this transition, which we address quantitatively with a novel Eulerian approach. This method, based on the coarse-graining of the Vlasov equation originally introduced in one of our previous studies, gives consistent results for inertial range scales. The potential applications of the coarse-graining approach beyond the shock–turbulence system are outlined.
Cosmic multipoles in galaxy surveys – I. How inferences depend on source counts and masks
Authors: Oayda Oliver T , Mittal Vasudev , Lewis Geraint F
Published: December 2024

We present a new approach to constructing and fitting dipoles and higher-order multipoles in synthetic galaxy samples over the sky. Within our Bayesian paradigm, we illustrate that this technique is robust to masked skies, allowing us to make credible inferences about the relative contributions of each multipole. We also show that dipoles can be recovered in surveys with small footprints, determining the requisite source counts required for concrete estimation of the dipole parameters. This work is motivated by recent probes of the cosmic dipole in galaxy catalogues. Namely, the kinematic dipole of the cosmic microwave background, as arising from the motion of our heliocentric frame at $\approx 370\ \text{km}\, \text{s}^{-1}$, implies that an analogous dipole should be observed in the number counts of galaxies in flux-density-limited samples. Recent studies have reported a dipole aligning with the kinematic dipole but with an anomalously large amplitude. Accordingly, our new technique will be important as forthcoming galaxy surveys are made available and for revisiting previous data.
Gargantuan chaotic gravitational three-body systems II. Dependence on angular momentum and astrophysical scale
Authors: Boekholt T C N , Portegies Zwart S F
Published: December 2024

Recently, we estimated that about 5 per cent of unstable supermassive black hole triple systems are fundamentally unpredictable. These gargantuan chaotic systems are able to exponentially magnify Planck length perturbations to astronomical scales within their dynamical lifetime. These results were obtained in the zero angular momentum limit, which we naively expected to be the most chaotic. Here, we generalize to weakly and non-hierarchical triple systems with a range of non-zero angular momenta by systematically varying the initial virial ratio. We find the surprising result that increasing the angular momentum enhances their ability to amplify small perturbations, which we tracked up to 90 orders of magnitude using the arbitrary-precision N-body code brutus. This result is partially explained by the fact that triples with higher angular momenta have longer lifetimes, allowing for a prolonged exponential growth. However, we also find that for a fixed lifetime, triples with higher angular momenta can amplify perturbations to larger values, indicating that the Lyapunov exponent is also a function of angular momentum. These empirical results provide targets for three-body theories which invoke chaos drivers such as resonance overlap and punctuated chaos. Comparing the zero angular momentum case to our new ensembles with higher angular momenta, we conclude that the percentage of unpredictable supermassive black hole triples increases up to about 30 per cent. A further increase up to about 50 per cent is reached when considering triples on smaller astrophysical scales. Fundamental unpredictability is thus a generic feature of chaotic, self-gravitating triple populations.
Panning for gold with the Neil Gehrels Swift Observatory: an optimal strategy for finding the counterparts to gravitational wave events
Authors: Eyles-Ferris R A J , Evans P A , Breeveld A A , Cenko S B , Dichiara S , Kennea J A , Klingler N J , Kuin N P M , Marshall F E , Oates S R , Page M J , Raman G , Ronchini S , Siegel M H , Tohuvavohu A , Campana S , D’Elia V , Hartmann D H , Osborne J P , Page K L , De Pasquale M , Troja E
Published: December 2024

The LIGO, Virgo, and KAGRA (LVK) gravitational wave observatories are currently undertaking their O4 observing run offering the opportunity to discover new electromagnetic counterparts to gravitational wave events. We examine the capability of the Neil Gehrels Swift Observatory (Swift) to respond to these triggers, primarily binary neutron star mergers, with both the UV/Optical Telescope (UVOT) and the X-ray Telescope (XRT). We simulate Swift’s response to a trigger under different strategies using model skymaps, convolving these with the 2MPZ catalogue to produce an ordered list of observing fields, deriving the time taken for Swift to reach the correct field and simulating the instrumental responses to modelled kilonovae and short gamma-ray burst afterglows. We find that UVOT, using the u filter with an exposure time of order 120 s, is optimal for most follow-up observations and that we are likely to detect counterparts in $\sim 6$ per cent of all binary neutron star triggers detectable by LVK in O4. We find that the gravitational wave 90 per cent error area and measured distance to the trigger allow us to select optimal triggers to follow-up. Focussing on sources less than 300 Mpc away, or 500 Mpc if the error area is less than a few hundred square degrees, distances greater than previously assumed, offer the best opportunity for discovery by Swift with $\sim 5\!-\!30$ per cent of triggers having detection probabilities $\ge 0.5$. At even greater distances, we can further optimise our follow-up by adopting a longer 250 s or 500 s exposure time.
Discontinuous Galerkin method with constrained transport for modelling solar wind in spherical coordinates
Authors: Zhang Man , Feng Xueshang , Li Caixia , Yang Liping , Zhou Yufen , Liu Xiaojing , Bai Yujuan
Published: December 2024

In this paper, the discontinuous Galerkin (DG) method is used to simulate the steady-state solar wind with constrained transport method. A cell-based piecewise quadratic polynomial solution is obtained through the DG scheme, while the face-averaged magnetic field is discretized using constrained-transport method. Then, a globally divergence-free magnetic field is constructed by combining the quadratic polynomial of magnetic field with the face-averaged magnetic field. For the time discretization, third-order Runge–Kutta method is applied. The resulting method can reach three order of accuracy in space and time. We test the method by computing the solar wind in Carrington rotation 2234, and compare the result with both remote sensing observations from SOHO and SDO as well as in situ observations from Parker Solar Probe and a dataset of Open to the Maximum Number of Investigators (OMNI). The agreement between the modelled results and the observations demonstrates the capability of the developed scheme.
Quantifying spectroscopic Ca ii exocomet transit occurrence in two decades of HARPS data
Authors: Bendahan-West Raphaël , Kennedy Grant M , Brown David J A , Strøm Paul A
Published: December 2024

The field of exocomets has been built around the unmatched number of detections made in the circumstellar disc of the archetypal star Beta Pictoris. An exocomet detection in spectroscopy is identified by variable atomic absorption features in a stellar spectrum, associated with transiting gas in and trailing an exocomet coma. This paper presents the largest spectroscopic search for exocomet transits to date, which overcomes the limitations of biased samples of stars with debris discs, and instead looks through the ${\approx} 7500$ stars in the High Accuracy Radial velocity Planet Searcher (HARPS) archive for signs of exocomets in the Ca ii doublet (H: 396.847 nm and K: 393.366 nm). The search resulted in 155 candidate stars, which after filtering for false positives (e.g. binaries, stellar activity, etc.) were cut down to 22 stars. These 22 stars are classified into Tier 1, Tier 2, and Tier 3 exocomet candidates, reflecting the confidence level of their exocomet detection. Our two best candidates (Tier 1: Beta Pictoris and HD 172555) and four lower confidence candidates (Tier 2: Gl 1, HIP 5158, HD 94771, and HR 1996) are discussed, yielding a detection rate of 0.03 per cent (Tier 1 only) and 0.1 per cent (Tier 1 and Tier 2) in the HARPS sample. Both Tier 1 stars are known exocomet host stars. These two young A-type stars correspond to 0.4 per cent of all A-types in the sample, suggesting that detecting signs of exocomet transits using Ca ii is more likely around young A-type stars. Reanalysing a past HARPS study, we found no evidence to support the previously claimed four exocomet detections, indicating either that those detections are not robust or that we are only sensitive to the strongest signals.
Navigating a Fine Balance: Point-Mutant Cheater Viruses Disrupt the Viral Replication Cycle
Authors: Meir Moran , Kahn Arielle , Farage Carmel , Maoz Yael , Harel Noam , Ben Zvi Adi , Segev Shir , Volkov Maria , Yahud Ravit , Gophna Uri , Stern Adi
Published: December 2024

Cheater viruses cannot replicate on their own yet replicate faster than the wild type (WT) when the 2 viruses coinfect the same cell. Cheaters must possess dual genetic features: a defect, which leads to their inability to infect cells on their own, and a selective advantage over WT during coinfection. Previously, we have discovered 2 point-mutant cheaters of the MS2 bacteriophage. Here, we set out to discover the possible repertoire of cheater MS2 viruses by performing experimental evolution at a very high multiplicity of infection. Our results revealed a third point-mutant cheater that arose in 8 biological replicas. Each of the 3 primary cheaters disrupts the fine balance necessary for phage replication, in different ways that create a defect + advantage. We found that over time, the point-mutant cheaters accumulate additional secondary mutations, which alter other stages of the viral replication cycle, complementing the disruptions created by the original cheater. Intriguingly, cheater and secondary mutations almost always reside in very close proximity on the genome. This region encodes for multiple functions: overlapping reading frames as well as overlapping RNA structures critical for transitioning from one stage to another in the viral replication cycle. This region of overlap explains the dual functions of cheaters, as one mutation can have pleiotropic effects. Overall, these findings underscore how viruses, whose dense genomes often have overlapping functions, can easily evolve point-mutant cheaters, and how cheaters can evolve to alter the intricate balance of the viral replication cycle.
The Staphylococcus aureus non-coding RNA IsrR regulates TCA cycle activity and virulence
Authors: Rios-Delgado Gustavo , McReynolds Aubrey K G , Pagella Emma A , Norambuena Javiera , Briaud Paul , Zheng Vincent , Munneke Matthew J , Kim Jisun , Racine Hugo , Carroll Ronan K , Zelzion Ehud , Skaar Eric , Bose Jeffrey L , Parker Dane , Lalaouna David , Boyd Jeffrey M
Published: December 2024

Staphylococcus aureus has evolved mechanisms to cope with low iron (Fe) availability in host tissues. Staphylococcus aureus uses the ferric uptake transcriptional regulator (Fur) to sense titers of cytosolic Fe. Upon Fe depletion, apo-Fur relieves transcriptional repression of genes utilized for Fe uptake. We demonstrate that an S. aureus Δfur mutant has decreased expression of acnA, which codes for the Fe-dependent enzyme aconitase. This prevents the Δfur mutant from growing with amino acids as sole carbon and energy sources. We used a suppressor screen to exploit this phenotype and determined that a mutation that decreases the transcription of isrR, which produces a regulatory RNA, increased acnA expression, thereby enabling growth. Directed mutation of bases predicted to facilitate the interaction between the acnA transcript and IsrR, decreased the ability of IsrR to control acnA expression in vivo and IsrR bound to the acnA transcript in vitro. IsrR also bound transcripts coding the alternate tricarboxylic acid cycle proteins sdhC, mqo, citZ and citM. Whole-cell metal analyses suggest that IsrR promotes Fe uptake and increases intracellular Fe not ligated by macromolecules. Lastly, we determined that Fur and IsrR promote infection using murine skin and acute pneumonia models.
Mechanistic insights into the formation of hydroxides with unconventional coordination environments to achieve their cost-effective synthesis
Authors: Chen Zongkun , Fan Qiqi , Wang Xingkun , Kang Liqun , Wan Wenchao , Avaro Jonathan Thomas , Zhang Siyuan , Scheu Christina , Zhou Jian , DeBeer Serena , Heumann Saskia , Huang Minghua , Jiang Heqing , Cölfen Helmut
Published: December 2024

Transition metal hydroxides, comprising metal-centered polyhedra, are abundant in nature and have a broad range of applications. Although the intercalation/deintercalation of polyhedra with unconventional coordination numbers (UCN) plays a pivotal role in their formation process and influences their chemical behavior, the detailed mechanism remains obscure. Here, taking the kinetically controlled growth of Co(OH)2 as a model system (where polyhedra with UCN refers to 4-coordinated tetrahedra), by combining in situ pH measurement and in situ ultraviolet–visible (UV–vis) spectroscopy, we tracked Co2+ tetrahedral intercalation/deintercalation with varying OH− concentrations, discovering that the initial Co2+ tetrahedral intercalation into the Co(OH)2 lattice is inevitable and its retention is influenced by the effective OH− concentration, challenging previous beliefs about the formation of Co(OH)2 and potentially other hydroxides. More importantly, an understanding of the intercalation mechanism would significantly contribute to optimization of the synthesis conditions of hydroxides with tunable coordination environments, which hold significant application potential, as evidenced by a proof-of-concept application in the oxygen evolution reaction.
Electronic-Cigarette and Heated Tobacco Product Use in the United Arab Emirates, an Emerging EC and HTP Market: A Cross-Sectional Analysis of the International Tobacco Control UAE Survey
Authors: Leinberger-Jabari Andrea , Ahmad Amar , Lindson Nicola , Oke Jason , Hartmann-Boyce Jamie , Fong Geoffrey T , El-Shahawy Omar , Ali Raghib , Sherman Scott E
Published: December 2024

Introduction

Electronic cigarettes (ECs) and heated tobacco products (HTPs) are recent arrivals to the nicotine product market in the Middle East, which are rapidly growing in popularity in the region. There is a lack of surveillance data at the country-level on use of these products and factors associated with their use.

Aims and Methods

This study analyzed a subset of data from the United Arab Emirates Healthy Future Study, a population-based cohort study of the Emirati population, to determine the factors associated with EC and HTP use among a sample of Emirati adults (≥18 years). The baseline assessment and supplementary questionnaires, conducted from 2016 to 2023, included data on combustible tobacco use, EC, and HTP use and sociodemographic characteristics.

Results

Of the 2041 individuals who answered questions on EC use, 32% reported ever using them. Of the 521 people who provided data on HTP, 30% reported ever using them. After adjusting for age, sex, education, perceived harms, and perceived addictiveness of EC, current EC use was associated with baseline combustible tobacco smoking (aOR = 27.63, 95% confidence interval [CI] 14.39, 53.06), users of a younger age (aOR = 0.91, 95% CI = 0.88, 0.95), and users of male sex (OR = 2.15, 95% CI = 1.21, 3.81). Current HTP use was less common but was also associated with baseline combustible tobacco use.

Conclusions

The use of ECs and HTPs was more common among those who used combustible tobacco. Future research should examine use trajectories among those who do and do not smoke, as well as the uptake of these products among youth.

Implications

Non-combustible nicotine products are growing in popularity in the Middle East Region. Our study found that EC and HTP use is associated with baseline combustible tobacco use and that concurrent users may use them to cut down on their combustible tobacco use. Continued comprehensive population-based monitoring of all-tobacco and nicotine products, especially EC and HTP use, will provide current data to aid in appropriately informing public health and harm reduction messages and programming
Supporting patients with advanced cancer and their spouses in parenting minor children: results of a randomized controlled trial
Authors: Milbury Kathrin , Ann-Yi Sujin , Whisenant Meagan S , Jones Morgan , Li Yisheng , Necroto Victoria , Yousuf Sania D , Chavez-MacGregor Mariana , Meyers Larrisa , Bruera Eduardo
Published: December 2024

Introduction

Patients with advanced cancer and their spousal caregivers who parent minor children report unmet parenting concerns and increased psychological distress. Seeking to address these important supportive care needs, this RCT examined the feasibility, acceptability, and initial evidence for the efficacy of a novel psychosocial intervention.

Patients and Methods

Patients with a metastatic solid malignancy and their spouses completed self-reported validated assessments of psychological symptoms and cancer-related parenting outcomes and were then randomized to the parent support intervention or a usual care (UC) group. Both groups were reassessed 6 and 12 weeks later. Dyads randomized to the counselor-led intervention attended the first 2 sessions jointly addressing illness communication and family routines. Spouses individually attended the last 2 sessions focusing on caregiver support and family death preparedness.

Results

Fifty patients and their spouses were randomized. All a priori feasibility benchmarks were met. Attendance in the intervention arm was high with 84% of caregivers attending all 4 sessions (mean = 3.48). The program was evaluated favorably by all patients and spouses deeming the intervention as beneficial. Caregivers rated the individual-level sessions as particularly helpful. Multilevel analyses revealed a significant reduction in anxiety symptoms (P = .05) and improvement in parenting efficacy (P = .03) at 6-week follow-up in the intervention group compared with UC.

Conclusions

The initial testing of our parent support intervention yielded promising results regarding feasibility and preliminary evidence for efficacy for reduced anxiety symptoms and improved parenting efficacy. This program may meet a frequent and distressing psychosocial need that is typically unaddressed by multidisciplinary oncology teams.
COBRA-LIKE 9 modulates cotton cell wall development via regulating cellulose deposition
Authors: He Qingfei , Yu Yujia , Qin Zhiguang , Duan Yujia , Liu Hanqiao , Li Weixi , Song Xiaohui , Zhu Guozhong , Shang Xiaoguang , Guo Wangzhen
Published: December 2024

Plant cell walls are complex and dynamic cellular structures critical for plant growth, development, physiology, and adaptation. Cellulose is one of the most important components of the cell wall. However, how cellulose microfibrils deposit and assemble into crystalline cellulose remains elusive. The COBRA-LIKE plant-specific protein family plays a vital role in modulating the deposition and orientation of cellulose microfibril in plant cell walls. Here, we investigate the role of GhCOBL9 in cotton (Gossypium hirsutum) fiber development, an ideal model for studying cell elongation and cell wall thickening. The expression period of GhCOBL9 is consistent with the thickening stage of the secondary wall of cotton fibers. Overexpression of GhCOBL9 results in increased cellulose content in the cell wall and produces shorter, thicker, and stronger fibers, while RNA interference (RNAi)-mediated downregulation of GhCOBL9 leads to the opposite phenotypes, indicating its crucial role in cell wall development. Subcellular localization and binding activity assays reveal that GhCOBL9 targets the cell wall and binds to crystalline cellulose with high affinity. Transcriptomic analysis of GhCOBL9 transgenic lines uncovers expression alterations in genes related to cellulose and monosaccharide biosynthesis. Furthermore, we identify a fasciclin-like arabinogalactan protein 9 (GhFLA9) as an interacting partner of GhCOBL9 to modulate cell wall development. Additionally, the R2R3-MYB transcription factor GhMYB46-5 activates GhCOBL9 expression by binding to the MYB46-responsive cis-regulatory element in the GhCOBL9 promoter. These findings broaden our knowledge of COBL function in modulating plant cell wall development.
The transcription factor ORA59 represses hypoxia responses during Botrytis cinerea infection and reoxygenation
Authors: Brunello Luca , Kunkowska Alicja B , Olmi Emma , Triozzi Paolo M , Castellana Simone , Perata Pierdomenico , Loreti Elena
Published: December 2024

Transcription factors belonging to the large ethylene response factor (ERF) family are involved in plant responses to biotic and abiotic stresses. Among the ERFs, OCTADECANOID-RESPONSIVE ARABIDOPSIS 59 (ORA59) integrates ethylene and jasmonic acid signaling to regulate resistance to necrotrophic pathogens. The ERF group ERFVII encodes oxygen-labile proteins that are required for oxygen sensing and are stabilized by hypoxia established at the site of Botrytis (Botrytis cinerea) infection. Here, we show that ORA59 represses ERFVII protein activity to induce the expression of hypoxia-responsive genes in Arabidopsis (Arabidopsis thaliana). Moreover, inhibition of ethanol fermentation enhances plant tolerance to Botrytis, indicating a trade-off between the hypoxia and defense responses. In addition, ERFVII members and ORA59 are both involved in the downregulation of hypoxia-responsive genes during reoxygenation. Taken together, our results reveal that the ERFVII transcription factor–ORA59 module ensures that the multiple roles of ERFVII proteins are correctly balanced to favor plant tolerance to biotic or abiotic stresses.
Improving Function in Older Adults With Hospital-Associated Deconditioning: Lessons Learned Comparing a Randomized Controlled Trial to Real World Practice
Authors: Garbin Alexander J , Tran Melissa K , Graber Jeremy , Derlein Danielle , Currier Deborah , Altic Rebecca , Will Robert , Cumbler Ethan , Forster Jeri E , Mangione Kathleen K , Stevens-Lapsley Jennifer E
Published: December 2024

Objective

The optimal approach for improving physical function following acute hospitalization is unknown. A recent clinical trial of home health physical therapy compared a high-intensity, progressive, multi-component (PMC) intervention to enhanced usual care (EUC). While both groups improved in physical function, no between-group differences were observed. However, the EUC group received care that differed from real world practice due to standardized treatments and a higher frequency of visits. This study compared a non-randomized true usual care (TUC) group to the EUC and PMC groups.

Methods

Participants in the parent trial were randomly assigned to the EUC group (n = 100) and PMC group (n = 100) following hospital discharge. A subset of eligible patients (n = 55) were concurrently enrolled in the TUC group. Both the PMC and EUC groups received strength, activities of daily living, and gait training that differed in intensity but were matched in frequency and duration. TUC group care was determined by the home health agency. The primary outcome at 60-days was the Short Physical Performance Battery (SPPB).

Results

In comparison to the TUC group, the EUC and PMC groups had significantly greater improvements in SPPB score (EUC: +1.04 points [CI = 0.18–1.90]; PMC: +1.12 points [CI = 0.23–2.00]).

Conclusion

While participants in the EUC and PMC groups experienced greater functional recovery compared to those in the TUC group, it cannot be determined whether these differences are due to the interventions received or confounding factors associated with the addition of a third, non-randomized, study group during the trial period.

Impact

This study illustrates the importance of design and interpretation of control groups for clinical trials. Further, the differences between the TUC group and the enhanced intervention groups warrant future research exploring whether increasing visits and standardizing care improve function in older adults receiving home health physical therapy after hospital associated deconditioning.

Lay summary

Participants in the intervention groups received standardized and more therapy than usual care, and experienced greater functional improvements. However, these differences may be due to factors associated with the addition of a non-randomized group during an ongoing clinical trial.
Association of estimated glomerular filtration rate with the incidence of sleep apnea syndrome
Authors: Azegami Tatsuhiko , Kaneko Hidehiro , Okada Akira , Suzuki Yuta , Ko Toshiyuki , Fujiu Katsuhito , Takeda Norifumi , Morita Hiroyuki , Takeda Norihiko , Yokoo Takashi , Yasunaga Hideo , Nangaku Masaomi , Hayashi Kaori
Published: December 2024

Study Objectives

Sleep apnea syndrome (SAS) is potentially linked to life-threatening conditions. The decline in kidney function is involved in the development of various diseases; however, it remains unclear whether it is implicated in the onset of SAS. Therefore, this study aimed to investigate the relationship between kidney function and the incidence of SAS.

Methods

The association of estimated glomerular filtration rate (eGFR) with the incidence of SAS was assessed retrospectively using real-world administrative claims and health checkup data collected between April 2014 and November 2022. To strengthen robustness, three stratified analyses and four sensitivity analyses were conducted.

Results

We assessed 1 589 259 individuals for the analysis. During a median (interquartile range) follow-up of 1167 (652–1699) days, 11 054 cases of SAS events were documented. Multivariable Cox regression analyses after adjusting for potential confounders, including age, sex, body mass index, hypertension, diabetes, dyslipidemia, cigarette smoking, alcohol drinking, and physical inactivity, demonstrated that the decrease in eGFR (eGFR ≥ 90, 60–89, 45–59, 30–44, and <30 mL/min/1.73 m2) was associated with a higher risk of SAS (hazard ratio [95% confidence intervals]; 1 [reference value], 1.13 [1.06–1.20], 1.22 [1.13–1.32], 1.34 [1.17–1.52], 1.82 [1.43–2.33]). In the restricted cubic spline regression model, the risk of developing SAS increased with the reduction in eGFR. The results of the sensitivity analyses were consistent with the primary findings.

Conclusion

Our analysis utilizing a large-scale population-based cohort concluded that reduced eGFR is associated with the risk of developing SAS in a dose-dependent manner.