bluuebunny/crossref_metadata_2025_split huggingface dataset:
B-Cell Activation Gene Signature in Blood and Liver of Hepatitis B e Antigen–Positive Patients With Immune Active Chronic Hepatitis B
Authors: Osmani Zgjim , Beudeker Boris J B , Groothuismink Zwier M A , de Knegt Robert J , Chung Raymond T , Aerssens Jeroen , Bollekens Jacques , Janssen Harry L A , Gehring Adam J , Lauer Georg M , Shalek Alex K , van de Werken Harmen J G , Boonstra Andre 
Published: June 2024

Abstract

Background
Studies on chronic hepatitis B virus (HBV) infection have shown immune dysfunction involving multiple cell types, including T cells. B cells have been evaluated more recently, but in contrast to T cells, more pronounced activation of circulating B cells has been reported. To gain more insight into the activation status of B cells, we investigated gene profiles of B cells in the blood and liver of patients with chronic HBV.

Methods
RNA-sequencing and flow cytometric analysis was performed on peripheral blood B cells of patients with immune active chronic HBV, comparing them with samples from healthy controls. In addition, gene expression profiles of B cells in the liver were analyzed by bulk and single-cell RNA-seq.

Results
Our data show a distinctive B-cell activation gene signature in the blood of patients with immune active chronic HBV, characterized by a significant upregulation of immune-related genes. This peripheral activation profile was also observed in B cells from the liver by single-cell RNA-seq, with naive and memory B-cell subsets being the primary carriers of the signature.

Conclusions
Our findings suggest that B-cell gene profiles reflect responsiveness to HBV infection; these findings are relevant for clinical studies evaluating immunomodulatory treatment strategies for HBV.
Transcriptomic responses of extensively drug resistant Klebsiella pneumoniae to N-acetyl cysteine reveals suppression of major biogenesis pathways leading to bacterial killing and biofilm eradication
Authors: Bhowmik Ankurita , Chakraborty Sambuddha , Rohit Anusha , Chauhan Ashwini 
Published: June 2024

Abstract

Aims
Carbapenemase-producing Klebsiella pneumoniae is categorized as a “critical global priority-one” pathogen by WHO and new and efficient treatment options are warranted. This study aims to assess the antibacterial and antibiofilm potential of N-acetyl cysteine (NAC), against clinical isolates of extensively drug resistant (XDR) K. pneumoniae and elucidate the mechanism of killing.

Methods and results
XDR-K. pneumoniae were isolated from patients admitted to Madras Medical Mission Hospital, India. Antibiofilm activity of NAC was checked using in vitro continuous flow model and RNA sequencing was done using Illumina Novoseq. Data quality was checked using FastQC and MultiQC software. Our findings revealed that NAC at a concentration of 100 mg/ml was safe, and could inhibit the growth and completely eradicate mature biofilms of all XDR-K. pneumoniae isolates. Transcriptomic responses in XDR-K. pneumoniae to NAC showed significant downregulation of the genes associated with crucial biogenesis pathways, including electron transport chain and oxidoreductase activity besides a specific cluster of genes linked to ribosomal proteins.

Conclusions
Our results indicate that NAC kills the XDR- K. pneumoniae clinical isolates by shutting the overall metabolism and, hence, successfully eradicate in vitro biofilms formed on catheters.
Monthly treatment with romosozumab for 1 year increases bone mineral at the hip, but not the knee, in women with chronic spinal cord injury
Authors: Crack Laura E , Simonian Narina , Schnitzer Thomas J , Edwards W Brent 
Published: June 2024

Abstract
Bone loss below the level of neurological lesion is a well-known complication of spinal cord injury (SCI). To date, most research has focused on pharmaceutical intervention using antiresorptives to prevent bone loss during the acute phase of SCI; however, limited research has investigated treatments for established osteoporosis during chronic SCI. Romosozumab, a monoclonal antibody with both antiresorptive and anabolic effects, has demonstrated significant increases in BMD for women with established PMO. Therefore, the purpose of this study was to examine the efficacy of monthly treatment with romosozumab to improve DXA-derived areal BMD at the hip, and CT-derived BMC and strength at the hip and knee in women with chronic SCI and an inability to ambulate. Twelve female participants with chronic SCI were recruited to receive 1 yr of monthly subcutaneous injections of romosozumab (210 mg). DXA and CT scans were taken at baseline, and months 3, 6, and 12 to quantify bone mineral, and finite element (FE) analysis was used to predict bone strength. Longitudinal mixed effects models were employed to determine the impact of treatment on bone properties. After 12 mo of treatment, areal BMD at the lumbar spine and total hip were significantly increased with median changes of 10.2% (IQR: 8.3–15.2%, p&lt;.001) and 4.2% (IQR: 3.4–7.7%, p = .009), respectively. Improvements at the hip were primarily due to increases in trabecular, not cortical, bone and effects were sufficient to significantly increase FE-predicted strength by 20.3% (IQR: 9.5–37.0%, p = .004). Treatment with romosozumab did not lead to any significant improvement in bone mineral at the distal femur or proximal tibia. These findings provide promising results for romosozumab treatment to improve bone mineral and reduce fracture risk at the hip, but not the knee, in women with chronic SCI.
A comparative study of body size evolution in moths: evidence of correlated evolution with feeding and phenology-related traits
Authors: Foerster Stênio Ítalo Araújo , Clarke John T , Õunap Erki , Teder Tiit , Tammaru Toomas 
Published: June 2024

Abstract
Interspecific variation in body size is one of the most popular topics in comparative studies. Despite recent advances, little is known about the patterns and processes behind the evolution of body size in insects. Here, we used a robust data set comprising all geometrid moth species occurring in Northern Europe to examine the evolutionary associations involving body size and several life-history traits under an explicitly phylogenetic framework. We provided new insights into the interactive effects of life-history traits on body size and evidence of correlated evolution. We further established the sequence of trait evolution linking body size with the life-history traits correlated with it. We found that most (but not all) of the studied life-history traits, to some extent, influenced interspecific variation in body size, but interactive effects were uncommon. Both bi- and multivariate phylogenetic analyses indicated that larger species tend to be nocturnal flyers, overwinter in the larval stage, feed on the foliage of trees rather than herbs, and have a generalist feeding behaviour. We found evidence of correlated evolution involving body size with overwintering stage, host-plant growth form, and dietary specialization. The examination of evolutionary transitions within the correlated evolution models signalled that overwintering as larvae commonly preceded the evolution of large sizes, as did feeding on tree foliage and the generalist feeding behaviour. By showing that both body size and all life-history traits correlated with it evolve at very slow rates, we caution against uncritical attempts to propose causal explanations for respective associations based on contemporary ecological settings.
Real-world treatment trends for patients with advanced prostate cancer and renal cell carcinoma and their cost—a survey in Japan
Authors: Osawa Takahiro , Sasaki Keita , Machida Ryunosuke , Matsumoto Takashi , Matsui Yoshiyuki , Kitamura Hiroshi , Nishiyama Hiroyuki 
Published: June 2024

Abstract

Background
Advanced (Stage IV) prostate and renal cancer have poor prognosis, and several therapies have been developed, but many are very costly. This study investigated drug regimens used in patients with untreated Stage IV prostate cancer and renal cell carcinoma and calculated the monthly cost of each.

Methods
We surveyed first-line drugs administered to patients with untreated Stage IV prostate cancer and renal cancer at Japan Clinical Oncology Group affiliated centers from April 2022 to March 2023. Drug costs were calculated according to drug prices in September 2023. Individual drug costs were calculated or converted to 28-day costs.

Results
A total of 700 patients with untreated Stage IV prostate cancer were surveyed. Androgen deprivation therapy + androgen receptor signaling inhibitor was the most common regimen (56%). The cost of androgen deprivation therapy + androgen receptor signaling inhibitor was 10.6–30.8-fold compared with conventional treatments. A total of 399 patients with Stage IV renal cancer were surveyed. Among them, 91% of patients received immune-oncology drug-based regimen. All patients received treatments with a monthly cost of ≥500 000 Japanese yen, and 80.4% of patients received treatments with a monthly cost of ≥1 million Japanese yen, of combination treatments. The cost of immune-oncology drug-based regimen was 1.2–3.1-fold that of TKI alone.

Conclusion
To the best of our knowledge, this is the first report of a survey of first-line drug therapy in untreated Stage IV prostate cancer and renal cell carcinoma stratified by age and treatment costs. Our results show that most Japanese patients received state-of-the-art, effective treatments with high financial burden.
Current status of the cost burden of first-line systemic treatment for patients with advanced hepatocellular carcinoma in Japan, 2021–22
Authors: Imaoka Hiroshi , Sasaki Keita , Machida Ryunosuke , Nagano Hiroaki , Satoi Sohei , Ikeda Masafumi , Kobayashi Satoshi , Yamashita Taro , Okusaka Takuji , Ido Akio , Hatano Etsuro , Miwa Haruo , Ueno Masaki , Nakao Kazuhiko , Shimizu Satoshi , Kuramochi Hidekazu , Sakamori Ryotaro , Tsumura Hidetaka , Okano Naohiro , Shioji Kazuhiko , Shirakawa Hirofumi , Akutsu Noriyuki , Tsuji Kunihiro , Ishii Hiroshi , Umemoto Kumiko , Asagi Akinori , Ueno Makoto ,   the JCOG Hepatobiliary and Pancreatic Oncology Group
Published: June 2024

Abstract

Background
Although recent advances in systemic therapies for hepatocellular carcinoma (HCC) have led to prolonged patient survival, the high costs of the drugs place a heavy burden on both patients and society. The objectives of this study were to examine the treatment regimens used as first-line systemic treatment for patients with advanced HCC in Japan and to estimate the treatment costs per regimen.

Methods
For this study, we aggregated the data of patients who had received first-line systemic treatment for advanced HCC between July 2021 and June 2022. The treatment cost per month of each regimen was estimated based on standard usage, assuming an average weight of 60 kg for male patients. The data were categorized by the treatment regimen, and the treatments were categorized based on the cost into very high-cost (≥1 000 000 Japanese yen [JPY]/month), high-cost (≥500 000 JPY/month) and other (&lt;500 000 JPY/month) treatments.

Results
Of the total of 552 patients from 24 institutions whose data were analyzed in this study, 439 (79.5%) received atezolizumab plus bevacizumab, 98 (17.8%) received lenvatinib and 15 (2.7%) received sorafenib as the first-line treatment. The treatment cost per month for each of the above regimens was as follows: atezolizumab plus bevacizumab, 1 176 284 JPY; lenvatinib, 362 295 JPY and sorafenib, 571 644 JPY. In total, 82.2% of patients received high-cost regimens, and the majority of these patients received a very high-cost regimen of atezolizumab plus bevacizumab.

Conclusions
Advances in systemic therapies for HCC have led to prolonged patient survival. However, the treatment costs are also increasing, imposing a burden on both the patients and society.
Characteristics of a cost-effective blood test for colorectal cancer screening
Authors: Nascimento de Lima Pedro , van den Puttelaar Rosita , Knudsen Amy B , Hahn Anne I , Kuntz Karen M , Ozik Jonathan , Collier Nicholson , Alarid-Escudero Fernando , Zauber Ann G , Inadomi John M , Lansdorp-Vogelaar Iris , Rutter Carolyn M 
Published: June 2024

Abstract

Background
Blood-based biomarker tests can potentially change the landscape of colorectal cancer (CRC) screening. We characterize the conditions under which blood test screening would be as effective and cost-effective as annual fecal immunochemical testing or decennial colonoscopy.

Methods
We used the 3 Cancer Information and Surveillance Modeling Network–Colon models to compare scenarios of no screening, annual fecal immunochemical testing, decennial colonoscopy, and a blood test meeting Centers for Medicare & Medicaid (CMS) coverage criteria (74% CRC sensitivity and 90% specificity). We varied the sensitivity to detect CRC (74%-92%), advanced adenomas (10%-50%), screening interval (1-3 years), and test cost ($25-$500). Primary outcomes included quality-adjusted life-years (QALY) gained from screening and costs for a US average-risk cohort of individuals aged 45 years.

Results
Annual fecal immunochemical testing yielded 125-163 QALY gained per 1000 at a cost of $3811-$5384 per person, whereas colonoscopy yielded 132-177 QALY gained at a cost of $5375-$7031 per person. A blood test with 92% CRC sensitivity and 50% advanced adenoma sensitivity yielded 117-162 QALY gained if used every 3 years and 133-173 QALY gained if used every year but would not be cost-effective if priced above $125 per test. If used every 3 years, a $500 blood test only meeting CMS coverage criteria yielded 83-116 QALY gained at a cost of $8559-$9413 per person.

Conclusion
Blood tests that only meet CMS coverage requirements should not be recommended to patients who would otherwise undergo screening by colonoscopy or fecal immunochemical testing because of lower benefit. Blood tests need higher advanced adenoma sensitivity (above 40%) and lower costs (below $125) to be cost-effective.
Pseudomonas otitidis-mediated synthesis of silver nanoparticles: characterization, antimicrobial and antibiofilm potential
Authors: Jose Ashitha , Asha Sneha , Rani Anaswara , T S Xavier , Kumar Praveen 
Published: June 2024

Abstract
This study explores the eco-friendly synthesis of silver nanoparticles (AgNPs) using soil bacteria, Pseudomonas otitidis. The bio-synthesized AgNPs were characterized using various techniques, including UV–visible spectroscopy, Fourier transform infrared (FTIR) spectroscopy, scanning electron microscopy (SEM), and X-ray diffraction (XRD). UV–visible spectroscopy revealed a distinct broad absorption band in the range of 443 nm, indicating the reduction of silver nitrate to AgNPs. XRD analysis provided evidence of the crystalline nature of the particles, with sharp peaks confirming their crystallinity and an average size of 82.76 nm. FTIR spectroscopy identified extracellular protein compounds as capping agents. SEM examination revealed spherical agglomeration of the crystalline AgNPs. The antimicrobial assay by a disc diffusion method, minimum inhibitory concentration, and minimum bactericidal concentration testing revealed that the biosynthesized AgNPs showed moderate antibacterial activity against both pathogenic Gram-negative (Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii) and Gram-positive (Bacillus cereus, Staphylococcus aureus, and Streptococcus mutans) bacterial strains. Furthermore, the AgNPs significantly disrupted the biofilm of P. aeruginosa, as confirmed by crystal violet assay and fluorescent microscopy. Overall, this study underscores the potential of microbial-synthesized nanoparticles in biomedical applications, particularly in combating pathogenic bacteria, offering a promising avenue for future research and development.
SUNBIRD: a simulation-based model for full-shape density-split clustering
Authors: Cuesta-Lazaro Carolina , Paillas Enrique , Yuan Sihan , Cai Yan-Chuan , Nadathur Seshadri , Percival Will J , Beutler Florian , de Mattia Arnaud , Eisenstein Daniel J , Forero-Sanchez Daniel , Padilla Nelson , Pinon Mathilde , Ruhlmann-Kleider Vanina , Sánchez Ariel G , Valogiannis Georgios , Zarrouk Pauline 
Published: June 2024

ABSTRACT
Combining galaxy clustering information from regions of different environmental densities can help break cosmological parameter degeneracies and access non-Gaussian information from the density field that is not readily captured by the standard two-point correlation function (2PCF) analyses. However, modelling these density-dependent statistics down to the non-linear regime has so far remained challenging. We present a simulation-based model that is able to capture the cosmological dependence of the full shape of the density-split clustering (DSC) statistics down to intra-halo scales. Our models are based on neural-network emulators that are trained on high-fidelity mock galaxy catalogues within an extended-ΛCDM framework, incorporating the effects of redshift-space, Alcock–Paczynski distortions, and models of the halo–galaxy connection. Our models reach sub-per cent level accuracy down to $1 \, h^{-1}\text{Mpc}$ and are robust against different choices of galaxy–halo connection modelling. When combined with the galaxy 2PCF, DSC can tighten the constraints on ωcdm, σ8, and ns by factors of 2.9, 1.9, and 2.1, respectively, compared to a 2PCF-only analysis. DSC additionally puts strong constraints on environment-based assembly bias parameters.
The MAGPI Survey: massive slow rotator population in place by z ∼ 0.3
Authors: Derkenne Caro , McDermid Richard M , D’Eugenio Francesco , Foster Caroline , Khalid Aman , Harborne Katherine E , van de Sande Jesse , Croom Scott M , Lagos Claudia D P , Bellstedt Sabine , Mendel J Trevor , Mun Marcie , Wisnioski Emily , Bagge Ryan S , Battisti Andrew J , Bland-Hawthorn Joss , Ferré-Mateu Anna , Peng Yingjie , Santucci Giulia , Sweet Sarah M , Thater Sabine , Valenzuela Lucas M , Ziegler Bodo 
Published: June 2024

ABSTRACT
We use the ‘Middle Ages Galaxy Properties with Integral field spectroscopy’ (MAGPI) survey to investigate whether galaxies have evolved in the distribution of their stellar angular momentum in the past 3–4 Gyr, as probed by the observational proxy for spin, λR. We use 2D stellar kinematics to measure λR along with detailed photometric models to estimate galaxy ellipticity. The combination of these measurements quantifies the kinematic classes of ‘fast rotators’ and the rarer ‘slow rotators’, which show no regular rotation in their line-of-sight velocity fields. We compare 51 MAGPI galaxies with log10 (M⋆/M⊙) &gt; 10 to carefully drawn samples of MaNGA galaxies in the local Universe, selected to represent possible descendants of the MAGPI progenitors. The EAGLE simulations are used to identify possible evolutionary pathways between the two samples, explicitly accounting for progenitor bias in our results and the varied evolutionary pathways a galaxy might take between the two epochs. We find that the occurrence of slow rotating galaxies is unchanged between the MAGPI (z ∼ 0.3) and MaNGA (z ∼ 0) samples, suggesting the massive slow rotator population was already in place ∼4 Gyr ago and has not accumulated since. There is a hint of the MAGPI sample having an excess of high λR galaxies compared to the MaNGA sample, corresponding to more ordered rotation, but statistically the samples are not significantly different. The large-scale stellar kinematics, as quantified through the λR parameter, of galaxies at z ∼ 0.3 have already evolved into the diversity of structures seen today in the local Universe.
Coma and tail of Comet 67P/Churyumov–Gerasimenko during the 2021–2022 apparition
Authors: Boehnhardt Hermann , Lara Luisa , Gray Zuri , Bagnulo Stefano 
Published: June 2024

ABSTRACT
We present results on the global activity of comet 67P/Churyumov–Gerasimenko (67P), the ROSETTA target, during its first perihelion passage after the mission and after an encounter with planet Jupiter. 67P was observed by broad-band filter imaging at 33 epochs during 2021 May 21 to 2022 June 1. The mean radial flux profiles suggest that ‘equilibrium’ conditions for the dust flow in the coma existed from around perihelion until about 100 d thereafter. We propose a scenario for the smaller and larger radial exponents, measured before and after the ‘equilibrium’ phase. Four coma fans with possible source regions at +40°, –10°, –50°, and –70° latitude on the nucleus are identified. The three fans at southern latitudes may be identical with fan sources seen during post-perihelion in 2015–2016. The rotation axis of 67P may not have changed at all or at least not much (&lt;5°) from the orientation measured during the Rosetta mission at the comet. The dust streamers in the coma originated from observed coma fans, containing mostly dust emitted within days to weeks before observation. Two dust streamers, a long- and a short-lasting one, contained heavy dust grains from emission periods hundreds of days before perihelion. Similar emission periods are obtained for the dust seen in the tail region of the comet. Similarities and differences in the dust activity during the recent apparition with that of the Rosetta mission at the comet are found.
FROST-CLUSTERS – I. Hierarchical star cluster assembly boosts intermediate-mass black hole formation
Authors: Rantala Antti , Naab Thorsten , Lahén Natalia 
Published: June 2024

ABSTRACT
Observations and high-resolution hydrodynamical simulations indicate that massive star clusters assemble hierarchically from subclusters with a universal power-law cluster mass function. We study the consequences of such assembly for the formation of intermediate-mass black holes (IMBHs) at low metallicities (Z = 0.01 Z⊙) with our updated N-body code bifrost based on the hierarchical fourth-order forward integrator. bifrost integrates few-body systems using secular and regularized techniques including post-Newtonian equations of motion up to order PN3.5 and gravitational-wave recoil kicks for BHs. Single stellar evolution is treated using the fast population synthesis code sevn. We evolve three cluster assembly regions with Ntot = 1.70–2.35 × 106 stars following a realistic IMF in ∼1000 subclusters for t = 50 Myr. IMBHs with masses up to m• ∼ 2200 M⊙ form rapidly mainly via the collapse of very massive stars (VMSs) assembled through repeated collisions of massive stars followed by growth through tidal disruption events and BH mergers. No IMBHs originate from the stars in the initially most massive clusters. We explain this by suppression of hard massive star binary formation at high velocity dispersions and the competition between core collapse and massive star lifetimes. Later the IMBHs form subsystems resulting in gravitational-wave BH–BH, IMBH–BH, and IMBH–IMBH mergers with a m• ∼ 1000 M⊙ gravitational-wave detection being the observable prediction. Our simulations indicate that the hierarchical formation of massive star clusters in metal poor environments naturally results in formation of potential seeds for supermassive black holes.