bluuebunny/crossref_metadata_2025 huggingface dataset:
The impact of underreported infections on vaccine effectiveness estimates derived from retrospective cohort studies
Authors: Sacco Chiara , Manica Mattia , Marziano Valentina , Fabiani Massimo , Mateo-Urdiales Alberto , Guzzetta Giorgio , Merler Stefano , Pezzotti Patrizio
Published: June 2024

Background

Surveillance data and vaccination registries are widely used to provide real-time vaccine effectiveness (VE) estimates, which can be biased due to underreported (i.e. under-ascertained and under-notified) infections. Here, we investigate how the magnitude and direction of this source of bias in retrospective cohort studies vary under different circumstances, including different levels of underreporting, heterogeneities in underreporting across vaccinated and unvaccinated, and different levels of pathogen circulation.

Methods

We developed a stochastic individual-based model simulating the transmission dynamics of a respiratory virus and a large-scale vaccination campaign. Considering a baseline scenario with 22.5% yearly attack rate and 30% reporting ratio, we explored fourteen alternative scenarios, each modifying one or more baseline assumptions. Using synthetic individual-level surveillance data and vaccination registries produced by the model, we estimated the VE against documented infection taking as reference either unvaccinated or recently vaccinated individuals (within 14 days post-administration). Bias was quantified by comparing estimates to the known VE assumed in the model.

Results

VE estimates were accurate when assuming homogeneous reporting ratios, even at low levels (10%), and moderate attack rates (<50%). A substantial downward bias in the estimation arose with homogeneous reporting and attack rates exceeding 50%. Mild heterogeneities in reporting ratios between vaccinated and unvaccinated strongly biased VE estimates, downward if cases in vaccinated were more likely to be reported and upward otherwise, particularly when taking as reference unvaccinated individuals.

Conclusions

In observational studies, high attack rates or differences in underreporting between vaccinated and unvaccinated may result in biased VE estimates. This study underscores the critical importance of monitoring data quality and understanding biases in observational studies, to more adequately inform public health decisions.
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

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

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

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<.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

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

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

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 (<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

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

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

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

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⊙) > 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

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 (<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

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.
Enhancing neural operator learning with invariants to simultaneously learn various physical mechanisms
Authors: Li Siran , Liu Chong , Ni Hao
Published: June 2024

We discuss the recent advancement in PDE learning, focusing on Physics Invariant Attention Neural Operator (PIANO). PIANO is a novel neural operator learning framework for deciphering and integrating physical knowledge from PDEs sampled from multi- physical scenarios.
A Geographically Weighted Cost-effectiveness Analysis of Newborn Cytomegalovirus Screening
Authors: Lantos Paul M , Gantt Soren , Janko Mark , Dionne Francois , Permar Sallie R , Fowler Karen
Published: June 2024

Background

Early identification of newborns with congenital cytomegalovirus (CMV) is necessary to provide antiviral therapy and other interventions that can improve outcomes. Prior research demonstrates that universal newborn CMV screening would be the most cost-effective approach to identifying newborns who are infected. CMV is not uniformly prevalent, and it is uncertain whether universal screening would remain cost-effective in lower-prevalence neighborhoods. Our aim was to identify geographic heterogeneity in the cost-effectiveness of universal newborn CMV screening by combining a geospatial analysis with a preexisting cost-effectiveness analysis.

Methods

This study used the CMV testing results and zip code location data of 96 785 newborns in 7 metropolitan areas who had been tested for CMV as part of the CMV and Hearing Multicenter Screening study. A hierarchical bayesian generalized additive model was constructed to evaluate geographic variability in the odds of CMV. The zip code–level odds of CMV were then used to weight the results of a previously published model evaluating universal CMV screening vs symptom-targeted screening.

Results

The odds of CMV were heterogeneous over large geographic scales, with the highest odds in the southeastern United States. Universal screening was more cost-effective and afforded more averted cases of severe hearing loss than targeted testing. Universal screening remained the most cost-effective option even in areas with the lowest CMV prevalence.

Conclusions

Universal newborn CMV screening is cost-effective regardless of underlying CMV prevalence and is the preferred strategy to reduce morbidity from congenital CMV.
Suppression of MyD88 disturbs gut microbiota and activates the NLR pathway and hence fails to ameliorate DSS-induced colitis
Authors: Li Jun-hua , Chen Yu , Ye Zheng-hao , Chen Li-ping , Xu Jia-xin , Han Jian , Xie Lin , Xing Shuai , Tian De-an , Seidler Ursula , Liao Jia-zhi , Xiao Fang
Published: June 2024

Background

Myeloid differentiation factor 88 (MyD88) is the core adaptor for Toll-like receptors defending against microbial invasion and initiating a downstream immune response during microbiota–host interaction. However, the role of MyD88 in the pathogenesis of inflammatory bowel disease is controversial. This study aims to investigate the impact of MyD88 on intestinal inflammation and the underlying mechanism.

Methods

MyD88 knockout (MyD88−/−) mice and the MyD88 inhibitor (TJ-M2010-5) were used to investigate the impact of MyD88 on acute dextran sodium sulfate (DSS)-induced colitis. Disease activity index, colon length, histological score, and inflammatory cytokines were examined to evaluate the severity of colitis. RNA transcriptome analysis and 16S rDNA sequencing were used to detect the potential mechanism.

Results

In an acute DSS-colitis model, the severity of colitis was not alleviated in MyD88−/− mice and TJ-M2010-5-treated mice, despite significantly lower levels of NF-κB activation being exhibited compared to control mice. Meanwhile, 16S rDNA sequencing and RNA transcriptome analysis revealed a higher abundance of intestinal Proteobacteria and an up-regulation of the nucleotide oligomerization domain-like receptors (NLRs) signaling pathway in colitis mice following MyD88 suppression. Further blockade of the NLRs signaling pathway or elimination of gut microbiota with broad-spectrum antibiotics in DSS-induced colitis mice treated with TJ-M2010-5 ameliorated the disease severity, which was not improved solely by MyD88 inhibition. After treatment with broad-spectrum antibiotics, downregulation of the NLR signaling pathway was observed.

Conclusion

Our study suggests that the suppression of MyD88 might be associated with unfavorable changes in the composition of gut microbiota, leading to NLR-mediated immune activation and intestinal inflammation.
Lanternfish larvae (Teleostei: Myctophidae) feeding ecology in the continental slope and off oceanic islands in the tropical Atlantic
Authors: de Santana Jana Ribeiro , da Costa Alejandro Esteweson Santos Faustino , Landaeta Mauricio F , Mafalda Jr. Paulo de Oliveira , Schwamborn Silvia Helena Lima , Neumann-Leitão Sigrid , Schwamborn Ralf
Published: June 2024

Myctophids are central in ocean food webs, yet knowledge of the ecology of larval stages is sparse. We investigated if larval feeding ecology is different in continental shelf break waters compared to waters off oceanic islands in the western Tropical Atlantic. The larvae were collected through diurnal and nocturnal oblique hauls using a Bongo net and stomach contents were analyzed. The larvae ranged between 2.27 and 16.5 mm in standard length. Diet composition was different in the slope and islands (Permutational Multivariate Analysis of Variance (PERMANOVA), P < 0.001). Diatoms (mainly Thalassiosira spp. and fragments of diatoms) were numerically important in the diet at the slope site (69% of relative importance). Copepods were the most relevant prey (71% of relative importance) near the islands. Copepods were the biomass-dominant dietary item at both areas, alongside ostracods near the islands. Smaller prey items were more important for smaller larvae, particularly those measuring up to 4 mm. Larger prey became relatively more important as the larvae grew to at least 8 mm. Larvae fed mostly during the daytime regardless of their size class.
A Markov chain model of Daphnia motion
Authors: Spade David A , Strickler J Rudi
Published: June 2024

Daphnia magna make turns through an antennae-whipping action. This action occurs every few seconds, so during the intervening time, the animal either remains in place or it continues movement roughly along its current course. We view their movement in two dimensions as being on a lattice, and construct a second-order Markov chain model to make predictions about which region of the lattice the animal moves to based on where it was at the last two time points. This model accounts for the animal’s morphology with respect to the antennae-whipping behavior.
Ocean-colour anomalies quantified by the human eye
Authors: Brewin Robert J W , Dall’Olmo Giorgio
Published: June 2024

Phytoplankton turn seawater green when their concentration increases. This allows us to monitor them using ocean colour. However, as the spectral properties of phytoplankton and their relationship with other coloured substances in seawater vary, subtle differences (anomalies) in ocean colour occur that can cause large errors in estimates of phytoplankton abundance. Identifying and understanding these anomalies is required to interpret ocean-colour data properly, but not all scientists have access to, or can afford, the in-situ instrumentation needed to do this. We show that practical, low-cost tools developed in the 19th century (a Secchi disk and Forel-Ule colour scale) can be used to quantify a colour anomaly in the Weddell Sea. Our findings imply that ocean-colour anomalies can be identified using affordable methods. Furthermore, records collected over the last century may contain clues on how ocean ecosystems have changed with climate.
Large-scale culturing of the subpolar foraminifera Globigerina bulloides reveals tolerance to a large range of environmental parameters associated to different life-strategies and an extended lifespan
Authors: Sykes Freya E , Meilland Julie , Westgård Adele , Chalk Thomas B , Chierici Melissa , Foster Gavin L , Ezat Mohamed M
Published: June 2024

The subtropical to subpolar planktic foraminifera Globigerina bulloides is a calcifying marine protist, and one of the dominant foraminiferal species of the Nordic Seas. Previously, the relative abundance and shell geochemistry of fossil G. bulloides have been studied for palaeoceanographic reconstructions. There is however a lack of biological observations on the species and a poor understanding of its ecological tolerances, especially for high latitude genotypes. Here, we present observations from the first extensive culturing of G. bulloides under subpolar conditions, including the first low temperature (6–13°C) and variable salinity (30–38) experiments. Carbonate chemistry (pH and [CO32−]) was also manipulated. Experimental conditions were chosen to reflect a range of plausible past and future scenarios for the Nordic Seas. We found G. bulloides to be tolerant of environmental conditions well outside their optimal range (<10°C, salinity <33, pH <8). Observed life span was up to three months, which was attributed to a microalgal diet. Two alternative life strategies were employed, whereby individuals either experienced rapid growth and death, or a prolonged lifespan with minimal growth and death via slow decay. We posit this could help explain differences in geochemical signals recorded from different size fractions of fossil specimens used for palaeoceanographic reconstructions.
Food, nutrition, and related policy issues: Evidence-based policy and the credibility crisis
Authors: Krasovskaia Elena , Just David R
Published: June 2024

In recent years, the push for evidence-based policy has gained momentum, particularly in the field of food and nutrition, where the stakes for public health are high, underscoring the need for aligning policy with robust scientific evidence. This paper examines the credibility crisis in evidence-based policymaking, highlighting challenges such as conflicts of interest and misuse of scientific findings. We delve into the complexities of food policies, including nutrition labeling and food assistance programs, and discuss the limitations of relying on single studies and short-term impacts for policymaking. The paper explores perverse incentives within the policy research ecosystem and illustrates potential bias and the lack of equipoise in research design. We conclude with recommendations for enhancing the credibility of evidence-based policy, emphasizing the importance of independence, relevance, and transparency in research citations and the need for dynamic policy responses informed by ongoing scientific developments.
The value of axillary, facial, occipital, subclavian and common carotid arteries ultrasound in the diagnosis of giant cell arteritis
Authors: Martins-Martinho Joana , Bandeira Matilde , James Lija , Verdiyeva Ayna , Fontes Tomás , Lopes Ana Rita , Naique Sofia , Velho Iolanda , Khmelinskii Nikita , Luqmani Raashid , Ponte Cristina
Published: June 2024

Objective

To assess the diagnostic value for GCA in adding the axillary arteries (AX) to the temporal artery (TA) ultrasound, particularly in patients with a cranial phenotype of the disease; and to investigate the utility of facial (FA), occipital (OC), subclavian (SC) and common carotid (CC) ultrasound in patients with suspected GCA.

Methods

Patients with new-onset GCA and a positive ultrasound of the TA, AX, FA, OC, SC or CC, followed at the rheumatology departments of two academic centres, were retrospectively included.

Results

Two hundred and thirty patients were assessed. TA halo sign was identified in 206/230 (89.6%) cases, FA in 40/82 (48.8%), OC in 17/69 (24.6%), AX in 56/230 (24.3%), SC in 31/57 (54.4%) and CC in 14/68 (20.6%). Negative TA ultrasound was found in 24/230 (10.4%) patients: 22 had AX involvement, one exclusive OC involvement and one exclusive SC involvement. Adding AX evaluation to the TA ultrasound increased the diagnostic yield for GCA by 9.6%, whereas adding OC or SCs to the TA and AX ultrasound increased it by 1.4% and 1.8%, respectively. No value was found in adding the FA or CCs. Notably, 13 patients with cranial symptoms and four with exclusively cranial symptoms showed negative TA ultrasound but positive AX ultrasound.

Conclusion

Adding the evaluation of AXs to the TA ultrasound increased the number of patients diagnosed with GCA, even in cases of predominantly cranial symptoms. In the subset of patients where these arteries were assessed, no substantial benefit was found in adding the FA, OC, SC or CC arteries to the TA and AX ultrasonographic assessment.
Genetically Informed Study Highlights Income-Independent Effect of Schizophrenia Liability on Mental and Physical Health
Authors: Kouakou Manuela R , Cabrera-Mendoza Brenda , Pathak Gita A , Cannon Tyrone D , Polimanti Renato
Published: June 2024

Background and Hypothesis

Individuals with schizophrenia (SCZ) suffer from comorbidities that substantially reduce their life expectancy. Socioeconomic inequalities could contribute to many of the negative health outcomes associated with SCZ.

Study Design

We investigated genome-wide datasets related to SCZ (52 017 cases and 75 889 controls) from the Psychiatric Genomics Consortium, household income (HI; N = 361 687) from UK Biobank, and 2202 medical endpoints assessed in up to 342 499 FinnGen participants. A phenome-wide genetic correlation analysis of SCZ and HI was performed, also assessing whether SCZ genetic correlations were influenced by the HI effect on SCZ. Additionally, SCZ and HI direct effects on medical endpoints were estimated using multivariable Mendelian randomization (MR).

Study Results

SCZ and HI showed overlapping genetic correlations with 70 traits (P < 2.89 × 10−5), including mental health, substance use, gastrointestinal illnesses, reproductive outcomes, liver diseases, respiratory problems, and musculoskeletal phenotypes. SCZ genetic correlations with these traits were not affected by the HI effect on SCZ. Considering Bonferroni multiple testing correction (P < 7.14 × 10−4), MR analysis indicated that SCZ and HI may affect medical abortion (SCZ OR = 1.07; HI OR = 0.78), panic disorder (SCZ OR = 1.20; HI OR = 0.60), personality disorders (SCZ OR = 1.31; HI OR = 0.67), substance use (SCZ OR = 1.2; HI OR = 0.68), and adjustment disorders (SCZ OR = 1.18; HI OR = 0.78). Multivariable MR analysis confirmed that SCZ effects on these outcomes were independent of HI.

Conclusions

The effect of SCZ genetic liability on mental and physical health may not be strongly affected by socioeconomic differences. This suggests that SCZ-specific strategies are needed to reduce negative health outcomes affecting patients and high-risk individuals.
Cell cycle machinery in oncology: A comprehensive review of therapeutic targets
Authors: Cavalu Simona , Abdelhamid Amir Mohamed , Saber Sameh , Elmorsy Elsayed A. , Hamad Rabab S. , Abdel‐Reheim Mustafa Ahmed , Yahya Galal , Salama Mohamed M.
Published: June 2024

The cell cycle is tightly regulated to ensure controlled cell proliferation. Dysregulation of the cell cycle machinery is a hallmark of cancer that leads to unchecked growth. This review comprehensively analyzes key molecular regulators of the cell cycle and how they contribute to carcinogenesis when mutated or overexpressed. It focuses on cyclins, cyclin‐dependent kinases (CDKs), CDK inhibitors, checkpoint kinases, and mitotic regulators as therapeutic targets. Promising strategies include CDK4/6 inhibitors like palbociclib, ribociclib, and abemaciclib for breast cancer treatment. Other possible targets include the anaphase‐promoting complex/cyclosome (APC/C), Skp2, p21, and aurora kinase inhibitors. However, challenges with resistance have limited clinical successes so far. Future efforts should focus on combinatorial therapies, next‐generation inhibitors, and biomarkers for patient selection. Targeting the cell cycle holds promise but further optimization is necessary to fully exploit it as an anti‐cancer strategy across diverse malignancies.
Comprehensive clinical imaging, histopathological analysis and liquid biopsy-based surveillance of human uveal melanoma in a prolonged rabbit xenograft model
Authors: Bustamante Prisca , Coblentz Jacqueline , Mastromonaco Christina , Youhnovska Emma , Ito Hiroaki , Proença Rita Pinto , Fonseca Cristina , Dickinson Kyle , Marcotte Emily , MacDonald Myriam , Toledo-Dias Ana-Beatriz , Bergeron Sabrina , Goyeneche Alicia , Schmidt Andujar Rafaella Atherino , Tsering Thupten , Laskaris Alexander , Jin Eva , Nadeau Amélie , Porraccio Tiffany , Burnier Miguel N. , Burnier Julia V.
Published: June 2024

Uveal melanoma is the most common intraocular tumor in adults. Our group has previously developed a human uveal melanoma animal model; however, adverse effects caused by the immunosuppressive agent, cyclosporine A, prevented animals from surviving more than 12 weeks. In this study, we tested multiple cyclosporine A doses over an extended disease course up to 20 weeks, providing complete clinical imaging of intraocular tumors, histopathological analysis and liquid biopsy biomarker analysis. Twenty albino rabbits were divided into four groups with different daily cyclosporine A schedules (0–10 mg/kg) and inoculated with human uveal melanoma cell lines, 92.1 or MP41, into the suprachoroidal space. Rabbits were monitored with fundoscopy, ultrasound and optical coherence tomography. Intraocular tumors (macroscopic or microscopic) were detected in all study animals. Tumor size and growth were correlated to cyclosporine A dose, with tumors regressing when cyclosporine A was arrested. All tumors expressed HMB-45 and MelanA; however, tumor size, pigmentation and cell morphology differed in 92.1 vs. MP41 tumors. Finally, across all groups, circulating tumor DNA from plasma and aqueous humor was detected earlier than tumor detection by imaging and correlated to tumor growth. In conclusion, using three clinically relevant imaging modalities (fundoscopy, ultrasonography and optical coherence tomography) and liquid biopsy, we were successfully able to monitor tumor progression in our rabbit xenograft model of human uveal melanoma.
Propranolol attenuates the establishment of conditioned context aversions: differential effects compared to MK-801 in an animal model of anticipatory nausea and vomiting
Authors: İlhan Çinar Furkan , Ülke Esra , Urcelay Gonzalo P. , Kişlal Sezen
Published: June 2024

Cancer patients often experience anticipatory nausea and vomiting (ANV) due to Pavlovian conditioning. Both N-methyl-D-aspartate and beta-adrenergic receptors are known to mediate memory formation, but their role in the development of ANV remains unclear. This study used a conditioned context aversion (CCA) paradigm, an animal model for ANV, to assess whether administration of the beta-adrenergic receptor antagonist propranolol or the N-methyl-D-aspartate receptor antagonist MK-801 immediately after CCA training has an effect on the later expression of CCA in CD1 male mice. In experiment 1, three groups were injected with lithium chloride (LiCl) to induce aversion in a novel context, resulting in CCA. A control group was injected with sodium chloride (NaCl). Following conditioning, two of the LiCl-treated groups received different doses of MK-801 (0.05 or 0.2 mg/kg), while the remaining LiCl-treated and NaCl-treated groups received a second NaCl injection. In experiment 2, two groups were injected with LiCl, and one group was injected with NaCl. After conditioning, one of the LiCl-treated groups received a propranolol injection (10 mg/kg). The remaining LiCl-treated and NaCl-treated groups received NaCl injections. Water consumption was measured in all groups 72 h later within the conditioning context. Postconditioning administration of propranolol, but not MK-801, attenuated CCA, as revealed by similar levels of water consumption in animals that received LiCl and propranolol relative to NaCl-treated animals. These findings suggest that beta-adrenergic receptor activation is crucial for the development of CCA. Therefore, propranolol may represent a novel therapeutic approach for cancer patients at high risk of ANV.
Protected Time for Self-Care for Veterans Health Administration Employees
Authors: Schult Tamara M. , Finnell John S. , Gray Charles , Reddy Kavitha P.
Published: June 2024

Objectives

Employee Whole Health (EWH) empowers VA employees to take charge of their well-being by integrating self-care into their workday, but employees lack time to participate.

Methods

Employees at three VA medical centers participated in a 12-month feasibility cohort study to protect 60 minutes of time per week for self-care. Questionnaire data were collected at three time points and qualitative data at two time points. Pilot offerings included education and complementary and integrative health modalities for well-being.

Results

Employees enrolled spring 2021 (n= 312). Complete-case regression analyses indicated significant improvements in wellness culture, resiliency, self-efficacy, perceived stress, and flourishing at 12 months. Multiple imputation analyses confirmed improvements except for self-efficacy. Qualitative findings supported quantitative findings.

Conclusions

Providing protected time for self-care was feasible and supported improvements in well-being. However, high workload was identified as an ongoing barrier to participation.
Daily Associations Between Presenteeism and Health-Related Factors Among Office Workers
Authors: Suwa Kaori , Nakamura Toru , Kishi Akifumi , Takeuchi Hiroki , Yoshiuchi Kazuhiro , Yamamoto Yoshiharu
Published: June 2024

Objective

The study examined daily associations between presenteeism and health-related factors among office workers using ecological momentary assessment (EMA).

Methods

Diurnal mood and physical symptoms were repeatedly recorded over 2 weeks with EMA. Daily work performance (WP) was also recorded. Recalled WP and baseline health conditions were assessed via questionnaires. Daily sleep was assessed using actigraphy. Reliability between recalled and daily WP was compared. Hierarchical linear modeling (HLM) was used to analyze the effects of sleep, mood, and physical symptoms on daily WP.

Results

Weak yet significant agreement was found between recalled and daily WP, with EMA capturing occasional declines in performance overlooked by recalled assessments. HLM indicated that longer sleep, reduced depressive mood, and decreased shoulder stiffness were significantly associated with increased daily WP.

Conclusions

These factors are associated with daily fluctuations in presenteeism, suggesting potential targets of intervention.