bluuebunny/crossref_metadata_2025 huggingface dataset:
Contrasting biomass allocations explain adaptations to cold and drought in the world’s highest-growing angiosperms
Authors: Doležal Jiří , Chondol Thinles , Chlumská Zuzana , Altman Jan , Čapková Kateřina , Dvorský Miroslav , Fibich Pavel , Korznikov Kirill A , Ruka Adam T , Kopecký Martin , Macek Martin , Řeháková Klára
Published: February 2024

Background and Aims

Understanding biomass allocation among plant organs is crucial for comprehending plant growth optimization, survival and responses to the drivers of global change. Yet, the mechanisms governing mass allocation in vascular plants from extreme elevations exposed to cold and drought stresses remain poorly understood.

Methodology

We analysed organ mass weights and fractions in 258 Himalayan herbaceous species across diverse habitats (wetland, steppe, alpine), growth forms (annual, perennial taprooted, rhizomatous and cushiony) and climatic gradients (3500–6150 m elevation) to explore whether biomass distribution adhered to fixed allometric or optimal partitioning rules, and how variations in size, phylogeny and ecological preferences influence their strategies for resource allocation.

Key Findings

Following optimal partitioning theory, Himalayan plants distribute more biomass to key organs vital for acquiring and preserving limited resources necessary for their growth and survival. Allocation strategies are mainly influenced by plant growth forms and habitat conditions, notably temperature, water availability and evaporative demands. Alpine plants invest primarily in below-ground stem bases for storage and regeneration, reducing above-ground stems while increasing leaf mass fraction to maximize carbon assimilation in their short growing season. Conversely, arid steppe plants prioritize deep roots over leaves to secure water and minimize transpiration. Wetland plants allocate resources to above-ground stems and below-ground rhizomes, enabling them to resist competition and grazing in fertile environments.

Conclusions

Himalayan plants from extreme elevations optimize their allocation strategies to acquire scarce resources under specific conditions, efficiently investing carbon from supportive to acquisitive and protective functions with increasing cold and drought. Intraspecific variation and shared ancestry have not significantly altered biomass allocation strategies of Himalayan plants. Despite diverse evolutionary histories, plants from similar habitats have developed comparable phenotypic structures to adapt to their specific environments. This study offers new insights into plant adaptations in diverse Himalayan environments and underscores the importance of efficient resource allocation for survival and growth in challenging conditions.
Translation and Adaptation of Cognistat in Hindi Language: For Computerized Evaluation of Cognitive Functioning
Authors: Sagar Rajesh , Talwar Shivangi , Verma Rohit , Tripathi Manjari
Published: February 2024

Objective

Cognitive assessment is a crucial element of the mental health screening process. However, there is a lack of culturally appropriate cognitive screening tools for the Hindi-speaking aging population in India. We aimed to translate and culturally tailor the English version of the computerized Cognistat test for the Hindi-speaking aging population.

Method

The computer-based Cognistat Assessment System was culturally adapted for the North Indian Hindi-speaking population. Participants with mild cognitive impairment (MCI) (n = 30), depression (n = 30), and healthy control (n = 30) groups between the age range of 50 and 83 years were assessed using the translated version of the tool. The group differences were analyzed using analysis of variance, multivariate analysis of variance, Tukey’s post hoc analysis for continuous variables, and Fisher’s exact test for categorical variables. The correlation between the Cognistat domains was analyzed using Pearson’s correlation, and test reliability was assessed using Cronbach’s alpha.

Results

The MCI group had significantly lower scores as compared with the depression and control groups on orientation, language, repetition, and calculation domain tasks. For attention and construction tasks, the MCI group had lower scores than the control group. MCI group scores were significantly lower than the control group on naming domain. The Hindi version of the test was reliable for the Hindi-speaking aging population.

Conclusions

Cognistat Hindi can be used by trained healthcare professionals with Hindi-speaking populations for culturally tailored primary evaluation of cognitive difficulties. Future research should focus on further validation and assessment of its properties.
Executive Function as a Predictor of Pain Perception in Healthy Young Adults
Authors: Garcia Sarah , Foster Elodie , Johnson Peter J , Thomas Brittany , Askew Robert L
Published: February 2024

Objective

Pain’s impact on executive function is understood and specific cognitive abilities may contribute to coping with pain, though past work is confounded by chronic pain populations. This study aims to understand how executive functioning may predict the experience of pain among healthy adults. It was hypothesized that poorer executive functioning would predict more intense pain perception.

Method

A total of 172 young adults were recruited for participation. Three aspects of executive functioning (i.e., impulsivity, cognitive flexibility, working memory) were assessed before randomizing participants to varying types and levels of stimulated pain.

Results

Results supported the hypothesis that poorer performance on tasks of working memory predicts more intense pain perception.

Conclusions

Findings are counter to past work that has found inhibition may be important for coping, and future research is needed to understand the impact of specific cognitive abilities as well as how this may differ for chronic pain.
Polyurethane Implants in Revisional Breast Augmentation: A Prospective 5-Year Study
Authors: Hamdi Moustapha , Kapila Ayush K , Peters Ellen , Ramaut Lisa , Waked Karl , Giunta Gabriele , De Baerdemaeker Randy , Zeltzer Assaf
Published: February 2024

Background

Revisional surgery for aesthetic breast augmentation remains a challenging procedure. Polyurethane (PU) implants have been found to avoid capsular contracture recurrence as well as to prevent implant displacement by bio-integrating with the pocket.

Objectives

Our study aimed to assess the use of PU implants in breast revisional surgery and to provide an algorithm.

Methods

Over a 5-year period, a prospective study was conducted involving consecutive patients undergoing implant revision. Patient demographics, previous breast procedures, and specific surgical details were documented. Postoperative outcomes were followed up.

Results

Out of 92 patients (184 breasts), 78 (156 breasts) were included in the analysis. The average age was 47.5, with a BMI of 22.3 and a mean follow-up of 5 years. A majority (63%) represented secondary revisional cases, while 37% were tertiary cases. Implant size averaged 296 cc, with 53% placed in retropectoral position and 47% prepectoral. Significantly more implants in secondary cases were changed from prepectoral to retropectoral (P = .005), and in tertiary changed from retropectoral to prepectoral (P = .002). Complete capsulectomy was performed in 61.5% and partial in 25.6%. Additional lipofilling was performed in 32%, and concurrent mastopexy in 40%. Revisional surgery in our series had a 1.9% acute complication rate, 4.5% longer-term reoperation rate for corrections, 0.6% implant exchange rate, and no recurrent capsular contracture.

Conclusions

This is the first study to provide data on outcomes of revisional breast augmentation surgery with PU implants. It shows that polyurethane implants offer consistent stability and have low rates of recurrent capsular contracture in revisional surgery.

Level of Evidence: 3
MetaQuad: shared informative variants discovery in metagenomic samples
Authors: Xu Sheng , Morgan Daniel C , Qian Gordon , Huang Yuanhua , Ho Joshua W K
Published: February 2024

Motivation

Strain-level analysis of metagenomic data has garnered significant interest in recent years. Microbial single nucleotide polymorphisms (SNPs) are genomic variants that can reflect strain-level differences within a microbial species. The diversity and emergence of SNPs in microbial genomes may reveal evolutionary history and environmental adaptation in microbial populations. However, efficient discovery of shared polymorphic variants in a large collection metagenomic samples remains a computational challenge.

Results

MetaQuad utilizes a density-based clustering technique to effectively distinguish between shared variants and non-polymorphic sites using shotgun metagenomic data. Empirical comparisons with other state-of-the-art methods show that MetaQuad significantly reduces the number of false positive SNPs without greatly affecting the true positive rate. We used MetaQuad to identify antibiotic-associated variants in patients who underwent Helicobacter pylori eradication therapy. MetaQuad detected 7591 variants across 529 antibiotic resistance genes. The nucleotide diversity of some genes is increased 6 weeks after antibiotic treatment, potentially indicating the role of these genes in specific antibiotic treatments.

Availability and implementation

MetaQuad is an open-source Python package available via https://github.com/holab-hku/MetaQuad.
RT-Transformer: retention time prediction for metabolite annotation to assist in metabolite identification
Authors: Xue Jun , Wang Bingyi , Ji Hongchao , Li WeiHua
Published: February 2024

Motivation

Liquid chromatography retention times prediction can assist in metabolite identification, which is a critical task and challenge in nontargeted metabolomics. However, different chromatographic conditions may result in different retention times for the same metabolite. Current retention time prediction methods lack sufficient scalability to transfer from one specific chromatographic method to another.

Results

Therefore, we present RT-Transformer, a novel deep neural network model coupled with graph attention network and 1D-Transformer, which can predict retention times under any chromatographic methods. First, we obtain a pre-trained model by training RT-Transformer on the large small molecule retention time dataset containing 80 038 molecules, and then transfer the resulting model to different chromatographic methods based on transfer learning. When tested on the small molecule retention time dataset, as other authors did, the average absolute error reached 27.30 after removing not retained molecules. Still, it reached 33.41 when no samples were removed. The pre-trained RT-Transformer was further transferred to 5 datasets corresponding to different chromatographic conditions and fine-tuned. According to the experimental results, RT-Transformer achieves competitive performance compared to state-of-the-art methods. In addition, RT-Transformer was applied to 41 external molecular retention time datasets. Extensive evaluations indicate that RT-Transformer has excellent scalability in predicting retention times for liquid chromatography and improves the accuracy of metabolite identification.

Availability and implementation

The source code for the model is available at https://github.com/01dadada/RT-Transformer. The web server is available at https://huggingface.co/spaces/Xue-Jun/RT-Transformer.
CAM3.0: determining cell type composition and expression from bulk tissues with fully unsupervised deconvolution
Authors: Wu Chiung-Ting , Du Dongping , Chen Lulu , Dai Rujia , Liu Chunyu , Yu Guoqiang , Bhardwaj Saurabh , Parker Sarah J , Zhang Zhen , Clarke Robert , Herrington David M , Wang Yue
Published: February 2024

Motivation

Complex tissues are dynamic ecosystems consisting of molecularly distinct yet interacting cell types. Computational deconvolution aims to dissect bulk tissue data into cell type compositions and cell-specific expressions. With few exceptions, most existing deconvolution tools exploit supervised approaches requiring various types of references that may be unreliable or even unavailable for specific tissue microenvironments.

Results

We previously developed a fully unsupervised deconvolution method—Convex Analysis of Mixtures (CAM), that enables estimation of cell type composition and expression from bulk tissues. We now introduce CAM3.0 tool that improves this framework with three new and highly efficient algorithms, namely, radius-fixed clustering to identify reliable markers, linear programming to detect an initial scatter simplex, and a smart floating search for the optimum latent variable model. The comparative experimental results obtained from both realistic simulations and case studies show that the CAM3.0 tool can help biologists more accurately identify known or novel cell markers, determine cell proportions, and estimate cell-specific expressions, complementing the existing tools particularly when study- or datatype-specific references are unreliable or unavailable.

Availability and implementation

The open-source R Scripts of CAM3.0 is freely available at https://github.com/ChiungTingWu/CAM3/(https://github.com/Bioconductor/Contributions/issues/3205). A user’s guide and a vignette are provided.
CryoTransformer: a transformer model for picking protein particles from cryo-EM micrographs
Authors: Dhakal Ashwin , Gyawali Rajan , Wang Liguo , Cheng Jianlin
Published: February 2024

Motivation

Cryo-electron microscopy (cryo-EM) is a powerful technique for determining the structures of large protein complexes. Picking single protein particles from cryo-EM micrographs (images) is a crucial step in reconstructing protein structures from them. However, the widely used template-based particle picking process requires some manual particle picking and is labor-intensive and time-consuming. Though machine learning and artificial intelligence (AI) can potentially automate particle picking, the current AI methods pick particles with low precision or low recall. The erroneously picked particles can severely reduce the quality of reconstructed protein structures, especially for the micrographs with low signal-to-noise ratio.

Results

To address these shortcomings, we devised CryoTransformer based on transformers, residual networks, and image processing techniques to accurately pick protein particles from cryo-EM micrographs. CryoTransformer was trained and tested on the largest labeled cryo-EM protein particle dataset—CryoPPP. It outperforms the current state-of-the-art machine learning methods of particle picking in terms of the resolution of 3D density maps reconstructed from the picked particles as well as F1-score, and is poised to facilitate the automation of the cryo-EM protein particle picking.

Availability and implementation

The source code and data for CryoTransformer are openly available at: https://github.com/jianlin-cheng/CryoTransformer.
In vitro culture alters cell lineage composition and cellular metabolism of bovine blastocyst
Authors: Ming Hao , Zhang Mingxiang , Rajput Sandeep , Logsdon Deirdre , Zhu Linkai , Schoolcraft William B , Krisher Rebecca L , Jiang Zongliang , Yuan Ye
Published: February 2024

Profiling bovine blastocyst transcriptome at the single-cell level has enabled us to reveal the first cell lineage segregation, during which the inner cell mass (ICM), trophectoderm (TE), and an undefined population of transitional cells were identified. By comparing the transcriptome of blastocysts derived in vivo (IVV), in vitro from a conventional culture medium (IVC), and in vitro from an optimized reduced nutrient culture medium (IVR), we found a delay of the cell fate commitment to ICM in the IVC and IVR embryos. Developmental potential differences between IVV, IVC, and IVR embryos were mainly contributed by ICM and transitional cells. Pathway analysis of these non-TE cells between groups revealed highly active metabolic and biosynthetic processes, reduced cellular signaling, and reduced transmembrane transport activities in IVC embryos that may lead to reduced developmental potential. IVR embryos had lower activities in metabolic and biosynthetic processes but increased cellular signaling and transmembrane transport, suggesting these cellular mechanisms may contribute to improved blastocyst development compared to IVC embryos. However, the IVR embryos had compromised development compared to IVV embryos with notably over-active transmembrane transport activities that impaired ion homeostasis.
Let us settle the controversy—gelfoam is a safe intravascular embolic agent
Authors: Clements Warren , Lukies Matthew , Zia Adil , Fitzgerald Mark , Kavnoudias Helen
Published: February 2024

Objectives

A 2021 safety alert restricted endovascular gelfoam use in Australia and resulted in an embargo on gelfoam sales to Interventional Radiology departments. This study aimed to show that gelfoam is safe in a population of trauma patients with pelvic injury, and discuss the basis of the recent controversies.

Methods

Retrospective cohort study was conducted between 1 January 2010 and 21 May 2021 for the patients who underwent gelfoam embolization for pelvic arterial haemorrhage. Primary outcome was the rate of adverse events related to intravascular gelfoam administration.

Results

Inclusion criteria met in 50 patients, comprising 58% males median age 59.9 years, and median injury severity score 31. There were 0 complications related to gelfoam use and 100% technical success. Thirty-five patients (70%) received a non-targeted embolization approach. All-cause mortality was observed in 5 patients (10%), unrelated to gelfoam.

Conclusions

Gelfoam is a safe and effective embolic agent in pelvic trauma. Patients are in urgent need of universal on-label registration of endovascular gelfoam products, as it is life-saving in major haemorrhage after trauma.

Advances in knowledge

Endovascular gelfoam is mandatory for a high-quality trauma service, and this study shows that it is safe to use intentionally in the endovascular space. Companies should work with interventional radiologists, sharing and collaborating to ensure positive outcomes for patients.
EFTA: An Efficient and Fault-Tolerant Data Aggregation Scheme without TTP in Smart Grid
Authors: Mei Xianyun , Wang Liangliang , Qin Baodong , Zhang Kai , Long Yu
Published: February 2024

With the rapid construction and implementation of smart grid, lots of studies have been conducted to explore how to ensure the security of information privacy. At present, most privacy-preserving data aggregation schemes in smart grid achieve privacy data protection through homomorphically encrypted data aggregation. However, these data aggregation schemes tend to rely on a trusted third party (TTP), and fail to efficiently handle the case of a meter failure. Besides, they are less flexible for overall user management, and resistance to collusion attacks needs to be improved. In this paper, we propose an efficient and robust privacy-preserving data aggregation scheme without TTP, called EFTA. Overall, the scheme eliminates the reliance on a TTP, combines with Shamir threshold secret sharing scheme to increase overall fault tolerance, supports flexible and dynamic user management, and effectively defends against entity initiated collusion attacks. According to security and performance analysis results, the scheme proposed in this paper meets the multiple security requirements of smart grid, and is more efficient in terms of overall overhead compared to the existing privacy-preserving data aggregation schemes.
Subcutaneous Vedolizumab Treatment in a Real-World Inflammatory Bowel Disease Cohort Switched From Intravenous Vedolizumab: Eighteen-Month Prospective Follow-up Study
Authors: Wiken Thea H , Høivik Marte L , Anisdahl Karoline , Buer Lydia , Warren David J , Bolstad Nils , Hagen Milada , Moum Bjørn A , Medhus Asle W
Published: February 2024

Background

Vedolizumab has since 2021 been available as a subcutaneous formulation. We aimed to assess 18-month drug persistence and possible predictive factors associated with discontinuation, safety, serum drug profile, drug dosing, and disease activity in a real-world cohort of patients with inflammatory bowel disease switched from intravenous to subcutaneous vedolizumab maintenance treatment.

Methods

Eligible patients were switched to subcutaneous vedolizumab and followed for 18 months or until discontinuation of subcutaneous treatment. Data on preferred route of administration, adverse events, drug dosing, serum-vedolizumab, disease activity, fecal calprotectin, and C-reactive protein were collected. Persistence was described using Kaplan–Meier analysis. The impact of clinical and biochemical variables on persistence was analyzed with Cox proportional hazard models.

Results

We included 108 patients, and the estimated 18-month drug persistence was 73.6% (95% CI [64.2–80.1]). Patients in clinical remission at switch were less likely to discontinue SC treatment (HR = 0.34, 95% CI [0.16–0.73], P = .006), and patients favoring intravenous treatment at switch were almost 3 times more likely to discontinue (HR = 2.78, 95% CI [1.31–5.90], P = .008). Four patients discontinued subcutaneous vedolizumab due to injection site reactions. At 18 months, 88% of patients administered subcutaneous vedolizumab with an interval of ≥ 14 days, and serum-vedolizumab was 39.1 mg/L. Disease activity was stable during follow-up.

Conclusions

Three of the four patients remained on subcutaneous vedolizumab after 18 months, a large proportion received treatment at standard dosing intervals, and disease activity remained stable. This indicates that switching from intravenous to subcutaneous vedolizumab treatment is convenient and safe.
Trapping strategy and diel periodicity affect capture rate ofHalyomorpha halys(Hemiptera: Pentatomidae) in agroecosystems
Authors: Tillman P Glynn , Grabarczyk Erin E , Kesheimer Katelyn A , Cottrell Ted
Published: February 2024

The polyphagous pest, Halyomorpha halys (Stål) (Hemiptera: Pentatomidae), damages fruit in orchards and field crops and is often found within nearby woodlands. Pheromone-baited traps can be used to monitor H. halys. However, the efficiency of trapping H. halys may vary depending on trapping strategy (live vs. dead capture), location (ground or canopy), and diel periodicity of captures. We compared H. halys capture within fruiting hosts for: (i) live and kill traps on the ground vs. traps in the canopy of black cherry (Prunus serotina Ehrh.) (Rosales: Rosaceae), sugarberry (Celtis laevigata Willdenow) (Rosales: Cannabaceae), and pecan (Carya illinoinensis (Wangenh.) K. Koch) (Fagales: Juglandaceae) trees, (ii) ground and canopy-live traps in sassafras (Sassafras albidum (Nutt.) Nees) (Laurales: Lauraceae), and (iii) whether diel periodicity was detected for live capture in sassafras and cotton. More H. halys adults and nymphs were captured in kill traps than in live traps. More nymphs were captured in kill traps in black cherry and sugarberry on the ground than in the canopy. Live adult capture was significantly greater in sassafras and pecan canopies than on the ground. In cotton and sassafras, more live adults were captured from 8 PM—noon, with the fewest captured from noon—6 PM. A better understanding of stink bug activity in the field allows for improved trapping and, possibly, improved timing of treatment applications.
Efficacy and safety of oral anticoagulants according to kidney function among patients with atrial fibrillation
Authors: Binding Casper , Blanche Paul , Lip Gregory Y H , Kamper Anne-Lise , Lee Christina J Y , Staerk Laila , Gislason Gunnar , Torp-Pedersen Christian , Olesen Jonas Bjerring , Bonde Anders Nissen
Published: February 2024

Background and aims

Patients with severely reduced kidney function have been excluded from randomized controlled trials and data on the safety and efficacy of direct oral anticoagulants (DOACs) according to kidney function remain sparse. The aim was to evaluate the safety and efficacy of the DOACs across subgroups of kidney function.

Methods

Using multiple Danish nationwide registers and laboratory databases, we included patients initiated on oral anticoagulants (OACs) with atrial fibrillation and available creatinine level and followed patients for 2 years to evaluate occurrence of stroke/thromboembolism (TE) and major bleeding.

Results

Among 26 686 included patients, 3667 (13.7%) had an estimated glomerular filtration rate (eGFR) of 30–49 mL/min/1.73 m2 and 596 (2.2%) had an eGFR below 30 mL/min/1.73 m2. We found no evidence of differences regarding the risk of stroke/TE between the OACs (P-value interaction >0.05 for all). Apixaban was associated with a lower 2-year risk of major bleeding compared to vitamin K antagonists (VKA) [hazard ratio 0.79, 95% confidence interval (CI) 0.67–0.93], and the risk difference was significantly larger among patients with reduced kidney function (P-value interaction 0.018). Rivaroxaban was associated with a higher risk of bleeding compared to apixaban (hazard ratio 1.78, 95%CI 1.32–2.39) among patients with eGFR 30–49 mL/min/1.73 m2.

Conclusions

Overall, we found no differences regarding the risk of stroke/TE, but apixaban was associated with a 21% lower relative risk of major bleeding compared to VKA. This risk reduction was even greater when comparing apixaban to VKA among patients with eGFR 15–30 mL/min/1.73 m2, and when comparing apixaban to dabigatran and rivaroxaban among patients with eGFR 30–49 mL/min/1.73 m2.
‘I drew it in as simply as my breath’: absence, presence, and ideal beauty in Dante Gabriel Rossetti’s Sibylla Palmifera (1866–70) ‘double work of art’
Authors: Dunn-McAfee Nicholas
Published: February 2024

Dante Gabriel Rossetti’s Sibylla Palmifera or Soul's Beauty (1866–1870) ‘double work of art’ is one of his most recognizable pictures and anthologized poems. His visual-verbal ‘double works’ – typically painting-sonnet composites that share a title, comment on each other, and elaborate on a joint subject – remain, however, understudied. Their cross-medium composition presents a challenge to segregated art-historical and literary scholarship. Almost all studies on these picture-word composites take a monodisciplinary approach and predominantly address a single component: the picture or the poem. Engagement with the other component is either cursory or non-existent. In (re)constructing the Sibylla ‘double works’, this essay argues for a renewed understanding of the viewer-reader and viewing-reading. The formation of the visual-verbal exchange at the heart of the ‘double work’ also results in problematic gaps, dissonances, and ruptures in visual-verbal representation. In a manner yet to be addressed in scholarship, this essay demonstrates how Rossetti exploits both alignment and divergence in the Sibylla ‘double work’ to inform and structure the viewer-reader’s encounter with the absence and presence generated by ideal beauty. By reassessing the wider relationship between (and experience of) picture and word, this essay situates the ‘double work’ form at the centre of image-text studies – and exposes the challenge that they present to disparate scholarship and methodologies.
Novel strains of Actinobacteria associated with neotropical social wasps (Vespidae; Polistinae, Epiponini) with antimicrobial potential for natural product discovery
Authors: Chavarría-Pizarro Laura , Núñez-Montero Kattia , Gutiérrez-Araya Mariela , Watson-Guido William , Rivera-Méndez William , Pizarro-Cerdá Javier
Published: February 2024

Antimicrobial resistance has been considered a public health threat. The World Health Organization has warned about the urgency of detecting new antibiotics from novel sources. Social insects could be crucial in the search for new antibiotic metabolites, as some of them survive in places that favor parasite development. Recent studies have shown the potential of social insects to produce antimicrobial metabolites (e.g. ants, bees, and termites). However, most groups of social wasps remain unstudied. Here, we explored whether Actinobacteria are associated with workers in the Neotropical Social Wasps (Epiponini) of Costa Rica and evaluated their putative inhibitory activity against other bacteria. Most isolated strains (67%) have antagonistic effects, mainly against Bacillus thuringensis and Escherichia coli ATCC 25992. Based on genome analysis, some inhibitory Actinobacteria showed biosynthetic gene clusters (BGCs) related to the production of antimicrobial molecules such as Selvamycin, Piericidin A1, and Nystatin. The Actinobacteria could be associated with social wasps to produce antimicrobial compounds. For these reasons, we speculate that Actinobacteria associated with social wasps could be a novel source of antimicrobial compounds, mainly against Gram-negative bacteria.
DHCR24 Insufficiency Promotes Vascular Endothelial Cell Senescence and Endothelial Dysfunction via Inhibition of Caveolin-1/ERK Signaling
Authors: Li Han , Yang Zhen , Liang Wukaiyang , Nie Hao , Guan Yuqi , Yang Ni , Ji Tianyi , Liu Yu , Huang Yi , Zhang Le , Yan Jinhua , Zhang Cuntai
Published: February 2024

Endothelial cells (ECs) senescence is critical for vascular dysfunction, which leads to age-related disease. DHCR24, a 3β-hydroxysterol δ 24 reductase with multiple functions other than enzymatic activity, has been involved in age-related disease. However, little is known about the relationship between DHCR24 and vascular ECs senescence. We revealed that DHCR24 expression is chronologically decreased in senescent human umbilical vein endothelial cells (HUVECs) and the aortas of aged mice. ECs senescence in endothelium-specific DHCR24 knockout mice was characterized by increased P16 and senescence-associated secretory phenotype, decreased SIRT1 and cell proliferation, impaired endothelium-dependent relaxation, and elevated blood pressure. In vitro, DHCR24 knockdown in young HUVECs resulted in a similar senescence phenotype. DHCR24 deficiency impaired endothelial migration and tube formation and reduced nitric oxide (NO) levels. DHCR24 suppression also inhibited the caveolin-1/ERK signaling, probably responsible for increased reactive oxygen species production and decreased eNOS/NO. Conversely, DHCR24 overexpression enhanced this signaling pathway, blunted the senescence phenotype, and improved cellular function in senescent cells, effectively blocked by the ERK inhibitor U0126. Moreover, desmosterol accumulation induced by DHCR24 deficiency promoted HUVECs senescence and inhibited caveolin-1/ERK signaling. Our findings demonstrate that DHCR24 is essential in ECs senescence.
Systematic adjustment of root dimensions to cusp size in aortic valve repair: a computer simulation
Authors: Marom Gil , Weltert Luca Paolo , Raanani Ehud , Chirirchilli Ilaria , Giebels Christian , Irace Francesco Giosuè , De Paulis Ruggero , Schäfers Hans-Joachim
Published: February 2024

OBJECTIVES

Aortic valve repair requires the creation of a normal geometry of cusps and aortic root. Of the different dimensions, geometric cusp height is the most difficult to change while annular and sinotubular dimensions can be easily modified. The objective of this study was to investigate, by computer simulation, ideal combinations of annular and sinotubular junction size for a given geometric height.

METHODS

Based on a literature review of anatomical data, a computational biomechanics model was generated for a tricuspid aortic valve. We aimed to determine the ideal relationships for the root dimensions, keeping geometric height constant and creating different combinations of the annular and sinotubular junction dimensions. Using this model, 125 virtual anatomies were created, with 25 different combinations of annulus and sinotubular junction. Effective height, coaptation height and mechanical cusp stress were calculated with the valves in closed configuration.

RESULTS

Generally, within the analysed range of geometric heights, changes to the annular diameter yielded a stronger impact than sinotubular junction diameter changes for optimal valve configuration. The best results were obtained with the sinotubular junction being 2–4 mm larger than the annulus, leading to higher effective height, normal coaptation height and lower stress. Within the range tested, stenosis did not occur due to annular reduction.

CONCLUSIONS

In tricuspid aortic valves, the geometric height can be used to predict ideal post-repair annular and sinotubular junction dimensions for optimal valve configuration. Such an ideal configuration is associated with reduced cusp stress.
Assessment of the Zoonotic Potential of Atypical Scrapie Prions in Humanized Mice Reveals Rare Phenotypic Convergence but Not Identity With Sporadic Creutzfeldt-Jakob Disease Prions
Authors: Marín-Moreno Alba , Reine Fabienne , Herzog Laetitia , Aron Naima , Jaffrézic Florence , Vilotte Jean-Luc , Rezaei Human , Andréoletti Olivier , Martin Davy , Béringue Vincent
Published: February 2024

Background

Atypical/Nor98 scrapie (AS) is an idiopathic infectious prion disease affecting sheep and goats. Recent findings suggest that zoonotic prions from classical bovine spongiform encephalopathy (C-BSE) may copropagate with atypical/Nor98 prions in AS sheep brains. Investigating the risk AS poses to humans is crucial.

Methods

To assess the risk of sheep/goat-to-human transmission of AS, we serially inoculated brain tissue from field and laboratory isolates into transgenic mice overexpressing human prion protein (Met129 allele). We studied clinical outcomes as well as presence of prions in brains and spleens.

Results

No transmission occurred on the primary passage, with no clinical disease or pathological prion protein in brains and spleens. On subsequent passages, 1 isolate gradually adapted, manifesting as prions with a phenotype resembling those causing MM1-type sporadic Creutzfeldt-Jakob disease in humans. However, further characterization using in vivo and in vitro techniques confirmed both prion agents as different strains, revealing a case of phenotypic convergence. Importantly, no C-BSE prions emerged in these mice, especially in the spleen, which is more permissive than the brain for C-BSE cross-species transmission.

Conclusions

The results obtained suggest a low zoonotic potential for AS. Rare adaptation may allow the emergence of prions phenotypically resembling those spontaneously forming in humans.
A Vicsek-type model of confined cancer cells with variable clustering affinities
Authors: Kirchner Zachary , Geohagan Anna , Truszkowska Agnieszka
Published: February 2024

Clustering of cells is an essential component of many biological processes from tissue formation to cancer metastasis. We develop a minimal, Vicsek-based model of cellular interactions that robustly and accurately captures the variable propensity of different cells to form groups when confined. We calibrate and validate the model with experimental data on clustering affinities of four lines of tumor cells. We then show that cell clustering or separation tendencies are retained in environments with higher cell number densities and in cell mixtures. Finally, we calibrate our model with experimental measurements on the separation of cells treated with anti-clustering agents and find that treated cells maintain their distances in denser suspensions. We show that the model reconstructs several cell interaction mechanisms, which makes it suitable for exploring the dynamics of cell cluster formation as well as cell separation.

Insight: We developed a model of cellular interactions that captures the clustering and separation of cells in an enclosure. Our model is particularly relevant for microfluidic systems with confined cells and we centered our work around one such emerging assay for the detection and research on clustering breast cancer cells. We calibrated our model using the existing experimental data and used it to explore the functionality of the assay under a broader set of conditions than originally considered. Future usages of our model can include purely theoretical and computational considerations, exploring experimental devices, and supporting research on small to medium-sized cell clusters.
Biology, distribution, and conservation of the Gamilaroi crayfish Euastacus gamilaroi Morgan, 1997 (Decapoda: Astacidea: Parastacidae), a freshwater crayfish from New South Wales, Australia
Authors: McCormack Robert B , Whiterod Nick S
Published: February 2024

Euastacus gamilaroi Morgan 1997, the Gamilaroi crayfish, was initially described based on specimens collected in 1954 from Hanging Rock, New South Wales, but since then scant subsequent records hinder conservation of this endangered species. Extensive sampling during 2006–2023 delineated the distribution, habitat preferences, biological traits, and conservation status of the species. Together with concurrent molecular taxonomic analyses were extend the species range from headwater regions of highland streams above 960 m altitude of Burrows Creek to include highland streams of Duncan and Dungowan creeks (Peel-Namoi River/western drainage) and Tomalla, Back, and Ben Halls creeks (Barnard-Manning River/eastern drainage). We provide information on the distribution, biology, and ecological associations of the species. Results advocate for the classification of E. gamilaroi as an endangered species, recognizing its distinctive ecological niche and its status as a climate refugee, aiming to protect this rare species from climate-related challenges. We also present a taxonomic key differentiating E. gamilaroi from other species of Parastacidae in the region.
A method for sampling parasitized Drosophila suzukii (Diptera: Drosophilidae) puparia from soil
Authors: Capko Clarissa , Thiessen Jason , Harach Lana , Fraser Jessica L , Franklin Michelle T , Abram Paul K
Published: February 2024

Methods to measure the diversity and biological control impact of parasitoids for the control of spotted-wing drosophila, Drosophila suzukii (Matsumura) (Diptera: Drosophilidae) are being developed in support of biological control programs around the world. Existing methods to determine parasitism levels and parasitoid species composition focus on sampling D. suzukii within fresh and rotting fruit. However, many D. suzukii pupate in the soil or in dropped fruit, where additional parasitism could occur and where their parasitoids are thought to overwinter. Here we introduce a method for extracting parasitized D. suzukii puparia from the soil through a sieve and flotation system, allowing for effective collection of puparia, from which parasitoids can then be reared. Although the method considerably underestimates the absolute number of puparia in soil samples, it nonetheless yields a high number of puparia relative to sampling effort and provides a robust estimate of the relative abundance of puparia among samples. Using this method, we confirmed that at least 5 species of parasitoids, including some that have rarely been detected in past studies, overwinter in their immature stages inside D. suzukii puparia in south coastal British Columbia, Canada. The ability to sample puparia from the soil will lead to a more comprehensive view of both D. suzukii and parasitoid abundance throughout the season, help confirm parasitoid establishment following intentional releases, and provide a way to measure the diversity of parasitoid species and potential interactions among parasitoids (e.g., hyper- or klepto-parasitism) that may often occur on the soil surface.
Parasitoid–host interaction behaviors in relation to host stages in the Tamarixia triozae (Hymenoptera: Eulophidae)–Bactericera cockerelli (Hemiptera: Triozidae) system
Authors: Chen Chen , He Xiong Z , Zhou Peng , Wang Qiao
Published: February 2024

Females of host-feeding parasitic wasps often partition hosts of different stages for feeding and parasitization, but the underlying behavioral mechanisms are largely unknown, making it difficult to evaluate parasitoid–host interactions and their effects on biological control success. Tamarixia triozae (Burks) is an ectoparasitoid of tomato-potato psyllid Bactericera cockerelli (Šulc), which utilizes nymphs and kills them both by parasitization and host feeding. In this study, we exposed female wasps to 1st- to 5th-instar psyllid nymphs simultaneously and made 13-h continuous video recording of parasitoid–host interactions. We then quantified host stage-dependent handling time for feeding and oviposition and behaviors of parasitoid attacks and host defenses from encountering to successful feeding and oviposition. Female wasps were more likely to encounter and evaluate older hosts. However, the encounter and evaluation did not necessarily result in the success of feeding and oviposition. Our findings suggest that (i) T. triozae continues to assess the host using its ovipositor after the evaluation phase, (ii) females prefer the mid-aged hosts for feeding piercing and feeding and the later instars for oviposition probing and oviposition, (iii) the combination of stage-specific host nutrition value, integument thickness and defense behavior determines the success of feeding attacks, and (iv) the optimal host resource for parasitoid offspring fitness defines host stage selection for oviposition. This study contributes to our understanding of parasitoid–host interactions and mechanisms behind host stage selections.
The Simple Math of Royalties and Drug Competition During the 180-Day Generic Exclusivity Period
Authors: Drake Keith M , McGuire Thomas G
Published: February 2024

In drug patent litigation settlements, the plaintiff brand commonly licenses the defendant generic to sell before patent expiry. Some agreements require the generic to pay the brand royalties. Despite the superficial flow of payments, royalty terms may function as part of an anticompetitive “reverse payment” made to the generic in exchange for delayed entry. Typically, the brand launches its own authorized generic (AG) during the first-to-file generic’s 180-day exclusivity period so initially there are two generic competitors. A royalty structure that deters the brand’s AG launch reduces the number of entrants to one, conveying net value to the generic by allowing it to capture the entire generic market, potentially inducing it to delay its entry. Royalties usually have no place in a brand–generic agreement between rational actors. However, our simple model shows that when royalties are conditioned on the brand’s AG launch, a range of royalty rates exists that conveys net value to the generic by deterring the brand from rationally introducing an AG. Royalty terms that are conditioned on the brand’s AG launch thus raise a red flag that the agreement is a pay-for-delay. Although the numbers are small, publicly available materials on industry experience corroborate this conclusion.
Pneumoperitoneum and Chilaiditi syndrome: navigating a diagnostic conundrum
Authors: Bourakkadi Idrissi Mehdi , Dkhissi Younes
Published: February 2024

Chilaiditi sign represents a rare condition marked by the interposition of the bowel between the diaphragm and liver, mimicking pneumoperitoneum on radiological imaging. The syndrome manifests with gastrointestinal symptoms and is often confused with more serious conditions. This case report presents a rare instance of Chilaiditi syndrome, initially misdiagnosed as pneumoperitoneum based on chest X-ray findings. The patient, a 61-year-old woman, arrived at the emergency department complaining of acute epigastric pain. Initial tests, including a chest X-ray, suggested pneumoperitoneum, but a subsequent contrast-enhanced abdominal CT-scan revealed the interposition of the right colon between the liver and diaphragm, characteristic of Chilaiditi sign. The patient’s symptoms, including abdominal pain and diarrhea, were consistent with Chilaiditi syndrome. The patient was treated successfully with intravenous antibiotics and fluids, showing significant improvement within 48 hours. The report highlights the importance of differentiating Chilaiditi syndrome from other acute abdominal conditions to avoid unnecessary surgical intervention.
Philosophical Protreptic and the Preface to Luke’s Gospel
Authors: Hubbard Jeffrey M
Published: February 2024

This article compares the preface of Luke’s Gospel to Philo’s preface to De Abrahamo and Arrian’s preface to his arrangement of the sayings of Epictetus. Scholars have usually sought ancient comparanda to Luke’s preface in order to identify the Gospel’s genre. This study moves beyond this traditional question of form (‘What ancient works bear the closest resemblance to the structure of Luke 1:1–4?’) and on to the question of function. The selected works of Philo and Arrian participate in different genres, but both belong to the rhetorical category of ‘philosophical protreptic’, a piece of writing intended to compel the reader towards a particular moral vision. I argue that Luke’s preface exhibits unexplored similarities with the prefaces of Arrian and Philo and can itself be fruitfully read as a kind of philosophical protreptic. This has implications for how we theorize about Luke’s audience and social situation.
Broad-band noise and quasi-periodic oscillation characteristics of the X-ray pulsar RX J0440.9+4431
Authors: Li P P , Tao L , Ma R C , Ge M Y , Zhao Q C , Zhao S J , Zhang L , Bu Q C , Kong L D , Tuo Y L , Ji L , Zhang S , Qu J L , Zhang S N , Huang Y , Ma X , Ye W T , Shui Q C
Published: February 2024

We present a comprehensive timing analysis on the Be/X-ray binary pulsar RX J0440.9+4431 using observations from NICER and Insight-HXMT during the 2022–2023 outburst. The power density spectrum (PDS) of RX J0440.9+4431 exhibits typical aperiodic variability in X-ray flux across a wide frequency range. During a supercritical accretion state, we detect quasi-periodic oscillations (QPOs) at 0.2–0.5 Hz in the light curves of five pulses for RX J0440.9+4431. The observed QPOs manifest during flares, while the flares appear at the peaks of the pulse profiles on a time-scale of seconds and are primarily caused by an increase in hard photons. These flares can be explained by increased material ingestion in the accretion column at a fixed phase, primarily generating hard photons. Alternatively, an increase in accretion rate, independent of phase, may result in highly beamed hard photons within the accretion column, causing the flares. We argue the origin of QPOs to instabilities within the accretion flow. Additionally, we find that the break frequencies in the noise power spectra align well with $\propto L_{\mathrm{x}}^{3 / 7}$ across three orders of magnitude in the luminosity, which points to a relatively strong magnetic field in RX J0440.9+4431, estimated to be ~1013 G.
Revisiting the TeV flare of PKS 2155-304 in 2006
Authors: Tan Hong-Bin , Liu Ruo-Yu , Böttcher Markus
Published: February 2024

Blazars, a subclass of active galactic nuclei (AGN), are known to be bright γ-ray sources, frequently exhibiting active (flaring) periods. Blazar PKS 2155-304 is a high synchrotron-peaked BL Lac object located at redshift z = 0.116. On 2006 July 28, an extremely remarkable outburst of VHE γ-ray emission from this blazar was reported by the H.E.S.S. experiment, with an average flux more than 10 times the low-state level. The variability time-scale of this extraordinary flare was as short as approximately 200 s. In order to guarantee the transparency of the emission region for TeV photons, the fast variability demands an extremely high Doppler factor δD > 50 of the jet within the classical one-zone model, leading to the so-called ‘Doppler factor crisis’. Here, we demonstrate that the stochastic dissipation model, which is a multiblob scenario for blazars, can self-consistently explain the giant TeV flares of PKS 2155-304 and the low-state emission before and after the flares, in terms of both multiwavelength spectral and variability characteristics. The required Doppler factor in this model can be as low as 20, which is a reasonable and typical value for blazar jets. The obtained model parameters may shed some light on the physical properties of the relativistic jet.