bluuebunny/crossref_metadata_2025 huggingface dataset:
Immunotherapy-mediated myocarditis and concurrent vasospastic angina in a patient with established ischaemic heart disease: a case report
Authors: Ko Jefferson , Wardill Thomas , Tan Sean , Ramkumar Satish
Published: November 2024

Background

Immunotherapy has become a pillar of modern oncological management but is associated with significant immunotherapy-related adverse events (IRAEs). While myocarditis is a prominent IRAE which clinicians are increasingly aware of, immunotherapy-related coronary vasospasm is far less appreciated and can be especially difficult to elucidate in pre-existing coronary artery disease. This case demonstrates the approach to diagnosis and management of multiple cardiovascular and non-cardiovascular IRAEs.

Case summary

A 57-year-old male with a history of metastatic melanoma on combined immunotherapy and ischaemic heart disease with multiple previous percutaneous coronary interventions presented with typical chest pain and troponin rise. Differential diagnoses for this presentation included a non-ST elevation myocardial infarction, myocarditis, and coronary vasospasm. Coronary angiogram did not reveal any new significant obstructive coronary artery disease while cardiac MRI did not reveal any radiological features consistent with myocarditis. However, empirical treatment for IRAEs resulted in both clinical and biochemical improvement and ability to discharge the patient on steroids and coronary vasodilators, having been GTN-infusion dependent as an inpatient.

Discussion

Cardiovascular IRAEs are important to be aware of when managing patients on immunotherapy and more than one IRAE can occur concurrently. Given the caveats of non-invasive imaging and invasive nature of endomyocardial biopsy, the clinical history is key in establishing these crucial diagnoses which will significantly impact ongoing oncological management.
High internal phase Pickering emulsions stabilized by walnut protein–galactooligosaccharide nanoparticles: effect of cinnamon oil entrapment
Authors: Qin Yizhen , Liu Jiongna , Yang Xiaoqin , Zhao Yueliang , Fan Fangyu
Published: November 2024

Objectives

Walnut protein–galactooligosaccharide (WalPI–GOS) nanoparticles were used to prepare high internal phase Pickering emulsions (HIPPEs).

Materials and Methods

The entrapment properties of HIPPEs for cinnamon oil were investigated by varying the volume ratios of camellia and cinnamon oils (cinnamon oil contents: 0%, 2.5%, 5.0%, 10%, 15%, and 20%), and the droplet size, rheological properties, Raman spectroscopy results, microstructure, thermal stability, storage stability, and antioxidant activity of HIPPEs were determined.

Results

The droplet size of HIPPEs increased with increasing cinnamon oil content. Among the samples, HIPPEs enriched with the cinnamon oil content of 10% had the highest storage modulus, loss modulus, and apparent viscosity (13.64 Pa·s). However, the thixotropic recovery ability of HIPPEs decreased with the increase in cinnamon oil content. Raman spectroscopy and microstructural analysis revealed that proteins covalently cross-linked with cinnamaldehyde to form a three-dimensional network structure, which showed the highest stability when the cinnamon oil content was 10%. HIPPEs exhibited high thermal stability without delamination after heating, as well as good storage stability without delamination or discoloration after 15 d of storage at 25 °C and 50 °C. Among the samples, HIPPEs enriched with 10% cinnamon oil had the lowest peroxide and malondialdehyde values during storage. The addition of cinnamon oil significantly enhanced the antioxidant activity of HIPPEs.

Conclusions

The best overall performance of HIPPEs was achieved at a cinnamon oil content of 10%. This result provides a theoretical foundation for the development of WalPI and the application of cinnamon oil in food, as well as a theoretical basis for the development of novel food delivery systems.
Overview of the Saccharomyces cerevisiae population structure through the lens of 3,034 genomes
Authors: Loegler Victor , Friedrich Anne , Schacherer Joseph
Published: November 2024

With the rise of high-throughput sequencing technologies, a holistic view of genetic variation within populations—through population genomics studies—appears feasible, although it remains an ongoing effort. Genetic variation arises from a diverse range of evolutionary forces, with mutation and recombination being key drivers in shaping genomes. Studying genetic variation within a population represents a crucial first step in understanding the relationship between genotype and phenotype and the evolutionary history of species. In this context, the budding yeast Saccharomyces cerevisiae has been at the forefront of population genomic studies. In addition, it has a complex history that involves adaptation to a wide range of wild and human-related ecological niches. Although to date more than 3,000 diverse isolates have been sequenced, there is currently a lack of a resource bringing together sequencing data and associated metadata for all sequenced isolates. To perform a comprehensive analysis of the population structure of S. cerevisiae, we collected genome sequencing data from 3,034 natural isolates and processed the data uniformly. We determined ploidy levels, identified single nucleotide polymorphisms (SNPs), small insertion–deletions (InDels), copy number variations (CNVs), and aneuploidies across the population, creating a publicly accessible resource for the yeast research community. Interestingly, we showed that this population captures ∼93% of the species diversity. Using neighbor-joining and Bayesian methods, we redefined the populations, revealing clustering patterns primarily based on ecological origin. This work represents a valuable resource for the community and efforts have been made to make it evolvable and integrable to future yeast population studies.
Comparative genomics reveals putative copper tolerance genes in a Fusarium oxysporum strain
Authors: Ragasa Lorenz Rhuel P , Cuomo Christina A , del Rosario Ricardo C H , Velarde Michael C
Published: November 2024

Copper has been widely used as a main component in fungicides due to its versatility and effectivity. However, copper contamination from the environment creates selective pressure for the emergence of copper-tolerant pathogenic fungal strains that may proliferate and further cause damage to important agricultural crops. Although some studies focused on specific cellular mechanisms of copper tolerance, comprehensive genomic data are lacking. Here, we examined the genes potentially involved in copper tolerance by conducting a comparative analysis of newly sequenced genomes of 2 Fusarium oxysporum strains, IB-SN1W (copper-tolerant) and Foc-3429 (copper-sensitive), with other Fusarium species. Whole-genome assembly and annotation identified 10 core chromosomes shared between the 2 strains. Protein prediction revealed 16,894 and 15,420 protein-coding genes for IB-SN1W and Foc-3429, respectively. There are 388 unique genes in IB-SN1W not found in Foc-3429, potentially contributing to copper tolerance. Furthermore, the identification of synteny between the 2 strains, including the analysis of orthologous genes within the Fusarium genus, confirmed the presence of accessory chromosomes that are specific to IB-SN1W, accounting for 13% of the genome. These accessory chromosomes consist of genes associated with cation transporter activity, vacuole, copper oxidases, and copper transporters which shed light on the potential mechanism of copper tolerance in this strain. Additionally, a region within an accessory chromosome contains a high density of copper-related genes, raising the possibility that horizontal transfer of these chromosomes may contribute to copper tolerance.
Imaging moveout in acoustic factorized orthorhombic media
Authors: Galtung Kristoffer Tesdal , Stovas Alexey
Published: November 2024

In velocity model building using full waveform inversion, diving waves are a source of the low-frequency information needed to update the low- to intermediate wavenumber components in the velocity model. Because full waveform inversion is a highly nonlinear optimization problem attempting to fit the information from the whole wavefield, it is prone to get stuck in local minimums and experience cycle skipping if the initial model does not contain accurate enough information about the low-wavenumbers to constrain the kinematics. Such initial velocity models will typically be estimated using alternative inversion methods that only apply information from parts of the wavefield in the forward modelling and recorded data. In migration velocity analysis, the unfocusing of the image, caused by inconsistency in the kinematics of reflected waves, is measured and is used to update the velocity model by applying differential semblance optimization. The same concept is applicable when using information from diving waves. For diving waves, little is known about the focusing behaviour, also known as imaging moveout, especially in the presence of azimuthal anisotropy, such as orthorhombic anisotropy, which is a good approximation for volcanic plains and sedimentary basins. Obtaining more knowledge about the focusing behaviour of diving waves for this type of anisotropy may help when choosing parameters to invert during inversion that yield a low trade-off between the parameters. Here, we derive approximate series-based equations describing the imaging moveout of diving qP waves in acoustic factorized orthorhombic anisotropic media. Due to the complexity of the analytical solutions for diving wave properties in such models, we find a vertical transverse isotropic type of simplification that manages to conserve the curvature and horizontal velocity of the diving qP wave. The accuracy of the simplified expressions is compared to the exact form and found to yield small errors. To verify the validity of the derived equations for imaging moveout, we compare the generated surfaces with images containing the shape of the unfocusing obtained using reverse time migration, showing a good fit. Of the anisotropic parameters defining the acoustic factorized orthorhombic model, the $\epsilon _1$ and $\epsilon _2$ parameters have the largest influence on the shape of the surface. The anelliptical parameters are shown only to induce minimal changes. Our method to obtain the series expressions describing the imaging moveout in the acoustic factorized orthorhombic model is also applicable to higher symmetry special cases of orthorhombic anisotropy by setting appropriate conditions. Here, this is demonstrated by additionally finding an approximate series expression describing the imaging moveout in acoustic factorized vertical transversely isotropic media, yielding a good match with the image obtained from reverse time migration.
Transcription factors MdEIL1 and MdHY5 integrate ethylene and light signaling to promote chlorophyll degradation in mature apple peels
Authors: Li Li-Xian , Yang San-Kui , Fang Yue , Wu Zhi-Meng , Ma Hua-Ying , Wang Shuo , Li Dan , Feng Shou-Qian
Published: November 2024

Although it is well-established that ethylene and light stimulate the process of chlorophyll degradation in mature apple peels, there is still a need for further exploration of the molecular mechanisms that regulate this process. This study identified MdEIL1 and MdHY5 as promoters of the chlorophyll degradation pathway in apple peels, activated by ethylene and light. Physiological and molecular tests demonstrated that MdEIL1 and MdHY5 are responsible for activating the expression of genes associated with chlorophyll degradation, including MdERF17, MdNYC1, MdPPH and MdPAO. Furthermore, the interaction between MdEIL1 and MdHY5 proteins enhances their regulatory activity on the target gene MdERF17. Moreover, MdEIL1 binds to the promoter of MdHY5, resulting in the upregulation of its expression, which is further enhanced in the presence of the MdEIL1-MdHY5 protein complex. These findings indicate that MdEIL1-MdHY5 module acts as positive regulator mediating ethylene and light signals that promote chlorophyll degradation in apple peels.
Feasibility, safety and quality of complex mitral valve repair in the early phase of a robotic surgery programme
Authors: Kobayashi Kei , Guo Yizhan , Rubino Thomas E , Ramirez Luis E , Waterford Stephen D , Sultan Ibrahim , Morell Victor D , Bonatti Johannes
Published: November 2024

OBJECTIVES

To evaluate the feasibility, safety and quality of robotic-assisted mitral valve repair in complex versus non-complex cases during the early phase of a programme.

METHODS

Since the programme launch in September 2021 until February 2024, 100 patients underwent robotic-assisted mitral valve repair. Of them, 21 patients had complex repairs, while 79 had non-complex repairs. The median age was 58 years for complex cases and 61 years for non-complex cases (P = 0.36).

RESULTS

Bileaflet prolapse was significantly more prevalent in the complex group (52.4% vs 12.7%, P < 0.001). Neochord placement (61.9% vs 13.9%, P < 0.001) and commissuroplasty (28.6% vs 5.1%, P = 0.005) were more frequent in the complex group. The complex group had longer cardiopulmonary bypass times (161 vs 141 min, P < 0.001), aortic cross-clamp times (123 vs 102 min, P < 0.001) and leaflet repair times (43 vs 24 min, P < 0.001). Second pump runs were required more often for complex cases (23.8% vs 3.8%, P = 0.01). All patients left the operating room with residual mitral regurgitation of mild or less. Fewer complex patients were extubated in the operating room (42.9% vs 70.9%, P = 0.02), yet hospital stay was similar (4 vs 4 days, P = 0.56). There were no significant differences in postoperative adverse events. There were no differences in mitral regurgitation of mild or less 4 weeks post-surgery (95.2% vs 98.7%, P = 0.47).

CONCLUSIONS

Complex mitral valve repair can be safely and effectively performed with robotic assistance, even in the early phase of a programme. Despite longer operative and ventilation times in the complex group, hospital stay and postoperative adverse events remained similar.
Transitive Phrasal Verbs in English–Chinese Learners’ Dictionaries: A Syntactic Perspective
Authors: Zhao Dan
Published: November 2024

This article explores the treatment of transitive phrasal verbs (TPVs) in English–Chinese learners’ dictionaries (ECLDs). Despite the syntactic and semantic complexities of TPVs, research on the systematic treatment of TPVs in ECLDs has been limited. By annotating syntactic structures, ECLDs can present the semantic and pragmatic characteristics of TPVs more accurately and assist learners in using appropriate syntactic structures to communicate deeper meanings in language output. Phrasal verbs (PVs) are a category of verb combinations with distinct syntactic structures, functioning as single-word lexical verbs despite being multiword verbs in form. A test administered to intermediate and advanced English learners revealed that Chinese EFL learners made frequent mistakes in using PVs, reflecting the confusion and uncertainty surrounding these structures. This paper presents a comparison of the different classifications of multiword verbs present in ECLDs, arguing that these variations have only further muddied the waters with relation to PVs. Based on an analysis of the unique syntactic features of PVs, it proposes that ECLDs can enhance English learners’ understanding of TPVs through the systematic use of tables, annotations, and examples.
Proposal of Patescibacterium danicum gen. nov., sp. nov. in the ubiquitous bacterial phylum Patescibacteriota phyl. nov.
Authors: Dutkiewicz Zuzanna , Singleton Caitlin M , Sereika Mantas , Villada Juan C , Mussig Aaron J , Chuvochina Maria , Albertsen Mads , Schulz Frederik , Woyke Tanja , Nielsen Per H , Hugenholtz Philip , Rinke Christian
Published: November 2024

Candidatus Patescibacteria is a diverse bacterial phylum that is notable for members with ultrasmall cell size, reduced genomes, limited metabolic capabilities, and dependence on other prokaryotic hosts. Despite the prevalence of the name Ca. Patescibacteria in the scientific literature, it is not officially recognized under the International Code of Nomenclature of Prokaryotes and lacks a nomenclatural type. Here, we rectify this situation by describing two closely related circular metagenome-assembled genomes and by proposing one of them (ABY1TS) to serve as the nomenclatural type for the species Patescibacterium danicumTS gen. nov., sp. nov. according to the rules of the SeqCode. Rank-normalized phylogenomic inference confirmed the stable placement of P. danicumTS in the Ca. Patescibacteria class ABY1. Based on these results, we propose Patescibacterium gen. nov. to serve as the type genus for associated higher taxa, including the phylum Patescibacteriota phyl. nov. We complement our proposal with a genomic characterization, metabolic reconstruction, and biogeographical analysis of Patescibacterium. Our results confirm small genome sizes (<1 Mbp), low GC content (>36%), and the occurrence of long gene coding insertions in the 23S rRNA sequences, along with reduced metabolic potential, inferred symbiotic lifestyle, and a global distribution. In summary, our proposal will provide nomenclatural stability to the fourth-largest phylum in the bacterial domain.
Low-calorie and high-protein diet has diverse impacts on the muscle, bone, and bone marrow adipose tissues
Authors: Romano Beatriz Coimbra , de Araújo Iana Mizumukai , Ribeiro Mariana S P , Parreiras e Silva Luciana T , Dick-de-Paula Ingid , Fukada Sandra Y , Porto Felipe Manoel , Jorgetti Vanda , de Assis Pereira Francisco , Elias Lucila Leico Kagohara , de Paula Francisco José Albuquerque
Published: November 2024

The present study was designed to evaluate the influence of a high-protein diet under conditions of calorie restriction (CR) in the muscle, adipose tissue, bone, and marrow adipose tissue (MAT). It included three groups of 20 female Wistar Hannover rats, fed with the following diets for 8 wk: control group (C) fed with an AIN93M diet, CR group (R) fed with an AIN-93M diet modified to 30% CR, and CR + high-protein group (H) fed with an AIN-93M diet modified to 30% CR with 40% protein. Body composition was determined by DXA. The femur was used for histomorphometry and the estimation of adipocytes. Microcomputed tomography (μCT) was employed to analyze the bone structure. Hematopoietic stem cells from the bone marrow were harvested for osteoclastogenesis. Body composition revealed that the gain in lean mass surpassed the increase in fat mass only in the H group. Bone histomorphometry and μCT showed that a high-protein diet did not mitigate CR-induced bone deterioration. In addition, the number of bone marrow adipocytes and the differentiation of hematopoietic stem cells into osteoclasts were higher in H than in the other groups. These results indicated that under CR, a high-protein diet was beneficial for muscle mass. However, as the μCT scanning detected significant bone deterioration, this combined diet might accentuate the detrimental effect on the skeleton caused by CR. Remarkably, the H group rats exhibited greater MAT expansion and elevated hematopoietic stem cell differentiation into osteoclasts than the CR and control counterparts. These data suggest that a high protein may not be an appropriate strategy to preserve bone health under CR conditions.
Electromagnetic–thermal–mechanical coupling analysis of bent rotor straightening via electromagnetic induction heating
Authors: Cho Hwangki , Park Jun Su , Han You Sung , Xu Guanshui , Sohn Dongwoo
Published: November 2024

Rotors of steam turbines in power plants can be locally deformed by undesired situations, such as rubbing between the rotors and stationary parts. A straightening process is required to correct bending without causing additional damage because a rotor bending displacement of ∼0.15 mm can stop turbine unit operation. In this study, a numerical framework was established to simulate the straightening process using electromagnetic induction heating, which is straightforward and economical among the methods for straightening bent rotors. The straightening process involves complex coupling of electromagnetic, thermal, and mechanical phenomena. For efficiency, sequential coupling was used in the simulations, dividing the multiphysics phenomena into electromagnetic–thermal and thermal–mechanical fields. The temperature distributions resulting from electromagnetic induction heating were calculated through two-way coupling of the electromagnetic–thermal analysis. The thermal deformations of the rotors were obtained by solving the coupled equations for the thermal field obtained from the electromagnetic–thermal analysis and the mechanical field. Using the established numerical framework, the thermal–mechanical behaviors and straightening mechanisms of bent rotors were investigated. Furthermore, the effects of process parameters, including the direction of gravity and heating and cooling conditions, on the straightening performance were determined. Appropriate parameters were identified to achieve the desired straightening performance with final bending displacements of <0.1 mm for bent rotors with initial bending displacements of 0.15–0.3 mm. For a rotor made of A182 F11 Class 2, the best straightening performance was obtained by heating the rotor to a maximum temperature of 650 °C for 20 h under insulation, followed by natural cooling. The simulation results revealed that the straightening performance can be improved when the rotor is rapidly heated to a high maximum temperature and cooled immediately, as long as the temperature conditions do not cause phase transformation or unintended plastic deformation of the bent rotors.
Tumor microtubes: A new potential therapeutic target for high-grade gliomas
Authors: Guo Yunzhu , Li Yangxin , Su Peng , Yan Min , Wang Ming , Li Shenjie , Xiang Wei , Chen Ligang , Dong Wei , Zhou Zhengjun , Zhou Jie
Published: November 2024

High-grade infiltrating gliomas are highly aggressive and fatal brain tumors that present significant challenges for research and treatment due to their complex microenvironment and tissue structure. Recent discovery of tumor microtubes (TMs) has provided new insights into how high-grade gliomas develop in the brain and resist treatment. TMs are unique, ultra-long, and highly functional membrane protrusions that form multicellular networks and play crucial roles in glioma invasiveness, drug resistance, recurrence, and heterogeneity. This review focuses on the different roles that TMs play in glioma cell communication, material transport, and tumor cell behavior. Specifically, non-connecting TMs primarily promote glioma invasiveness, likely related to their role in enhancing cell motility. On the other hand, interconnecting TMs form functional and communication networks by connecting with surrounding astrocytes and neurons, thereby promoting glioma malignancy. We summarize the factors that influence the formation of TMs in gliomas and current strategies targeting TMs. As the understanding of TMs advances, we are closer to uncovering whether they might be the long-sought Achilles’ heel of treatment-resistant gliomas. By delving deeper into TMs research, we hope to develop more effective therapeutic strategies for patients with malignant gliomas.
Machine learning applications to reveal the difference in Robinia pseudoacacia growth and its drivers on China’s Loess Plateau
Authors: Su Bingqian , Xu Wenlong , Su Zhuoxia , Shangguan Zhouping
Published: November 2024

The decline in tree growth has become a global issue. It is critically important to explore the factors affecting tree growth under the background of global climate change to understand tree growth models. A database was established based on Robinia pseudoacacia growth and its driving factors on China’s Loess Plateau. Linear regression and three machine learning methods, including support vector machine, random forest (RF) and gradient boosting machine were used to develop R. pseudoacacia growth models considering forest age, density, climate factors and topographic factors. The root mean square deviation method was adopted to quantitatively assess the relationship between tree growth and soil properties. The average tree height of R. pseudoacacia on the Loess Plateau was 8.8 ± 0.1 m, the average diameter at breast height (DBH) was 10.4 ± 0.1 cm and the average crown diameter was 3.2 ± 0.1 m. The RF model was a fast and effective machine learning method for predicting R. pseudoacacia growth, which showed the best simulation capability and could account for 67% of tree height variability and 55% of DBH variability. Model importance indicated that forest age and stand density were the main factors predicting R. pseudoacacia growth, followed by climate factors. The trade-off between R. pseudoacacia growth and soil properties revealed that soil texture and soil pH were the primary determinants of R. pseudoacacia growth in this region. Our synthesis provides a good framework for sustainable forest management in vulnerable ecological areas under future climate change.
Transgluteal approach for excision of pelvic lipoma causing sciatic pain
Authors: Gecheva Nia , Ilkov Petar , Uzunov Konstantin
Published: November 2024

Sciatic nerve pain, affecting 12%-27% of the general population, often arises from a myriad of etiologies due to the complex anatomy of the sciatic region. The intricate relationship between the sciatic nerve and surrounding structures in the pelvis poses significant challenges in both diagnosis and surgical management. We report two cases of adult female patients presenting with chronic sciatic pain, refractory to conservative treatment. Imaging studies, including magnetic resonance imaging and computed tomography, identified retroperitoneal lipomas exerting compressive effects on the sciatic nerve. Both patients underwent surgical excision of the lipomas via a transgluteal approach with complete resection of the benign tumors in both cases. The successful outcomes in these cases underscore the potential of the transgluteal approach as a novel and effective treatment strategy in the management of complex retroperitoneal tumors causing sciatic pain.
The salty emission of the intermediate-mass AGB star OH 30.1−0.7
Authors: Danilovich T , Richards A M S , Van de Sande M , Gottlieb C A , Millar T J , Karakas A I , Müller H S P , Justtanont K , Plane J M C , Etoka S , Wallström S H J , Decin L , Engels D , Groenewegen M A T , Kerschbaum F , Khouri T , de Koter A , Olofsson H , Paladini C , Stancliffe R J
Published: November 2024

We analyse continuum and molecular emission, observed with Atacama Large Millimetre/submillimetre Array, from the dust-enshrouded intermediate-mass asymptotic giant branch (AGB) star OH 30.1−0.7. We find a secondary peak in the continuum maps, ‘feature B’, separated by 4.6 arcsec from the AGB star, which corresponds to a projected separation of $1.8\times 10^{4}$ au, placing a lower limit on the physical separation. This feature is most likely composed of cold dust and is likely to be ejecta associated with the AGB star, though we cannot rule out that it is a background object. The molecular emission we detect includes lines of CO, SiS, CS, $\mathrm{SO}_2$, NS, NaCl, and KCl. We find that the NS emission is off centre and arranged along an axis perpendicular to the direction of feature B, indicative of a UV-emitting binary companion (e.g. a G-type main sequence star or hotter), perhaps on an eccentric orbit, contributing to its formation. However, the NaCl and KCl emission constrain the nature of that companion to not be hotter than a late B-type main-sequence star. We find relatively warm emission arising from the inner wind and detect several vibrationally excited lines of SiS ($\upsilon =1$), NaCl (up to $\upsilon =4$), and KCl (up to $\upsilon =2$), and emission from low-energy levels in the mid to outer envelope, as traced by $\mathrm{SO}_2$. The CO emission is abruptly truncated around 3.5 arcsec or 14 000 au from the continuum peak, suggesting that mass loss at a high rate may have commenced as little as 2800 yr ago.
Functional and molecular insights into the role of Sae2 C-terminus in the activation of MRX endonuclease
Authors: Colombo Chiara Vittoria , Casari Erika , Gnugnoli Marco , Corallo Flavio , Tisi Renata , Longhese Maria Pia
Published: November 2024

The yeast Sae2 protein, known as CtIP in mammals, once phosphorylated at Ser267, stimulates the endonuclease activity of the Mre11-Rad50-Xrs2 (MRX) complex to cleave DNA ends that possess hairpin structures or protein blocks, such as the Spo11 transesterase or trapped topoisomerases. Stimulation of the Mre11 endonuclease by Sae2 depends on a Rad50–Sae2 interaction, but the mechanism by which this is achieved remains to be elucidated. Through genetic studies, we show that the absence of the last 23 amino acids from the Sae2 C-terminus specifically impairs MRX-dependent DNA cleavage events, while preserving the other Sae2 functions. Employing AlphaFold3 protein structure predictions, we found that the Rad50–Sae2 interface involves not only phosphorylated Ser267 but also the phosphorylated Thr279 residue and the C-terminus of Sae2. This region engages in multiple interactions with residues that are mutated in rad50-s mutants, which are known to be specifically defective in the processing of Spo11-bound DNA ends. These interactions are critical for stabilizing the association between Sae2 and Rad50, thereby ensuring the correct positioning of Mre11 in its active endonucleolytic state.
OncoSplicing 3.0: an updated database for identifying RBPs regulating alternative splicing events in cancers
Authors: Zhang Yangjun , Liu Kai , Xu Zhenzhen , Li Bo , Wu Xiaoliang , Fan Ruixin , Yao Xiangyang , Wu Huahui , Duan Chen , Gong Yan , Chen Ke , Zeng Jin , Li Lu , Xu Hua
Published: November 2024

Alternative splicing (AS) is a crucial mechanism to regulate gene expression and protein complexity. RNA-binding proteins (RBPs) play an important role in regulating abnormal alternative splicing in cancers. However, few resources are available to identify specific RBPs responsible for regulating individual AS event. We have developed the OncoSplicing database for integrative analysis of clinically relevant alternative splicing events in TCGA cancers. Here, we further updated the OncoSplicing database by performing correlation analysis between the splicing and mRNA expression data from the TCGA cancers or GTEx tissues, mapping known RNA-binding motifs and eCLIP-seq peaks to all AS events, conducting splicing analysis for RNA-seq data from RBP perturbation experiments in the ENCODE project, and integrating exon and intron sequences for each AS event. With this updated database, users can easily identify potential RBPs responsible for the queried AS event and obtain sequences to design AS-specific primers and minigene constructs for experiment validation. Overall, compared to the previous version, the substantially updated OncoSplicing database (www.oncosplicing.com) offers a more valuable resource for users to identify RBPs responsible for regulating alternative splicing events in cancers.
The STRING database in 2025: protein networks with directionality of regulation
Authors: Szklarczyk Damian , Nastou Katerina , Koutrouli Mikaela , Kirsch Rebecca , Mehryary Farrokh , Hachilif Radja , Hu Dewei , Peluso Matteo E , Huang Qingyao , Fang Tao , Doncheva Nadezhda T , Pyysalo Sampo , Bork Peer , Jensen Lars J , von Mering Christian
Published: November 2024

Proteins cooperate, regulate and bind each other to achieve their functions. Understanding the complex network of their interactions is essential for a systems-level description of cellular processes. The STRING database compiles, scores and integrates protein–protein association information drawn from experimental assays, computational predictions and prior knowledge. Its goal is to create comprehensive and objective global networks that encompass both physical and functional interactions. Additionally, STRING provides supplementary tools such as network clustering and pathway enrichment analysis. The latest version, STRING 12.5, introduces a new ‘regulatory network’, for which it gathers evidence on the type and directionality of interactions using curated pathway databases and a fine-tuned language model parsing the literature. This update enables users to visualize and access three distinct network types—functional, physical and regulatory—separately, each applicable to distinct research needs. In addition, the pathway enrichment detection functionality has been updated, with better false discovery rate corrections, redundancy filtering and improved visual displays. The resource now also offers improved annotations of clustered networks and provides users with downloadable network embeddings, which facilitate the use of STRING networks in machine learning and allow cross-species transfer of protein information. The STRING database is available online at https://string-db.org/.
GenBank 2025 update
Authors: Sayers Eric W , Cavanaugh Mark , Frisse Linda , Pruitt Kim D , Schneider Valerie A , Underwood Beverly A , Yankie Linda , Karsch-Mizrachi Ilene
Published: November 2024

GenBank® (https://www.ncbi.nlm.nih.gov/genbank/) is a comprehensive, public data repository that contains 34 trillion base pairs from over 4.7 billion nucleotide sequences for 581 000 formally described species. Daily data exchange with the European Nucleotide Archive and the DNA Data Bank of Japan ensures worldwide coverage. We summarize the content of the database in 2025 and recent updates such as accelerated processing of influenza sequences and the ability to upload feature tables to Submission Portal for messenger RNA sequences. We provide an overview of the web, application programming and command-line interfaces that allow users to access GenBank data. We also discuss the importance of creating BioProject and BioSample records during submissions, particularly for viruses and metagenomes. Finally, we summarize educational materials and recent community outreach efforts.
Yield of Targeted Polymerase Chain Reaction in Probable Early-Onset Sepsis: A Prospective Cohort Study in Term and Near-Term Neonates With Negative Blood Culture Results
Authors: Keij Fleur M , Klaassen Corné H W , Kornelisse René F , van Westreenen Mireille , Tramper-Stranders Gerdien A
Published: November 2024

Background

Discriminating noninfected from infected neonatal cases remains challenging, and subsequently many neonates are treated with antibiotics in the first week of life. We aimed to study the additional value of a targeted polymerase chain reaction (PCR) for group B streptococcus (GBS) and Escherichia coli on leftover blood culture media from term and near-term neonates with probable early-onset sepsis (EOS).

Methods

Leftover blood culture material from neonates participating in the RAIN study was stored after 5 days of incubation. The RAIN study evaluated intravenous-oral antibiotic switch in probable bacterial infection, defined as risk factors and/or clinical signs and elevated inflammatory parameters but negative blood culture results. We applied 2 targeted PCRs for GBS and E coli, the main pathogens in EOS, and analyzed the samples batchwise in triplicate for each PCR.

Results

PCR was performed in triplicate on blood culture media from 284 neonates. In 23 neonates, the PCR result was positive (3 cycle threshold values <37) for GBS (n = 1) or E coli (n = 22). Inflammatory parameters did not discriminate for positive PCR result, nor did risk factors for sepsis, such as maternal GBS status and prolonged rupture of membranes. However, 96% of neonates with a positive PCR result were born vaginally vs 74% in the PCR-negative group (P = .05); furthermore, 96% vs 81% (P = .21) of neonates had clinical symptoms.

Conclusions

Blood culture–negative “probable” EOS in neonates is accompanied by an 8% rate of PCR positivity, suggesting low-grade bacteriemia after birth with yet unclear clinical consequences. Further research should focus on how PCR can contribute to more targeted antibiotic use of neonates, specifically in those highly suspected of infection but in the absence of a positive blood culture result.
Relapse-free survival with adjuvant dabrafenib/trametinib therapy after relapse on a prior adjuvant CPI in BRAF V600-mutated stage III/IV melanoma
Authors: Weber Jeffrey , Haque Waqas , Markovic Svetomir N , Salama April K S , Mehmi Inderjit , Sullivan Ryan J , Najjar Yana G , van Akkooi Alexander C J , Menzies Alexander M , Long Georgina V , Taylor Amelia M , Haanen John , Zijlker Lisanne P , Davis Keith L , Karanth Siddharth , Norton Deborah , Connolly Lucy
Published: November 2024

Background

In BRAF-mutated high-risk melanoma, targeted therapy (BRAF/MEK inhibitors) and checkpoint inhibitor (CPI) immunotherapy have durable benefits as first-line (1L) adjuvant therapy. Based on differing action mechanisms of BRAF/MEK inhibitors and CPI immunotherapies, there is interest in evaluating the activity of 2L adjuvant targeted therapy in decreasing the risk of subsequent recurrence after repeat resection following relapse on/after 1L adjuvant CPI.

Patients and methods

This was a retrospective review of BRAF V600-mutated resected stage III/IV melanoma patients in the United States, Australia, and The Netherlands who received 1L adjuvant CPI immunotherapy, relapsed locoregionally/distantly, were again resected to no evidence of disease, and received dabrafenib/trametinib (dab/tram) as 2L adjuvant therapy. The primary endpoint was relapse-free survival (RFS) from initiation of 2L adjuvant dab/tram (RFS-2), analyzed via Kaplan-Meier methods.

Results

Thirty-eight patients were included (median age 50 years, 63% male, 87% stage III, median follow-up 19 months from 2L dab/tram initiation). Median dab/tram duration was 10.1 months (range: 1 day–22.7 months), with half discontinuing due to progression or adverse events. Median (95% CI) RFS-2 was 18.9 (14.9–28.1) months, with 91%, 81%, and 58% remaining relapse-free at 6, 12, and 18 months, respectively. Most patients remained distant metastasis-free at 6, 12, and 18 months (97%, 85%, and 71%, respectively). Two patients were deceased at the last follow-up, with 97% alive at 18 months.

Conclusions

Over 80% of patients remained relapse- and metastasis-free at 12 months after 2L dab/tram initiation, with only 2 deaths observed. Dab/tram appears to have activity in the 2L adjuvant setting, although more follow-up is required.
Leptin levels are associated with coronary artery calcification in patients with advanced prostate cancer
Authors: Koutroumpakis Efstratios , Venkatesh Neha , Aparicio Ana , Song Juhee , Panaretakis Theocharis , Deswal Anita , Logothetis Christopher J , Frigo Daniel E , Hahn Andrew W
Published: November 2024

Background

Convergent data suggest that advanced prostate cancer and coronary heart disease (CHD) share biological vulnerabilities that may be linked to adiposity. Here we explore whether leptin, as a marker and mediator of adiposity, could link prostate cancer to CHD.

Methods

Patients with metastatic castration-resistant prostate cancer (mCRPC) enrolled in a phase II trial (NCT02703623) studying androgen deprivation therapy, abiraterone, prednisone, and apalutamide were eligible if they had plasma and a chest CT scan available. Coronary artery calcium (CAC) scores and adipokine levels were measured upon enrollment.

Results

Of 164 patients, 87% were white. The mean age was 65.6 ± 7.5 years, 88% were either overweight or obese, 59% had hypertension, 48% had hyperlipidemia (HLD), 20% had type 2 diabetes mellitus, and 41% were former or current smokers. Coronary calcifications were found in 115 patients (70%). Among 47 patients with non-contrast chest CT scans, the median total CAC score was 133 AU (IQR 22.6-704.6). Four patients (9%) had a score of 0 AU (low risk) and 24 (51%) scores ≥100 AU, associated with high risk for major adverse cardiovascular events. Leptin levels correlated positively with the right coronary artery (RCA) CAC score [Pearson correlation coefficient (ρ) = 0.3715 (P = .0142)]. In a multivariate logistic regression analysis, older age, HLD, and higher leptin levels were independently associated with RCA calcification and a higher number of calcified coronary arteries.

Conclusion

Among men with mCRPC, there was a high burden of CHD, and higher leptin levels were associated with coronary atherosclerosis independently of traditional cardiac risk factors.
Objects in Transit
Authors: Pizzato Fedra A.
Published: November 2024

A widespread view in archaeology holds that, without a systematization in the proper scientific framework, a collection of artifacts is just a bunch of old things. By adopting a novel perspective, which combines science studies and cultural studies, the aim of this chapter is to show that archaeological collecting can be regarded as a form of sociability and therefore imbued with social, political, and cultural values. It is also argued that one of the goals of a historian of archaeology is to decontextualize and recontextualize archaeological objects, that is to address them as scientific, discursive, epistemic, and boundary objects. The importance of the history of collections for subaltern and gender studies applied to archaeology is also explored. Reframing the history of collections in this fashion enables us to better see historical continuities and to appreciate the history of archaeology in a long-durée perspective. Finally, some recent trends in museum practices are considered. One of them—digitalization—suggests new possibilities for the elaboration of a novel history of archaeology throughout the study of historical collections.
International Congresses in the History of Archaeology
Authors: Sommer Ulrike
Published: November 2024

The chapter follows the history of international congresses between 1866 and the present, with a special emphasis on the relationship between the development of international scholarly communication and politics. The Congrès international d’Anthropologie et d’archéologie Préhistoriques was founded in 1865 and met, with decreasing regularity, till 1912. For practical purposes, this predominantly European association ended with World War I among nationalist animosities. The interwar years saw the French-dominated Institut international d’Anthropologie and the foundation of the Congrès international des Sciences pré- et protohistoriques, the latter placing emphasis on political neutrality and the inclusion of scholars from all nations, irrespective of their ideology. This congress is still in existence in the guise of the Union international des Sciences pré- et protohistoriques. The year 1986 saw the foundation of the anglophone World Archaeological Congress, which aimed at inclusivity beyond the First World and academics; which understands itself as a partisan and explicitly political body.
Collecting Antiquities in the Nineteenth Century
Authors: Achim Miruna
Published: November 2024

In the course of the nineteenth century, pre-Hispanic artifacts became an archaeological category—both plastic enough to adapt to local needs and robust enough to become recognizable and valuable aesthetically, epistemologically, and commercially. Starting from the premise that antiquities do not have intrinsic meanings, but acquire them as they move geographically and conceptually, this chapter draws on an ecological approach to study the connections and follow the trajectories of three collections of a specific case study—Mexican antiquities at the National Museum of Mexico in Mexico City, at the American Philosophical Society in Philadelphia, and at the Louvre (whose collection of Mexican antiquities was later incorporated into the Ethnographic Museum at the Trocadéro, in Paris). The chapter compares the ways in which Mexican antiquities were configured by temporally and spatially situated institutional ecologies, with their specific intellectual traditions, disciplinary practices, political agendas, aesthetic sensibilities, technologies of classification and representation, and social and material infrastructures. Ultimately, the chapter reflects on the tangled, often contingent, processes by which the past matters to the present.
Adorno’s Ethical Materialism
Authors: Whyman Tom
Published: November 2024

When scholars use the word “materialism,” in either a specifically Marxist or generally philosophical sense, the term is not applied in such a way that it would seem to be inclusive of the work of Theodor Adorno: Adorno was not a deterministic historical materialist nor was Adorno a reductionist philosopher of mind. However, Adorno frequently invokes “materialist” motifs at prominent points throughout his work: his philosophical outlook was, at least in terms of his own self-conception, always a “materialist” one. This chapter clears up any mysteries surrounding Adorno’s materialism by explaining that he was an “inclusive” (as opposed to “exclusive”) materialist—and that the main point of his holding the version of materialism that he did, was to make an ethical point, as opposed to a metaphysical one.
The Chimaera
Authors: Smith R. Scott
Published: November 2024

The Chimaera—part lion, part goat, and part serpent—offers an unforgettable image of a monster that remains useful today for exploring hybridity. As is typical, the monster acted as a foil for a Greek hero, in this case Bellerophon from Corinth. After covering the most important early sources and artwork from the Greek period, this chapter will consider the Lycian setting of the myth and assess the theories that assert that the image and myth of the Chimaera developed in the east, even though there is no exact analogy for the Chimaera to be found in Near Eastern art. This chapter takes the position that, whatever the origins of the beast, the Chimaera and the myths that surround it are uniquely Greek. In addition, this chapter recounts the rationalizing and allegorical interpretations that later ancient Greeks brought to bear to explain the creation of this fantastical hybrid.
Image and Monster in Ancient Greek Art
Authors: Winkler-Horaček Lorenz
Published: November 2024

From the seventh century bce on, images of monsters are gradually linked to ancient mythological stories. Examples show to what extent the same myth images can have very different meanings in different eras. Through these images, the myth is rooted in its temporal context and can be connected to the questions, fears, and hopes specific to each period. The monsters differ not only in their physical composition, but also in their respective ability to communicate. As myth images, they play an identity-forming role, whether as part of the development of Greek poleis and the confrontation with the unknown peripheries of the world, or as a visualization of enemies. They stand for the uncivilized and hostile but are not limited to this: the case of the centaurs also shows an ambivalent attitude towards ‘monsters’. Outside the myth images we also find monsters in ancient imagery as part of different taxonomic world views.
Ancient Monsters in Modern Speculative Fiction
Authors: Stevens Benjamin Eldon , Weiner Jesse , Rogers Brett M.
Published: November 2024

This chapter examines how monsters from ancient Greek and Roman materials may be found in every genre and medium of modern speculative fiction: in science fiction, horror, and fantasy, and in formats including print, film and television, and games. It first argues that ancient monsters continue to do what they did in classical sources: they ‘demonstrate’ or reveal the imaginary but consequential boundaries that separate categories of being, especially ‘human’ and ‘natural’ from purported ‘others’, and indicate the limits of human knowledge. Next it describes three examples—the Cyclops, Medusa, and the Minotaur—to suggest the complexity of reception histories and of interrelated definitions of monster/monstrosity and human/humanity. The chapter explores an understanding of modern speculative fiction in terms of Promethean science fiction, Sphinxian horror, and Protean fantasy. It concludes by examining how two modern monsters—Frankenstein’s Creature and the Kraken—in their classical entanglements are suggestive of a potential teratopolitics.