bluuebunny/crossref_metadata_2025 huggingface dataset:
Towards discovery: an end-to-end system for uncovering novel biomedical relations
Authors: Almeida Tiago , Jonker Richard A A , Antunes Rui , Almeida João R , Matos Sérgio
Published: July 2024

Biomedical relation extraction is an ongoing challenge within the natural language processing community. Its application is important for understanding scientific biomedical literature, with many use cases, such as drug discovery, precision medicine, disease diagnosis, treatment optimization and biomedical knowledge graph construction. Therefore, the development of a tool capable of effectively addressing this task holds the potential to improve knowledge discovery by automating the extraction of relations from research manuscripts. The first track in the BioCreative VIII competition extended the scope of this challenge by introducing the detection of novel relations within the literature. This paper describes that our participation system initially focused on jointly extracting and classifying novel relations between biomedical entities. We then describe our subsequent advancement to an end-to-end model. Specifically, we enhanced our initial system by incorporating it into a cascading pipeline that includes a tagger and linker module. This integration enables the comprehensive extraction of relations and classification of their novelty directly from raw text. Our experiments yielded promising results, and our tagger module managed to attain state-of-the-art named entity recognition performance, with a micro F1-score of 90.24, while our end-to-end system achieved a competitive novelty F1-score of 24.59. The code to run our system is publicly available at https://github.com/ieeta-pt/BioNExt.

Database URL: https://github.com/ieeta-pt/BioNExt
Mushroom poisoning with cardiogenic shock caused by Russula subnigricans successfully treated with mechanical circulatory support devices: a case report
Authors: Iseki Shota , Yamaguchi Shogo , Ozaki Yuta , Uemura Yusuke
Published: July 2024

Background

Mushroom poisoning caused by the ingestion of Russula subnigricans has been reported to cause rhabdomyolysis and cardiac dysfunction, leading to death. There have been few reports of cardiogenic shock induced by mushroom poisoning that was successfully treated using mechanical circulatory support devices.

Case Summary

A 38-year-old man presented with gastrointestinal symptoms a day after consuming a curry made with forest-collected mushrooms and was admitted with a diagnosis of rhabdomyolysis. Despite appropriate fluid management for severe rhabdomyolysis, the patient experienced anuria and cardiogenic shock with a remarkably reduced left ventricular ejection function, followed by the development of ventricular fibrillation. Mechanical support using Impella CP, veno-arterial extracorporeal membranous oxygenation (VA-ECMO), and continuous haemodiafiltration were administered for cardiogenic shock and severe rhabdomyolysis. His cardiac and renal function gradually improved, and the patient was successfully weaned off VA-ECMO on day 4, Impella CP on day 5, and renal replacement therapy on day 23. The left ventricular ejection fraction returned to normal without any neurological, respiratory, or renal sequelae. The remaining mushroom samples were identified as R. subnigricans by polymerase chain reaction testing.

Discussion

This is the first reported case of cardiogenic shock caused by R. subnigricans poisoning, successfully treated with Impella CP and VA-ECMO. The optimal use of mechanical circulatory support devices plays an important role in the treatment of cardiogenic shock caused by mushroom toxicity.
Recent and speculative remote myocardial trauma: a case series
Authors: Lu Zhijuan , Zhang Xiaocong , Huang Yanling , Song Jia , Zhang Chaoqun , Wang Qiang , Wu Handong , Huang Xinsheng
Published: July 2024

Background

Cardiac blunt trauma clinically presents as a spectrum of injuries of varying severity. However, the diagnosis of complications of remote myocardial trauma is often challenging, especially if the patient forgets to mention a remote history of chest trauma.

Case summary

In this study, we present a patient who recently experienced traumatic myocardial dissection and interventricular septal rupture, alongside three patients exhibiting a mimic double-chambered left ventricle, indicative of prior remote myocardial trauma potentially associated with myocardial dissecting tear.

Discussion

Patients with recent severe myocardial injury are detectable through cardiac imaging. However, forgotten remote myocardial trauma can lead to adverse myocardial remodelling, heart failure, and arrhythmias. Long-term myocardial remodelling can obscure initial myocardial imaging characteristics, posing challenges in interpretation. Our case series suggests that remote myocardial trauma may be more prevalent than commonly thought of in clinical practice.
Effect of urban environment on cardiovascular health: a feasibility pilot study using machine learning to predict heart rate variability in patients with heart failure
Authors: van Es Valerie A A , De Lathauwer Ignace L J , Lopata Richard G P , Kemperman Astrid D A M , van Dongen Robert P , Brouwers Rutger W M , Funk Mathias , Kemps Hareld M C
Published: July 2024

Aims

Urbanization is related to non-communicable diseases such as congestive heart failure (CHF). Understanding the influence of diverse living environments on physiological variables such as heart rate variability (HRV) in patients with chronic cardiac disease may contribute to more effective lifestyle advice and telerehabilitation strategies. This study explores how machine learning (ML) models can predict HRV metrics, which measure autonomic nervous system responses to environmental attributes in uncontrolled real-world settings. The goal is to validate whether this approach can ascertain and quantify the connection between environmental attributes and cardiac autonomic response in patients with CHF.

Methods and results

A total of 20 participants (10 healthy individuals and 10 patients with CHF) wore smartwatches for 3 weeks, recording activities, locations, and heart rate (HR). Environmental attributes were extracted from Google Street View images. Machine learning models were trained and tested on the data to predict HRV metrics. The models were evaluated using Spearman’s correlation, root mean square error, prediction intervals, and Bland–Altman analysis. Machine learning models predicted HRV metrics related to vagal activity well (R > 0.8 for HR; 0.8 > R > 0.5 for the root mean square of successive interbeat interval differences and the Poincaré plot standard deviation perpendicular to the line of identity; 0.5 > R > 0.4 for the high frequency power and the ratio of the absolute low- and high frequency power induced by environmental attributes. However, they struggled with metrics related to overall autonomic activity, due to the complex balance between sympathetic and parasympathetic modulation.

Conclusion

This study highlights the potential of ML-based models to discern vagal dynamics influenced by living environments in healthy individuals and patients diagnosed with CHF. Ultimately, this strategy could offer rehabilitation and tailored lifestyle advice, leading to improved prognosis and enhanced overall patient well-being in CHF.
Genome assembly of Hibiscus sabdariffa L. provides insights into metabolisms of medicinal natural products
Authors: Kim Taein , Lee Jeong Hun , Seo Hyo Hyun , Moh Sang Hyun , Choi Sung Soo , Kim Jun , Kim Sang-Gyu
Published: July 2024

Hibiscus sabdariffa L. is a widely cultivated herbaceous plant with diverse applications in food, tea, fiber, and medicine. In this study, we present a high-quality genome assembly of H. sabdariffa using more than 33 Gb of high-fidelity (HiFi) long-read sequencing data, corresponding to ∼20× depth of the genome. We obtained 3 genome assemblies of H. sabdariffa: 1 primary and 2 partially haplotype-resolved genome assemblies. These genome assemblies exhibit N50 contig lengths of 26.25, 11.96, and 14.50 Mb, with genome coverage of 141.3, 86.0, and 88.6%, respectively. We also utilized 26 Gb of total RNA sequencing data to predict 154k, 79k, and 87k genes in the respective assemblies. The completeness of the primary genome assembly and its predicted genes was confirmed by the benchmarking universal single-copy ortholog analysis with a completeness rate of 99.3%. Based on our high-quality genomic resources, we constructed genetic networks for phenylpropanoid and flavonoid metabolism and identified candidate biosynthetic genes, which are responsible for producing key intermediates of roselle-specific medicinal natural products. Our comprehensive genomic and functional analysis opens avenues for further exploration and application of valuable natural products in H. sabdariffa.
ONeSAMP 3.0: estimation of effective population size via single nucleotide polymorphism data from one population
Authors: Hong Aaron , Cheek Rebecca G , De Silva Suhashi Nihara , Mukherjee Kingshuk , Yooseph Isha , Oliva Marco , Heim Mark , W. Funk Chris , Tallmon David , Boucher Christina
Published: July 2024

The genetic effective size (Ne) is arguably one of the most important characteristics of a population as it impacts the rate of loss of genetic diversity. Methods that estimate Ne are important in population and conservation genetic studies as they quantify the risk of a population being inbred or lacking genetic diversity. Yet there are very few methods that can estimate the Ne from data from a single population and without extensive information about the genetics of the population, such as a linkage map, or a reference genome of the species of interest. We present ONeSAMP 3.0, an algorithm for estimating Ne from single nucleotide polymorphism data collected from a single population sample using approximate Bayesian computation and local linear regression. We demonstrate the utility of this approach using simulated Wright–Fisher populations, and empirical data from five endangered Channel Island fox (Urocyon littoralis) populations to evaluate the performance of ONeSAMP 3.0 compared to a commonly used Ne estimator. Our results show that ONeSAMP 3.0 is broadly applicable to natural populations and is flexible enough that future versions could easily include summary statistics appropriate for a suite of biological and sampling conditions. ONeSAMP 3.0 is publicly available under the GNU General Public License at https://github.com/AaronHong1024/ONeSAMP_3.
gNOMO2: a comprehensive and modular pipeline for integrated multi-omics analyses of microbiomes
Authors: Arikan Muzaffer , Muth Thilo
Published: July 2024

Background

In recent years, omics technologies have offered an exceptional chance to gain a deeper insight into the structural and functional characteristics of microbial communities. As a result, there is a growing demand for user-friendly, reproducible, and versatile bioinformatic tools that can effectively harness multi-omics data to provide a holistic understanding of microbiomes. Previously, we introduced gNOMO, a bioinformatic pipeline tailored to analyze microbiome multi-omics data in an integrative manner. In response to the evolving demands within the microbiome field and the growing necessity for integrated multi-omics data analysis, we have implemented substantial enhancements to the gNOMO pipeline.

Results

Here, we present gNOMO2, a comprehensive and modular pipeline that can seamlessly manage various omics combinations, ranging from 2 to 4 distinct omics data types, including 16S ribosomal RNA (rRNA) gene amplicon sequencing, metagenomics, metatranscriptomics, and metaproteomics. Furthermore, gNOMO2 features a specialized module for processing 16S rRNA gene amplicon sequencing data to create a protein database suitable for metaproteomics investigations. Moreover, it incorporates new differential abundance, integration, and visualization approaches, enhancing the toolkit for a more insightful analysis of microbiomes. The functionality of these new features is showcased through the use of 4 microbiome multi-omics datasets encompassing various ecosystems and omics combinations. gNOMO2 not only replicated most of the primary findings from these studies but also offered further valuable perspectives.

Conclusions

gNOMO2 enables the thorough integration of taxonomic and functional analyses in microbiome multi-omics data, offering novel insights in both host-associated and free-living microbiome research. gNOMO2 is available freely at https://github.com/muzafferarikan/gNOMO2.
Haplotype-resolved genome and mapping of freezing tolerance in the wild potato Solanum commersonii
Authors: Dong Jianke , Li Jingwen , Zuo Yingtao , Wang Jin , Chen Ye , Tu Wei , Wang Haibo , Li Chenxi , Shan Yacheng , Wang Ying , Song Botao , Cai Xingkui
Published: July 2024

Solanum commersonii (2n = 2x = 24, 1EBN, Endosperm Balance Number), native to the southern regions of Brazil, Uruguay, and northeastern Argentina, is the first wild potato germplasm collected by botanists and exhibits a remarkable array of traits related to disease resistance and stress tolerance. In this study, we present a high-quality haplotype-resolved genome of S. commersonii. The two identified haplotypes demonstrate chromosome sizes of 706.48 and 711.55 Mb, respectively, with corresponding chromosome anchoring rates of 94.2 and 96.9%. Additionally, the contig N50 lengths are documented at 50.87 and 45.16 Mb. The gene annotation outcomes indicate that the haplotypes encompasses a gene count of 39 799 and 40 078, respectively. The genome contiguity, completeness, and accuracy assessments collectively indicate that the current assembly has produced a high-quality genome of S. commersonii. Evolutionary analysis revealed significant positive selection acting on certain disease resistance genes, stress response genes, and environmentally adaptive genes during the evolutionary process of S. commersonii. These genes may be related to the formation of diverse and superior germplasm resources in the wild potato species S. commersonii. Furthermore, we utilized a hybrid population of S. commersonii and S. verrucosum to conduct the mapping of potato freezing tolerance genes. By combining BSA-seq analysis with traditional QTL mapping, we successfully mapped the potato freezing tolerance genes to a specific region on Chr07, spanning 1.25 Mb, with a phenotypic contribution rate of 18.81%. In short, current research provides a haplotype-resolved reference genome of the diploid wild potato species S. commersonii and establishes a foundation for further cloning and unraveling the mechanisms underlying cold tolerance in potatoes.
Phospholipid production and signaling by a plant defense inducer against Podosphaera xanthii is genotype-dependent
Authors: Margaritopoulou Theoni , Baira Eirini , Anagnostopoulos Christos , Vichou Katerina-Eleni , Markellou Emilia
Published: July 2024

Biotrophic phytopathogenic fungi such as Podosphaera xanthii have evolved sophisticated mechanisms to adapt to various environments causing powdery mildews leading to substantial yield losses. Today, due to known adverse effects of pesticides, development of alternative control means is crucial and can be achieved by combining plant protection products with resistant genotypes. Using plant defense inducers, natural molecules that stimulate plant immune system mimicking pathogen attack is sustainable, but information about their mode of action in different hosts or host genotypes is extremely limited. Reynoutria sachalinensis extract, a known plant defense inducer, especially through the Salicylic acid pathway in Cucurbitaceae crops against P. xanthii, was employed to analyze the signaling cascade of defense activation. Here, we demonstrate that R. sachalinensis extract enhances phospholipid production and signaling in a Susceptible to P. xanthii courgette genotype, while limited response is observed in an Intermediate Resistance genotype due to genetic resistance. Functional enrichment and cluster analysis of the upregulated expressed genes revealed that inducer application promoted mainly lipid- and membrane-related pathways in the Susceptible genotype. On the contrary, the Intermediate Resistance genotype exhibited elevated broad spectrum defense pathways at control conditions, while inducer application did not promote any significant changes. This outcome was obvious and at the metabolite level. Main factor distinguishing the Intermediate Resistance form the Susceptible genotype was the epigenetic regulated increased expression of a G3P acyltransferase catalyzing phospholipid production. Our study provides evidence on phospholipid-based signaling after plant defense inducer treatment, and the selective role of plant’s genetic background.
Clinical Impact of Plasma Metagenomic Next-Generation Sequencing on Infection Diagnosis and Antimicrobial Therapy in Immunocompromised Patients
Authors: Yin Guankun , Yin Yuyao , Guo Yifan , Sun Lingxiao , Ma Shuai , Chen Hongbin , Wang Qi , Wang Hui
Published: July 2024

Background

The clinical impact of plasma metagenomic next-generation sequencing (mNGS) on infection diagnosis and antimicrobial therapy in immunocompromised patients with suspected infection remains unclear.

Methods

Between March and December 2022, 424 cases with fever, infection history, mechanical ventilation, or imaging abnormalities underwent plasma mNGS testing at a single center. Eleven patients had received solid organ transplantation, and the remaining patients were categorized into febrile neutropenia (FN), non-neutropenia (NN), and non-transplant and non-hematologic disease (NTHD) groups based on immunosuppression severity. The diagnostic rate of infection and the utilization of antimicrobial agents based on mNGS were assessed.

Results

The use of mNGS significantly improved the diagnostic rates for fungi in the FN (65.1%, P = .001) and NN (58.8%, P = .008) groups versus the NTHD group (33.3%). Positive impacts associated with therapy were significantly greater than negative impacts across all 3 groups (all P < .001), and the utilization of escalation therapy was significantly more frequent in the FN group than in the NN group (P = .006). More than 70% of cases with negative mNGS results across the 3 groups underwent de-escalation therapy, with more than one-third being discontinued, preventing antimicrobial overuse.

Conclusions

Plasma mNGS has a clinically confirmed positive impact in immunocompromised patients with neutropenia, improving the diagnosis of fungal infections and antimicrobial therapy.
Quantification of Total Sulfites in Shrimp by BIOFISH 300/3000 SUL Method, Collaborative Study: Final Action 2021.09
Authors: Garate Jone , Ortiz de Zarate Itziar , Gonzalez Roberto , Añorga Larraitz , Salleres Sandra
Published: July 2024

Background

In December 2021, the BIOFISH 300 SUL method for the determination of total sulfites in shrimp was adopted as a First Action Official Method of AnalysisSM by the AOAC INTERNATIONAL.

Objective

A collaborative study was conducted in February 2023 in order to test the reproducibility of the method.

Methods

The method is based on the use of a benchtop biosensor device that relates the concentration of sulfite to a quantifiable electric current signal. The sensing element, the Biotest, harbors an enzyme that specifically oxidizes sulfite, and the reaction products are electrochemically detected by the device in less than 3 min. The sulfite is extracted from the solid using an aqueous-based buffer solution, which ensures that all sulfite is present as a free anion.

Results

Eleven collaborators participated in the study of nine different shrimp samples. Values of repeatability and reproducibility relative standard deviation (RSDr and RSDR) obtained from the statistical analysis of valid data ranged from 2.1–8.1% and 7.5–14.3%, respectively, for shrimp samples above the quantification limit of the method, set at 7 mg/kg.

Conclusion

These results showed good repeatability and reproducibility of the method, even at concentrations below the legal threshold for sulfite in food, where the reference optimised Monier-Williams (OMW) method shows relatively high imprecision.

Highlights

On the basis of these results, the enzymatic amperometric biosensor method developed by BIOLAN Microbiosensores was adopted as Final Action Official Method in September 2023.
Dietary Spirulina effects in Eimeria-challenged broiler chickens: growth performance, nutrient digestibility, intestinal morphology, serum biomarkers, and gene expression
Authors: Alagbe Emmanuel Oluwabukunmi , Schulze Hagen , Adeola Olayiwola
Published: July 2024

This study investigated the growth performance, nutrient utilization, and intestinal health responses of Eimeria-challenged broiler chickens to dietary Spirulina (Arthrospira platensis). On day 1, birds were assigned to 2 diets supplemented with Spirulina (0 or 5 g/kg) in a randomized complete block design. The birds within each diet were divided into 2 Eimeria-challenge groups (challenge or no-challenge) and that resulted in a 2 × 2 factorial arrangement with 2 levels each of Spirulina and challenge on day 14. On day 15, the birds in the challenge or no-challenge groups were orally gavaged with a solution containing Eimeria oocysts or 1% PBS, respectively. Samples were collected on days 21 and 26 (6- and 11-d post-infection; dpi). Data collected from days 1 to 26 were analyzed using the MIXED procedure of SAS. Birds that were fed Spirulina-supplemented diets had increased (P < 0.05) BW gain, gain-to-feed ratio, and total tract retention nitrogen from days 14 to 21. The ileal villus perimeter and area, serum catalase, HMOX1 and SOD1 jejunal abundance were all increased (P < 0.05) in birds fed Spirulina-supplemented diets on day 21 (6 dpi). However, there was no effect on bone ash or oocyst count. From days 21 to 26, there was a tendency (P = 0.059) for a Spirulina × Challenge interaction on the BW gain of birds. Moreover, dietary Spirulina addition increased (P < 0.05) serum catalase, total antioxidant capacity, ileal villus perimeter, tibia bone ash, and the relative mRNA expression of HMOX1, SOD1, claudin 1, and TNFα in the jejunal mucosa of birds on day 26 (11 dpi). On both 6 and 11 dpi, the Eimeria challenge negatively (P < 0.05) impacted growth performance, gut morphology, and the relative mRNA expression of genes. Overall, assessing the impact of Spirulina in broilers revealed its positive antioxidant, immune-modulating, and health benefits. However, its dietary addition did not completely reverse the Eimeria-induced effects in these birds. Ultimately, this study outlines the positive properties of dietary Spirulina beyond its use in the diet of healthy broiler chickens.
VP1 of human and murine noroviruses recognizes glycolipid sulfatide via the P domain
Authors: Tsukamoto Bunta , Kurebayashi Yuuki , Takahashi Tadanobu , Abe Yusuke , Ota Ryohei , Wakabayashi Yoshiki , Nishiie Anju , Minami Akira , Suzuki Takashi , Takeuchi Hideyuki
Published: July 2024

Noroviruses are a prevalent cause of human viral gastroenteritis, yet the precise mechanisms underlying their infection cycle, particularly their interactions with and entry into cells, remain poorly understood. Human norovirus (HuNoV) primarily targets human small intestinal epithelial cells, within which 3-O-sulfogalactosylceramide (sulfatide) ranks among the most abundant glycosphingolipids (GSLs). While sulfatide involvement in the binding and infection mechanism of several viruses has been documented, its interaction with noroviruses remains underexplored. This study investigated whether noroviruses interact with sulfatide. We found that the recombinant viral capsid protein VP1 of HuNoV (genogroups I and II) and murine norovirus (genogroup V) exhibited robust binding to sulfatide compared with other tested GSLs using enzyme-linked immunosorbent assay, thin-layer chromatography binding assay and real-time quantitative reverse transcription polymerase chain reaction binding assay. VP1 also bound 3-O-sulfated lactosylceramide, which shares the 3-O-sulfated galactose moiety with sulfatide. However, both VP1 and its P domain, identified as the sulfatide-binding domain, exhibited limited binding to structural analogues of sulfatide and other sulfated compounds. These findings suggest a specific recognition of the 3-O-sulfated galactose moiety. Notably, we found that sulfatide is a novel binding target for norovirus particles. Overall, our findings reveal a previously unknown norovirus–sulfatide interaction, proposing sulfatide as a potential candidate for norovirus infection receptors.
Dedicated Breast CT: Getting Ready for Prime Time
Authors: Aminololama-Shakeri Shadi , Boone John M
Published: July 2024

Dedicated breast CT is an imaging modality that provides true 3D imaging of the breast with many advantages over current conventional breast imaging modalities. The addition of intravascular contrast increases the sensitivity of breast CT substantially. As such, there are immediate potential applications in the clinical workflow. These include using breast CT to replace much of the traditional diagnostic workup when faced with indeterminate breast lesions. Contrast-enhanced breast CT may be appropriate as a supplemental screening tool for women at high risk of breast cancer, similar to breast MRI. In addition, emerging studies are demonstrating the utility of breast CT in neoadjuvant chemotherapy tumor response monitoring as well as planning for surgical treatment options. While short exam times and fully 3D imaging in a noncompressed position are advantages of this modality, limited coverage of chest wall/axilla due to prone positioning and use of ionizing radiation are drawbacks. To date, several studies have reported on the performance characteristics of this promising modality.
Ocular findings in Jansen metaphyseal chondrodysplasia
Authors: Obiezu Fiona , Magone De Quadros Costa M Teresa , Huryn Laryssa A , Pan Kristen , Almpani Konstantinia , Ninan Anisha , Roszko Kelly L , Weinstein Lee S , Gafni Rachel I , Ferreira Carlos R , Lee Janice , Collins Michael T , Jha Smita
Published: July 2024

Jansen metaphyseal chondrodysplasia (JMC) is an ultra-rare disorder caused by germline heterozygous PTHR1 variants resulting in constitutive activation of parathyroid hormone type 1 receptor. A description of ocular manifestations of the disease is lacking. Six patients with JMC underwent a detailed ophthalmic evaluation, spectral-domain optical coherence tomography (OCT), visual field testing, and craniofacial CT scans. Five of 6 patients had good visual acuity. All patients had widely spaced eyes; 5/6 had downslanted palpebral fissures. One patient had proptosis, and another had bilateral ptosis. Two patients had incomplete closure of the eyelids (lagophthalmos), one had a history of progressive right facial nerve palsy with profuse epiphora, while the second had advanced optic nerve atrophy with corresponding retinal nerve fiber layer (RNFL) thinning on OCT and significant bilateral optic canal narrowing on CT scan. Additionally, this patient also had central visual field defects and abnormal color vision. A third patient had normal visual acuity, subtle temporal pallor of the optic nerve head, normal average RNFL, but decreased temporal RNFL and retinal ganglion cell layer analysis (GCA) on OCT. GCA was decreased in 4/6 patients indicating a subclinical optic nerve atrophic process. None of the patients had glaucoma or high myopia. These data represent the first comprehensive report of ophthalmic findings in JMC. Patients with JMC have significant eye findings associated with optic canal narrowing due to extensive skull base dysplastic bone overgrowth that appear to be more prevalent and pronounced with age. Progressive optic neuropathy from optic canal narrowing may be a feature of JMC, and OCT GCA can serve as a useful biomarker for progression in the setting of optic canal narrowing. We suggest that patients with JMC should undergo regular ophthalmic examination including color vision, OCT, visual field testing, orbital, and craniofacial imaging.
Evidence for peri-lacunar remodeling and altered osteocyte lacuno-canalicular network in mouse models of myeloma-induced bone disease
Authors: Evans Holly , Andrews Rebecca , Abedi Fatma Ali , Sprules Alexandria , Trend Jacob , Lovric Goran , Green Alanna , Chantry Andrew , Clarkin Claire , Brown Janet , Lawson Michelle
Published: July 2024

Myeloma bone disease (MBD) affects ~90% of multiple myeloma patients, but current treatment options are suboptimal. Therefore, to successfully develop new therapies or optimize current ones, we must improve our fundamental knowledge of how myeloma affects bone microstructure and function. Here, we have investigated the osteocyte lacuno-canalicular network (LCN) in MBD, as bone porosity affects bone quality and resilience. We used the syngeneic 5TGM1-C57BL-Kalwrij and the xenograft U266-NSG models at end stage and compared them to healthy controls (naïve). Micro-computed tomography (μCT) and histomorphometry indicated the 5TGM1 and U266 models developed mild and extensive MBD, respectively, with the U266 model producing large osteolytic lesions. High-resolution synchrotron micro-CT (SR-μCT) revealed significant osteocyte lacunae changes in U266 bones but not 5TGM1, with a reduction in lacunae number and sphericity, and an increase in lacunae volume compared with naïve. Canalicular length, visualized using histological Ploton silver staining, appeared significantly shorter in 5TGM1 and U266 bones compared with naïve. Canalicular area as a proportion of the bone was also decreased by 24.2% in the U266 model. We observed significant upregulation of genes implicated in peri-lacunar remodeling (PLR), but immunohistochemistry confirmed that the osteocyte-specific protein sclerostin, a known driver of PLR, was unchanged between MBD and naïve bones. In summary, we have demonstrated evidence of PLR and altered organization of the osteocyte LCN in MBD mouse models. The next step would be to further understand the drivers and implications of PLR in MBD, and whether treatments to manipulate PLR and the LCN may improve patient outcomes.
Detecting diversifying selection for a trait from within and between-species genotypes and phenotypes
Authors: Latrille T , Bastian M , Gaboriau T , Salamin N
Published: July 2024

To quantify selection acting on a trait, methods have been developed using either within or between-species variation. However, methods using within-species variation do not integrate the changes at the macro-evolutionary scale. Conversely, current methods using between-species variation usually discard within-species variation, thus not accounting for processes at the micro-evolutionary scale. The main goal of this study is to define a neutrality index for a quantitative trait, by combining within- and between-species variation. This neutrality index integrates nucleotide polymorphism and divergence for normalizing trait variation. As such, it does not require estimation of population size nor of time of speciation for normalization. Our index can be used to seek deviation from the null model of neutral evolution, and test for diversifying selection. Applied to brain mass and body mass at the mammalian scale, we show that brain mass is under diversifying selection. Finally, we show that our test is not sensitive to the assumption that population sizes, mutation rates and generation time are constant across the phylogeny, and automatically adjust for it.
Merging Responsibilities
Authors: Koenig Alexa , Ghaly Anthony , Levine Simone Lieban
Published: July 2024

In emergent fields of practice, there is often an ‘ethics lag’ — a period of significant innovation during which the focus is on what can be accomplished more than on the safeguards that should be put in place to protect the public from the unanticipated consequences of that innovation. This is true of the emergent field of digital open-source investigations conducted for international criminal justice purposes, in which researchers and analysts comb the Internet for information relevant to their research. One sub-field where the ethics lag is particularly of concern is digital investigations of conflict-related sexual and gender-based violence (CRSV), especially with regards to whether and when investigators need consent from social media posters, survivors, bystanders and others to use information discovered in online spaces. This article explores options for centring and promoting victim safety and dignity by clarifying ethical issues that investigators should consider before using open-source information to support international investigations and prosecutions of CRSV. After identifying where the relevant law leaves gaps in guidance, the authors discuss a series of considerations that may help investigators ethically handle such sensitive data. Ultimately, the authors underscore the importance of securing consent from survivors when engaging in digital open-source investigations into sexual violence. What arguably varies is who should seek that consent, when, and how.
Politics and gender in the executive suite
Authors: Cohen Alma , Hazan Moshe , Weiss David
Published: July 2024

Recent years have seen increased interest in gender diversity within corporate America. CEOs’ political preferences have been shown to influence many corporate decisions. Evidence suggests that views on gender equality align more with political preferences than an individual’s gender. We investigate if CEOs’ political leanings correlate with female representation and compensation in the executive suite. We discover that Democratic CEOs (those donating more to Democratic candidates) correlate with greater female presence in the executive suite. Using an event-study method, we find replacing a Republican with a Democratic CEO leads to a 20%–50% rise in executive suite female representation. Additionally, Democratic CEOs significantly reduce, or eliminate, the gender pay gap in executive compensation levels and performance sensitivity.
A Review of Respiratory Syncytial Virus Epidemiology Among Children: Linking Effective Prevention to Vulnerable Populations
Authors: Daniels Danielle
Published: July 2024

Respiratory syncytial virus (RSV) is the greatest contributor to lower respiratory tract infections (LRTI) in children less than 5 years of age and the leading cause for infant hospitalizations in the United States (US). The burden of severe disease disproportionately impacts racial and ethnic minority groups, highlighting the need for interventions that promote health equity. Recent advancements in effective prophylactic agents have the potential to drastically alter the landscape of RSV disease among all young children. The effectiveness of prophylaxis, however, will rely on a clear understanding of RSV epidemiology. The purpose of this review is to discuss key aspects of RSV epidemiology while focusing on efforts to support equitable distribution of prophylactic agents to mitigate existing health disparities.
RSV Prevention Within Reach for Older Infants and Toddlers: The Role of Active Immunization
Authors: Mejias Asuncion , Ramilo Octavio
Published: July 2024

This review article will summarize the vaccines and monoclonal antibodies currently under evaluation for the prevention of RSV disease in older infants, toddlers and young children. We will review the rationale for passive protection during the first months of life, and the role of active immunization afterwards, either with live attenuated, protein-based or mRNA vaccines.
Application of the Knife-Edge Technique on Transition Metal Dichalcogenide Monolayers for Resolution Assessment of Nonlinear Microscopy Modalities
Authors: Jelić Jovana Z , Bukumira Marta , Denčevski Aleksa , Senkić Ana , Žužić Livio , Radatović Borna , Vujičić Nataša , Pajić Tanja , Rabasović Mihailo D , Krmpot Aleksandar J
Published: July 2024

We report application of the knife-edge technique at the sharp edges of WS2 and MoS2 monolayer flakes for lateral and axial resolution assessment in all three modalities of nonlinear laser scanning microscopy: two-photon excited fluorescence (TPEF), second- and third-harmonic generation (SHG, THG) imaging. This technique provides a high signal-to-noise ratio, no photobleaching effect and shows good agreement with standard resolution measurement techniques. Furthermore, we assessed both the lateral resolution in TPEF imaging modality and the axial resolution in SHG and THG imaging modality directly via the full-width at half maximum parameter of the corresponding Gaussian distribution. We comprehensively analyzed the factors influencing the resolution, such as the numerical aperture, the excitation wavelength and the refractive index of the embedding medium for the different imaging modalities. Glycerin was identified as the optimal embedding medium for achieving resolutions closest to the theoretical limit. The proposed use of WS2 and MoS2 monolayer flakes emerged as promising tools for characterization of nonlinear imaging systems.
A highly-selective biomimetic potassium channel
Authors: Zhu Junliang , Qiu Hu , Guo Wanlin
Published: July 2024

Reproducing the outstanding selectivity achieved by biological ion channels in artificial channel systems can revolutionize applications ranging from membrane filtration to single-molecule sensing technologies, but achieving this goal remains a challenge. Herein, inspired by the selectivity filter structure of the KcsA potassium channel, we propose a design of biomimetic potassium nanochannels by functionalizing the wall of carbon nanotubes with an array of arranged carbonyl oxygen atoms. Our extensive molecular dynamics simulations show that the biomimetic nanochannel exhibits a high K+ permeation rate along with a high K+/Na+ selectivity ratio. The free energy calculations suggest that the low Na+ permeability is the result of the higher energy barrier for Na+ than K+ at the channel entrance and ion binding sites. In addition, reducing the number of ion binding sites leads to an increase in the permeation rate but a decrease in selectivity. These findings not only hold promise for the design of high-performance membranes but also help understand the mechanism of selective ion transport in biological ion channels.
Identification of Anncaliia algerae in Ascites in an Immunosuppressed Patient, China
Authors: Wang Zanzan , Li Dan , Lu Lingling , Xu Zhijuan , Ouyang Guifang , Sun Yongcheng
Published: July 2024

Anncaliia algerae, a microsporidium, has risen to prominence as an opportunistic pathogen, particularly afflicting individuals who are immunocompromised with conditions such as rheumatoid arthritis, organ transplantation, and hematologic malignancy. Surprisingly, despite its recognized impact, the identification of A algerae in ascitic fluid has not been documented. As such, we pinpointed A algerae as the probable instigator of ascitic accumulation in a patient with a history of acute myeloid leukemia and extended periods of immunosuppressive therapy. For this patient, there were no signs of A algerae–related infections (eg, myositis), vocal cord involvement, or disseminated infection. The presence of A algerae was finally identified by next-generation metagenomic sequencing analysis of the ascitic fluid. Clinical presentation was characterized by elevated C-reactive protein levels (110.7 mg/L), diminished platelet count (48 × 109/L), abdominal distension secondary to ascitic fluid accumulation, and lower limb pain, and it showed marked improvement following a 4-day regimen of sulfamethoxazole/trimethoprim and albendazole. Despite this promising response, the patient succumbed to aspiration of vomitus. This case underscores the importance of considering rarer organisms, such as A algerae infection, in patients who are immunocompromised and present with unexplained ascites accumulation. It highlights the potential effectiveness of sulfamethoxazole/trimethoprim and albendazole in managing such cases. Further research is warranted to elucidate optimal management strategies and improve outcomes in similar clinical scenarios.
CYTOSOLIC INVERTASE2 regulates flowering and reactive oxygen species-triggered programmed cell death in tomato
Authors: Zhang Qiongqiong , Wang Xi , Zhao Tianying , Luo Junfeng , Liu Xin , Jiang Jing
Published: July 2024

Cytosolic invertase (CIN) in plants hydrolyzes sucrose into fructose and glucose, influencing flowering time and organ development. However, the underlying molecular mechanisms remain elusive. Through expressional, genetic, and histological analyses, we identified a substantially role of SlCIN2 (localized in mitochondria) in regulating flowering and pollen development in tomato (Solanum lycopersicum). The overexpression of SlCIN2 resulted in increased hexose accumulation and decreased sucrose and starch content. Our findings indicated that SlCIN2 interacts with Sucrose transporter2 (SlSUT2) to inhibit the sucrose transport activity of SlSUT2, thereby suppressing sucrose content in flower buds and delaying flowering. We found that higher levels of glucose in SlCIN2-overexpressing anthers result in the accumulation of abscisic acid (ABA) and reactive oxygen species (ROS), thereby disrupting programmed cell death (PCD) in anthers and delaying the end of tapetal degradation. Exogenous sucrose partially restored fertility in SlCIN2-overexpressing plants. This study revealed the mechanism by which SlCIN2 regulates pollen development and demonstrated a strategy for creating sugar-regulated gene male sterility lines for tomato hybrid seed production.
The cochlear hook region detects harmonics beyond the canonical hearing range
Authors: Horii Kazuhiro , Ogawa Bakushi , Nagase Noriko , Morimoto Iori , Abe Chikara , Ogawa Takenori , Choi Samuel , Nin Fumiaki
Published: July 2024

Ultrasound, or sound at frequencies exceeding the conventional range of human hearing, is not only audible to mice, microbats, and dolphins, but also creates an auditory sensation when delivered through bone conduction in humans. Although ultrasound is utilized for brain activation and in hearing aids, the physiological mechanism of ultrasonic hearing remains unknown. In guinea pigs, we found that ultrasound above the hearing range delivered through ossicles of the middle ear evokes an auditory brainstem response and a mechano-electrical transduction current through hair cells, as shown by the local field potential called the cochlear microphonic potential (CM). The CM synchronizes with ultrasound, and like the response to audible sounds is actively and nonlinearly amplified. In vivo optical nano-vibration analysis revealed that the sensory epithelium in the hook region, the basal extreme of the cochlear turns, resonates in response both to ultrasound within the hearing range and to harmonics beyond the hearing range. The results indicate that hair cells can respond to stimulation at the optimal frequency and its harmonics, and the hook region detects ultrasound stimuli with frequencies more than two octaves higher than the upper limit of the ordinary hearing range.
Circadian transcriptome oscillations in human adipose tissue depend on napping status and link to metabolic and inflammatory pathways
Authors: Rodríguez-Martín María , Pérez-Sanz Fernando , Zambrano Carolina , Luján Juan , Ryden Mikael , Scheer Frank A J L , Garaulet Marta
Published: July 2024

Study Objectives

Napping is a common habit in many countries. Nevertheless, studies about the chronic effects of napping on obesity are contradictory, and the molecular link between napping and metabolic alterations has yet to be studied. We aim to identify molecular mechanisms in adipose tissue (AT) that may connect napping and abdominal obesity.

Methods

In this cross-sectional study, we extracted the RNA repeatedly across 24 hours from cultured AT explants and performed RNA sequencing. Circadian rhythms were analyzed using six consecutive time points across 24 hours. We also assessed global gene expression in each group (nappers vs. non-nappers).

Results

With napping, there was an 88% decrease in the number of rhythmic genes compared to that in non-nappers, a reduction in rhythm amplitudes of 29%, and significant phase changes from a coherent unimodal acrophase in non-nappers, towards a scattered and bimodal acrophase in nappers. Those genes that lost rhythmicity with napping were mainly involved in pathways of glucose and lipid metabolism, and of the circadian clock. Additionally, we found differential global gene expression between nappers and non-nappers with 34 genes down- and 32 genes upregulated in nappers. The top upregulated gene (IER3) and top down-regulated pseudogene (VDAC2P2) in nappers have been previously shown to be involved in inflammation.

Conclusions

These new findings have implications for our understanding of napping’s relationship with obesity and metabolic disorders.
Silencing endomucin in bone marrow sinusoids improves hematopoietic stem and progenitor cell homing during transplantation
Authors: Li Yue , Ren Miao , Li Hu , Zhang Zuo , Yuan Ke , Huang Yujin , Yuan Shengnan , Ju Wen , He Yuan , Xu Kailin , Zeng Lingyu
Published: July 2024

Efficient homing of infused hematopoietic stem and progenitor cells (HSPCs) into the bone marrow (BM) is the prerequisite for successful hematopoietic stem cell transplantation. However, only a small part of infused HSPCs find their way to the BM niche. A better understanding of the mechanisms that facilitate HSPC homing will help to develop strategies to improve the initial HSPC engraftment and subsequent hematopoietic regeneration. Here, we show that irradiation upregulates the endomucin expression of endothelial cells in vivo and in vitro. Furthermore, depletion of endomucin in irradiated endothelial cells with short-interfering RNA (siRNA) increases the HSPC-endothelial cell adhesion in vitro. To abrogate the endomucin of BM sinusoidal endothelial cells (BM-SECs) in vivo, we develop a siRNA-loaded bovine serum albumin nanoparticle for targeted delivery. Nanoparticle-mediated siRNA delivery successfully silences endomucin expression in BM-SECs and improves HSPC homing during transplantation. These results reveal that endomucin plays a critical role in HSPC homing during transplantation and that gene-based manipulation of BM-SEC endomucin in vivo can be exploited to improve the efficacy of HSPC transplantation.
Dealing with registrations and jurisdiction in aircraft financing
Authors: Sipos Attila
Published: July 2024

In aircraft financing, dealing with jurisdiction and applicable law is of paramount importance. Given the global nature of the aviation industry, the parties involved in aircraft-financing transactions must carefully consider the jurisdiction in which disputes may arise as well as the relevant laws that govern such disputes. In aircraft financing, there are a great number of jurisdictions that may be selected by the parties. The existing international treaties in aircraft financing, such as the 1948 Geneva Convention and the 2001 Cape Town Convention with its Aircraft Equipment Protocol, unified international law considerably. Nevertheless, these treaties have not resulted in the elimination of the conflict of laws, and the choice of law in the agreements has limited effect. Despite the registration obligations of aircraft being unified enough due to the rigorous requirements of the 1944 Chicago Convention and its Annexes, further unification is necessary to manage the conflicts of laws. Such uniformity is still awaited, although the Cape Town Convention and its Aircraft Equipment Protocol provide a standardized legal regime for aircraft financing, transactions, and registrations. These international instruments and the registration requirement therein (International Registry) help establish uniformity and clarity in the rights and priorities of the parties involved. This article introduces the complexity of these areas of the aviation industry and focuses on the jurisdictional challenges regarding registration and contractual relations.