bluuebunny/crossref_metadata_2025 huggingface dataset:
‘Brexit and the Legal Legitimacy of the Unitary Patent Court’ – A Response
Authors: Tilmann Winfried
Published: May 2024

In GRUR International 2024, pp. 191-197, Nicolas Binctin (Professor in Poitiers, France) and Craig A. Nard (Professor in Cleveland, USA) come to the surprising conclusion that the conditions for the entry into force of the Agreement on a Unified Patent Court (UPCA), as set out in its Art. 89(1), are still not met. If their opinion were correct, not only would a new ratification by the contracting member states (including referenda in Denmark and Ireland) be necessary (this is what the authors advocate), the Unified Patent Court (as it is properly called) would be up in the air, along with its decisions and orders to date.

In short, the authors assume that effective ratification by the United Kingdom is still required for the application of Art. 89(1) UPCA as long as the said provision has not been amended removing its alleged reference to a ratification by the United Kingdom. They derive this view essentially from the wording of Art. 7(2) UPCA (according to which a division of the central division is located in London) and from Art. 3(1) of the Protocol on the Provisional Application of the UPCA (referring to a ratification of the UPCA by the United Kingdom as a precondition for the entry into force of the Protocol).
The centrality of food in Norwegian adolescents’ life; a photo elicitation study among Norwegian youth
Authors: Aronsen-Kongerud Helene , Bastien Sheri , Klepp Knut-Inge
Published: May 2024

The purpose of the study was to explore how adolescents from a high school in Viken county define and interact with food systems in their immediate environments to understand if and how health and sustainability affect their food choices. A qualitative case study design and a participatory approach were employed. Data were collected through photo elicitation combined with group interviews. Pictures were analyzed in collaboration with participants, and the group interview through systematic text condensation. Results indicate that adolescents perceive food systems as being a substantial part of their everyday life, that they care about their health and that of the planet, and they wish to take sustainability and health into consideration when making food choices. Their food choices are affected by aspects such as family, friends, marketing, price, time, availability and accessibility. They perceive that their agency to influence their own diet and food systems is limited. Adolescents hold unique and important knowledge of their food-related behaviors and value their autonomy to make food choices. Future research and policies aiming to help adolescents make healthy and sustainable food choices should therefore actively include adolescents.
Nasal and Pharyngeal Mucosal Immunity to Poliovirus in Children Following Routine Immunization With Inactivated Polio Vaccine in the United States
Authors: Godin Audrey , Connor Ruth I , Degefu Hanna N , Rosato Pamela C , Wieland-Alter Wendy F , Axelrod Katherine S , Kovacikova Gabriela , Weiner Joshua A , Ackerman Margaret E , Chen Eunice Y , Arita Minetaro , Bandyopadhyay Ananda S , Raja Amber I , Modlin John F , Brickley Elizabeth B , Wright Peter F
Published: May 2024

Background

Although polioviruses (PVs) replicate in lymphoid tissue of both the pharynx and ileum, research on polio vaccine–induced mucosal immunity has predominantly focused on intestinal neutralizing and binding antibody levels measured in stool.

Methods

To investigate the extent to which routine immunization with intramuscularly injected inactivated polio vaccine (IPV) may induce nasal and pharyngeal mucosal immunity, we measured PV type-specific neutralization and immunoglobulin (Ig) G, IgA, and IgM levels in nasal secretions, adenoid cell supernatants, and sera collected from 12 children, aged 2–5 years, undergoing planned adenoidectomies. All participants were routinely immunized with IPV and had no known contact with live PVs.

Results

PV-specific mucosal neutralization was detected in nasal and adenoid samples, mostly from children who had previously received 4 IPV doses. Across the 3 PV serotypes, both nasal (Spearman ρ ≥ 0.87, P ≤ .0003 for all) and adenoid (Spearman ρ ≥ 0.57, P ≤ .05 for all) neutralization titers correlated with serum neutralization titers. In this small study sample, there was insufficient evidence to determine which Ig isotype(s) was correlated with neutralization.

Conclusions

Our findings provide policy-relevant evidence that routine immunization with IPV may induce nasal and pharyngeal mucosal immunity. The observed correlations of nasal and pharyngeal mucosal neutralization with serum neutralization contrast with previous observations of distinct intestinal and serum responses to PV vaccines. Further research is warranted to determine which antibody isotype(s) correlate with polio vaccine–induced nasal and pharyngeal mucosal neutralizing activity and to understand the differences from intestinal mucosal immunity.
Implementation and outcomes of a statewide TBI screening program for underserved populations
Authors: Akaberi Seyedeh Melika , Nguyen Elaine , Carr Glenda , Spearman Russell , Shadduck Stefanie
Published: May 2024

The purpose of this paper is to describe the implementation and outcomes of a unique traumatic brain injury (TBI) screening initiative serving the community, with a focus on underserved populations. Idaho’s definition of underserved populations includes people living in rural/frontier areas, people experiencing homelessness or intimate partner violence, people with co-occurring disorders, and people with cultural and/or linguistically diverse backgrounds. The goals of screenings are to help participants gain awareness about the likelihood of having experienced a TBI, bridge the gap in TBI reporting, and provide needed support to underserved populations in a rural state. Our work represents a cross-sectional study. Beginning in 2014, TBI screenings were conducted by the Institute of Rural Health within a public health university with several internal and external partners, as well as grant funding for work. Trained interprofessional health students and/or members of the Institute of Rural Health performed TBI screenings using the Ohio State University TBI Identification Method—Interview Form. Those who screened as likely experiencing a TBI received resources for care and follow-up telephone calls. Data were collected on the number of individuals screened and their results and reported using descriptive statistics. From 2014 to 2022, a total of 1333 individuals were screened at 23 different community events across Idaho. Over 30% of screened individuals reported a history of head or neck injury, primarily due to falls and being hit by objects. The majority of identified cases of TBI were characterized by no loss of consciousness or <30 min of unconsciousness. Screenings targeting underserved populations showed higher TBI prevalence. Targeting underserved populations proved valuable in identifying TBI cases. The collaborative and interprofessional approach of this screening is unique and highlights the potential to address complex health issues effectively. These findings offer valuable insights for others implementing TBI screening programs in community settings.
Insights into invasive fungal infection diagnostic and treatment capacities in tertiary care centres of Germany
Authors: Salmanton-García Jon , Simon Michaela , Groll Andreas H , Kurzai Oliver , Lahmer Tobias , Lehrnbecher Thomas , Schroeder Maria , Cornely Oliver A , Stemler Jannik
Published: May 2024

Introduction

In Germany, the growing incidence of invasive fungal infections (IFIs) is a significant health concern, particularly impacting individuals with compromised immune systems due to factors like increasing transplant recipients, an ageing population, and heightened use of immunosuppressive medications. Diagnosing IFI remains challenging, and the integration of biomarker assays into clinical practice is difficult. Antifungal resistance, exemplified by pan-antifungal-resistant Candida auris cases, adds complexity to treatment. This study aims to provide a concise overview of the diagnostic and treatment landscape for IFI in Germany, identifying areas for improvement and paving the way for targeted interventions.

Methods

Data were collected using an online electronic case report form from October 2021 to February 2023. The survey included questions about institutional practices related to fungal infection diagnosis and treatment, with invitations extended to researchers nationwide.

Results

The study surveyed 58 hospitals across Germany. Notably, 77.6% managed high-risk patients for IFI. While 86% had onsite microbiology labs, a significant difference was noted for high-risk patients (93% in specialized hospitals versus 62% in others). Microscopy services had 96% coverage, while overall access to culture was 96%. Antigen tests had 96% coverage, and antibody access was reported at 98%. PCR testing was available at 98%. Imaging access showed no significant access differences. Variability existed in amphotericin B formulations based on patient profiles. Therapeutic drug monitoring was more common in high-risk patient institutions (89.5% versus 50.0%). All analysed institutions reported access to surgery (100%).

Conclusions

Addressing identified disparities in diagnostic and therapeutic resources for IFI is crucial to improving patient outcomes. The study calls for ongoing research and collaboration to optimize strategies for the prevention and treatment of IFI, emphasizing the importance of equitable access to resources, especially in high-risk patient populations.
Evaluation of 13 Formulae for Calculated LDL-C Using Direct Homogenous Assay in a South Indian Population
Authors: Ramesh Janani , Selvarajan Sathya , Krishnamurthy Sowmya , Kopula Sathyamoorthy Sridharan , Senthil Kumar Dhivya
Published: May 2024

Background

LDL cholesterol (LDL-C) is regarded as a significant therapeutic target and a known risk factor for atherosclerosis. It can be calculated using the results of the other lipid tests or tested directly. Despite its shortcomings, the Friedewald formula is most frequently utilized since it is simple and practical. Until now, several formulae have been proposed for calculating LDL-C; however, their accuracy has not been evaluated across different populations. We sought to evaluate the validity of calculated LDL-C by comparing the findings with values acquired by the direct homogeneous technique, utilizing 13 distinct formulae from the literature.

Methods

This study was a retrospective observational study conducted for a year at SRIHER, Chennai, Tamil Nadu, India. From the total 25 043 patients who had their serum lipid profile tested, 16 314 participants had their fasting blood sugar and fasting lipid profile measured simultaneously, and they were chosen for the research.

Results

The de Cordova, Chen, Martin/Hopkins (initial), and Teerakanchana equations correlated well with the direct LDL-C assay. When the dataset was stratified according to triglycerides, the Chen and Martin/Hopkins initial equations had the better measurement of agreement compared to other equations. The Martin/Hopkins initial equation outperformed all the other equations when the whole dataset irrespective of the triglyceride population was considered.

Conclusions

Our study suggests that the Martin/Hopkins initial equation outperformed all the other equations and can be used as an alternative to direct LDL-C measurement in a South Indian population.
Dietary supplementation with dihydroartemisinin improves intestinal barrier function in weaned piglets with intrauterine growth retardation by modulating the gut microbiota
Authors: Niu Yu , Zhang Ruiqiang , Yang Caimei , He Jintian , Wang Tian
Published: May 2024

The aim of this study was to investigate whether dietary dihydroartemisinin (DHA) supplementation could improve intestinal barrier function and microbiota composition in intrauterine growth restriction (IUGR) weaned piglets. Twelve normal birth weight (NBW) piglets and 24 IUGR piglets at 21 d of age were divided into three groups, which were fed a basal diet (NBW-CON and IUCR-CON groups) and an 80 mg/kg DHA diet (IUGR-DHA group). At 49 d of age, eight piglets of each group with similar body weights within groups were slaughtered, and serum and small intestine samples were collected. The results showed that IUGR piglets reduced growth performance, impaired the markers of intestinal permeability, induced intestinal inflammation, decreased intestinal immunity, and disturbed the intestinal microflora. Dietary DHA supplementation increased average daily gain, average daily feed intake, and body weight at 49 d of age in IUGR-weaned piglets (P < 0.05). DHA treatment decreased serum diamine oxidase activity and increased the numbers of intestinal goblet cells and intraepithelial lymphocytes, concentrations of jejunal mucin-2 and ileal trefoil factor 3, and intestinal secretory immunoglobin A and immunoglobin G (IgG) concentrations of IUGR piglets (P < 0.05). Diet supplemented with DHA also upregulated mRNA abundances of jejunal IgG, the cluster of differentiation 8 (CD8), major histocompatibility complex-I (MHC-I), and interleukin 6 (IL-6) and ileal IgG, Fc receptor for IgG (FcRn), cluster of differentiation 8 (CD4), CD8, MHC-I, IL-6 and tumor necrosis factor α (TNF-α), and enhanced mRNA abundance and protein expression of intestinal occludin and ileal claudin-1 in IUGR piglets (P < 0.05). In addition, DHA supplementation in the diet improved the microbial diversity of the small intestine of IUGR piglets and significantly increased the relative abundance of Actinobacteriota, Streptococcus, Blautia and Streptococcus in the jejunum, and Clostridium sensu_ stricto_in the ileum (P < 0.05). The intestinal microbiota was correlated with the mRNA abundance of tight junction proteins and inflammatory response-related genes. These data suggested that DHA could improve the markers of intestinal barrier function in IUGR-weaned piglets by modulating gut microbiota. DHA may be a novel nutritional candidate for preventing intestinal dysfunction in IUGR pigs.
Developing Financial Acumen as a Breast Imaging Radiologist
Authors: McGinty Geraldine
Published: May 2024

The economics of health care and payment policy are complex and continually evolving. Breast imaging radiologists may not feel equipped to understand the financial aspect of their practice, but this is a critical competency from residency to senior leadership, especially for breast imaging radiologists. From conducting effective negotiations for new equipment as technology evolves to understanding how insurance benefit design affects patient access to care, breast imaging radiologists need to grasp the financial structures that underpins their practice. Fortunately, resources exist that are appropriate for each career stage, and this article directs the breast imaging radiologist to those resources.
Neoadjuvant therapy increases the risk of metabolic disorders and osteosarcopenia in patients with early breast cancer
Authors: Zhang Yan , Kang Hua , Zhao Jing , Wang Yajun , Cai Wei , Zhang Xiaoli , Li Kaifu , Zhao Ye
Published: May 2024

Background

The purpose of this study is to evaluate the effects of neoadjuvant therapy on glucose and lipid metabolism, bone mineral density (BMD) and muscle, and to explore the relationship between metabolic disorders and changes in body composition, so as to provide better health management strategies for breast cancer survivors.

Methods

The clinical data of 43 patients with breast cancer who received neoadjuvant therapy in Xuanwu Hospital from January 2020 to June 2021 were analyzed retrospectively. The biochemical results, including albumin, blood glucose, triglyceride and cholesterol, were collected before neoadjuvant therapy and before surgery. The pectoral muscle area, pectoral muscle density and cancellous bone mineral density of the 12th thoracic vertebra were also measured by chest CT.

Results

After neoadjuvant therapy, fasting blood glucose, triglyceride and cholesterol were significantly increased, albumin was decreased. At the same time, pectoral muscle area, pectoral muscle density and T12 BMD were decreased. After treatment, BMD was positively correlated with pectoral muscle area, R2 = 0.319, P = 0.037, and BMD was also positively correlated with pectoral muscle density, R2 = 0.329, P = 0.031. Multivariate analysis showed that BMD and pectoral muscle density were correlated with menstrual status, and pectoral muscle area was correlated with body mass index before treatment, none of which was related to glucose and lipid metabolism.

Conclusion

Neoadjuvant therapy can cause glucose and lipid metabolism disorder, BMD decrease and muscle reduction. BMD was positively correlated with muscle area and density after treatment, suggesting that patients had an increased chance of developing osteosarcopenia.
Arabidopsis transcription factor ANAC102 predominantly expresses a nuclear protein and acts as a negative regulator of methyl viologen-induced oxidative stress responses
Authors: Luo Xiaopeng , Jiang Xinqiang , Schmitt Vivian , Kulkarni Shubhada R , Tran Huy Cuong , Kacprzak Sylwia M , Van Breusegem Frank , Van Aken Olivier , Vandepoele Klaas , De Clercq Inge
Published: May 2024

Plants, being sessile organisms, constantly need to respond to environmental stresses, often leading to the accumulation of reactive oxygen species (ROS). While ROS can be harmful, they also act as second messengers guiding plant growth and stress responses. Because chloroplasts are sensitive to environmental changes and are both a source and a target of ROS during stress conditions, they are important in conveying environmental changes to the nucleus, where acclimation responses are coordinated to maintain organellar and overall cellular homeostasis. ANAC102 has previously been established as a regulator of β-cyclocitral-mediated chloroplast-to-nucleus signaling, protecting plants against photooxidative stress. However, debates persist about where ANAC102 is located—in chloroplasts or in the nucleus. Our study, utilizing the genomic ANAC102 sequence driven by its native promoter, establishes ANAC102 primarily as a nuclear protein, lacking a complete N-terminal chloroplast-targeting peptide. Moreover, our research reveals the sensitivity of plants overexpressing ANAC102 to severe superoxide-induced chloroplast oxidative stress. Transcriptome analysis unraveled a dual role of ANAC102 in negatively and positively regulating genome-wide transcriptional responses to chloroplast oxidative stress. Through the integration of published data and our own study, we constructed a comprehensive transcriptional network, which suggests that ANAC102 exerts direct and indirect control over transcriptional responses through downstream transcription factor networks, providing deeper insights into the ANAC102-mediated regulatory landscape during oxidative stress.
Analysis of sulfide signaling in rice highlights specific drought responses
Authors: Zhang Jing , Aroca Angeles , Hervás Manuel , Navarro José A , Moreno Inmaculada , Xie Yanjie , Romero Luis C , Gotor Cecilia
Published: May 2024

Hydrogen sulfide regulates essential plant processes, including adaptation responses to stress situations, and the best characterized mechanism of action of sulfide consists of the post-translational modification of persulfidation. In this study, we reveal the first persulfidation proteome described in rice including 3443 different persulfidated proteins that participate in a broad range of biological processes and metabolic pathways. In addition, comparative proteomics revealed specific proteins involved in sulfide signaling during drought responses. Several proteins are involved in the maintenance of cellular redox homeostasis, the tricarboxylic acid cycle and energy-related pathways, and ion transmembrane transport and cellular water homeostasis, with the aquaporin family showing the highest differential levels of persulfidation. We revealed that water transport activity is regulated by sulfide which correlates with an increasing level of persulfidation of aquaporins. Our findings emphasize the impact of persulfidation on total ATP levels, fatty acid composition, levels of reactive oxygen species, antioxidant enzymatic activities, and relative water content. Interestingly, the role of persulfidation in aquaporin transport activity as an adaptation response in rice differs from current knowledge of Arabidopsis, which highlights the distinct role of sulfide in improving rice tolerance to drought.
Protein kinase SnRK2.6 phosphorylates transcription factor bHLH3 to regulate anthocyanin homeostasis during strawberry fruit ripening
Authors: Huang Fuli , Sun Mimi , Yao Zhijin , Zhou Jing , Bai Qian , Chen Xuexue , Huang Yun , Shen Yuanyue
Published: May 2024

Strawberry (Fragaria × ananassa) is a model plant for studying non-climacteric fruit ripening regulated by abscisic acid (ABA); however, the signaling of ABA in the regulation of fruit coloration is not fully understood. In this study, we identified the transcription factor BASIC HELIX-LOOP-HELIX 3 (bHLH3) as being key to fruit coloration via yeast two-hybrid library screening using the bait SUCROSE NONFERMENTING 1 (SNF1)-RELATED PROTEIN KINASE 2 (SnRK2.6), which is a core ABA signaling component that negatively regulates ripening. The interaction was also confirmed by firefly luciferase complementation assays and pull-down assays. RT-qPCR and western blot analysis confirmed that bHLH3 is expressed ubiquitously in strawberry tissues, and it is expressed stably during fruit development. Overexpression and RNAi of both bHLH3 and SnRK2.6 demonstrated that bHLH3 and SnRK2.6 promote and inhibit strawberry fruit coloration, respectively. Using EMSAs, we showed that bHLH3 promotes the expression of UDP-GLUCOSE: FLAVONOL-O-GLUCOSYLTRANSFERASE (UFGT), a key gene for anthocyanin biosynthesis, by directly binding to its promoter. We determined that SnRK2.6 can phosphorylate bHLH3 and that this inhibits its binding to the UFGT promoter, consequently suppressing expression. Altogether, we propose that increased ABA content during strawberry fruit ripening leads to decreased expression of SnRK2.6, which in turn releases the phosphorylation of bHLH3 and thereby enhances UFGT expression, ultimately promoting the coloration of the fruit.
Expression of dehydroshikimate dehydratase in poplar induces transcriptional and metabolic changes in the phenylpropanoid pathway
Authors: Akyuz Turumtay Emine , Turumtay Halbay , Tian Yang , Lin Chien-Yuan , Chai Yen Ning , Louie Katherine B , Chen Yan , Lipzen Anna , Harwood Thomas , Satish Kumar Kavitha , Bowen Benjamin P , Wang Qian , Mansfield Shawn D , Blow Matthew J , Petzold Christopher J , Northen Trent R , Mortimer Jenny C , Scheller Henrik V , Eudes Aymerick
Published: May 2024

Modification of lignin in feedstocks via genetic engineering aims to reduce biomass recalcitrance to facilitate efficient conversion processes. These improvements can be achieved by expressing exogenous enzymes that interfere with native biosynthetic pathways responsible for the production of the lignin precursors. In planta expression of a bacterial 3-dehydroshikimate dehydratase in poplar trees reduced lignin content and altered the monomer composition, which enabled higher yields of sugars after cell wall polysaccharide hydrolysis. Understanding how plants respond to such genetic modifications at the transcriptional and metabolic levels is needed to facilitate further improvement and field deployment. In this work, we acquired fundamental knowledge on lignin-modified poplar expressing 3-dehydroshikimate dehydratase using RNA-seq and metabolomics. The data clearly demonstrate that changes in gene expression and metabolite abundance can occur in a strict spatiotemporal fashion, revealing tissue-specific responses in the xylem, phloem, or periderm. In the poplar line that exhibited the strongest reduction in lignin, we found that 3% of the transcripts had altered expression levels and ~19% of the detected metabolites had differential abundance in the xylem from older stems. The changes affected predominantly the shikimate and phenylpropanoid pathways as well as secondary cell wall metabolism, and resulted in significant accumulation of hydroxybenzoates derived from protocatechuate and salicylate.
Full spectroscopic model and trihybrid experimental-perturbative-variational line list for NH
Authors: Perri Armando N , McKemmish Laura K
Published: May 2024

Imidogen (NH) is a reactive molecule whose presence in astrochemical environments is of interest due to its role in the formation of nitrogen-containing molecules and as a potential probe of nitrogen abundance. Spectroscopic NH monitoring is useful for Earth-based combustion and photolysis processes of ammonia and other nitrogen-containing species. NH is also relevant to ultracold molecular physics and plasma studies. To enable these diverse applications, high-quality molecular spectroscopic data are required. Here, a new line list with significant advantages over existing data is presented. Most notably, this line list models isotopologue spectroscopy and forbidden transitions (important for NH visible absorption), alongside some overall improvements to accuracy and completeness. This approach takes advantage of existing experimental data (from a previous MARVEL compilation) and perturbative line lists together with new MRCI ab initio electronic data. These are used to produce a novel variational spectroscopic model and trihybrid line list for the main 14N1H isotopologue, as well as isotopologue-extrapolated hybrid line lists for the 14N2H, 15N1H, and 15N2H isotopologues. The new 14N1H ExoMol-style trihybrid line list, kNigHt, comprises 4076 energy levels (1078 experimental) and 327 014 transitions up to 47 500 cm−1 (211 nm) between five low-lying electronic states (X 3Σ−, a 1Δ, b 1Σ+, A 3Π, and c 1Π). For most anticipated applications aside from far-infrared studies, this line list will be of sufficient quality; any improvements should focus on the b 1Σ+ energies, and the a 1Δ – A 3Π and b 1Σ+ – A 3Π spin–orbit couplings.
Lung ultrasound in the assessment of interstitial lung disease in patients with connective tissue disease: Performance in comparison with high-resolution computed tomography
Authors: Watanabe Shinji , Yomono Keina , Yamamoto Shintaro , Suzuki Mikito , Gono Takahisa , Kuwana Masataka
Published: May 2024

Objective

To investigate clinical relevance of performing lung ultrasound (LUS) in patients with connective tissue disease (CTD)-associated interstitial lung disease (ILD) in comparison with high-resolution computed tomography (HRCT).

Methods

This single-centre study enrolled eligible patients with CTD-ILD from the prospective LUS registry. Total B-lines were detected by assessment at 14 sites via LUS. Forced vital capacity, diffusing lung capacity for carbon monoxide (DLCO), DLCO/alveolar volume, 6-minute walking distance, and the ILD-GAP index were used as ILD prognostic parameters. Correlations were examined using single and multiple regression analyses.

Results

Sixty-seven patients were enrolled, including 29 with idiopathic inflammatory myopathy or anti-synthetase syndrome, 25 with systemic sclerosis (SSc), 10 with rheumatoid arthritis, and 3 with mixed CTD. The total number of B-lines correlated with ILD extent on HRCT in patients with CTD-ILD (r = 0.66; P < .001), particularly in patients with SSc-ILD (r = 0.78; P < .001). Total B-lines and ILD extent on HRCT showed comparable correlations with prognostic parameters, while multiple regression analysis revealed the limited benefit of performing LUS in addition to HRCT in predicting correlations with prognostic factors.

Conclusions

LUS serves as an alternative tool for assessing the severity and prognosis of patients with CTD-ILD.
Pseudogenes in plasmid genomes reveal past transitions in plasmid mobility
Authors: Hanke Dustin M , Wang Yiqing , Dagan Tal
Published: May 2024

Evidence for gene non-functionalization due to mutational processes is found in genomes in the form of pseudogenes. Pseudogenes are known to be rare in prokaryote chromosomes, with the exception of lineages that underwent an extreme genome reduction (e.g. obligatory symbionts). Much less is known about the frequency of pseudogenes in prokaryotic plasmids; those are genetic elements that can transfer between cells and may encode beneficial traits for their host. Non-functionalization of plasmid-encoded genes may alter the plasmid characteristics, e.g. mobility, or their effect on the host. Analyzing 10 832 prokaryotic genomes, we find that plasmid genomes are characterized by threefold-higher pseudogene density compared to chromosomes. The majority of plasmid pseudogenes correspond to deteriorated transposable elements. A detailed analysis of enterobacterial plasmids furthermore reveals frequent gene non-functionalization events associated with the loss of plasmid self-transmissibility. Reconstructing the evolution of closely related plasmids reveals that non-functionalization of the conjugation machinery led to the emergence of non-mobilizable plasmid types. Examples are virulence plasmids in Escherichia and Salmonella. Our study highlights non-functionalization of core plasmid mobility functions as one route for the evolution of domesticated plasmids. Pseudogenes in plasmids supply insights into past transitions in plasmid mobility that are akin to transitions in bacterial lifestyle.
Biochemical properties of chromatin domains define genome compartmentalization
Authors: Lucini Federica , Petrini Cristiano , Salviato Elisa , Pal Koustav , Rosti Valentina , Gorini Francesca , Santarelli Philina , Quadri Roberto , Lembo Giovanni , Graziano Giulia , Di Patrizio Soldateschi Emanuele , Tagliaferri Ilario , Pinatel Eva , Sebestyén Endre , Rotta Luca , Gentile Francesco , Vaira Valentina , Lanzuolo Chiara , Ferrari Francesco
Published: May 2024

Chromatin three-dimensional (3D) organization inside the cell nucleus determines the separation of euchromatin and heterochromatin domains. Their segregation results in the definition of active and inactive chromatin compartments, whereby the local concentration of associated proteins, RNA and DNA results in the formation of distinct subnuclear structures. Thus, chromatin domains spatially confined in a specific 3D nuclear compartment are expected to share similar epigenetic features and biochemical properties, in terms of accessibility and solubility. Based on this rationale, we developed the 4f-SAMMY-seq to map euchromatin and heterochromatin based on their accessibility and solubility, starting from as little as 10 000 cells. Adopting a tailored bioinformatic data analysis approach we reconstruct also their 3D segregation in active and inactive chromatin compartments and sub-compartments, thus recapitulating the characteristic properties of distinct chromatin states. A key novelty of the new method is the capability to map both the linear segmentation of open and closed chromatin domains, as well as their compartmentalization in one single experiment.
WebGestalt 2024: faster gene set analysis and new support for metabolomics and multi-omics
Authors: Elizarraras John M , Liao Yuxing , Shi Zhiao , Zhu Qian , Pico Alexander R , Zhang Bing
Published: May 2024

Enrichment analysis, crucial for interpreting genomic, transcriptomic, and proteomic data, is expanding into metabolomics. Furthermore, there is a rising demand for integrated enrichment analysis that combines data from different studies and omics platforms, as seen in meta-analysis and multi-omics research. To address these growing needs, we have updated WebGestalt to include enrichment analysis capabilities for both metabolites and multiple input lists of analytes. We have also significantly increased analysis speed, revamped the user interface, and introduced new pathway visualizations to accommodate these updates. Notably, the adoption of a Rust backend reduced gene set enrichment analysis time by 95% from 270.64 to 12.41 s and network topology-based analysis by 89% from 159.59 to 17.31 s in our evaluation. This performance improvement is also accessible in both the R package and a newly introduced Python package. Additionally, we have updated the data in the WebGestalt database to reflect the current status of each source and have expanded our collection of pathways, networks, and gene signatures. The 2024 WebGestalt update represents a significant leap forward, offering new support for metabolomics, streamlined multi-omics analysis capabilities, and remarkable performance enhancements. Discover these updates and more at https://www.webgestalt.org.
LowTempGAL: a highly responsive low temperature-inducibleGALsystem inSaccharomyces cerevisiae
Authors: Lu Zeyu , Shen Qianyi , Bandari Naga Chandra , Evans Samuel , McDonnell Liam , Liu Lian , Jin Wanli , Luna-Flores Carlos Horacio , Collier Thomas , Talbo Gert , McCubbin Tim , Esquirol Lygie , Myers Chris , Trau Matt , Dumsday Geoff , Speight Robert , Howard Christopher B , Vickers Claudia E , Peng Bingyin
Published: May 2024

Temperature is an important control factor for biologics biomanufacturing in precision fermentation. Here, we explored a highly responsive low temperature-inducible genetic system (LowTempGAL) in the model yeast Saccharomyces cerevisiae. Two temperature biosensors, a heat-inducible degron and a heat-inducible protein aggregation domain, were used to regulate the GAL activator Gal4p, rendering the leaky LowTempGAL systems. Boolean-type induction was achieved by implementing a second-layer control through low-temperature-mediated repression on GAL repressor gene GAL80, but suffered delayed response to low-temperature triggers and a weak response at 30°C. Application potentials were validated for protein and small molecule production. Proteomics analysis suggested that residual Gal80p and Gal4p insufficiency caused suboptimal induction. ‘Turbo’ mechanisms were engineered through incorporating a basal Gal4p expression and a galactose-independent Gal80p-supressing Gal3p mutant (Gal3Cp). Varying Gal3Cp configurations, we deployed the LowTempGAL systems capable for a rapid stringent high-level induction upon the shift from a high temperature (37–33°C) to a low temperature (≤30°C). Overall, we present a synthetic biology procedure that leverages ‘leaky’ biosensors to deploy highly responsive Boolean-type genetic circuits. The key lies in optimisation of the intricate layout of the multi-factor system. The LowTempGAL systems may be applicable in non-conventional yeast platforms for precision biomanufacturing.
Bioinformatic analysis of type III CRISPR systems reveals key properties and new effector families
Authors: Hoikkala Ville , Graham Shirley , White Malcolm F
Published: May 2024

Recognition of RNA from invading mobile genetic elements (MGE) prompts type III CRISPR systems to activate an HD nuclease domain and/or a nucleotide cyclase domain in the Cas10 subunit, eliciting an immune response. The cyclase domain can generate a range of nucleotide second messengers, which in turn activate a diverse family of ancillary effector proteins. These provide immunity by non-specific degradation of host and MGE nucleic acids or proteins, perturbation of membrane potentials, transcriptional responses, or the arrest of translation. The wide range of nucleotide activators and downstream effectors generates a complex picture that is gradually being resolved. Here, we carry out a global bioinformatic analysis of type III CRISPR loci in prokaryotic genomes, defining the relationships of Cas10 proteins and their ancillary effectors. Our study reveals that cyclic tetra-adenylate is by far the most common signalling molecule used and that many loci have multiple effectors. These typically share the same activator and may work synergistically to combat MGE. We propose four new candidate effector protein families and confirm experimentally that the Csm6-2 protein, a highly diverged, fused Csm6 effector, is a ribonuclease activated by cyclic hexa-adenylate.
Treatment strategies of the thromboembolic risk in kidney failure patients with atrial fibrillation
Authors: Genovesi Simonetta , Camm A John , Covic Adrian , Burlacu Alexandru , Meijers Björn , Franssen Casper , Luyckx Valerie , Liakopoulos Vassilios , Alfano Gaetano , Combe Christian , Basile Carlo
Published: May 2024

The incidence and prevalence of atrial fibrillation (AF) in patients affected by kidney failure, i.e. glomerular filtration rate <15 ml/min/1.73 m2, is high and probably underestimated. Numerous uncertainties remain regarding how to prevent thromboembolic events in this population because both cardiology and nephrology guidelines do not provide clear recommendations. The efficacy and safety of oral anticoagulant therapy (OAC) in preventing thromboembolism in patients with kidney failure and AF has not been demonstrated for either vitamin K antagonists (VKAs) or direct anticoagulants (DOACs). Moreover, it remains unclear which is more effective and safer, because estimated creatinine clearance <25–30 ml/min was an exclusion criterion in the randomized controlled trials (RCTs). Three RCTs comparing DOACs and VKAs in kidney failure failed to reach the primary endpoint, as they were underpowered. The left atrial appendage is the main source of thromboembolism in the presence of AF. Left atrial appendage closure (LAAC) has recently been proposed as an alternative to OAC. RCTs comparing the efficacy and safety of LAAC versus OAC in kidney failure were terminated prematurely due to recruitment failure. A recent prospective study showed a reduction in thromboembolic events in haemodialysis patients with AF and undergoing LAAC compared with patients taking or not taking OAC. We review current treatment standards and discuss recent developments in managing the thromboembolic risk in kidney failure patients with AF. The importance of shared decision-making with the multidisciplinary team and the patient to consider individual risks and benefits of each treatment option is underlined.
Toward Sustainable Diets—Interventions and Perceptions Among Adolescents: A Scoping Review
Authors: Lanham Adeline R , van der Pols Jolieke C
Published: May 2024

Adolescence is an important life stage during which shifts toward more healthy and sustainable diets can be promoted. Adolescents have increasing influence over their food choices, informed by their developing personal knowledge and values, affecting long-term dietary behaviors into adulthood. The recent literature regarding adolescents’ (1) perceptions of environmentally sustainable diets and (2) interventions to support adolescents to eat sustainably was reviewed in this study. We reviewed published literature that focused on adolescent participants and their perceptions of, or interventions to support, sustainable dietary habits. Five electronic databases were searched to include studies published since 2012 that met the inclusion criteria, including reporting of participants aged between 11 and 18 years, reporting on adolescents’ perceptions of sustainable diets or interventions implemented to improve the sustainability of adolescents’ diets, and framed in the context of sustainability. Data were extracted, including study and participant characteristics, methodology, and results in relation to each of the 2 research focus areas. Twenty-eight articles were included in the review. Findings suggest that adolescents’ understanding of what constitutes sustainable eating is poor. Adolescents who had previously received education regarding sustainable diets valued nature and health, or were from a rural or indigenous community, were more likely to value environmentally sustainable-food choices. Interventions which target adolescents’ understanding of and aspiration to make sustainable-food choices appears to improve their attitudes toward sustainable food, whereas interventions to increase the availability of sustainable foods improved the environmental sustainability of adolescents’ dietary intake. Multicomponent, tailored, and community-based interventions were most effective; however, the long-term effect of these interventions remains unclear. More research is needed in low- and middle-income countries, with consideration of adolescents’ level of autonomy in food choice in local food environments and the long-term effectiveness of interventions.

Systematic Review Registration: Open Science Framework identifier osf.io/h3jz6.
Investigating the effect of virtual reality glasses during inhaler therapy use in children: A randomized clinical trial
Authors: Okay Berker , Üze Okay Zeynep
Published: May 2024

Objectives

Virtual reality (VR) glasses have been used in the medical field, as they are perceived to be suitable for distracting children. In this study, we aimed to compare patients who received inhaler treatment with VR glasses with those who received treatment without the aid of any device in terms of treatment compliance.

Materials and Methods

A prospective, randomized controlled study was conducted on pediatric patients aged 2 to 5 years requiring inhaler treatment (salbutamol), with the informed consent of their families. Participating patients who received standard care were divided into three groups via randomization: roller coaster VR group, wild dolphin VR group, and no additional device group. The patients were observed during their 15-minute inhaler treatment, and the groups were compared in terms of crying times, pre- and post-treatment physician and family questionnaire data (Face, Legs, Activity, Cry, Consolabity Scale [FLACC], Modified Yale Anxiety Scale [MYPAS], Modifiye Parents’ Pain Measure [MPMM], Wong–Baker Faces Pain Rating Scale [WBS]), and respiratory rate (RR), peripheral oxygen saturation, and heart rate value changes to determine any differences between them.

Results

Post-treatment questionnaire scores, RR, crying duration, and efficacy of treatment exhibited significant differences in Groups 1 and 2 compared to the control group. A significant difference was found in the post-treatment RR between groups 1 and 2, but no difference was observed in the other parameters.

Conclusions

Utilizing VR glasses during inhaler therapy has the potential to minimize adverse effects, such as pain, and enhance the overall comfort of the treatment environment for patients.
Molecular Mimicry of Transposable Elements in Plants
Authors: Chu Jie , Newman Josephine , Cho Jungnam
Published: May 2024

Transposable elements (TEs) are mobile DNA elements that are particularly abundant in the plant genomes. They have long been considered as junk DNA; however, a growing body of evidence suggests that TE insertions promote genetic diversity that is essential for the adaptive evolution of a species. Thus far, studies have mainly investigated the cis-acting regulatory roles of TEs generated by their insertions nearby or within the host genes. However, the trans-acting effects of TE-derived RNA and DNA remained obscure to date. TEs contain various regulatory elements within their sequences that can accommodate the binding of specific RNAs and proteins. Recently, it was suggested that some of these cellular regulators are shared between TEs and the host genes, and the competition for the common host factors underlies the fine-tuned developmental reprogramming. In this review, we will highlight and discuss the latest discoveries on the biological functions of plant TEs, with a particular focus on their competitive binding with specific developmental regulators.
The Lethality Assessment Program 2.0: Adjusting intimate partner violence risk assessment to account for strangulation risk
Authors: Messing Jill Theresa , Campbell Jacquelyn , Holly Darrell , Corwin Dave
Published: May 2024

The Lethality Assessment Program (LAP) assists police responding to intimate partner violence incidents by connecting victims identified as high risk with advocates while police are at the scene. The Lethality Screen is the risk assessment used with the LAP. This manuscript focuses on evaluating and refining changes to the Lethality Screen that prioritize strangulation as a risk item that automatically places a survivor in the high-danger category. Secondary data from the Oklahoma Lethality Assessment (OK-LA) Study (n=234) were utilized for analysis. Researchers and community partners collaborated to explore various options for revising the Lethality Screen given the goal of the community partner to prioritize strangulation on the risk assessment. The final adaptation of the Lethality Screen was examined for its ability to predict near fatal violence, severe violence, violence and abuse by an intimate partner at 7 months follow-up. The revised Lethality Screen has high sensitivity (84-93%), low specificity (14-16%), and broad ranges of negative predictive value (47-94%) and positive predictive value (12-63%). Revisions to the Lethality Screen are discussed in conjunction with additional adaptations that were made to the LAP, resulting in the LAP 2.0.
When code isn’t law: rethinking regulation for artificial intelligence
Authors: Judge Brian , Nitzberg Mark , Russell Stuart
Published: May 2024

This article examines the challenges of regulating artificial intelligence (AI) systems and proposes an adapted model of regulation suitable for AI’s novel features. Unlike past technologies, AI systems built using techniques like deep learning cannot be directly analyzed, specified, or audited against regulations. Their behavior emerges unpredictably from training rather than intentional design. However, the traditional model of delegating oversight to an expert agency, which has succeeded in high-risk sectors like aviation and nuclear power, should not be wholly discarded. Instead, policymakers must contain risks from today’s opaque models while supporting research into provably safe AI architectures. Drawing lessons from AI safety literature and past regulatory successes, effective AI governance will likely require consolidated authority, licensing regimes, mandated training data and modeling disclosures, formal verification of system behavior, and the capacity for rapid intervention.
Collective Excitations of Self-Gravitating Bose–Einstein Condensates: Breathing Mode and Appearance of Anisotropy under Self-Gravity
Authors: Asakawa Kenta , Ishihara Hideki , Tsubota Makoto
Published: May 2024

We investigate the collective mode of a self-gravitating Bose–Einstein condensate (BEC) described by the Gross–Pitaevskii–Poisson (GPP) equations. The self-gravitating BEC has garnered considerable attention in cosmology and astrophysics, being proposed as a plausible candidate for dark matter. Our inquiry delves into the breathing and anisotropic collective modes by numerically solving the GPP equations and using the variational method. The breathing mode demonstrates a reduction in period with increasing total mass due to the density dependence of the self-gravitating BEC, attributed to the density-dependent nature of self-gravitating BECs, aligning quantitatively with our analytical findings. Additionally, we investigate an anisotropic collective mode in which the quadrupole mode intertwines with the breathing mode. The period of the quadrupole mode exhibits similar total mass dependence to that of the breathing mode. The characteristics of these periods differ from those of a conventional BEC confined by an external potential. Despite the differences in density dependence, the ratio of their periods equals that of the BEC confined by an isotropic harmonic potential. Furthermore, an extension of the variational method to a spheroidal configuration enables the isolation of solely the quadrupole mode from the anisotropic collective mode.