bluuebunny/crossref_metadata_2025 huggingface dataset:
Sometimes Small Is Beautiful: Discovery of the Janus Kinases (JAK) and Signal Transducer and Activator of Transcription (STAT) Pathways and the Initial Development of JAK Inhibitors for IBD Treatment
Authors: Kaunitz Jonathan D.
Published: January 2025

The Janus kinase/signal transducer and activator of transfection (JAK/STAT) system is comprised of multiple cell surface receptors, receptor tyrosine kinases, and signal transducers that are key components of numerous systems involved in malignancy, inflammation, immune surveillance and development, cellular proliferation, metabolism, differentiation, apoptosis, and hematologic disorders, all of which when disrupted can produce severe disease. Nevertheless, small molecule inhibitors of the four known JAKs, termed JAKinibs, have found therapeutic indications for a broad category of diseases. In this perspective, I will summarize the development of JAK inhibitors, whose origins were in antiquity, with particular attention to their use in treating patients with inflammatory bowel disease (IBD). This perspective is accompanied by a companion publication addressing how JAKinibs have forever altered the landscape of IBD therapy.
Predicting odor concentration for environmental sustainability: a comparison among machine Learning methods
Authors: Palma Monica , Distefano Veronica , Giungato Giuseppina , Mazuruse Gideon
Published: January 2025

Odor emissions from a treatment plant is one of the major environmental issues that results in negative health consequences and repercussions on economic, commercial, and touristic activities. To address this problem an accurate assessment of the odor sources is of crucial interest. In this paper, different machine learning methods are applied to identify the most suitable model to estimate odor concentrations through the responses of a multiparametric system. It is observed that random forest regression method shows superior performance compared to the other methods. In this context, advanced data analytics technologies, such as machine learning methods, have provided data-driven decision-making capabilities to address the challenges that arise in the analysis and evaluation of a sustainable development. The findings of the proposed study can help implement proactive actions to minimize the effects of odors and prevent any potential health and environmental concerns.
Integrating the milk microbiome signatures in mastitis: milk-omics and functional implications
Authors: Reuben Rine Christopher , Torres Carmen
Published: January 2025

Mammalian milk contains a variety of complex bioactive and nutritional components and microorganisms. These microorganisms have diverse compositions and functional roles that impact host health and disease pathophysiology, especially mastitis. The advent and use of high throughput omics technologies, including metagenomics, metatranscriptomics, metaproteomics, metametabolomics, as well as culturomics in milk microbiome studies suggest strong relationships between host phenotype and milk microbiome signatures in mastitis. While single omics studies have undoubtedly contributed to our current understanding of milk microbiome and mastitis, they often provide limited information, targeting only a single biological viewpoint which is insufficient to provide system-wide information necessary for elucidating the biological footprints and molecular mechanisms driving mastitis and milk microbiome dysbiosis. Therefore, integrating a multi-omics approach in milk microbiome research could generate new knowledge, improve the current understanding of the functional and structural signatures of the milk ecosystem, and provide insights for sustainable mastitis control and microbiome management.
Light buckets and laser beams: mechanisms and applications of photobiomodulation (PBM) therapy
Authors: Frankowski David W. , Ferrucci Luigi , Arany Praveen R. , Bowers Dawn , Eells Janis T. , Gonzalez-Lima Francisco , Lohr Nicole L. , Quirk Brendan J. , Whelan Harry T. , Lakatta Edward G.
Published: January 2025

Photobiomodulation (PBM) therapy, a non-thermal light therapy using nonionizing light sources, has shown therapeutic potential across diverse biological processes, including aging and age-associated diseases. In 2023, scientists from the National Institute on Aging (NIA) Intramural and Extramural programs convened a workshop on the topic of PBM to discuss various proposed mechanisms of PBM action, including the stimulation of mitochondrial cytochrome C oxidase, modulation of cell membrane transporters and receptors, and the activation of transforming growth factor-β1. They also reviewed potential therapeutic applications of PBM across a range of conditions, including cardiovascular disease, retinal disease, Parkinson’s disease, and cognitive impairment. Workshop participants largely agreed that PBM holds immense potential as a safe and effective therapeutic approach for a wide range of age-related diseases and cognitive decline. While further research is needed to fully elucidate its mechanisms and optimize treatment protocols, the findings presented at the NIA workshop provide strong evidence for the continued investigation and clinical translation of this promising, inexpensive, safe technology, to aging and age-associated diseases. Here, we review the research presented and discussion held at the meeting. In addition, the text has been updated, where applicable, with recent research findings that have been made since the meeting occurred.
Enhancing cognitive functions in aged dogs and cats: a systematic review of enriched diets and nutraceuticals
Authors: Blanchard Tiphaine , Eppe Justine , Mugnier Amélie , Delfour Fabienne , Meynadier Annabelle
Published: January 2025

With advancements in veterinary care and the growing recognition of pets as integral member of the family, the lifespans of dogs and cats have significantly increased, leading to a higher prevalence of age-related conditions, including cognitive dysfunction syndrome (CDS). CDS adversely impacts pets’ quality of life and presents emotional and practical challenges for owners. Given its similarities to Alzheimer’s disease in humans, CDS has gained attention as a target for nutrition-based interventions aimed at preserving cognitive function. This systematic review evaluates the efficacy of enriched diets and nutraceuticals in improving cognition in aging companion animals. A literature search was conducted using PubMed, CAB Abstracts, Web of Science, and Dimensions to identify clinical trials published in English that investigated the effects of enriched diets or nutraceuticals on cognitive functions in aged cats or dogs. Study quality was assessed using a modified CAMARADES checklist. A total of 30 studies (27 canine and 2 feline trials) published between 2002 and 2023 were reviewed. Studies on enriched diets generally demonstrated higher methodological quality compared to those on supplements. Omega-3 fatty acids showed cognitive benefits in aging pets, especially at higher doses, while antioxidants from plant extracts and products and vitamins E and C alone were less effective but remain essential for stabilizing omega-3 fatty acids. Other supplements, including S-adenosyl methionine, medium-chain triglycerides, homotaurine, and apoaequorin, also showed promise. However, future studies must standardize protocols, include robust control groups, and utilize both objective tasks and subjective questionnaires to strengthen conclusions.
Storage Stability and Antioxidant Properties of Vegetable and Marine Lecithin Liposomes Loaded with Sea Cucumber (Holothuria forskali) and Musky Octopus (Eledone moschata) Protein Hydrolysates
Authors: Pascual-Silva C. , Alemán A. , Montero M. P. , Gómez-Guillén M. C.
Published: January 2025

This study is aimed at comparing how the lipid composition of lecithins from vegetable and marine sources affects the properties and storage stability of liposomes and at evaluating their capacity to encapsulate two protein hydrolysates derived from undervalued marine invertebrates. The particle properties (size, polydispersity index or PDI, and ζ potential), thermal properties, in vitro antioxidant properties, and angiotensin-converting enzyme (ACE) inhibitory capacity of liposomes produced from soybean, sunflower, and herring roe lecithin were compared. All lecithins exhibited a high polyunsaturated fatty acid (PUFA) content (52.7 − 59.18%); however, for the marine-derived lecithin, rich in long chain ω-3 fatty acids, a partial purification process of phospholipids was required to obtain a stable liposomal dispersion. Mean particle sizes of 212 nm, 130 nm, and 96 nm were obtained for sunflower lecithin (LSun), soy lecithin (LSoy), and partially purified marine lecithin (LMarP) liposomes, respectively, all with electronegative zeta potential. Two protein hydrolysates obtained from sea cucumber and musky octopus protein concentrates were successfully encapsulated in liposomes prepared with the respective lecithins and then characterised. The hydrolysates provided liposomes with high ACE-inhibitory capacity; however, antioxidant properties were highly dependent on the lecithin source. Unloaded and loaded liposomes presented high colloidal stability during 4 weeks of chilled storage. Finally, a principal component analysis (PCA) was conducted to summarise and interpret the results. Liposomes derived from marine phospholipids offer a nutritious alternative, due to their long-chain omega-3 fatty acid content, high biological activity, and favourable structural attributes.
Introducing digital air-traffic controllers for urban-air mobility to ensure safe and energy-efficient flight operations
Authors: Schier-Morgenthal S. , Abdellaoui R. , Metz I. C.
Published: January 2025

Facing the continued growth of cities, the introduction of urban-air mobility intends to reduce traffic congestion and improve the quality of services such as on-demand-transport, reduced travel times and increased connectivity. Nevertheless, its integration into existing air-traffic flows remains one of the biggest challenges ahead, especially once controlled airspace overlaps with urban-air mobility areas, such as at airport control zones. Here, air-traffic control needs to coordinate amobng urban-air mobility vehicles and conventional air traffic. In 2022, DLR conducted a human-in-the-loop simulation with ten air-traffic controllers to validate previously developed workflows for that coordination task applied for Hamburg airport. The simulation results revealed that additional urban-air mobility traffic increases controllers’ experienced workload up to 30% while slightly reducing their perceived situation awareness. Thus, a majority of controllers participating in the trials suggested to introduce an additional controller working position to exclusively control airtaxis and traffic following visual flight rules. This option is assessed as owning a high potential as cost intensive adaptions of regulations and procedures can be omitted. Nevertheless, the feasibility of this option is rather low due to the limited availability of endorsed human controllers.

This study proposes a concept for a digital controller taking the responsibility of guidance for airtaxis under visual flight rules traffic (abbr. VFR) within a control zone. This digital controller is named “UAM digital controller” (abbr. UDC) and based on algorithms calculating slots and trajectories which have been validated in previous DLR projects. The UDC coordinates with the human controller once a potential conflict is detected. Within the study, first the concept of the digital controller is defined, following existing work. As a second step, a theoretical evaluation based on an air-traffic control task model and an operational concept for airtaxi integration will analyze the task load reduction for the human controller. Last but not least, the expected energy saving of flight operations by the digital controllers will be assessed.
Apatite Geochemical Perspectives on the Maturation of Continental Arc Crust via Mush‐Facilitated Processes During Magmatic Flare‐Up
Authors: Chen Long , Gao Peng , Somerville Ian , Li San‐Zhong , Deng Jiang‐Hong , Li Dong‐Yong , Yu Sheng‐Yao , Li Xiao‐Hui , Cao Hua‐Hua , Zhao Zi‐Fu , Yin Zhi‐Feng
Published: January 2025

In volcanic arcs, magma evolves from basaltic to intermediate and felsic composition, resulting in arc crust maturation. It remains unclear whether processes involving mush during magmatic flare‐ups would enhance this evolution. This study revealed a temporal‐compositional evolution of plutonic rocks from mafic (∼94 Ma) to intermediate (∼92–88 Ma) to felsic (∼88 Ma) during a magmatic flare‐up event in the Gangdese arc, Tibet, with increasing radiogenic Sr–Nd isotope enrichment. Apatites in mafic and felsic rocks have εNd(t) values similar to their hosts, while intermediate rocks show higher values. The elemental composition of apatites in mafic and intermediate rocks is similar but differs from those in felsic rocks. Textural and compositional features indicate varying degrees of influence of mafic rock compositions by accumulation. Triangular and linear covariation relationships between apatite‐compatible (e.g., La) and ‐incompatible (e.g., Rb) elements with SiO2, respectively, for all plutonic rocks as a whole, confirm the incorporation of apatite‐rich mushes into the mixing process. These findings suggest that mafic magma crystallized into apatite‐rich mush, which was later remobilized and mixed with felsic magma to form intermediate magma. Felsic rocks represent end‐member magmas resulting from crustal anatexis and/or mafic magma differentiation. Thus, the Gangdese arc's maturation during the magmatic flare‐up progressed sequentially through mafic magma crystallization and mush formation, mush remobilization and mixing with felsic magma, and the eventual accumulation and segregation of felsic magma. This sequence of events during flare‐ups illustrates a common crustal maturation process in volcanic arcs, as also seen in the Andean Cordillera.
Helicobacter pylori reduces METTL14-mediated VAMP3 m6A modification and promotes the development of gastric cancer by regulating LC3C-mediated c-Met recycling
Authors: Cui Xixi , Chang Mingjie , Wang Yuqiong , Liu Jiayi , Sun Zenghui , Sun Qiyu , Sun Yundong , Ren Juchao , Li Wenjuan
Published: January 2025

Helicobacter pylori (H. pylori) plays an important role in the malignant transformation of the gastric mucosa from chronic inflammation to cancer. However, the mechanisms underlying the epigenetic regulation of gastric carcinogenesis mediated by H. pylori remain unclear. Here, we uncover that H. pylori inhibits METTL14 by upregulating ATF3. METTL14 inhibits gastric cancer (GC) cell proliferation and metastasis in vitro and in vivo. Downregulation of METTL14 inhibits Vesicle-associated membrane protein-3 (VAMP3) by reducing the m6A modification level of VAMP3 mRNA and the stability of IGF2BP2-dependent mRNA. H. pylori also accelerates the malignant progression of GC by regulating VAMP3/LC3C-mediated c-Met recycling. Moreover, the expression of METTL14 and VAMP3 in Hp+ chronic gastritis tissues is much lower than that in Hp− chronic gastritis tissues. METTL14 and VAMP3 expression levels are downregulated notably in cancerous tissues of patients with GC. Therefore, our results show a novel METTL14-VAMP3-LC3C-c-Met signalling axis in the GC development mediated by H. pylori infection, which reveals a novel m6A epigenetic modification mechanism for GC and provides potential prognostic biomarkers for GC progression.
Impact of stain variation and color normalization for prognostic predictions in pathology
Authors: Lin Siyu , Zhou Haowen , Watson Mark , Govindan Ramaswamy , Cote Richard J. , Yang Changhuei
Published: January 2025

In recent years, deep neural networks (DNNs) have demonstrated remarkable performance in pathology applications, potentially even outperforming expert pathologists due to their ability to learn subtle features from large datasets. One complication in preparing digital pathology datasets for DNN tasks is the variation in tinctorial qualities. A common way to address this is to perform stain normalization on the images. In this study, we show that a well-trained DNN model trained on one batch of histological slides failed to generalize to another batch prepared at a different time from the same tissue blocks, even when stain normalization methods were applied. This study used sample data from a previously reported DNN that was able to identify patients with early-stage non-small cell lung cancer (NSCLC) whose tumors did and did not metastasize, with high accuracy, based on training and then testing of digital images from H&E stained primary tumor tissue sections processed at the same time. In this study, we obtained a new series of histologic slides from the adjacent recuts of the same tissue blocks processed in the same lab but at a different time. We found that the DNN trained on either batch of slides/images was unable to generalize and failed to predict progression in the other batch of slides/images (AUCcross-batch = 0.52 - 0.53 compared to AUCsame-batch = 0.74 - 0.81). The failure to generalize did not improve even when the tinctorial difference corrections were made through either traditional color-tuning or stain normalization with the help of a Cycle Generative Adversarial Network (CycleGAN) process. This highlights the need to develop an entirely new way to process and collect consistent microscopy images from histologic slides that can be used to both train and allow for the general application of predictive DNN algorithms.
Quantitative study on the environmental impact of Beijing’s urban rail transit based on carbon emission reduction
Authors: Jia Cai , Wang Xudong , Qian Chengyang , Cao Zini , Zhao Long , Lin Luzhou
Published: January 2025

Urban rail transit, as an efficient and eco-friendly mode of transportation, plays a pivotal role in mitigating traffic congestion and lowering urban carbon emissions. Despite the significant contributions by scholars in this area, debates surrounding the quantification of carbon emissions during the operational phase of urban rail transit persist, particularly in assessing its impact on reducing ground traffic congestion. This study examines the passenger flow during Beijing’s morning and evening peak hours, assuming that all passengers initially using urban rail transit switch to buses and taxis during these periods. A traffic congestion prediction model is developed based on the analysis of actual traffic operation data under this assumption. Through this model, the study calculates the potential congestion times across various scenarios, employing a bottom-up approach to carbon emission estimation to analyze the impact on carbon emissions. Results spanning 2015 to 2021 suggest that substituting urban rail transit with buses could increase congestion by 37–92 min and 46–59 min during morning and evening peaks, respectively, leading to a 24-82% and 27-56% surge in carbon emissions. The conversion of all these vehicles to taxis would result in a direct paralysis of Beijing’s road transport network, with a corresponding increase in carbon emissions of between 289% and 556% and 333% and 614%, respectively.These outcomes emphasize the substantial efficacy of urban rail transit in curbing traffic congestion and carbon emissions.
Investigating the role of the metabolic score for visceral Fat in assessing the prevalence of chronic kidney disease from the NHANES 1999–2018
Authors: Zhou Xingcheng , Xiang Jiayi , Zhang Shuxian , Yang Jun , Tang Yi , Wang Yalan
Published: January 2025

This study investigates the association between the Metabolic Score for Visceral Fat (METS-VF) and chronic kidney disease (CKD), assessing METS-VF as a potential predictor of CKD risk. Utilizing data from the 1999–2018 National Health and Nutrition Examination Survey (NHANES), this cross-sectional study included 24,387 adult participants. Multivariable logistic regression, restricted cubic spline models, and threshold effect analyses were employed to explore the relationship. The results revealed a significant positive association, with multivariable logistic regression showing that each unit increase in METS-VF was associated with an 86% higher risk of CKD (OR: 1.86, 95% CI: 1.48–2.34). Critical METS-VF thresholds (6.10 and 7.55) were identified, at which CKD risk increased substantially. Subgroup analyses indicated that the association was particularly pronounced among older adults and males. These findings suggest that METS-VF is a reliable predictor for assessing CKD risk and that lifestyle interventions, including dietary modifications and exercise programs, may mitigate this risk.
Improving mechanical properties and electrical conductivity of Al-Cu-Mg matrix composites by GNPs and sc additions
Authors: Yuan Li , Liu Fengguo , Wu Chun , Lou Changsheng
Published: January 2025

To enhance the mechanical properties and electrical conductivity of Al-Cu-Mg-based composites, aluminum matrix composites containing scandium (Sc) and graphene nanoplatelets (GNPs) were fabricated by means of stepwise ball milling, vacuum hot pressing sintering, and hot rolling techniques. When Sc and GNPs were incorporated at concentrations of 0.1 wt% and 0.2 wt% respectively, the resultant composites demonstrated a maximum tensile strength of 326.81 MPa, an elongation of 3.2%, an electrical conductivity of 46.95% IACS, and a hardness of 112.96 HV. In comparison with the 2024 aluminum alloy matrix, enhancements of 39%, 255%, 51% and 51.21% were witnessed in tensile strength, elongation, electrical conductivity, and hardness respectively. These improvements can be primarily ascribed to the addition of Sc, which facilitated the precipitation of solute atoms and enhanced the interfacial bonding between the GNPs and the matrix, as well as the remarkable heterogeneous layered microstructure induced by the incorporation of GNPs. This study presents a feasible approach to concurrently enhance the strength and electrical conductivity of composites through the combined addition of Sc and GNPs.
A slab window in the south rim of the Parece-Vela Basin
Authors: Zhen Zhang , dong Xu , Lintao Zhao
Published: January 2025

Slab windows represent regions within the mantle that are largely devoid of slab material, facilitating direct communication between the mantle above and below the subducting slab. This unprecedented interaction disrupts the conventional material-energy exchange mechanisms between the subducted slab and mantle wedge, giving rise to anomalous heat flow, distinct magmatism, metamorphism, and geophysical features. Geochemical analyses of samples collected from the southern margin of the Parece-Vela Basin have illuminated the magmatic processes associated with a slab window. C20-3 is indicative of a hot and dry mantle upwelling that occurs through the slab window. On the other hand, C20-1 signifies an adakitic rock, which originates from the melting of oceanic crust at the periphery of the slab window. Slightly east of the slab window, C21-1 reveals evidence of a heated depleted mantle, influenced by the hot and dry mantle upwelling through the slab window. Additionally, a common Island Arc Basalt (IAB), denoted as C21-2, was also observed in the island arc region. Topographical data highlights the irregular distribution of numerous seamounts between the West Mariana Ridge and the Parece-Vela Basin spreading center. Seismological records reveal a preponderance of strike-slip earthquakes in the southern seamount region, alongside exceptionally high heat flow measurements at the northwest extremity of this area. The shape of the slab window can be roughly modeled by analyzing the distribution of earthquakes. Collectively, these observations lead us to postulate the existence of a slab window beneath the southern rim of the Parece-Vela Basin, likely attributed to the tearing of the subducting Pacific Plate along the strike-slip fault situated between the Ulithi and Fais Atolls.
Inferring single-cell and spatial microRNA activity from transcriptomics data
Authors: Herbst Efrat , Mandel-Gutfreund Yael , Yakhini Zohar , Biran Hadas
Published: January 2025

The activity of miRNA varies across different cell populations and systems, as part of the mechanisms that distinguish cell types and roles in living organisms and in human health and disease. Typically, miRNA regulation drives changes in the composition and levels of protein-coding RNA and of lncRNA, with targets being down-regulated when miRNAs are active. The term “miRNA activity" is used to refer to this transcriptional effect of miRNAs. This study introduces miTEA-HiRes, a method designed to facilitate the evaluation of miRNA activity at high resolution. The method applies to single-cell transcriptomics, type-specific single-cell populations, and spatial transcriptomics data. By comparing different conditions, differential miRNA activity is inferred. For instance, miTEA-HiRes analysis of peripheral blood mononuclear cells comparing Multiple Sclerosis patients to control groups revealed differential activity of miR-20a-5p and others, consistent with the literature on miRNA underexpression in Multiple Sclerosis. We also show miR-519a-3p differential activity in specific cell populations.
Intensified gas diffusion in ordered mesoporous PtCo alloys for enhanced oxygen reduction electrocatalysis
Authors: Song Kunming , Kong Fantao , Shen Ruxiang , Yu Xu , Tian Han , Guo Qiuyun , Zhang Gang , Sun Wenping , Cui Xiangzhi
Published: January 2025

Three-dimensional ordered meso-structured PtCo alloy nanoparticles are fabricated to enhance O2 diffusion and accelerate the kinetics of oxygen reduction in proton-exchange membrane fuel cells.
Land Property Rights and Investment Incentives in Movable Farm Assets: Evidence from Post-Soviet Central Asia
Authors: Kurbanov Zafar , Djanibekov Nodir , Herzfeld Thomas
Published: January 2025

We examined whether perceived land rights—use, management, transfer, and tenure security—are associated with investment in movable farm assets. Using micro-level data from crop-specialized farmers in Kazakhstan and Uzbekistan, we distinguish investment incentives linked to tenure security, transferability, and decision-making autonomy (use and management rights). Comparing market-oriented versus government-controlled contexts provides insights into differential role of land rights on investment behavior. Our findings underscore significant investment incentives linked to use and management rights rather than tenure security or transferability. Moreover, we reveal how country-specific institutional contexts influence the effectiveness of these land rights in stimulating agricultural investments.
Association of cognitive deficits with sociodemographic characteristics among adults with post-COVID conditions: Findings from the United States household pulse survey
Authors: Wu Daniel J , Liu Nianjun
Published: January 2025

People infected with coronavirus disease-19 (COVID-19) may continue to experience symptoms for several weeks or even months after acute infection, a condition known as long COVID. Cognitive problems such as memory loss are among the most commonly reported symptoms of long COVID. However, a comprehensive evaluation of the risks of cognitive decline following COVID-19 infection among different sociodemographic groups has not been undertaken at the national level in the USA. We conducted a secondary analysis on the datasets from the U.S. Census Bureau Household Pulse Survey, encompassing data collected from 1 June 2022 to 19 December 2022. Based on a cohort of 385 370 individuals aged 18 years or older, we employed logistic regression analysis to examine the association between self-reported cognitive deficits and different sociodemographic factors among individuals with long COVID conditions. We have demonstrated that individuals with long COVID had a significantly higher risk of cognitive deficits compared to those with no history of COVID infection. Cognitive deficits vary across sociodemographic groups. In individuals without long COVID, men, older adults, and those with higher education reported fewer cognitive deficits, while Hispanics and residents of the South reported more. Long COVID had similar impacts across genders and regions but appeared to have the smallest impact on Hispanics compared to other racial groups. Conversely, the effects of long COVID were most significant in older adults and individuals with higher education. The state-level analysis further suggests potential variation in long COVID’s effects across different states. The risks of cognitive deficits among adults with post-COVID conditions are substantial. Various sociodemographic groups can have different risks of developing cognitive deficits after experiencing long COVID. The findings of this large-scale study can help identify sociodemographic groups at higher risk of cognitive deficits, facilitate medical interventions, and guide resource allocation to target populations at risk and prioritize areas with a high rate of cognitive decline.
Development of a yeast-based sensor platform for evaluation of ligands recognized by the human free fatty acid 2 receptor
Authors: Clausen Lind Andrea , De Castro Gomes Davi , Bisquert Ricardo , Mårtensson Jonas , Sundqvist Martina , Forsman Huamei , Dahlgren Claes , David Florian , Siewers Verena
Published: January 2025

Yeast-based sensors have shown great applicability for deorphanization of G protein-coupled receptors (GPCRs) and screening of ligands targeting these. A GPCR of great interest is free fatty acid 2 receptor (FFA2R), for which short-chain fatty acids such as propionate and acetate are agonists. FFA2R regulates a wide array of downstream receptor signaling pathways in both adipose tissue and immune cells and has been recognized as a promising therapeutic target, having been implicated in several metabolic and inflammatory diseases. While research aiming to identify ligands recognized by FFA2R for translational applications is ongoing, screening is complicated by the complex regulatory and cell-specific responses mediated by the receptor. To simplify screening towards identification of novel ligands, heterologous platforms are valuable tools that offer efficient identification of ligand activity in the absence of regulatory mechanisms. Here, we present a yeast-based sensor designed to evaluate G protein α i1-mediated FFA2R signaling, with an assay time of 3 h. We verify this platform towards the natural agonists, propionate and acetate, and show applicability towards evaluation of synthetic agonists, antagonists, and allosteric agonists. As such, we believe that the developed yeast strain constitutes a promising screening platform for effective evaluation of ligands acting on FFA2R.
Larval development and parasitism of emerald ash borer (Agrilus planipennis) in Oregon ash (Fraxinus latifolia) and European olive (Olea europaea): implications for the West Coast invasion
Authors: Callahan Heather L , Duan Jian J , Ragozzino Max L , Tallamy Douglas W
Published: January 2025

The invasive emerald ash borer (Agrilus planipennis Fairmaire) (EAB) has been devastating North American ash (Fraxinus spp.) resources for over 2 decades. In its native range, EAB attacks and kills primarily stressed ash trees. In North America, however, EAB also attacks healthy trees of every Fraxinus species encountered, most recently Oregon ash (Fraxinus latifolia Benth.). Successful EAB development has also been reported in European olive (Olea europaea L.). The recent detection of EAB in Oregon puts the future of these 2 hosts into question, as little is known about EAB’s development in these species or how introduced biocontrol agents will respond. We conducted laboratory and field infestations of olive and ash in Delaware and Oregon to assess EAB development and associated parasitoid responses. We found no difference in the net population growth rate of EAB developing in Oregon ash versus green ash. However, these species supported significantly more population growth than olive, in which EAB net population growth rate was zero, with most larvae dying prematurely. Artificially infested olives were small, which may have negatively impacted phloem availability and larval survival. Future studies should be conducted investigating EAB development on larger olive material. Although no parasitism was observed in infested olive, as EAB larvae seldom reached life stages (third or fourth instars) susceptible to larval parasitism, late-instar larvae developing in Oregon ash were attacked by both Tetrastichus planipennisi Yang and Spathius galinae Belokobylskij and Strazanac, suggesting that biocontrol is a suitable option for this newly invaded region.
Occurrence of multidrug-resistant ESBL-producing Enterobacteriaceae in livestock and in silico identification of probable catalytic domains in circulating ESBL variants
Authors: Sunder Jai , Mukherjee Ayan , Sujatha T , De Arun Kumar , Bhattacharya Debasis , Bandyopadhyay Samiran , Paul Aditya , Samanta Indranil
Published: January 2025

This study was conducted to detect the occurrence and phenotypic resistance pattern of extended spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae in livestock using docking-based analysis to reveal the classes of antibiotics against which ESBL-producers are active. Rectal swabs from healthy cattle (n = 100), goats (n = 88), and pigs (n = 66) were collected from backyard farms in Andaman and Nicobar Island (India). In total, 304 isolates comprising Escherichia coli (131), Salmonella (75), and Klebsiella pneumoniae (98) were recovered. The phenotypic resistance pattern showed that the highest resistance was found against erythromycin, followed by ampicillin/cloxacillin, ciprofloxacin, amoxicillin/clavulanic acid, and oxytetracycline. Screening of the isolates demonstrated maximum presence of blaTEM-Type, followed by blaCTX-M-Type, and blaSHV-Type. Sequence homology revealed the presence of CTX-M-15, SHV-228, SHV-40, and TEM-82. The possible interactions of CTX-M-15 with cephalosporins and SHV with carbapenems have been identified by docking analysis. The study revealed the occurrence of ESBL-producers with circulating emerging ESBL variants like SHV-40, along with the common variants with clinical relevance (CTX-M-15, TEM-82), highlighting the potential role of livestock as reservoirs for antimicrobial resistance genes. Identifying these ESBLs in livestock is crucial for understanding their contribution to the dissemination of antimicrobial resistant bacteria into the human food chain.
Digital debating cultures: communicative practices on Reddit
Authors: Messerli Thomas C , Dayter Daria , Leuckert Sven , Liimatta Aatu , Mahler Hanna , Bohmann Axel , Kozma Gustavo , Tosin Rafaela
Published: January 2025

Reddit as a platform for online forum interaction hosts various communities (subreddits), which give rise to specific digital communicative practices. Communication on Reddit is on the one hand unified by a set of common affordances, and on the other hand it is characterized by a great deal of variation in terms of topics, interactional patterns, and linguistic features. In this article, we aim to map the communicative space(s) of Reddit by means of vignettes of studies from four research groups, each of them describing a different approach to one or several subreddits. Study 1 examines concessive constructs in r/changemyview posts, Study 2 focuses on expert-lay communication on r/mountaineering, Study 3 addresses register variation within a large corpus of Reddit comments from many different communities, and Study 4 looks across different subreddits to explore the function of text-length. Drawing on these four vignettes, we show the range of discourses that Reddit has hosted in recent years, while also exploring the methodological tools as well as the insights that qualitative, text-based digital humanities, critical discourse analysis and computational text analysis can provide. The map to the Reddit language research space we create here can help digital humanities researchers to make sense of the variety of different theoretical vantage points and methodologies that are currently being employed to Reddit, and it can serve as a guideline when it comes to choosing research agendas and relevant literature on current forum interaction.
Peculiar radio-bright behaviour of the Galactic black hole transient 4U 1543−47 in the 2021–2023 outburst
Authors: Zhang X , Yu W , Carotenuto F , Motta S E , Fender R , Miller-Jones J C A , Russell T D , Bahramian A , Woudt P , Hughes A K , Sivakoff G R
Published: January 2025

Correlated behaviours between the radio emission and the X-ray emission in Galactic black hole X-ray binaries (BH XRBs) in the X-ray hard state are crucial to the understanding of disc-jet coupling of accreting black holes. The BH transient 4U 1543–47 went into outburst in 2021 following $\sim$19 yr of quiescence. We followed it up with $\sim$ weekly cadence with MeerKAT for about one year and a half until it faded into quiescence. Multi-epoch quasi-simultaneous MeerKAT and X-ray observations allowed us to trace the compact jet emission and its X-ray emission. In its hard spectral state across three orders of magnitude of X-ray luminosities above $\sim$10$^{34}$ ergs s$^{-1}$, we found the correlation between radio and X-ray emission had a power-law index of 0.82$\pm$0.09, steeper than the canonical value of $\sim$0.6 for BH XRBs. In addition, the radio versus X-ray correlation show a large range of the power-law normalization, with the maximum significantly larger than that obtained for most BH XRBs, indicating it can be particularly radio-bright and variable in the X-ray binary sample. The radio emission is unlikely diluted by discrete jet components. The observed peculiar radio-bright and variable behaviours provide the evidence for the relativistic effects of a variable Lorentz factor in the range between 1 and $\sim$2 of the compact jet.
Complete heart block with SARS-COV-2 infection inducing permanent pacing: a case report from a tertiary private hospital In Tanzania
Authors: Ibrahim Pendo , Kabakama Clement , Wilfred Venance , Daudi Zahra , Mvungi Robert
Published: January 2025

There is an increased risk of cardiac complications in COVID-19 among patients with pre-existing comorbidities due to their existing pro-inflammatory status. The manifestation of complete heart block has been evidenced as transient and in no need of intervention. This case presents a previously healthy woman who was diagnosed with SARS-CoV-2 infection and complete heart block; she underwent permanent dual-chamber pacemaker implantation after successful treatment and a negative COVID-19 test. She was then discharged from the hospital with an uneventful follow-up. Persistence of complete heart block symptoms post-COVID-19 resolution and the need for permanent pacing indicate a potential association between COVID-19 and complete heart block. Healthcare workers should consider electrographic examination in the initial assessment of suspected COVID-19 cases, even among those with no pre-existing conditions. This report highlights the need for further research to explore the relationship between COVID-19 and complete heart block.
A case of testicular leiomyoma in androgen insensitivity syndrome: exploring malignancy controversies
Authors: Neupane Neha , Pyakurel Devish , Shrestha Abha , Gautam Keyoor , Shrestha Srijana , Pradhan Santosh , Pant Vivek
Published: January 2025

Testicular leiomyoma is an exceptionally rare finding in patients with androgen insensitivity syndrome (AIS). Here, we present a report of a 30-year-old individual diagnosed with complete AIS who presented with an inguinal mass subsequently identified as a right sided testicular leiomyoma. While leiomyoma are generally considered benign, controversies persist regarding the potential for malignancy in inguinal masses among AIS patients. This case underscores the complexity of diagnosing and managing such rare occurrences, particularly when considering the diverse opinions found in the scientific literature regarding the malignant potential of inguinal masses in AIS individuals. By presenting this case, we contribute to the ongoing debate on the evaluation and treatment of inguinal masses in AIS patients, emphasizing the need for further research and consensus in this area.
Parkinson's disease exacerbation following Levetiracetam administration: an unusual phenomenon
Authors: Alqahtani Laila , Alkhaibary Ali , Bouhouf Farid
Published: January 2025

Background: Several studies have investigated the potential beneficial and side effects of levetiracetam on Parkinson's disease (PD). We hereby report a case of PD exacerbation following Levetiracetam administration for seizure prophylaxis. Case Description: A 77-year-old female, known to have PD, presented with a head injury following a fall. Brain CT showed diffuse subarachnoid hemorrhage. The patient was started on Levetiracetam for seizure prophylaxis. Four days after, the patient dropped GCS from 15 to 9. She was having progressive exacerbation of Parkinson’s disease symptoms. After ruling out all possible causes of PD exacerbation, Levetiracetam was gradually weaned until it was discontinued. Consequently, the patient had rapid significant clinical improvement after discontinuation of Levetiracetam. Conclusion: The use of Levetiracetam for seizure prophylaxis in patients with PD can rarely lead to acute exacerbation of symptoms and worst outcome. Close monitoring of patients with PD is recommended when prescribing anti-epileptics.
Progression to end-stage renal disease due to IgG4-related nephritis: a case report
Authors: Kudsi Maysoun , Tarcha Raghad , Khalayli Naram , Rabah Nour , Rabah Karam , Alghawe Fatima Alzahraa
Published: January 2025

IgG4-related disease (IgG4-RD) is a rare but increasingly recognised condition that can involve multiple organs, including the kidneys which often presents as tubulointerstitial nephritis.

Treatment with glucocorticoids is the first line of therapy, but other options may be needed in refractory cases.

This case report explores a 68-year-old female, diagnosed with the patient initially responded to glucocorticoids but had a relapse, leading to progressive renal insufficiency and ultimately death.

Our case is a rare case observing the progression to end-stage kidney disease from IgG4-RD, and the first case of which the patient had died in a short period.
Cardiovascular outcomes and safety assessment of SGLT2i on heart failure patients: a systematic review and meta-analysis
Authors: Waseem Radeyah , Moaaz Bin Sultan Syed Muhammad , Hussain Muhammad Sheheryar , Shah Hussain Haider , Haque Md Ariful
Published: January 2025

Background:

Sodium-glucose co-transporter 2 inhibitors (SGLT2is) are used in treating type 2 diabetes mellitus and show promise in improving outcomes in heart failure patients. This systematic review and meta-analysis aims to quantify the benefits and side effects of SGLT2i in heart failure patients with a reduced ejection fraction.

Methods:

A systematic search was conducted using PubMed, Cochrane Library, and Google Scholar with keywords such as “Sodium-Glucose Cotransporter 2 Inhibitor,” “Myocardial Infarction,” and “Cardiovascular.” Inclusion criteria were randomized controlled trials involving patients with heart failure. Primary outcomes were hospitalization due to heart failure and cardiovascular mortality. Secondary outcomes included discontinuation due to adverse effects, amputation, fractures, and urinary tract infections.

Results:

Eight randomized controlled trials were included. The interventional group showed significantly lower hospitalizations (P = 0.00001) and cardiovascular deaths (P = 0.0008). Secondary outcomes, including adverse effects like amputation, fractures, and UTI, were not statistically significant across groups.

Conclusion:

SGLT2 inhibitors, due to their natriuretic, cardio-metabolic, and vaso-modulatory effects, offer a promising role in reducing cardiovascular complications in patients with type 2 diabetes mellitus.
Comprehensive analysis the role of cuproptosis related genes in abdominal aortic aneurysm
Authors: Xiao Xiaoyong , Deng Zhe , Huang Zhenhua , Liang Chunhua , Chen Zhongqing , Xiao Xiaohua , Liu Dehong
Published: January 2025

Immune infiltration plays an important role in the course of abdominal aortic aneurysm (AAA) development, and copper death (cuproptosis) is a new type of programmed cell death recently discovered. At present, there are no studies on the role of cuproptosis regulating immune infiltration in AAA. We extracted a published GEO dataset (GSE57691), with 49 AAA and 10 control transcriptome sequencing samples. Then we analyzed the difference of cuproptosis related genes (CRGs) expression between AAA and normal groups. LIPT1, FDX1 and CDKN2A were upregulated in AAA samples (P < 0.05). Subsequently, we analyzed the difference of immune infiltrate cells between the AAA and normal samples. Compared to the normal group, Dendritis cells, Mast activated cells, Monocytes, M0 macrophages, neutrophils, Plasma cells, CD4-naive T cells, follicular-helper T cells and Treg cells were upregulated in the AAA group, while M1 and M2 macrophages, CD4-memory T cells and gamma delta T cells were downregulated. AAA samples were then classified into two subtypes according to the expression profiles of CRGs, the immunological characteristics and function had significant differences between subtypes. Furthermore, we mined 20 hub genes by used Weighted Gene Co-expression Network Analysis (WGCNA) to construct a co-expression network. Three drugs were identified that interacting with eight hub genes based on the gene-drug interaction database. We finally verified the mRNA differences of the CRGs in the aorta of AAA and healthy mice in vitro. LIPT1, CDKN2A and FDX1 may play a role in regulating the development of AAA through immune infiltration. Eight NDUF subunits, including NDUFA1, NDUFA4, and NDUFB1, may also play an important role in this process. In addition, Metformin, ME-344 and NV-128 may be therapeutic agents for AAA by regulating the cuproptosis.
Biochemical Profiling and Structural Basis of ADAR1-Mediated RNA Editing
Authors: Deng Xiangyu , Sun Lina , Zhang Min , Basavaraj Rashmi , Wang Jin , Weng Yi-Lan , Gao Yang
Published: January 2025

ADAR1 is a pivotal regulator in RNA-induced immune responses by catalyzing the conversion of adenosine to inosine on double-stranded RNA. Mutations on ADAR1 are associated with human autoimmune disease, and targeting ADAR1 has been proposed for cancer immunotherapy. However, the molecular mechanisms governing ADAR1-mediated RNA editing remain enigmatic. Here, we provide detailed biochemical and structural characterizations of human ADAR1. Our biochemical profiling reveals that ADAR1 editing is both sequence and RNA duplex length-dependent, but can well tolerate mismatches near the editing site. Moreover, our high-resolution structures of ADAR1-RNA complexes, coupled with mutagenesis studies, revealed the molecular basis for RNA binding, substrate selection, dimerization, and the crucial role of the RNA-binding domain 3 for ADAR1 editing. The ADAR1 structures also help explain the potential defects of disease-associated mutations, where biochemical and RNA-sequencing analysis further indicate some of the mutations preferentially impact the editing of RNAs with short duplex. Our findings illustrate the molecular mechanism of ADAR1 editing and provide clues for deciphering its role in immune regulation and drug targeting.

HIGHLIGHTS

Biochemical profiling of ADAR1 RNA substrate preference

Atomic resolution structures of ADAR1 with two physiological RNA substrates

Disease-related mutations of ADAR1 preferentially impact RNA editing with short dsRNA.

RNA-binding domain 3 is essential for ADAR1 RNA capture and editing