bluuebunny/crossref_metadata_2025 huggingface dataset:
Ecotoxicological screening of an e-liquid mixture using computational tools
Authors: Massarsky Andrey , Bonin Adam , Atalay Yasemin , Jones Antony
Published: January 2025

E-liquids used in electronic nicotine delivery systems (ENDS) are mixtures composed of a variety of chemicals, with nicotine, propylene glycol, and glycerol typically representing the primary ingredients. The U.S. Food and Drug Administration (USFDA) requires manufacturers to evaluate the environmental impacts of manufacture, use, and disposal of ENDS, e-liquids, and other tobacco products as a component of the premarket tobacco product application (PMTA). Environmental impacts may be assessed by examining the potential ecotoxicological risks of e-liquid ingredients in National Environmental Policy Act (NEPA) of 1969 environmental assessments as part of the PMTA. Although ecotoxicological characteristics have been assessed for myriad industrial chemicals, pharmaceuticals, and personal care products, to date, no published study has evaluated the ecotoxicological characteristics of e-liquids. Hence, this study describes a novel framework to screen complex e-liquid mixtures for chemicals that exhibit the greatest potential ecological risk. Specifically, the U.S. Environmental Protection Agency (USEPA) Ecological Structure Activity Relationships program was used to predict toxicity of e-liquid ingredients to several aquatic organisms; the relative toxicity of each chemical was then calculated, accounting for toxicity thresholds and chemical concentration. The potential environmental fate of seven chemicals exhibiting the greatest toxicity was then evaluated using the USEPA Exposure and Fate Assessment Screening Tool. Concentrations of chemicals released to the environment under hypothetical manufacturing and end-use release scenarios were estimated in surface water and compared with toxicological benchmarks to determine the potential impacts to aquatic organisms. The described framework is a robust high-throughput method to screen the chemicals of greatest ecological concern in complex chemical mixtures, including but not limited to e-liquids, to enable a targeted assessment of potential ecological impacts.
Galaxy as a gateway to bioinformatics: Multi-Interface Galaxy Hands-on Training Suite (MIGHTS) for scRNA-seq
Authors: Goclowski Camila L , Jakiela Julia , Collins Tyler , Hiltemann Saskia , Howells Morgan , Loach Marisa , Manning Jonathan , Moreno Pablo , Ostrovsky Alex , Rasche Helena , Tekman Mehmet , Tyson Graeme , Videm Pavankumar , Bacon Wendi
Published: January 2025

Background

Bioinformatics is fundamental to biomedical sciences, but its mastery presents a steep learning curve for bench biologists and clinicians. Learning to code while analyzing data is difficult. The curve may be flattened by separating these two aspects and providing intermediate steps for budding bioinformaticians. Single-cell analysis is in great demand from biologists and biomedical scientists, as evidenced by the proliferation of training events, materials, and collaborative global efforts like the Human Cell Atlas. However, iterative analyses lacking reinstantiation, coupled with unstandardized pipelines, have made effective single-cell training a moving target.

Findings

To address these challenges, we present a Multi-Interface Galaxy Hands-on Training Suite (MIGHTS) for single-cell RNA sequencing (scRNA-seq) analysis, which offers parallel analytical methods using a graphical interface (buttons) or code. With clear, interoperable materials, MIGHTS facilitates smooth transitions between environments. Bridging the biologist–programmer gap, MIGHTS emphasizes interdisciplinary communication for effective learning at all levels. Real-world data analysis in MIGHTS promotes critical thinking and best practices, while FAIR data principles ensure validation of results. MIGHTS is freely available, hosted on the Galaxy Training Network, and leverages Galaxy interfaces for analyses in both settings. Given the ongoing popularity of Python-based (Scanpy) and R-based (Seurat & Monocle) scRNA-seq analyses, MIGHTS enables analyses using both.

Conclusions

MIGHTS consists of 11 tutorials, including recordings, slide decks, and interactive visualizations, and a demonstrated track record of sustainability via regular updates and community collaborations. Parallel pathways in MIGHTS enable concurrent training of scientists at any programming level, addressing the heterogeneous needs of novice bioinformaticians.
Diminished DNA binding affinity of DMRT1 caused by heterozygous DM domain mutations is a cause of male infertility
Authors: Marić Tihana , Castillo-Madeen Helen , Klarić Monika Logara , Barišić Antun , Trgovec-Greif Lovro , Murphy Mark W , Juchnewitsch Anna-Grete , Lillepea Kristiina , Dutta Avirup , Žunić Lucija , Stendahl Alexandra M , Punab Margus , Pomm Kristjan , Mendoza Daniel M , Lopes Alexandra M , Šorgić Ana Merkler , Vugrek Oliver , Gonçalves Joao , Almstrup Kristian , Aston Kenneth I , Belužić Robert , Ježek Davor , Bertoša Branimir , Laan Maris , Bojanac Ana Katušić , Conrad Donald F , Barbalić Maja
Published: January 2025

The most severe form of male infertility is idiopathic non-obstructive azoospermia (NOA), a complete sperm absence in the ejaculate. We performed exome sequencing in the Croatian infertile brothers with NOA and found a variant in DMRT1 (Doublesex and mab-3 related transcription factor 1) gene that was further assessed by the EMSA assay and molecular dynamic simulations. We additionally screened for DMRT1 mutations in 1940 infertile men diagnosed with spermatogenic failure, 644 normozoospermic controls, and 105 females with primary ovarian insufficiency (POI) recruited to the GEnetics of Male INfertility Initiative (GEMINI) or Estonian Andrology (ESTAND) cohorts. DMRT1 p.Pro74Leu (chr9:g.842059C > T) variant was detected in infertile brothers in the highly conserved position within the DNA binding DM domain of the protein. EMSA assay showed reduced DNA binding of DMRT1P74L and molecular dynamic simulations showed differences in structural and dynamical properties between the wild type protein and DMRT1P74L. Plausible disease-causing DMRT1 variants were only identified in infertile men (13/1940; 0.67%), and none in 639 fertile controls. Burden testing showed an excess of rare deleterious DM domain mutations in the infertility cohort compared to gnomAD v.4.0 population-based controls (Fisher’s exact test, p = 1.44 x 10−5). Three rare deleterious variants in DMRT1 were found in 104 cases of POI. The findings of this study strengthen the evidence of DMRT1 variants being a causal factor for male infertility and provide the distribution of likely pathogenic variants across the gene. This is also the first study to suggest that DMRT1 variants may also be linked to POI.
Decanoylcarnitine Improves Liver Mitochondrial Dysfunction in Hepatitis B Virus Infection by Enhancing Fatty Acid β-Oxidation
Authors: Sun Ye , Chen Qingling , Liu Yuxiao , Jiao Mengfan , Dai Zixing , Hou Xiaoxue , Liu Rui , Li Yuwen , Zhu Chuanlong
Published: January 2025

Background

The incidence of metabolic-associated steatotic liver disease in patients with chronic hepatitis B is increasing annually; however, the interaction between hepatitis B virus (HBV) infection and lipid metabolism remains unclear. This study attempted to clarify whether fatty acid metabolism regulation could alleviate mitochondrial dysfunction caused by HBV infection.

Methods

A public gene set of human livers was analyzed, and a proteomic analysis on mouse livers was conducted to explore metabolic disorders and affected organelles associated with HBV infection. The effect of decanoylcarnitine on fatty acid β-oxidation and mitochondria was investigated in vivo and in vitro. The pathways involved were shown by proteomic analysis and confirmed by Western blot.

Results

HBV infection could cause fatty acid β-oxidation disorder and mitochondrial dysfunction in vivo and in vitro. CPT1A overexpression could improve mitochondrial function in hepatocytes. Furthermore, decanoylcarnitine supplementation could activate CPT1A expression, thus improving fatty acid metabolism and repairing mitochondrial dysfunction. Proteomic analysis of mouse livers suggests that decanoylcarnitine stimulates the peroxisome proliferator–activated receptor (PPAR) signaling pathway, and PPARα was the most important among PPARs.

Conclusions

Impaired fatty acid metabolism and mitochondrial dysfunction in hepatocytes caused by HBV infection could be partially restored by exogenous supplementation of decanoylcarnitine. This work elucidates the therapeutic potential of decanoylcarnitine in HBV infection and provides a new approach for diseases related to mitochondrial dysfunction.
Abundant and active community members respond to diel cycles in hot spring phototrophic mats
Authors: Shelton Amanda N , Yu Feiqiao B , Grossman Arthur R , Bhaya Devaki
Published: January 2025

Photosynthetic microbial mats in hot springs can provide insights into the diel behaviors of communities in extreme environments. In this habitat, photosynthesis dominates during the day, leading to super-oxic conditions, with a rapid transition to fermentation and anoxia at night. Multiple samples were collected from two springs over several years to generate metagenomic and metatranscriptomic datasets. Metagenome-assembled genomes comprised 71 taxa (in 19 different phyla), of which 12 core taxa were present at high abundance in both springs. The eight most active taxa identified by metatranscriptomics were an oxygenic cyanobacterium (Synechococcus sp.), five anoxygenic phototrophs from three different phyla, and two understudied heterotrophs from phylum Armatimonadota. In all eight taxa, a significant fraction of genes exhibited a diel expression pattern, although peak timing varied considerably. The two abundant heterotrophs exhibit starkly different peak timing of expression, which we propose is shaped by their metabolic and genomic potential to use carbon sources that become differentially available during the diel cycle. Network analysis revealed pathway expression patterns that had not previously been linked to diel cycles, including ribosome biogenesis and chaperones. This provides a framework for analyzing metabolically coupled communities and the dominant role of the diel cycle.
Pacmanvirus isolated from the Lost City hydrothermal field extends the concept of transpoviron beyond the family Mimiviridae
Authors: Santini Sébastien , Lartigue Audrey , Alempic Jean-Marie , Couté Yohann , Belmudes Lucid , Brazelton William J , Lang Susan Q , Claverie Jean-Michel , Legendre Matthieu , Abergel Chantal
Published: January 2025

The microbial sampling of submarine hydrothermal vents remains challenging, with even fewer studies focused on viruses. Here we report what is to our knowledge the first isolation of a eukaryotic virus from the Lost City hydrothermal field, by co-culture with the laboratory host Acanthamoeba castellanii. This virus, named pacmanvirus lostcity, is closely related to previously isolated pacmanviruses (strains A23 and S19), clustering in a divergent clade within the long-established family Asfarviridae. The icosahedral particles of this virus are 200 nm in diameter, with an electron-dense core surrounded by an inner membrane. The viral genome of 395 708 bp (33% G + C) has been predicted to encode 473 proteins. However, besides these standard properties, pacmanvirus lostcity was found to be associated with a new type of selfish genetic element, 7 kb in length, whose architecture and gene content are reminiscent of those of transpovirons, hitherto specific to the family Mimiviridae. As in previously described transpovirons, this selfishg genetic element propagates as an episome within its host virus particles and exhibits partial recombination with its genome. In addition, an unrelated episome with a length of 2 kb was also found to be associated with pacmanvirus lostcity. Together, the transpoviron and the 2-kb episome might participate in exchanges between pacmanviruses and other DNA virus families. It remains to be elucidated if the presence of these mobile genetic elements is restricted to pacmanviruses or was simply overlooked in other members of the Asfarviridae.
Inflation and Monetary Policy in a Low-Income and Fragile State: The Case of Guinea
Authors: Carrière-Swallow Yan , Koumtingué Nelnan Fidèle , Weber Sebastian
Published: January 2025

Inflation in low-income countries is often high and volatile, driven by external shocks. In addition, inflation in fragile states is affected by highly volatile domestic factors that complicate monetary policy's ability to deliver price stability. We estimate the drivers of inflation in Guinea since the early 2000s, a period in which the country suffered major shocks from pandemics, commodity price movements, and multiple military coups, and during which inflation averaged 12%. Results confirm that global commodity and transport prices account for a large share of the variation in inflation. The contribution of monetary policy shocks to inflation is moderate, reflecting its broadly neutral stance throughout most of the last two decades. However, monetary policy has occasionally made larger contributions to inflation, and recently helped contain price pressures from high commodity prices. The effectiveness of monetary policy reflects a strong relationship between monetary aggregates and the exchange rate.
Paradoxical combination of osteosclerosis and osteopenia in an adult woman with biallelic TNFRSF11A loss-of-function variants escaping nonsense-mediated decay
Authors: Gajewski Dario , Hennig Anna Floriane , Grün Regina , Siggelkow Heide , Vishnolia Svenja , Bastian Leonard , Taipaleenmäki Hanna , Schulz Ansgar , Kornak Uwe , Hesse Eric
Published: January 2025

Osteoclasts are essential for bone resorption, playing a crucial role in skeletal development, homeostasis, and remodeling. Their differentiation depends on the RANK receptor encoded by the TNFRSF11A gene, with defects in this gene linked to osteoclast-poor sclerosing skeletal dysplasias. This report presents a 37-yr-old woman with normal height, valgus deformities that were treated surgically, frequent fractures, scoliosis, mildly elevated BMD, sclerotic diaphyseal bone, and metaphyseal widening. Initially suspected of having dysosteosclerosis, her diagnosis shifted toward Pyle disease due to the valgus deformity and prominent metaphyseal widening and translucency. Genetic analysis identified 2 pathogenic TNFRSF11A variants: a nonsense mutation c.1093G>T, p.(Glu365*) and a frameshift mutation c.1266_1268delinsCC, p.(Leu422Phefs*104). Thus, genetic and clinical assessment converged on the diagnosis of a mild form of dysosteosclerosis. Both mutations introduced premature stop codons but escaped complete nonsense-mediated decay, potentially permitting residual protein function. Analysis of patient-derived osteoclasts cultured on glass surfaces showed partial differentiation. However, in vitro resorptive function was strongly impaired, which was clinically reflected by reduced serum concentration of the bone resorption marker CTx. Despite this impairment, the retained residual resorptive function likely explains the patient’s relatively mild clinical presentation. These findings underscore the complex genetic interactions that affect osteoclast function, leading to a spectrum of phenotypes in osteoclast-related bone disorders.
Optimization using kriging metamodel and CMA-ES to improve temperature uniformity of electric vehicle liquid-cooled cylindrical Li-ion battery BTMS
Authors: Park Seokjun , Lee Hamin , Park Cheonha , An Jaewook , Kim Chang-Wan
Published: January 2025

Temperature uniformity in Li-ion battery thermal management systems (BTMS) is crucial for achieving thermal safety and optimal performance in electric vehicles. This study proposes a method to enhance the temperature uniformity of a liquid-cooled BTMS by using a kriging metamodel and the covariance matrix adaptation evolution strategy (CMA-ES). The heat generation rate of the battery was determined based on voltage and current data, followed by thermal fluid analysis to evaluate the cooling performance. Key design variables included the outer and inner dimensions of the cooling plate and the coolant flow rate, constrained by the BTMS mass. The kriging metamodel was used to reduce computational costs significantly, while CMA-ES provided a robust optimization method capable of efficiently handling complex, multimodal design spaces. The combined approach resulted in a 21.15% reduction in temperature difference without increasing the BTMS mass, demonstrating the effectiveness of this optimization strategy in improving the thermal management of Li-ion battery modules.
Thymic Eosinophils: What Are You Doing Here?
Authors: Gatti Dominique M , Reynolds Lisa A
Published: January 2025

The thymus is a primary lymphoid organ where major types of T lymphocytes undergo essential developmental processes. Eosinophils are among the cell types present in microenvironments within the thymus, and perhaps surprisingly, the role of thymic eosinophils, especially during homeostatic conditions, remains unclear. Major physiological events impact thymic organization and function throughout life: including age-related involution, pregnancy, and exposure to chemotherapy or radiation. In this Review, we summarize literature that has explored factors that regulate the accumulation, phenotype, and location of thymic eosinophils during homeostatic development and during conditions where homeostasis is perturbed. Further, we discuss the current theories as to the function of thymic eosinophils, and we consider how the heterogeneity of thymic eosinophil populations may reflect a temporal, spatial, and situational multi-functionality of thymic eosinophils.
Imported tick-borne encephalitis in a traveller returning to North Macedonia from Switzerland June 2024
Authors: Jakimovski Dejan , Poposki Kostadin , Bosilkovski Mile , Bogdan Ivana , Simin Verica , Banovic Pavle
Published: January 2025

A 26-year-old man from North Macedonia developed tick-borne encephalitis (TBE) after a tick bite in Switzerland, experiencing severe neurological symptoms before a full recovery. This case highlights the importance of vaccination and awareness for travellers from non-endemic regions visiting TBE-endemic areas.
Under the Moon’s Healing Influence: George MacDonald’s Literary Re-envisioning of Women’s Health
Authors: Little Ariel
Published: January 2025

This article demonstrates how the work of fantasist George MacDonald interacted with Victorian debates regarding women’s health. Participating in the trend to interpret MacDonald’s fiction as invested in contemporary societal issues, I bring to the forefront MacDonald’s interest in women’s rights and alternative medicine. Emphasizing MacDonald’s belief in the persuasive power of appealing indirectly to the imagination, I argue that MacDonald aimed to participate in women’s health reform through his short fiction. Focusing on works published between 1850 and 1880, I discuss MacDonald’s fairy tales in conjunction with his realist fiction in order to discern a pattern of literary tropes, such as the cursed princess, deployed to subvert dominant medical views of women’s bodies. I consider how MacDonald represents elements of Victorian medicine, such as the clinical objectification of patients, the medicalization of disability, and the early social eugenics movement. In his countercultural representation of impaired female characters as empowered heroines, I argue that MacDonald challenges the medical stigmatization of women’s bodies. This article also considers how MacDonald challenges the interventionism of Victorian allopathy by celebrating the practices of established alternative approaches, such as homeopathy and hydropathy. As an early proponent of bibliotherapy, MacDonald demonstrates his belief in the healing potential of narrative both within the context of his narratives and in his use of narrative to improve women’s health practices.
Benchmarking cross-species single-cell RNA-seq data integration methods: towards a cell type tree of life
Authors: Zhong Huawen , Han Wenkai , Gomez-Cabrero David , Tegner Jesper , Gao Xin , Cui Guoxin , Aranda Manuel
Published: January 2025

Cross-species single-cell RNA-seq data hold immense potential for unraveling cell type evolution and transferring knowledge between well-explored and less-studied species. However, challenges arise from interspecific genetic variation, batch effects stemming from experimental discrepancies and inherent individual biological differences. Here, we benchmarked nine data-integration methods across 20 species, encompassing 4.7 million cells, spanning eight phyla and the entire animal taxonomic hierarchy. Our evaluation reveals notable differences between the methods in removing batch effects and preserving biological variance across taxonomic distances. Methods that effectively leverage gene sequence information capture underlying biological variances, while generative model-based approaches excel in batch effect removal. SATURN demonstrates robust performance across diverse taxonomic levels, from cross-genus to cross-phylum, emphasizing its versatility. SAMap excels in integrating species beyond the cross-family level, especially for atlas-level cross-species integration, while scGen shines within or below the cross-class hierarchy. As a result, our analysis offers recommendations and guidelines for selecting suitable integration methods, enhancing cross-species single-cell RNA-seq analyses and advancing algorithm development.
High-dose MTX-based polychemotherapy for primary CNS lymphoma in younger patients: Long-term efficacy of the modified Bonn protocol
Authors: Zeyen Thomas , Weller Johannes , Schneider Matthias , Potthoff Anna-Laura , Schaub Christina , Roever Lea , Gkika Eleni , Vatter Hartmut , Holderried Tobias A W , Brossart Peter , Herrlinger Ulrich , Schaefer Niklas
Published: January 2025

Background

Polychemotherapy based on high-dose methotrexate (HD-MTX) is the standard therapy for newly diagnosed younger patients (<65 years) with primary CNS lymphoma (PCNSL). In the modified Bonn protocol, consolidation therapy consists of intraventricular chemotherapy that is added to the continuation of HD-MTX-based chemotherapy. This study investigates the efficacy and toxicity of the modified Bonn protocol in first-line therapy of young patients with PCNSL.

Methods

All consecutive immunocompetent patients aged <65 years who were newly diagnosed with PCNSL from 2012 to 2021 and started first-line therapy with the modified Bonn protocol at the Neurooncology Center Bonn were included in this retrospective analysis. Treatment comprised 3 courses of rituximab/HD-MTX/IFO followed by consolidation therapy with 2 courses of HD-AraC and 2 courses of HD-MTX/IFO, including intrathecal MTX and intrathecal AraC. Progression-free and overall survival were evaluated.

Results

Forty-three patients were included. Thirty-seven patients (86%) reached intrathecal consolidation therapy. Grade 3/4 toxicity was observed in 58.1%. The median PFS was 102.8 months; 5-year OS rate was 76% (median not reached). Eighteen patients developing refractory/relapsed PCNSL received second-line therapy using the modified Freiburg protocol (AraC/TT +/- HD-MTX/rituximab followed by BCNU/TT-based HD-ASCT). A second relapse was observed in 11/18 patients (median follow-up of 17 months (IQR 5-43.7 months)).

Conclusions

First-line treatment of PCNSL with the modified Bonn protocol is highly effective. The outcome compares well with other seemingly more toxic PCNSL protocols for younger patients. In patients with disease recurrence, second-line therapy according to the modified Freiburg protocol appears to be effective.
An epH-driven DNA nanodevice for impeding metastasis in vivo by selectively blocking cell signaling
Authors: Yuan Kun , Meng Hong-Min , Sun Hongzhi , Qu Lingbo , Li Zhaohui , Tan Weihong
Published: January 2025

Invasion and metastasis dominate tumor progression, causing a substantial proportion of cancer-related deaths. However, the efficacy of current antimetastatic treatments is hampered by the dearth of targeted therapeutics. Recently developed synthetic-receptor toolkits offer potential for artificially regulating cellular behavior. However, to the best of our knowledge, none has yet successfully suppressed tumor metastasis in vivo. Here, we report the first extracellular pH (epH)-driven DNA nanodevice for use in antimetastatic treatment in vivo by manipulating heterogeneous receptors on the tumor cell surface. This DNA nanodevice was constructed by partially locking tumorigenic receptor-specific aptamers with two i-motifs. Acidic extracellular pH induced dynamic allosteric reassembly within the nanodevice. The restructured nanodevice enabled oligomerization of c-Met and TfR, which inhibited tumor metastasis by blocking the HGF/c-Met signaling pathway. A suppressive efficacy of 86.25% was verified in an early hepatocarcinoma-pulmonary-metastasis mouse model. Such impressive antimetastatic efficacy suggests an efficient paradigm for developing adaptive antimetastatic therapeutics.
Systems analysis of long-term heat stress responses in the C4 grass Setaria viridis
Authors: Zhang Peng , Sharwood Robert , Carroll Adam , Estavillo Gonzalo M , von Caemmerer Susanne , Furbank Robert T
Published: January 2025

Many C4 plants are used as food and fodder crops and often display improved resource use efficiency compared to C3 plants. However, the response of C4 plants to future extreme conditions such as heatwaves is less understood. Here, Setaria viridis, an emerging C4 model grass, was grown under long-term high temperature stress for two weeks (42°C, compared to 28°C). This resulted in stunted growth, but surprisingly had little impact on leaf thickness, leaf area-based photosynthetic rates and bundle sheath leakiness. Dark respiration rates increased and there were major alterations in carbon and nitrogen metabolism in the heat-stressed plants. Abscisic acid and indole-acetic acid–amino acid conjugates accumulated in the heat-stressed plants, consistent with transcriptional changes. Leaf transcriptomics, proteomics and metabolomics analyses were carried out and mapped onto the metabolic pathways of photosynthesis, respiration, carbon/nitrogen metabolism and phytohormone biosynthesis and signaling. An in-depth analysis of correlations between transcripts and their corresponding proteins revealed strong differences between groups in the strengths and signs of correlations. Overall, many stress signaling pathways were upregulated, consistent with multiple signals leading to reduced plant growth. A systems-based model of the plant response to long-term heat stress is presented based on the oxidative stress, phytohormone and sugar signaling pathways.
Endocytosis-mediated healing: recombinant human collagen type III chain-induced wound healing for scar-free recovery
Authors: Jin Jian , Li Hai-Hang , Chen Zheng-Li , Liu Qing-Song , Chen Ji-Qiu , Tao Zi-Han , Hong Xu-Dong , Ding Yin-Jia , Zhou Yue , Chen Ai-Fen , Zhang Xu-Dong , Lv Kai-Yang , Zhu Liang-Liang , Zhu Shi-Hui
Published: January 2025

Scar formation can be effectively prevented when the proportion of collagen type I (Col I)/type III (Col II) is reduced. Unlike Col III, recombinant human collagen type III chain (RHC III chain) does not possess a triple helical structure. This study aimed to elucidate the capacity of fibroblasts to uptake RHC III chain, reduce the Col I/Col III ratio, and determine its effects on wound healing and scar. RHC III chain demonstrates qualified cell compatibility. In cell experiments, immunofluorescence and Western Blot (WB) analyses revealed an increase in the polyhistidine tag level, indicating that RHC III chain in internalized by these cells. Transmission electron microscopy (TEM) showed increased intracellular phagocytic activity, indicating that RHC III chain enters fibroblasts by endocytosis. The immunofluorescence and WB showed that Col III synthesis enhanced, and Col I/Col III ratio reduced. However, the polyhistidine tag disappeared with time, indicating that RHC III chain degraded within cells and then synthesized into Col III. The content of newly synthesized Col III increases, but Real-time fluorescence quantitative showed a decrease in Col III related gene content suggests the formation of negative feedback. However, due to the sufficient raw materials, the amount of Col III synthesis is still increasing, leading to the reduction of the ratio of type I collagen/type III collagen, which beneficial to wound healing and reduce scar hyperplasia. In animal experiments, the SD rat full-thickness skin defect model of Wound suggests that RHC III chain also takes effect through endocytosis and ultimately promotes wound healing. The rabbit ear scar model suggests that RHC III chain inhibits scar proliferation by reducing the ratio of Col I/Col III. In summary, RHC III chain was endocytosed by fibroblasts to promote native Col III synthesis, as well as promote wound healing and reduce scar hyperplasia.
Contemporary uses of “lethal” or “life limiting” terminology in perinatal research
Authors: Gatta Luke A. , McCarthy Allison M. , Osmundson Sarah S.
Published: January 2025

Purpose of review

A life-limiting fetal diagnosis (LLD) refers to a medical condition identified during pregnancy that is expected to lead to stillbirth, preclude ex utero survival, or significantly reduce neonatal life expectancy. The terms ‘lethal’ or ‘life-limiting’ are used to prognosticate early death for various anatomic or physiologic causes, although the expected timeframe is nonspecific. The purpose of this manuscript is to review how the terms ‘lethal’ or ‘life limiting’ are used in contemporary perinatal research.

Recent findings

Depending on the study design, ‘life-limiting’ is defined either prior to data analysis (such as prospective cohort studies), or after outcomes are assessed (such as case series). When ‘life-limiting’ is defined prior to data analysis, study-specific specific definitions may include timeframes from birth to death, probability of neonatal mortality, or a list of diagnoses based off billing codes.

Professional societies have guidelines to standardize the reporting of vital statistics, including early death. While these fall short of defining LLDs comprehensively, they present an opportunity for more specific prognostication following prenatal diagnosis, which may improve research standardization to facilitate a clearer understanding of LLDs in clinical practice.
CD36 in liver diseases
Authors: Liu Yi , Yin Wenwei
Published: January 2025

Cluster of differentiation 36 (CD36) is a transmembrane glycoprotein with the ability to bind to multiple ligands and perform diverse functions. Through the recognition of long-chain fatty acids, proteins containing thrombospondin structural homology repeat domains such as thrombospondin-1, and molecules with molecular structures consistent with danger- or pathogen-associated molecular patterns, CD36 participates in various physiological and pathological processes of the body. CD36 is widely expressed in various cell types, including hepatocytes and KCs in the liver, where it plays a pivotal role in lipid metabolism, inflammation, and oxidative stress. Accumulating evidence suggests that CD36 plays a complex role in the development of nonalcoholic simple fatty liver disease and NASH and contributes to the pathogenesis of inflammatory liver injury, hepatitis B/hepatitis C, liver fibrosis, and liver cancer. This review summarizes the current understanding of the structural properties, expression patterns, and functional mechanisms of CD36 in the context of liver pathophysiology. Furthermore, the potential of CD36 as a therapeutic target for the prevention and treatment of liver diseases is highlighted.
Comparing the cost of cirrhosis to other common chronic diseases: A longitudinal study in a large national insurance database
Authors: Obradović Filip , Vitello Dominic J. , Hasjim Bima J. , Obayemi Joy , Polineni Praneet , Gmeiner Michael , Koep Eleena , Jain Aditya , Crippa Federico , Duarte-Rojo Andrés , Rohan Vinayak S. , Kulik Laura , Doll Julianna M. , Banea Therese , McNatt Gwen E. , Zhao Lihui , VanWagner Lisa B. , Manski Charles F. , Ladner Daniela P.
Published: January 2025

Background and Aims:

Cirrhosis prevalence is increasing, yet costs associated with its chronic, complex care are poorly understood. The aim was to characterize the costs of care for patients with cirrhosis and compare them to other chronic diseases such as heart failure (HF) and chronic obstructive pulmonary disease (COPD), for which the public health burden is better recognized.

Approach and Results:

Patients enrolled in Medicare Advantage plans from a large national insurer between 2011 and 2020 with cirrhosis, HF, and COPD were identified by ICD-9/-10 codes. Costs (USD) of care were calculated per patient-month and included inpatient medical, emergency medical, pharmacy, and other costs. In all, 93,308 patients with cirrhosis, 355,520 patients with HF, and 318,949 patients with COPD were analyzed. Patients with cirrhosis, HF, and COPD had a mean (SD) age of 69.6 (9.5), 75.9 (9.7), and 72.9 (9.8) years, respectively. The most frequent etiologies were metabolic dysfunction–associated steatohepatitis (37.7%) and alcohol-associated cirrhosis (22.1%). The total monthly cost of care for patients with cirrhosis, HF, and COPD was $3032.00, $2491.60, and $1955.60 respectively. The cost for patients with cirrhosis exceeded that for HF by $540.40 (21.7% higher) and COPD by $1076.30 (55.0% higher). The monthly cost of care for decompensated cirrhosis was $3969.30, which was 59.3% ($1477.70) higher than for HF and 103.0% ($1,955.60) higher than for COPD.

Conclusions:

The cost of care for cirrhosis is high, significantly higher than HF and COPD. Interventions directed at optimizing care to prevent progression to cirrhosis and decompensation are likely to alleviate this public health burden.
CONVENIENCE SAMPLING FOR PANDEMIC SURVEILLANCE OF SEVERE ACUTE RESPIRATORY SYNDROME CORONAVIRUS 2 IN CHILDREN IN JACKSON, MISSISSIPPI
Authors: Inagaki Kengo , Penny Amanda , Gwyn Sarah , Malloch Lacy , Martin Lora , Hankins Emma , Ray Chuck , Byers Paul , Harrison Austin , Handali Sukwan , Martin Diana , Hobbs Charlotte V.
Published: January 2025

We assessed severe acute respiratory syndrome coronavirus 2 seroprevalence on residual blood samples for pediatric COVID-19 surveillance: 2263 samples were collected during routine outpatient visits (<18 years, April 2020–August 2021). Seroprevalence increased over time, coinciding with or preceding virus circulation in the community and with or preceding pediatric severe COVID-19 hospitalization peaks. Residual blood sample seroprevalence may be a useful surveillance tool in future outbreaks.
Associations among tooth loss, denture use, and dementia in older Taiwanese adults
Authors: Chen Yi-Wen , Li Chung-Yi , Lee Shang-Chi , Ku Li-Jung Elizabeth , Chou Yu-Tsung , Hargono Arief , Chiu Chang‑Ta , Hou Wen-Hsuan
Published: January 2025

Background:

The literature has mainly focused on the association between tooth loss and dementia, and evidence regarding the separate and joint effects of tooth loss and denture use on the risk of dementia is limited. This study investigated the links among tooth loss, denture use, and dementia risk in Taiwanese adults aged 65 years or older.

Methods:

This retrospective cohort study utilized data from the 2009 National Health Interview Survey and 2008–2017 National Health Insurance claim records, including the records of 2247 individuals free from dementia treatment in 2008–2009. Dementia diagnoses were tracked until 2017. The Cox proportional hazards model was used to calculate hazard ratios (HRs) for exploring the correlations among tooth loss, denture use, and dementia risk.

Results:

Although older adults who had 20 or more natural teeth and used dentures had the lowest dementia incidence (1.43 per 100 person-years) among participants, those with fewer than 20 natural teeth, with or without dentures, experienced high dementia incidence rates of 2.31 and 3.33 per 100 person-years, respectively. After adjusting for sociodemographic characteristics, health conditions/comorbidities, and lifestyles, having fewer than 20 natural teeth (vs. ≥20 remaining natural teeth) or not using dentures (vs. ≥20 remaining natural teeth) was found to be associated with increased but not statistically significant HRs of 1.299 (95% confidence interval [CI], 0.986–1.710) and 1.199 (95% CI, 0.945–1.521). Subgroup analysis revealed that compared with older adults with 20 or more natural teeth and dentures, those with fewer than 20 natural teeth and not wearing dentures had a significantly increased risk of dementia (adjusted HR, 1.569; 95% CI, 1.038–2.370).

Conclusion:

This study found that having fewer than 20 natural teeth and not using dentures was significantly associated with an increased risk of dementia in Taiwanese individuals aged 65 years or above.
What Gastroenterologists Should Know About Microplastics and Nanoplastics
Authors: Ali Sareena , Peña Alexis N. , Lafazanos Yannis S. , Ehrenpreis Eli D.
Published: January 2025

Global production and widespread use of plastics are increasing dramatically. With current limited recycling and recovery options, microplastics and nanoplastics (MNPs) persist in the natural environment. Due to their ubiquity, human exposure to MNPs is inevitable. In addition to their inherent toxic effects, MNPs can adsorb harmful contaminants and act as vectors for microorganisms, compounding toxicological effects. After entering the body, bioaccumulation occurs in several tissues and organs, including the liver and the gastrointestinal (GI) tract. Proposed clinical effects of MNP absorption include endocrine disruption, alteration of the GI microbiome, and promotion of chronic inflammatory conditions. MNPs can also influence energy metabolism, activate inflammatory pathways, and increase oxidative stress leading to apoptosis. The GI tract is a major site of bioaccumulation for the MNPs in animals and humans. In this editorial, the current understanding of how MNPs are processed is discussed. Discussion on MNP effects on internal microflora, and their proposed role in developing inflammatory bowel diseases, MNP toxicokinetics, and their significance in health and disease are also reviewed. There is a need to understand the impact of MNP exposure on gut health and gut microbiota and identify current research gaps.
Combined single-photon emission computed tomography-myocardial perfusion imaging with coronary calcium score for assessing coronary disease
Authors: Calandri Enrico , Verdoia Monica , Sirovich Roberta , Giraudo Maria Teresa , Pultrone Mirco , Frantellizzi Viviana , Viola Orazio , Crivelli Francesca , Gallina Sonya , Serralunga Monica , Rognoni Andrea , De Vincentis Giuseppe
Published: January 2025

Purpose

Coronary artery disease (CAD) underestimation represents a major pitfall of single-photon emission computed tomography-myocardial perfusion imaging (SPECT-MPI). Coronary artery calcium score (CACS) has emerged as a sensitive tool for the assessment of suspect CAD; however, the integration of SPECT-MPI with CACS has been seldom evaluated, so far, and was therefore the aim of the present study.

Methods

Patients undergoing SPECT-MPI with CACS and subsequent coronary angiography were included. ROC curves were used to identify the CACS values best predictive for CAD. In SPECT-MPI negative patients, the formula:

defined the optimal CACS cut-points. The Systematic Coronary Risk Evaluation 2 was applied for 10-year cardiovascular risk estimation. Significant CAD was defined for an epicardial coronary stenosis >70 or 50% for the left main.

Results

Among 124 patients, 61 (49.19%) displayed positive SPECT-MPI, whereas 69 (56%) had significant CAD at angiography. Sensitivity, specificity, and positive predictive value (PPV) for SPECT-MPI were, respectively, 74, 82, and 84%. Considering 63 SPECT-MPI negative cases, the index values for CACS at the optimal cutoff value of 1949 were: sensitivity 28%, specificity 89%, and PPV 50%, allowing to further detect five (8%) of the patients with significant CAD. The increased discriminative power of the combined SPECT-MPI with CACS was not conditioned by the pretest cardiovascular risk.

Conclusion

Among patients with suspect CAD undergoing SPECT-MPI, the addition of CACS in negative cases allows to detect a consistent further 8% of patients with significant CAD, thus limiting the risk of disease underestimation and offering potential prognostic benefits.
Factors associated with quality of life in long-COVID syndrome
Authors: Artemiadis Artemios , Tofarides Andreas G. , Liampas Andreas , Ioannou Christiana , Christodoulou Katerina , Louka Rafaela , Vavougios George , Zis Panagiotis , Bargiotas Panagiotis , Hadjigeorgiou Georgios
Published: January 2025

Approximately 10% of patients experience persistent symptoms following COVID-19, known as long-COVID syndrome. This cross-sectional study explored factors of quality of life (QoL) in 53 long-COVID patients. QoL was measured using the World Health Organization-Five Well-Being Index, fatigue with the Fatigue Visual Analogue Scale, and psychological health with the Depression-Anxiety-Stress-21 questionnaire. Six neuropsychological tests assessed information processing speed, verbal memory, visual memory, working memory, attention, language, fluency, recall, and visuospatial function with a composite score calculated by averaging z scores. Patients (76% female, mean age: 54.1 years) were assessed 8.7 months postinfection. Cognitive impairment, present in 49% of the sample, was not associated with QoL. In multiple linear regression, gender, fatigue, and psychological distress accounted for 42% of QoL variance, with fatigue and distress contributing 7% and 11%, respectively. Further studies are needed to determine if fatigue and psychological distress are causally related to QoL in long-COVID and could be treatment targets.
Predicting the effect of landscape structure on epidemic invasion using an analytical estimate for infection rate
Authors: Suprunenko Yevhen F. , Cornell Stephen J. , Gilligan Christopher A.
Published: January 2025

The influence of landscape structure on epidemic invasion of agricultural crops is often underestimated in the construction and analysis of epidemiological models. Computer simulations of individual-based models (IBMs) are widely used to characterize disease spread under different management scenarios but can be slow in exploring large numbers of different landscape configurations. Here, we address the problem of finding an analytical measure of the impact of the spatial structure of a crop landscape on the invasion and spread of plant pathogens. We explore the potential of using an analytical approximation for the rate,

r

, at which susceptible crop fields become infected at the start of an epidemic to predict the effect that the spatial structure of a host landscape will have on an epidemic. We demonstrate the validity of this approach using two models: (i) a general IBM of the invasion and spread of a pathogen through an abstract host landscape; and (ii) an IBM of a real-life example for a virus disease spreading through a cassava landscape. Finally, we demonstrate that the analytical approach based on an estimate of the rate,

r

, can be used to identify spatial structures that effect deceleration of an invading pathogen.
CO- and H
2
S-adsorbed one-dimensional AlSi structures for gas sensing applications
Authors: Ngoc Hoang Van
Published: January 2025

The potential applications of low-dimensional materials continue to inspire significant interest among researchers worldwide. This study investigates the properties of one-dimensional AlSi monolayers, specifically AlSi nanoribbons, and their adsorption behaviour with CO and H
2
S molecules. The electronic, magnetic and optical properties of these systems are calculated using density functional theory and the Vienna Ab initio Simulation Package. Results indicate that the structures remain relatively planar with negligible buckling heights. All three studied structures exhibit non-zero magnetic moments; notably, CO adsorption enhances the magnetic moment of the pristine AlSi nanoribbon, whereas H
2
S adsorption reduces it. Adsorption energy calculations reveal that CO exhibits stronger adsorption compared to H
2
S. Furthermore, a detailed investigation of the optical properties—including the real and imaginary parts of the dielectric function, absorption coefficient and electron–hole density—demonstrates the potential of these structures in nanotechnology applications, particularly for CO and H
2
S gas sensing.
Recent advances in metal-catalysed oxidation reactions
Authors: Raju Aleena , Jothish Subhiksha , Sakthivel Kokila , Mishra Shachi , Gana R. J. , Kikushima Kotaro , Dohi Toshifumi , Singh Fateh V.
Published: January 2025

Oxidation reactions are vital tools in synthetic organic chemistry. Oxidation of organic species such as alcohols, phenols, aldehydes and ketones provides synthetically valuable organic compounds, especially synthetic intermediates for several biologically active compounds. Some of these synthetic intermediates have shown their synthetic utility in the total synthesis of natural products. Several classical and modern synthetic approaches have been used to achieve these oxidation reactions. In this review article, various oxidation reactions achieved by metal catalysis are highlighted.
AI Thinking: a framework for rethinking artificial intelligence in practice
Authors: Newman-Griffis Denis
Published: January 2025

Artificial intelligence is transforming the way we work with information across disciplines and practical contexts. A growing range of disciplines are now involved in studying, developing and assessing the use of AI in practice, but these disciplines often employ conflicting understandings of what AI is and what is involved in its use. New, interdisciplinary approaches are needed to bridge competing conceptualizations of AI in practice and help shape the future of AI use. I propose a novel conceptual framework called AI Thinking, which models key decisions and considerations involved in AI use across disciplinary perspectives. AI Thinking addresses five practice-based competencies involved in applying AI in context: motivating AI use, formulating AI methods, assessing available tools and technologies, selecting appropriate data and situating AI in the sociotechnical contexts it is used in. A hypothetical case study is provided to illustrate the application of AI Thinking in practice. This article situates AI Thinking in broader cross-disciplinary discourses of AI, including its connections to ongoing discussions around AI literacy and AI-driven innovation. AI Thinking can help to bridge between the work of diverse disciplines, contexts and actors in the AI space, and shape AI efforts in education, industrial development and policy.