bluuebunny/crossref_metadata_2025_split huggingface dataset:
Derived Intoxicating Cannabis Vape Product Attributes and Marketing in an Online Retail Environment
Authors: Chen-Sankey Julia , LoParco Cassidy R. , La Capria Kathryn , Meng Siyan , Mazzeo Rosanna , Vijayakumar Neha , Kong Amanda Y. , Tillett Kayla K. , Berg Carla , Rossheim Matthew E. 
Published: January 2025

ABSTRACTIntroductionThe 2018 Farm Bill unintentionally allowed the proliferation of derived intoxicating cannabis vape products (DICVPs), raising concerns about associated health risks. To inform public health prevention efforts, this study analyzed the product attributes and marketing features of DICVPs in an online retail environment.MethodsIn 2023, we extracted information on product attributes and descriptions of 490 DICVPs from two online retail websites with high web traffic. In 2024, two trained coders thematically coded product descriptions for their product characteristics and marketing features.ResultsOverall, 95 unique brands and 26 unique intoxicating cannabinoids were identified. The most frequent marketing features were overall vape product design and use (99.0%), including vaping satisfaction, discreetness, convenience, and use instructions. Regulation and compliance messages (91.6%) were also prevalent, including lab testing for additives and/or chemicals, health warnings, hemp-derived labels, references to the 2018 Farm Bill, and FDA approval statements. Other prominent themes included: flavor and sensation claims (79.6%, i.e., flavor variety, fruit flavors); psychoactive effect claims (43.3%, e.g., potency or expected user experience); product quality claims (38.4%, e.g., “quality,” “natural,” “purity”); and other positive effect claims (33.9%, e.g., mood enhancement, relaxation).DiscussionThe DICVP online marketplace is highly fragmented with a variety of brands and intoxicating compounds. Common marketing strategies promoting appealing flavors and positive vaping experiences may increase product use interest among young people. Features related to product legality and quality may reduce perceived barriers and risks of using products. Continuous monitoring of the DICVP marketplace is needed to inform policymaking.
Brain injury biomarkers in major and simple neurocognitive psychosis: association with tryptophan catabolites
Authors: Al-Hakeim Hussein Kadhem , Al-Issa Ameer Abdul Razzaq , Niu Mengqi , Zhang Yingqian , Maes Michael 
Published: January 2025

AbstractBackgroundSchizophrenia is categorized into qualitatively distinct classes, i.e. major (MNP) and simple (SNP) neurocognitive psychosis. MNP is accompanied by more severe neurocognitive deficits and symptomatology, activated immune-inflammatory and oxidative stress pathways, and induction of the tryptophan catabolite (TRYCAT) pathway with increased quinolinic acid (QA) and lowered kynurenic acid (KA) levels.AimsTo examine whether MNP and increased QA levels are associated with increased brain injury markers, including S100 calcium-binding protein B (S100B), neuroepithelial stem cell protein (Nestin), neuron-specific enolase (NSE), phosphorylated tau217 (pTau217), and glial fibrillary acidic protein (GFAP).MethodsThis case-control study included 52 MNP subjects, 68 SNP subjects, and 60 healthy controls and assessed the above brain injury biomarkers and TRYCATs.ResultsNSE and GFAP were significantly higher in MNP than in SNP, and in both MNP or SNP than in controls. Serum S100B levels were substantially higher in MNP than in controls and SNP. The results indicate injuries to neurofilaments in MNP and SBP, and that MNP is additionally characterized by damage to cell bodies, axons, glial cell projections, reduced neurogenesis and synaptic plasticity as compared with SNP. Increased QA levels and lowered KA predict increased pTau217, NSE and GFAP. The QA/KA ratio is the best predictor of these three brain injury markersConclusionsThese findings validate the differentiation between the two distinct subclasses with MNP being characterized by more profound injuries to brain cells and structures as compared with SNP. Increases in peripheral QA levels may contribute to these brain injuries in MNP.
A Cysteine-Less and Ultra-Fast Split Intein Rationally Engineered from Being Aggregation-Prone to Highly Efficient in Protein trans-Splicing
Authors: Humberg Christoph , Yilmaz Zahide , Fitzian Katharina , Dörner Wolfgang , Kümmel Daniel , Mootz Henning D. 
Published: January 2025

AbstractSplit inteins ligate their fused extein protein sequences while undergoing self-removal. This unique proteintrans-splicing reaction has been harnessed for numerous applications in protein modification. However, several purified split intein precursors splice only partially or are entirely inactive for unknown reasons. We have studied the split Aes123 PolB1 intein, which splices only to about 30%. As a rare representative of cysteine-less split inteins, the Aes intein is attractive due to its resistance to oxidative conditions and orthogonality to thiol chemistries. We revealed that the reduced splicing efficiency is caused by the formation of soluble, β-sheet dominated aggregates of the N-terminal precursor. We computationally, biochemically and biophysically characterized the fully active monomeric fraction to identify sequence regions important for aggregation. Guided by a crystal structure we designed stably monomeric mutants with virtually complete splicing activity. The triple mutant CLm intein (Cysteine-Less and monomeric) retained the ultra-fast rate discovered for the wildtype and exhibits superior utility as a thiol-independent protein modification tool. Characterization of two other benchmark split inteins suggests that the discovered aggregation propensity reflects an inherent challenge to keep the split intein precursor in the partially disordered form required to fold with its complementary partner into the active complex.
Innate Immune Memory is Stimulus Specific
Authors: O’Farrell Aoife , Niu Zijian , Li Jingxin , Van Eyndhoven Laura C. , Sarma Kavitha , Raj Arjun 
Published: January 2025

ABSTRACTInnate immune memory (also termed trained immunity) is defined in part by its ability to cross-protect against heterologous pathogens, and can be generated by many different stimuli, suggesting a “universal” trained state. However, different stimuli could form distinct memories, leading to stimulus-specific trained responses. Here, we use primary human monocyte-derived macrophages to demonstrate phenotypic and epigenetic stimulus specificity of innate immune memory six days after initial exposure. Quantification of cytokine production with single-molecule RNA imaging demonstrates stimulus-specific patterns of response to restimulation at the single cell level. Differential licensing of inflammatory transcription factors is associated with encoding of specificities in chromatin. Trained cells show stronger responses to secondary stimuli that are more similar to the initial stimulus they experienced, suggesting a functional role for these stimulus-specific memories. Rather than activating a universal training state, our findings demonstrate that different stimuli impart specific memories that generate distinct training phenotypes in macrophages.
DMEM and EMEM are suitable surrogate media to mimic host environment and expand leptospiral pathogenesis studies usingin vitrotools
Authors: Garcia Leandro E. , Lin Zitong , Culos Sophie , Muenker M Catherine , Johnson Emily E. , Wang Zheng , Lopez-Giraldez Francesc , Giraud-Gatineau Alexandre , Jackson Angela , Picardeau Mathieu , Goodlett David R. , Townsend Jeffrey P. , Pětrošová Helena , Wunder Elsio A. 
Published: January 2025

ABSTRACTPathogenicLeptospiraspecies can survive and thrive in a wide range of environments. Distinct environments expose the bacteria to different temperatures, osmolarities, and amounts and sources of nutrition. However, leptospires are mostly cultured, in a laboratory setting underin vitroconditions that do not reflect natural environments. This constraint on laboratory cultures limits the applicability ofin vitrostudies to the understanding of even simple pathogenic processes. Here we report, investigate, and identify a medium and conditions that mimic the host environment during leptospirosis infection, expanding the availablein vitrotools to evaluate leptospiral pathogenesis. We quantified genome-wide gene expression of pathogenicLeptospira interroganscultured in differentin vitromedia compositions (EMJH, DMEM, EMEM, and HAN). Using EMJH as standard, we compared gene expression in these compositions to genome-wide gene expression gathered in a host environment: whole blood (WB) of hamsters after infection with pathogenic leptospires. Leptospires cultured in DMEM and EMEM media shared 40% and 47% of all differentially expressed genes (DEGs) of leptospires present within WB (FDR<0.01), while leptospires cultured in HAN media only shared 20% of DEGs with those from WB. Furthermore, gene and pathway expression of leptospires cultured on DMEM and EMEM media exhibited a better correlation with leptospires grown in WB, including promoting expression of a similar leptospiral lipid A profile to the one identified directly in host tissues. Taken together, these results indicate that commercial cell-culture media EMEM or DMEM are better surrogates forin vivopathogenic studies than EMJH or HAN media inLeptospira. These alternative culture conditions, using media that are a standard supply worldwide, provide a reproducible and cost-effective approach that can accelerate research investigation and reduce the number of animal infections necessary for basic research of leptospirosis.
Differential regulation of histone H1 subtypes by N6-methyladenosine RNA methylation
Authors: García-Gomis D , López-Gómez J , Andrés M , Serna-Pujol N , Ponte I , Jordan A , Roque A 
Published: January 2025

AbstractHistone H1 is involved in the regulation of chromatin structure and gene expression. Up to seven H1 subtypes or variants are expressed in human somatic cells. The H1 complement, defined as the subtype composition and proportions in a given cell, is highly variable depending on the cell type, cell cycle, developmental stage, and several diseases such as cancer. It is the result of the combined action of the different regulatory processes. Epitranscriptome modifications have emerged as a new regulatory mechanism able to control all aspects of mRNA metabolism. In this work, we have examined the role of the most prevalent mRNA modification, N6-methyladenosine RNA methylation (m6A), in the regulation of H1 subtypes. MeRIP-seq showed that H1.0 and H1.4 are enriched in m6A, while H1.2 has medium levels of this mark. We found that m6A inhibition altered transcript and protein levels, de novo transcription, and ribosome occupancy at the translation start site of specific H1 subtypes. Pull-down experiments using biotinylated-specific probes followed by mass spectrometry or RNA-immunoprecipitation coupled with RT-qPCR, allowed the identification of IGF2BP1, hnRNPD, and YTHDF2 as m6A readers of H1 subtypes. Integration of the functional studies, with m6A inhibition and partial depletion of the m6A readers led us to propose the first model of the differential regulation of H1 subtypes by m6A. In this model, m6A promotes the degradation of H1.0 mRNA mediated by YTHDF2, the stabilization of H1.2 mRNA by IGF2BP1 binding, and the H1.4 mRNA translation mediated by hnRNPD. These findings suggest that m6A is involved in the subtype-specific regulation of H1 subtypes, adding another layer to their complex regulation and contributing to the variability of the H1 complement in cancer.
Fabricating microfluidic co-cultures of immortalised cell lines uncovers robust design principles for the simultaneous formation of patterned, vascularised, and stem cell-derived adipose tissue
Authors: Murphy Ashley R. , Franco Rose Ann , Allenby Mark C. 
Published: January 2025

AbstractIn vitroculture processes supporting the simultaneous formation of vessel networks alongside differentiation towards mature parenchymal tissue have numerous clinical and agricultural applications but remain unrealised due to contrasting culture requirements. Of specific interest is lab-grown vascularised adipose tissue to study metabolic syndrome, diabetes, obesity, cardiovascular diseases, and to advance cultivated meat technologies. We report a microfluidic 3D hydrogel culture device capable of supporting live-imaging of fluorescent reporter cell lines and generating counter-current gradients of vasculogenic and adipogenic growth factors. for the first time, we report experimental conditions capable of reproducibly forming diverse microvascular networks from telomerase immortalised endothelial and mesenchymal stem cells in both 2D and 3D hydrogel-embedded cultures. Using our novel microfluidic culture design, we demonstrate the generation of growth factor environments which support the 3D co-formation of integrated robust microvascular networks and lipid-producing adipocytes after 31 days gradient culture. We demonstrate microvascular networks substantially support parenchymal stromal cell differentiation to mature adipose tissue (67.4% lipid coverage), unachieved in avascular cultures (1.86% lipid coverage). We attempt to validate our co-culture model by applying inhibitors of vessel-mediated lipogenesis (spermidine and VO-OHpic), which are demonstrated to be ineffective in our novel human preclinical model.HighlightsAn optimised co-culture protocol for vasculogenesis of immortalised cell lines.Immortalised co-cultures form reproducible microvessel networks up to 31 days.Gradient co-culture enables simultaneous MSC adipogenesis and EC vasculogenesis.MSC differentiation to dense, lipid-laden adipose tissue relies on EC co-culture.Human vascularised adipose tissue formation is unaffected by a murine regulator.Graphical Abstract
The microbiome of the human facial skin is unique compared to that of other hominids
Authors: Degregori Samuel , Manus Melissa B. , Qu Evan B. , Mendall Calen P. , Baker Jacob S. , Hopper Lydia M. , Amato Katherine R. , Lieberman Tami D. 
Published: January 2025

AbstractThe human facial skin microbiome is remarkably similar across all people sampled to date, dominated by facultative anaerobeCutibacterium. The origin of this genus is unknown, with no close relatives currently described from samples of primate skin. This apparent human-specific bacterial taxon could reflect the unique nature of human skin, which is significantly more oily than that of our closest primate relatives. However, previous studies have not sampled the facial skin microbiome of our closest primates. Here, we profiled the skin microbiome of zoo-housed chimpanzees (Pan troglodytes), and gorillas (Gorilla gorilla gorilla), alongside their human care staff, using both 16S and shotgun sequencing. We showed that facial skin microbiomes differ significantly across host species, with humans having the lowest diversity and most unique community among the three species. We were unable to find a close relative ofCutibacteriumon either chimpanzee or gorilla facial skin, consistent with human-specificity. Hominid skin microbiome functional profiles were more functionally similar compared to their taxonomic profiles. However, we still found notable functional differences including lower proportions of fatty acid biosynthesis on humans, consistent with microbes’ reliance on host-derived lipids. Our study highlights the uniqueness of the human facial skin microbiome and supports a horizontal acquisition of its dominant resident from a yet unknown source.ImportanceUnderstanding how and why human skin bacteria differ from our closest animal relatives provides crucial insights into human evolution and health. While we have known that human facial skin hosts distinct bacteria—particularlyCutibacterium acnes—we did not know if these bacteria and their associated genes were also present on the faces of our closest relatives, chimpanzees and gorillas. Our study shows that human facial skin hosts markedly different bacteria than other primates, withC. acnesbeing uniquely abundant on human faces. This finding suggests that this key bacterial species may have adapted specifically to human skin, which produces more oils than other primates.
South African brown locusts,Locustana pardalina, hosts fluconazole resistantCandidozyma(Candida)auris(Clade III)
Authors: Ogundeji Adepemi , Bello-Akinosho Maryam , Swart Vaughn , Featherston Jonathan , Bolsenbroek Armand , Beneke Carel , Musoke Jolly , Baker Tyla , Ismail Arshad , Sebolai Olihile , Albertyn Jacobus , Pohl Carolina 
Published: January 2025

AbstractThe environmental niche and mode of transmission from the environment to humans of the emerging pathogenic yeast,Candidozyma(Candida)aurisis a subject of speculation, with hypotheses including avian species and marine environments. Interestingly, yeasts related toC. aurishave been repeatedly observed associated with various insects. This lprompted us to investigate a thermophilic insect,Locustana pardalinaas possible host forC. auris. Here we report the isolation and identification of threeC aurisstrains from the gut ofL. pardalinaas well as the phenotypic characterisation of one of these isolates. Interestingly, the isolate was able to survive at 50oC and grew at 15% NaCl. In addition, it was susceptible to the tested disinfectants and antifungals, except fluconazole. Genome sequencing and SNP analyses placed the isolate in Clade III, which is common is South Africa. This highlights the role of insects in the evolution and dissemination of emerging pathogenic yeasts.
Ultrasound Applications in the Treatment of Major Depressive Disorder (MDD): A Systematic Review of Techniques and Efficacy
Authors: Tan Gansheng , Chen Hong , Leuthardt Eric C. 
Published: January 2025

AbstractObjectiveMajor depressive disorder (MDD) is a debilitating mental health condition characterized by persistent feelings of sadness, loss of interest, and impaired daily functioning. It affects approximately 8% of the U.S. population, posing a significant personal and economic burden. Around 30% of patients with MDD do not respond to conventional antidepressant and psychotherapeutic treatments. Current treatment options for refractory MDD include transcranial magnetic stimulation (TMS) and invasive surgical procedures such as surgical ablation, vagus nerve stimulation, and deep brain stimulation. TMS has modest efficacy, and surgical procedures are associated with surgical risk and low patient acceptance. With the unique advantage of combining non-invasiveness with selective targeting, therapeutic ultrasound emerges as a promising alternative for treating refractory MDD. Over the past 10 years, there has been a growth in focused ultrasound research, leading to an exponential increase in academic and public interest in the technology. To support the continued development of ultrasound for treating MDD, we conducted a systematic review following Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines.MethodsWe included peer-reviewed prospective cohort studies, case-control studies, and randomized control trials that evaluate the efficacy of ultrasonic treatment for depression (PROSPERO registration number: CRD42024626093). We summarized ultrasonic techniques for treating depression and their efficacy. Furthermore, we identified key challenges and future directions for applying ultrasound in treating MDD.ResultsWe identified 67 potentially relevant articles, of which 18 studies met all inclusion criteria. The techniques of applying ultrasound to treat depression include magnetic resonance-guided focused ultrasound (MRgFUS) for capsulotomy and low-intensity focused ultrasound (LIFUS) neuromodulation. In human trials, the response rate (≥50% improvement from baseline on depression score) is 53.85% for MRgFUS and 80.49% for LIFUS neuromodulation. In all preclinical studies using rodent models (8 studies), LIFUS neuromodulation had a medium to large effect (|Cohen’s d| > 0.6) on resolving depressive-like behavior in rodents without causing adverse effects such as tissue damage. MRgFUS faces inconsistent lesioning success and a limited response rate, while LIFUS neuromodulation lacks systematic exploration of parameter space and a clear understanding of its mechanistic effects. Future work should refine patient selection for MRgFUS and focus on individualized functional targeting.ConclusionLIFUS neuromodulation showed a medium to large effect in reducing depressive behaviors in both rodent models and human trials, representing a promising, noninvasive option for treating refractory MDD.
An updated vocal repertoire of wild adult bonobos (Pan paniscus)
Authors: Wegdell Franziska , Schamberg Isaac , Berthet Mélissa , Rothacher Yannik , Dellwo Volker , Surbeck Martin , Townsend Simon 
Published: January 2025

AbstractWhile research over the last 20 years has shed important light on the vocal behaviour of our closest living relatives, bonobos and chimpanzees, a quantitative description of their full vocal repertoire is absent. Such data are critical for a holistic understanding of a species’ communication system and unpacking how these systems compare more broadly with other primate and non-primate species. Here we make key progress by providing the first quantitativePanvocal repertoire, specifically for wild bonobos. Using data comprising over 1500 calls from 53 adult individuals collected over 33 months, we employ machine-learning-based random forest analyses and describe 11 acoustically distinguishable call types. We discuss issues associated with resolving vocal repertoires from wild data in great apes and highlight potential future approaches to further capture the complexity of the bonobo vocal system.
Inverse hourglass pattern of conservation in rodent molar development
Authors: Ganofsky Jérémy , Estevez-Villar Mathilde , Mouginot Marion , Moretti Sébastien , Nyamari Marion , Robinson-Rechavi Marc , Pantalacci Sophie , Sémon Marie 
Published: January 2025

ABSTRACTAlthough it is well established that certain stages of development are more conserved than others, the reasons for this phenomenon remain largely unknown. We study molecular conservation in the development of an organ, the molar, by comparing the temporal profiles of expression in mice and hamsters. We find that molar development is characterized by a rarely observed pattern of conservation of expression level and coding sequences forming an inverse hourglass, with more conservation at the beginning and end of morphogenesis than at intermediate stages. As the development of the rodent molar is well described, we were able to link this pattern to the properties of the expressed genes and the activity of different developmental processes. Early and late stages mobilize different sets of pleiotropic genes, cell division for bud growth and secretion for tooth mineralization. The particularities of dental morphogenesis and homeostasis, with the degradation of certain tissues at the end of development and the hosting of immune cells, as well as heterochronies linked to adaptations, also probably contribute to the pattern. Our study of the different actors explains the inverted hourglass of molars by a combination of processes intrinsic to the teeth, and by negative and positive selection which is mostly extrinsic to the teeth. This is likely translatable to explain molecular conservation patterns in many other biological systems.