tbuckley/cabot-search huggingface dataset:
<i>Fusobacterium sphaericum</i> sp. nov., isolated from a human colon tumor adheres to colonic epithelial cells and induces IL-8 secretion
Authors: Martha A. Zepeda-Rivera, Yannick Eisele, Alexander Baryiames, Hanrui Wu, Claudia Mengoni, Gianmarco Piccinno, Elsa F. McMahon, Kaitlyn D. LaCourse, Dakota S. Jones, Hans Hauner, Samuel S. Minot, Nicola Segata, Floyd E. Dewhirst, Christopher D. Johnston, Susan Bullman
Journal: Gut Microbes (2024)

Cancerous tissue is a largely unexplored microbial niche that provides a unique environment for the colonization and growth of specific bacterial communities, and with it, the opportunity to identify novel bacterial species. Here, we report distinct features of a novel Fusobacterium species, F. sphaericum sp. nov. (Fs), isolated from primary colon adenocarcinoma tissue. We acquire the complete closed genome and associated methylome of this organism and phylogenetically confirm its classification into the Fusobacterium genus, with F. perfoetens as its closest neighbor. Fs is phenotypically and genetically distinct, with morphological analysis revealing its coccoid shape, that while similar to F. perfoetens is rare for most Fusobacterium members. Fs displays a metabolic profile and antibiotic resistance repertoire consistent with other Fusobacterium species. In vitro, Fs has adherent and immunomodulatory capabilities, as it intimately associates with human colon cancer epithelial cells and promotes IL-8 secretion. An analysis of the prevalence and abundance of Fs in > 20,000 human metagenomic samples shows that it is a rarely detected member within human stool with variable relative abundance, found in both healthy controls and patients with colorectal cancer (CRC). Our study sheds light on a novel bacterial species isolated directly from the human CRC tumor niche and given its in vitro interaction with cancer epithelial cells suggests that its role in human health and disease warrants further investigation.
Gut microbes with the <i>gbu</i> genes determine TMAO production from L-carnitine intake and serve as a biomarker for precision nutrition
Authors: Wei-Kai Wu, Yi-Ling Lo, Jian-Ying Chiu, Chia-Lang Hsu, I-Hsuan Lo, Suraphan Panyod, Yu-Chieh Liao, Tina H. T. Chiu, Yu-Tang Yang, Han-Chun Kuo, Hsin-Bai Zou, Yi-Hsun Chen, Hsiao-Li Chuang, Jeffrey J. Y. Yen, Jin-Town Wang, Han-Mo Chiu, Cheng-Chih Hsu, Ching-Hua Kuo, Lee-Yan Sheen, Hsien-Li Kao, Ming-Shiang Wu
Journal: Gut Microbes (2024)

Gut microbial metabolism of L-carnitine, which leads to the production of detrimental trimethylamine N-oxide (TMAO), offers a plausible link between red meat consumption and cardiovascular risks. Several microbial genes, including cntA/B, the cai operon, and the recently identified gbu gene cluster, have been implicated in the conversion of dietary L-carnitine into TMA(O). However, the key microbial genes and associated gut microbes involved in this pathway have not been fully explored. Utilizing the oral carnitine challenge test (OCCT), which specifically measures TMAO production from L-carnitine intake and identifies TMAO producer phenotypes, we compared the abundance of microbial genes between low- and high-TMAO producers across three independent cohorts. Our findings consistently revealed that the gbu gene cluster, rather than cntA/B or the cai operon, was significantly enriched in high-TMAO producers. We further analyzed 292 paired multi-omic datasets from OCCT and shotgun metagenomic sequencing, which demonstrated a significant positive correlation between the abundance of fecal gbu genes and L-carnitine-induced TMAO production, with gbuB showing the strongest correlation. Interestingly, these fecal gbu genes were found to increase with L-carnitine supplementation and decrease with a plant-based diet. Notably, we verified a previously uncultured gbu-containing bacterium, JAGTTR01 sp018223385, as the major contributor to TMA formation in the human gut. We isolated these gbu-containing gut microbes and confirmed their role in TMA/TMAO production using anaerobic incubation and a gnotobiotic mouse model. Using an in-house collection of gbu-containing isolates, we developed a qPCR-based method to quantify fecal gbuB and validated its correlation with L-carnitine-mediated TMAO production as measured by OCCT. Overall, these findings suggest that gbu-containing gut microbes are crucial for TMAO increases following L-carnitine intake and may serve as biomarkers or targets for personalized nutrition.
Digital solutions for migrant and refugee health: a framework for analysis and action
Authors: Stephen A Matlin, Johanna Hanefeld, Ana Corte-Real, Paulo Rupino da Cunha, Thea de Gruchy, Karima Noorali Manji, Gina Netto, Tiago Nunes, İlke Şanlıer, Amirhossein Takian, Muhammad Hamid Zaman, Luciano Saso
Journal: The Lancet Regional Health - Europe (2024)
Fast and accurate prediction of drug induced proarrhythmic risk with sex specific cardiac emulators
Authors: Paula Dominguez-Gomez, Alberto Zingaro, Laura Baldo-Canut, Caterina Balzotti, Borje Darpo, Christopher Morton, Mariano Vázquez, Jazmin Aguado-Sierra
Journal: npj Digital Medicine (2024)

In silico trials for drug safety assessment require many high-fidelity 3D cardiac simulations to predict drug-induced QT interval prolongation, which is often computationally prohibitive. To streamline this process, we developed sex-specific emulators for a fast prediction of QT interval, trained on a dataset of 900 simulations. Our results show significant differences between 3D and 0D single-cell models as risk levels increase, underscoring the ability of 3D modeling to capture more complex cardiac responses. The emulators demonstrated an average error of 4% compared to simulations, allowing for efficient global sensitivity analysis and fast replication of in silico clinical trials. This approach enables rapid, multi-dose drug testing on standard hardware, addressing critical industry challenges around trial design, assay variability, and cost-effective safety evaluations. By integrating these emulators into drug development, we can improve preclinical reliability and advance the practical application of digital twins in biomedicine.
Maternal Allergic Disease Phenotype and Infant Birth Season Influence the Human Milk Microbiome
Authors: Jie Ma, Debra J. Palmer, Donna Geddes, Ching Tat Lai, Alethea Rea, Susan L. Prescott, Nina D'Vaz, Lisa F. Stinson
Journal: Allergy (2024)

Early infancy is a critical period for immune development. In addition to being the primary food source during early infancy, human milk also provides multiple bioactive components that shape the infant gut microbiome and immune system and provides a constant source of exposure to maternal microbiota. Given the potential interplay between allergic diseases and the human microbiome, this study aimed to characterise the milk microbiome of allergic mothers. Full-length 16S rRNA gene sequencing was performed on milk samples collected at 3 and 6 months postpartum from 196 women with allergic disease. Multivariate linear mixed models were constructed to identify the maternal, infant, and environmental determinants of the milk microbiome. Human milk microbiome composition and beta diversity varied over time (PERMANOVA R
Exposure Profiles for the Long‐Term Use of Disinfectants and Cleaning Products and Asthma
Authors: Emilie Pacheco Da Silva, Tobias Weinmann, Jessica Gerlich, Gudrun Weinmayr, Jon Genuneit, Dennis Nowak, Erika von Mutius, Christian Vogelberg, Katja Radon, Felix Forster
Journal: Allergy (2024)

ABSTRACT Background Using disinfectants and cleaning products (DCPs) at home and work is known to influence both the onset and course of asthma, but most epidemiological studies did not consider the multiplicity and correlations of exposures to DCPs. We aimed to identify exposure profiles for the long‐term weekly use of DCPs by latent class analysis (LCA) and assess their associations with asthma. Methods LCA was conducted on data from 1143 young adults initially recruited in the German centers of Phase II of the International Study of Asthma and Allergies in Childhood (ISAAC) and followed up three times. In our LCA model, we included the use of cleaning sprays, disinfectant sprays, and nonspray disinfection methods, measured at ages 19–24 (first assessment) and 29–34 years (second assessment). Associations between identified exposure profiles and current as well as incident asthma/wheeze were evaluated by logistic regression. Results We identified five long‐term exposure profiles to DCPs (latent classes): no weekly use of DCPs (55% of participants), use in first assessment (7%), use in second assessment (18%), persistent use (8%), and persistent cleaning sprays use (12%). Compared to “no weekly use,” being in the “persistent use” profile was associated with both current asthma (OR = 1.68, 95% CI = [0.48–5.88]) and current wheeze (OR = 1.71, 95% CI = [0.75–3.90]). For incident asthma/wheeze, interval estimates were very wide. Conclusions Our study identified five distinct long‐term exposure profiles to DCPs. Among those, only a persistent weekly use of multiple DCPs over time seemed to have an adverse effect on asthma. However, large confidence intervals indicate considerable uncertainty.
Genotype‐Guided Asthma Treatment Reduces Exacerbations in Children: Meta‐Analysis of Two <scp>RCTs</scp>
Authors: Elise M. A. Slob, Susanne J. H. Vijverberg, Tom Ruffles, Lieke C. E. Noij, Jacqueline Biermann, Alwin F. J. Brouwer, Kristel van den Brink, Annette de Bruin‐Kok, Bart E. Van Ewijk, Eric Haarman, Sanne C. Hammer, Simone Hashimoto, Fiona Hogarth, Christina J. Jones, Arvid W. A. Kamps, Elin T. G. Kersten, Ismé de Kleer, Brian J. Lipworth, Roberta Littleford, Marieke Mérelle, Alexander Moeller, Colin N. A. Palmer, Kristina Pilvinyte, Niels W. Rutjes, Ron H. N. van Schaik, Helen E. Smith, Roger Tavendale, Suzanne W. J. Terheggen‐Lagro, Steve Turner, Jos W. R. Twisk, Anja Vaessen‐Verberne, Mariël Verwaal, Tjalling de Vries, Judit Wesseling, Mariëlle W. Pijnenburg, Gerard H. Koppelman, Somnath Mukhopadhyay, Anke H. Maitland‐van der Zee
Journal: Allergy (2024)

ABSTRACT Background Long‐acting beta2‐agonists (LABA) in combination with inhaled corticosteroids (ICS) are commonly used to treat asthma, however, some children lack response to the addition of LABA. This might be partially due to the presence of the Arg16Gly polymorphism, encoded by rs1042713 G&gt;A in the ADRB2 gene. Carrying the A allele (Arg16) at this variant has been associated with an increased risk of exacerbations despite LABA treatment. We investigated whether genotype‐guided treatment improved asthma‐related outcomes. Methods We conducted an individual participant data meta‐analysis of two randomised controlled trials: PUFFIN (Dutch and Swiss 6–18 year‐olds) and PACT (English and Scottish 12–18 year‐olds). Children with uncontrolled asthma despite ICS who required a step‐up in treatment were included. Participants were randomised to genotype‐guided treatment or the control group with a follow‐up of at least 6 months. Genotype‐guided treatment consisted of adding LABA for children with ADRB2 Gly16/Gly16, whilst children with ADRB2 Arg16/Arg16 or Arg16/Gly16 were treated with double dose ICS (PUFFIN) or add‐on montelukast (PACT). The primary outcome was a change in asthma control; secondary outcomes included exacerbation rate and time to exacerbation. Repeated measures mixed models and Cox regression were used. Results Fifty‐nine out of 102 (PUFFIN) and 59 out of 91 (PACT) children had at least one Arg (A allele). Amongst all 193 children, no difference was observed in asthma control between the study groups. However, genotype‐guided treatment resulted in lower asthma exacerbation rates (−0.08 (95%CI −0.16 to −0.00, p = 0.04)) compared to the control group. Conclusion Genotype‐guided step‐up treatment for children with uncontrolled asthma on ICS may lower asthma exacerbation rates and may be useful for personalising asthma care.
Current trends in sensitizing immune checkpoint inhibitors for cancer treatment
Authors: Jing Wei, Wenke Li, Pengfei Zhang, Fukun Guo, Ming Liu
Journal: Molecular Cancer (2024)

Immune checkpoint inhibitors (ICIs) have dramatically transformed the treatment landscape for various malignancies, achieving notable clinical outcomes across a wide range of indications. Despite these advances, resistance to immune checkpoint blockade (ICB) remains a critical clinical challenge, characterized by variable response rates and non-durable benefits. However, growing research into the complex intrinsic and extrinsic characteristics of tumors has advanced our understanding of the mechanisms behind ICI resistance, potentially improving treatment outcomes. Additionally, robust predictive biomarkers are crucial for optimizing patient selection and maximizing the efficacy of ICBs. Recent studies have emphasized that multiple rational combination strategies can overcome immune checkpoint resistance and enhance susceptibility to ICIs. These findings not only deepen our understanding of tumor biology but also reveal the unique mechanisms of action of sensitizing agents, extending clinical benefits in cancer immunotherapy. In this review, we will explore the underlying biology of ICIs, discuss the significance of the tumor immune microenvironment (TIME) and clinical predictive biomarkers, analyze the current mechanisms of resistance, and outline alternative combination strategies to enhance the effectiveness of ICIs, including personalized strategies for sensitizing tumors to ICIs.
Identification of Gut Biomarkers of <scp>FPIES</scp> in a Longitudinal Comparative Pediatric Study
Authors: A. Lemoine, N. Kapel, I. Nicolis, P. Tounian, A. Bruneau, N. Kapandji, K. Adel‐Patient, M. Thomas
Journal: Allergy (2024)

ABSTRACT Background Food protein‐induced enterocolitis syndrome (FPIES) is a non‐IgE‐mediated allergy without known biomarkers. We aimed to compare fecal biomarkers related to gut inflammation and immunity in children with FPIES, with resolved FPIES (tolerant), and in matched controls. Methods Stools were collected from FPIES children on elimination diet, before and after an oral food challenge (OFC) performed to assess their natural tolerance, at the end of a follow‐up in tolerant FPIES children, and in matched controls (1:1 ratio). Concentrations of calprotectin, EDN (eosinophilic derived neurotoxin), and secretory IgA (sIgA) underwent comparative paired analysis. Results Thirty‐eight patients were included (age: 1.3 years old, interquartile range: IQR [0.9–2.0]), of which 22 became tolerant during follow‐up. Upon inclusion, allergic patients and controls had similar concentrations of calprotectin (38 μg/g [8–85] vs. 27 μg/g [11–46], p = 0.15) and EDN (504 ng/g [275–1252] vs. 516 ng/g [215–844], p = 0.86). However, concentrations of these inflammatory biomarkers increased transiently after a failed OFC ( p &lt; 0.001 and p = 0.01 respectively), without correlating with the severity of an allergic reaction. sIgA were higher in allergic than in tolerant patients: 2224 μg/g [878–3529] vs. 794 μg/g [699–1767] ( p &lt; 0.01). Calprotectin, EDN, and sIgA were comparable in tolerant patients and controls. sIgA less than 2637 μg/g had a negative predictive value of 75.3% for the differentiation allergic patients from tolerant patients and controls (area under curve: 0.63, 95% CI: 0.52–0.74). Conclusion A few days after an acute allergic reaction, there was no detectable chronic gut inflammation in FPIES. sIgA may be a useful tool for clinicians in timing OFC.
Allergen Specific <scp>IgE</scp> is a Stronger Predictor of Remission Following Peanut Oral Immunotherapy Than Age in Children Aged 1–10 Years
Authors: Sarah E. Ashley, Melanie Lloyd, Paxton Loke, Francesca Orsini, Adriana C. Lozinsky, Michael D. O'Sullivan, Patrick Quinn, Michael Gold, Mimi L. K. Tang
Journal: Allergy (2024)

Remission is the desired outcome following OIT as it allows individuals to discontinue treatment and eat the allergen freely. Early initiation of OIT in infants and toddlers has been embraced as an approach to increase the likelihood of remission. However, there is no high-quality evidence supporting younger age as an independent factor driving remission; available studies are limited by small samples of younger subjects and lack of adjustment for confounding covariates, particularly peanut-specific IgE (sIgE) levels which is closely correlated with age.
The Relationship Between Dietary Patterns and the Epidemiology of Food Allergy
Authors: Agnes Sze‐Yin Leung, Yuhan Xing, Montserrat Fernández‐Rivas, Gary Wing‐Kin Wong
Journal: Allergy (2024)

ABSTRACT Food allergies are increasing globally, particularly in Asia; however, the etiologies of allergic diseases remain poorly understood despite comprehensive studies conducted across a variety of populations. Epidemiological research demonstrates that food allergy is more prevalent in Westernized or urbanized societies than in rural or developing ones. As such, comparing the distribution and patterns of food allergies as well as the environmental exposures between regions may provide insight into potential causal and protective factors of food allergy. Diet is an important exposome that has been shown to modulate the immune system both directly and indirectly via pathways involving the microbiota. Changes in dietary patterns, especially the shift to a Westernized diet with reduced dietary fiber and an abundance of processed foods, impact the gut and skin epithelial barrier and contribute to the development of chronic inflammatory diseases, such as food allergy. Although dietary intervention is believed to have tremendous potential as a strategy to promote immunological health, it is essential to recognize that diet is only one of many factors that have changed in urbanized societies. Other factors, such as pollution, microplastics, the use of medications like antibiotics, and exposure to biodiversity and animals, may also play significant roles, and further research is needed to determine which exposures are most critical for the development of food allergies.
Successful repositioning of mertansine for improved chemotherapy by combining a polymer prodrug approach and PET imaging
Authors: Soizic Martin-Aubert, Kevin Avrillon, Nicolas Tournier, Alexandre Bordat, Vu Long Tran, Nada Ibrahim, Dimitri Kereselidze, Benoit Jego, Léa Potiron, Nicolas Tsapis, Julien Nicolas, Tanguy Boissenot, Charles Truillet
Journal: Journal of Controlled Release (2024)

Mertansine (DM1), a potent tumor-killing maytansinoid, requires conjugation to antibodies or incorporation into nanocarriers due to its high toxicity. However, these carriers often result in undesirable biodistribution, leading to rapid and long-term accumulation in the kidneys or liver and potentially increased toxicity. To overcome this limitation, we used the hydrophilic, biocompatible, and stealth properties of polyacrylamide (PAAm) as a scaffold to develop water-soluble PAAm-DM1 polymer prodrugs, leveraging PAAm's previous success in delivering paclitaxel via subcutaneous administration. To monitor distribution and predict efficacy, we have imparted Positron Emission Tomography (PET) imaging capabilities to well-defined PAAm-DM1 polymer prodrugs. Our studies demonstrated the same tumor accumulation and the same distribution of PAAm-DM1 in the main organs such as liver, kidneys muscle, regardless of delivery route (subcutaneous or intravenous). Interestingly, tumor accumulation of PAAm-DM1 was primarily driven by passive accumulation, as indicated by PET imaging, without significantly altering treatment efficacy. This suggests complex mechanisms, possibly involving immune system interactions by influencing notably the metabolism and clearance. To enhance therapeutic outcomes, we combined the polymer prodrug with immunotherapy, specifically anti-CTLA4. Our findings highlight the promising potential of PAAm-DM1, offering a novel formulation strategy for DM1 in cancer therapy.
Tunable Viscoelasticity of Alginate Hydrogels via Serial Autoclaving (Adv. Healthcare Mater. 32/2024)
Authors: Hamidreza Moheimani, Samuel Stealey, Sydney Neal, Eya Ferchichi, Jialiang Zhang, Marcus Foston, Lori A. Setton, Guy M. Genin, Nathaniel Huebsch, Silviya P. Zustiak
Journal: Advanced Healthcare Materials (2024)
Self‐Assembled Peptide Hydrogels Loaded with Umbilical Cord‐Derived Mesenchymal Stem Cells Repairing Injured Endometrium and Restoring Fertility (Adv. Healthcare Mater. 32/2024)
Authors: Xue Lv, Wenjing Niu, Bin Zhang, Jingbo Chen, Shicong Yang, Yuhuan Xue, Yutian Dong, Peiyan Yuan, Yue Pan, Jeremy Tan, Yi Yan Yang, Xin Ding, Xiaomiao Zhao
Journal: Advanced Healthcare Materials (2024)
Automated Microfluidics‐Assisted Hydrogel‐Based Wet‐Spinning for the Biofabrication of Biomimetic Engineered Myotendinous Junction (Adv. Healthcare Mater. 32/2024)
Authors: Marina Volpi, Alessia Paradiso, Ewa Walejewska, Cesare Gargioli, Marco Costantini, Wojciech Swieszkowski
Journal: Advanced Healthcare Materials (2024)
Systemic Administration of Neurotransmitter‐Derived Lipidoids‐PROTACs‐DNA Nanocomplex Promotes Tau Clearance and Cognitive Recovery for Alzheimer's Disease Therapy (Adv. Healthcare Mater. 32/2024)
Authors: Baofeng Gong, Weicong Zhang, Wei Cong, Yuankai Gu, Wenbo Ji, Tong Yin, Honglei Zhou, Honggang Hu, Jianhua Zhuang, Yi Luo, Yan Liu, Jie Gao, You Yin
Journal: Advanced Healthcare Materials (2024)
An In Vitro Model of the Blood–Brain Barrier for the Investigation and Isolation of the Key Drivers of Barriergenesis (Adv. Healthcare Mater. 32/2024)
Authors: Christina Schofield, Stylianos Sarrigiannidis, Alejandro Moran‐Horowich, Emma Jackson, Aleixandre Rodrigo‐Navarro, Tom van Agtmael, Marco Cantini, Matthew J. Dalby, Manuel Salmeron‐Sanchez
Journal: Advanced Healthcare Materials (2024)
Controlled Release of Ceria and Ferric Oxide Nanoparticles via Collagen Hydrogel for Enhanced Osteoarthritis Therapy (Adv. Healthcare Mater. 32/2024)
Authors: Xian Chen, Lili Wang, Jingting Zhang, Huiyu Yan, Shenghong Wang, Jianxi Xiao
Journal: Advanced Healthcare Materials (2024)
Current status and perspectives of esophageal cancer: a comprehensive review
Authors: Wei Jiang, Bo Zhang, Jiaqi Xu, Liyan Xue, Luhua Wang
Journal: Cancer Communications (2024)

Abstract Esophageal cancer (EC) continues to be a significant global health concern, with two main subtypes: esophageal squamous cell carcinoma and esophageal adenocarcinoma. Prevention and changes in etiology, improvements in early detection, and refinements in the treatment have led to remarkable progress in the outcomes of EC patients in the past two decades. This seminar provides an in‐depth analysis of advances in the epidemiology, disease biology, screening, diagnosis, and treatment landscape of esophageal cancer, focusing on the ongoing debate surrounding multimodality therapy. Despite significant advancements, EC remains a deadly disease, underscoring the need for continued research into early detection methods, understanding the molecular mechanisms, and developing effective treatments.