tbuckley/cabot-search huggingface dataset:
Environmentally Controlled Microfluidic System Enabling Immune Cell Flow and Activation in an Endothelialised Skin‐On‐Chip
Authors: Elisabetta Michielon, Matteo Boninsegna, Taco Waaijman, Dario Fassini, Sander W. Spiekstra, Jeremy Cramer, Pierre Gaudriault, János Kodolányi, Tanja D. de Gruijl, Antoni Homs‐Corbera, Susan Gibbs
Journal: Advanced Healthcare Materials (2024)

Abstract Integration of reconstructed human skin (RhS) into organ‐on‐chip (OoC) platforms addresses current limitations imposed by static culturing. This innovation, however, is not without challenges. Microfluidic devices, while powerful, often encounter usability, robustness, and gas bubble issues that hinder large‐scale high‐throughput setups. This study aims to develop a novel re‐usable multi‐well microfluidic adaptor (MMA) with the objective to provide a flexible tool for biologists implementing complex 3D biological models (e.g., skin) while enabling simultaneous user control over temperature, medium flow, oxigen (O 2 ), nitrogen (N 2 ), and carbon dioxide (CO 2 ) without the need for an incubator. The presented MMA device is designed to be compatible with standard, commercially available 6‐well multi‐well plates (6MWPs) and 12‐well transwells. This MMA‐6MWP setup is employed to generate a skin‐on‐chip (SoC). RhS viability is maintained under flow for three days and their morphology closely resembles that of native human skin. A proof‐of‐concept study demonstrates the system's potential in toxicology applications by combining endothelialised RhS with flowing immune cells. This dynamic setting activates the monocyte‐like MUTZ‐3 cells (CD83 and CD86 upregulation) upon topical exposure of RhS to a sensitizer, revealing the MMA‐6MWP's unique capabilities compared to static culturing, where such activation is absent.
H<sub>2</sub>O<sub>2</sub> Self‐Supplied MoS<sub>2</sub>/CaO<sub>2</sub> Nanozyme Hydrogel with Near‐Infrared Photothermal Synergetic Cascade Peroxidase‐Like Activity for Wound Disinfection
Authors: Jinyi Huang, Ihsan Ullah, Linjie Chen, Ke Peng, Yujie Ou, Zehua Gong, Aimin Wu, Zhimin He, Wenyan Yin, Huaqiong Li
Journal: Advanced Healthcare Materials (2024)

Abstract In wound healing and clinical anti‐infection therapy, the current feasibility of nanocatalysts is extremely limited because of inadequate reactive oxygen species (ROS) generation. Herein, a novel H 2 O 2 self‐supplying nanocomposite (M/C/AEK) consists of molybdenum disulfide (MoS 2 ) decorated with calcium peroxide (CaO 2 ) prepared at ambient temperature and encapsulated in AEK hydrogel. In the presence of H 2 O 2 and poly(vinyl pyrrolidone) (PVP), CaO 2 nanoclusters, ≈30 nm, are anchored on the MoS 2 surface. MoS 2 /CaO 2 can induce both a cascaded peroxidase (POD)‐like and catalase (CAT)‐like catalytic activity to produce toxic hydroxyl radicals through self‐supplied H 2 O 2 and O 2 responsive to the faintly acidic environment of acute wounds. The POD‐like activity is increased under acidic compared with neutral conditions, allowing selective treatment of acute, slightly acidic wounds while avoiding the side effects of high‐concentration antibacterial agents on normal tissues. The high near‐infrared photothermal effect synergistically with POD‐like/CAT‐like activity of MoS 2 /CaO 2 boosts the production of more ROS to eradicate Staphylococcus aureus and Escherichia coli bacteria (98.6% and 98.9%) effectively and selectively stimulate wound healing. The porous M/C/AEK hydrogel in the wound microenvironment can efficiently capture bacteria, and its Ca 2+ ions and keratin stimulate healing, revealing excellent potential in advanced wound care and infection control therapies.
Development of a Microfluidic Vascularized Osteochondral Model as a Drug Testing Platform for Osteoarthritis
Authors: Shima Salehi, Stefania Brambilla, Marco Rasponi, Silvia Lopa, Matteo Moretti
Journal: Advanced Healthcare Materials (2024)

Abstract Osteoarthritis (OA) is a degenerative joint disease characterized by changes in cartilage and subchondral bone. To date, there are no available drugs that can counteract the progression of OA, partly due to the inadequacy of current models to recapitulate the relevant cellular complexity. In this study, an osteochondral microfluidic model is developed using human primary cells to mimic an OA‐like microenvironment and this study validates it as a drug testing platform. In the model, the cartilage compartment is created by embedding articular chondrocytes in fibrin hydrogel while the bone compartment is obtained by embedding osteoblasts, osteoclasts, endothelial cells, and mesenchymal stem cells in a fibrin hydrogel enriched with calcium phosphate nanoparticles. After developing and characterizing the model, Interleukin‐1 β is applied to induce OA‐like conditions. Subsequently, the model potential is evaluated as a drug testing platform by assessing the effect of two anti‐inflammatory drugs (Interleukin‐1 Receptor antagonist and Celecoxib) on the regulation of inflammation‐ and matrix degradation‐related markers. The model responded to inflammation and demonstrated differences in drug efficacy. Finally, it compares the behavior of the “Cartilage” and “Cartilage+Bone” models, emphasizing the necessity of incorporating both cartilage and bone compartments to capture the complex pathophysiology of OA.
Immunomodulatory Biomaterials: Tailoring Surface Properties to Mitigate Foreign Body Reaction and Enhance Tissue Regeneration
Authors: Hamed Amani, Mahdieh Alipour, Elahe Shahriari, Juan M Taboas
Journal: Advanced Healthcare Materials (2024)

The immune cells have demonstrated the ability to promote tissue repair by removing debris, breaking down the extracellular matrix, and regulating cytokine secretion profile. If the behavior of immune cells is not well directed, chronic inflammation and foreign body reaction (FBR) will lead to scar formation and loss of biomaterial functionality. The immunologic response toward tissue repair or chronic inflammation after injury and implantation can be modulated by manipulating the surface properties of biomaterials. Tailoring surface properties of biomaterials enables the regulation of immune cell fate such as adhesion, proliferation, recruitment, polarization, and cytokine secretion profile. This review begins with an overview of the role of immune cells in tissue healing and their interactions with biomaterials. It then discusses how the surface properties of biomaterials influence immune cell behavior. The core focus is reviewing surface modification methods to create innovative materials that reduce foreign body reactions and enhance tissue repair and regeneration by modulating immune cell activities. The review concludes with insights into future advancements in surface modification techniques and the associated challenges.
Erratum to “Ketoconazole exacerbates mitophagy to induce apoptosis by downregulating cyclooxygenase-2 in hepatocellular carcinoma” [J Hepatol 70 (1) 2019 66–77]
Authors: Yan Chen, Hai-Ning Chen, Kui Wang, Lu Zhang, Zhao Huang, Jiayang Liu, Zhe Zhang, Maochao Luo, Yunlong Lei, Yong Peng, Zong-Guang Zhou, Yuquan Wei, Canhua Huang
Journal: Journal of Hepatology (2024)
Safety and immunogenicity of a delayed booster dose of the rVSVΔG-ZEBOV-GP vaccine for prevention of Ebola virus disease: a multicentre, open-label, phase 2 randomised controlled trial
Authors: Richard T Davey, Gary L Collins, Nadine Rouphael, Guillaume Poliquin, Rosemary McConnell, Gabrielle Grubbs, Susan L Moir, Joanne M Langley, Marc Teitelbaum, Angela L Hewlett, Susan L F McLellan, Nahid Bhadelia, Vanessa N Raabe, Mark J Mulligan, Irina Maljkovic Berry, Bonnie Dighero-Kemp, Jonathan R Kurtz, Lisa E Hensley, Nelson C E Dozier, Lindsay C B Marron, Alain DuChene, Jens H Kuhn, Shawn K Brown, Surender Khurana, H Clifford Lane, James D Neaton
Journal: The Lancet Microbe (2024)

rVSVΔG-ZEBOV-GP is the first approved vaccine with clinical efficacy against Ebola virus disease. Although a seroprotective threshold has not been defined for those at occupational risk of exposure, the current vaccine strategy is to attain a sustained high level of antibody titres. The aim of this trial was to explore the effects of delayed boosting upon both the height and duration of antibody titres following primary immunisation.
Visualizing scRNA-Seq data at population scale with GloScope
Authors: Hao Wang, William Torous, Boying Gong, Elizabeth Purdom
Journal: Genome biology (2024)

Increasingly, scRNA-Seq studies explore cell populations across different samples and the effect of sample heterogeneity on organism's phenotype. However, relatively few bioinformatic methods have been developed which adequately address the variation between samples for such population-level analyses. We propose a framework for representing the entire single-cell profile of a sample, which we call a GloScope representation. We implement GloScope on scRNA-Seq datasets from study designs ranging from 12 to over 300 samples and demonstrate how GloScope allows researchers to perform essential bioinformatic tasks at the sample-level, in particular visualization and quality control assessment.
Integrated large-scale metagenome assembly and multi-kingdom network analyses identify sex differences in the human nasal microbiome
Authors: Yanmei Ju, Zhe Zhang, Mingliang Liu, Shutian Lin, Qiang Sun, Zewei Song, Weiting Liang, Xin Tong, Zhuye Jie, Haorong Lu, Kaiye Cai, Peishan Chen, Xin Jin, Wenwei Zhang, Xun Xu, Huanming Yang, Jian Wang, Yong Hou, Liang Xiao, Huijue Jia, Tao Zhang, Ruijin Guo
Journal: Genome biology (2024)

Respiratory diseases impose an immense health burden worldwide. Epidemiological studies have revealed extensive disparities in the incidence and severity of respiratory tract infections between men and women. It has been hypothesized that there might also be a nasal microbiome axis contributing to the observed sex disparities.
DEMINING: A deep learning model embedded framework to distinguish RNA editing from DNA mutations in RNA sequencing data
Authors: Zhi-Can Fu, Bao-Qing Gao, Fang Nan, Xu-Kai Ma, Li Yang
Journal: Genome biology (2024)

Precise calling of promiscuous adenosine-to-inosine RNA editing sites from transcriptomic datasets is hindered by DNA mutations and sequencing/mapping errors. Here, we present a stepwise computational framework, called DEMINING, to distinguish RNA editing and DNA mutations directly from RNA sequencing datasets, with an embedded deep learning model named DeepDDR. After transfer learning, DEMINING can also classify RNA editing sites and DNA mutations from non-primate sequencing samples. When applied in samples from acute myeloid leukemia patients, DEMINING uncovers previously underappreciated DNA mutation and RNA editing sites; some associated with the upregulated expression of host genes or the production of neoantigens.
Optimizing and benchmarking polygenic risk scores with GWAS summary statistics
Authors: Zijie Zhao, Tim Gruenloh, Meiyi Yan, Yixuan Wu, Zhongxuan Sun, Jiacheng Miao, Yuchang Wu, Jie Song, Qiongshi Lu
Journal: Genome biology (2024)

Polygenic risk score (PRS) is a major research topic in human genetics. However, a significant gap exists between PRS methodology and applications in practice due to often unavailable individual-level data for various PRS tasks including model fine-tuning, benchmarking, and ensemble learning.
Efficacy and safety of gene therapy with onasemnogene abeparvovec in children with spinal muscular atrophy in the D-A-CH-region: a population-based observational study
Authors: Claudia Weiß, Lena-Luise Becker, Johannes Friese, Astrid Blaschek, Andreas Hahn, Sabine Illsinger, Oliver Schwartz, Günther Bernert, Maja von der Hagen, Ralf A Husain, Klaus Goldhahn, Janbernd Kirschner, Astrid Pechmann, Marina Flotats-Bastardas, Gudrun Schreiber, Ulrike Schara, Barbara Plecko, Regina Trollmann, Veronka Horber, Ekkehard Wilichowski, Matthias Baumann, Andrea Klein, Astrid Eisenkölbl, Cornelia Köhler, Georg M Stettner, Sebahattin Cirak, Oswald Hasselmann, Angela M Kaindl, Sven F Garbade, Jessika Johannsen, Andreas Ziegler
Journal: The Lancet Regional Health - Europe (2024)
Terez Shea-Donohue: Optimism helps, and confidence in your work is critical
Authors: Montserrat Cols
Journal: The Journal of Experimental Medicine (2024)

Terez Shea-Donohue is the program director of the Division of Digestive Diseases and Nutrition at the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health. As a program director, Terez supports basic and translational research related to neurogastroenterology, gastrointestinal (GI), and GI epithelial barrier function. We spoke to Terez about the transition from active research to a predominantly administrative job, the need for life-long mentorship, and the continued sex/gender bias in health care.
Molecular and clinical heterogeneity within <i>MYC</i>-family amplified medulloblastoma is associated with survival outcomes: A multicenter cohort study
Authors: Edward C Schwalbe, Janet C Lindsey, Marina Danilenko, Rebecca M Hill, Stephen Crosier, Sarra L Ryan, Daniel Williamson, Jemma Castle, Debbie Hicks, Marcel Kool, Till Milde, Andrey Korshunov, Stefan M Pfister, Simon Bailey, Steven C Clifford
Journal: Neuro-Oncology (2024)

Abstract Background MYC/MYCN are the most frequent oncogene amplifications in medulloblastoma (MB) and its primary biomarkers of high-risk (HR) disease. However, while many patients’ MYC(N)-amplified tumors are treatment-refractory, some achieve long-term survival. We therefore investigated clinicobiological heterogeneity within MYC(N)-amplified MB and determined its relevance for improved disease management. Methods We characterized the clinical and molecular correlates of MYC- (MYC-MB; n = 64) and MYCN-amplified MBs (MYCN-MB; n = 95), drawn from &amp;gt;1600 diagnostic cases. Results Most MYC-MBs were molecular group 3 (46/58; 79% assessable) and aged ≥3 years at diagnosis (44/64 [69%]). We identified a “canonical” very high-risk (VHR) MYC-amplified group (n = 51/62; 82%) with dismal survival irrespective of treatment (11% 5-year progression-free survival [PFS]), defined by co-occurrence with ≥1 additional established risk factor(s) (subtotal surgical-resection [STR], metastatic disease, LCA pathology), and commonly group 3/4 subgroup 2 with a high proportion of amplified cells. The majority of remaining noncanonical MYC-MBs survived (i.e. non-group 3/group 3 without other risk features; 11/62 (18%); 61% 5-year PFS). MYCN survival was primarily related to molecular group; MYCN-amplified SHH MB, and group 3/4 MB with additional risk factors, respectively defined VHR and HR groups (VHR, 39% [35/89]; 20% 5-year PFS/HR, 33% [29/89]; 46% 5-year PFS). Twenty-two out of 35 assessable MYCN-amplified SHH tumors harbored TP53 mutations; 9/12 (75%) with data were germline. MYCN-amplified group 3/4 MB with no other risk factors (28%; 25/89) had 70% 5-year PFS. Conclusions MYC(N)-amplified MB displays significant clinicobiological heterogeneity. Diagnostics incorporating molecular groups, subgroups, and clinical factors enable their risk assessment. VHR “canonical” MYC tumors are essentially incurable and SHH-MYCN-amplified MBs fare extremely poorly (20% survival at 5 years); both require urgent development of alternative treatment strategies. Conventional risk-adapted therapies are appropriate for more responsive groups, such as noncanonical MYC and non-SHH-MYCN MB.
MYC-dependent upregulation of the de novo serine and glycine synthesis pathway is a targetable metabolic vulnerability in group 3 medulloblastoma
Authors: Magretta Adiamah, Bethany Poole, Janet C Lindsey, Sarah Kohe, Alaide Morcavallo, Florence Burté, Rebecca M Hill, Helen Blair, Dean Thompson, Mankaran Singh, Shanel Swartz, Stephen Crosier, Tong Zhang, Oliver D K Maddocks, Andrew Peet, Louis Chesler, Ian Hickson, Ross J Maxwell, Steven C Clifford
Journal: Neuro-Oncology (2024)

Abstract Background Group 3 medulloblastoma (MBGRP3) represents around 25% of medulloblastomas and is strongly associated with c-MYC (MYC) amplification, which confers significantly worse patient survival. Although elevated MYC expression is a significant molecular feature in MBGRP3, direct targeting of MYC remains elusive, and alternative strategies are needed. The metabolic landscape of MYC-driven MBGRP3 is largely unexplored and may offer novel opportunities for therapies. Methods To study MYC-induced metabolic alterations in MBGRP3, we depleted MYC in isogenic cell-based model systems, followed by 1H high-resolution magic-angle spectroscopy (HRMAS) and stable isotope-resolved metabolomics, to assess changes in intracellular metabolites and pathway dynamics. Results Steady-state metabolic profiling revealed consistent MYC-dependent alterations in metabolites involved in one-carbon metabolism such as glycine. 13C-glucose tracing further revealed a reduction in glucose-derived serine and glycine (de novo synthesis) following MYC knockdown, which coincided with lower expression and activity of phosphoglycerate dehydrogenase (PHGDH), the rate-limiting enzyme in this pathway. Furthermore, MYC-overexpressing MBGRP3 cells were more vulnerable to pharmacological inhibition of PHGDH compared to those with low expression. Using in vivo tumor-bearing genetically engineered and xenograft mouse models, pharmacological inhibition of PHGDH increased survival, implicating the de novo serine/glycine synthesis pathway as a pro-survival mechanism sustaining tumor progression. Critically, in primary human medulloblastomas, increased PHGDH expression correlated strongly with both MYC amplification and poorer clinical outcomes. Conclusions Our findings support a MYC-induced dependency on the serine/glycine pathway in MBGRP3 that represents a novel therapeutic treatment strategy for this poor prognosis disease group.
Brain imaging and clinical outcome of embodied VR-BCI training in chronic stroke patients: a longitudinal pilot study
Authors: Athanasios Vourvopoulos, Mathis Fleury, Diego Andres Blanco-Mora, Jean-Claude Fernandes, Patr´ıcia Figueiredo, Sergi Bermúdez i Badia
Journal: Brain-Computer Interfaces (2024)

Introduction Restorative Brain–Computer Interfaces (BCIs) provide an alternative non-muscular channel for stroke patients lacking volitional movement by enhancing sensorimotor rhythm modulation through motor imagery (MI). MI practice can be augmented with embodied feedback via virtual reality (VR). However, the clinical impact of embodied VR-BCI training remains under-explored.
Outcomes and prognostic factors in 3306 patients with relapsed/refractory chronic lymphocytic leukemia treated with ibrutinib outside of clinical trials: A nationwide study
Authors: Gian Matteo Rigolin, Pier Paolo Olimpieri, Valentina Summa, Simone Celant, Lydia Scarfò, Maria Pia Ballardini, Antonio Urso, Silvia Gambara, Francesco Cavazzini, Paolo Ghia, Antonio Cuneo, Pierluigi Russo
Journal: HemaSphere (2024)

We performed a cohort study that included all patients with relapsed/refractory chronic lymphocytic leukemia (R/R CLL) who received ibrutinib in the Italian National Health Service. With a median follow-up of 42.2 months (IQR 30.8-54.6 months), the study involved 3306 patients with a median age of 72.1 years, of whom 42.6% had received ≥2 previous lines of treatment. The estimated 24-month probabilities of being on treatment and alive were 57.9% (95% confidence interval [CI]: 59.6-56.2) and 76.6% (95% CI: 75.2-78.1), respectively. The median time to treatment discontinuation (TTD) was 31.3 months (95% CI: 29.5-33.5). Out of 3306 patients, 2015 (60.9%) discontinued treatment, with 993 cases attributed to death or disease progression (30.0% of all cases). Among the 1022 patients who discontinued treatment for reasons other than progression or death, 564 (17.1%) patients did so due to toxicity or medical decision, while 458 patients (13.8%) were lost to follow-up. Multivariable analysis revealed that age, Eastern Cooperative Oncology Group Performance Status, the number of previous lines of therapy, refractoriness to the last treatment, and reduced renal function were associated with shorter TTD and overall survival (OS). The coexistence of 17p- and
Air Pollution and Breast Cancer Incidence in the Multiethnic Cohort Study
Authors: Anna H. Wu, Jun Wu, Chiuchen Tseng, Daniel O. Stram, Salma Shariff-Marco, Timothy Larson, Deborah Goldberg, Scott Fruin, Anqi Jiao, Pushkar P. Inamdar, Ugonna Ihenacho, Loïc Le Marchand, Lynne Wilkens, Christopher Haiman, Beate Ritz, Iona Cheng
Journal: Journal of Clinical Oncology (2024)

PURPOSE Recent studies suggested fine particulate matter (PM 2.5 ) exposure increases the risk of breast cancer, but evidence among racially and ethnically diverse populations remains sparse. MATERIALS AND METHODS Among 58,358 California female participants of the Multiethnic Cohort (MEC) Study followed for an average of 19.3 years (1993-2018), we used Cox proportional hazards regression to examine associations of time-varying PM with invasive breast cancer risk (n = 3,524 cases; 70% African American and Latino females), adjusting for sociodemographics and lifestyle factors. Subgroup analyses were conducted for race and ethnicity, hormone receptor status, and breast cancer risk factors. RESULTS Satellite-based PM 2.5 was associated with a statistically significant increased incidence of breast cancer (hazard ratio [HR] per 10 μg/m 3 , 1.28 [95% CI, 1.08 to 1.51]). We found no evidence of heterogeneity in associations by race and ethnicity and hormone receptor status. Family history of breast cancer showed evidence of heterogeneity in PM 2.5 -associations ( P heterogeneity = .046). In a meta-analysis of the MEC and 10 other prospective cohorts, breast cancer incidence increased in association with exposure to PM 2.5 (HR per 10 μg/m 3 increase, 1.05 [95% CI, 1.00 to 1.10]; P = .064). CONCLUSION Findings from this large multiethnic cohort with long-term air pollutant exposure and published prospective cohort studies support PM 2.5 as a risk factor for breast cancer. As about half of breast cancer cannot be explained by established breast cancer risk factors and incidence is continuing to increase, particularly in low- and middle-income countries, our results highlight that breast cancer prevention should include not only individual-level behavior-centered approaches but also population-wide policies and regulations to curb PM 2.5 exposure.