tbuckley/cabot-search huggingface dataset:
Ecologically sustainable benchmarking of AI models for histopathology
Authors: Yu-Chia Lan, Martin Strauch, Pourya Pilva, Nikolas E. J. Schmitz, Alireza Vafaei Sadr, Leon Niggemeier, Huong Quynh Nguyen, David L. Hölscher, Tri Q. Nguyen, Jesper Kers, Roman D. Bülow, Peter Boor
Journal: npj Digital Medicine (2024)

Abstract Deep learning (DL) holds great promise to improve medical diagnostics, including pathology. Current DL research mainly focuses on performance. DL implementation potentially leads to environmental consequences but approaches for assessment of both performance and carbon footprint are missing. Here, we explored an approach for developing DL for pathology, which considers both diagnostic performance and carbon footprint, calculated as CO 2 or equivalent emissions (CO 2 eq). We evaluated various DL architectures used in computational pathology, including a large foundation model, across two diagnostic tasks of low and high complexity. We proposed a metric termed ‘environmentally sustainable performance’ (ESPer), which quantitatively integrates performance and operational CO 2 eq during training and inference. While some DL models showed comparable diagnostic performance, ESPer enabled prioritizing those with less carbon footprint. We also investigated how data reduction approaches can improve the ESPer of individual models. This study provides an approach facilitating the development of environmentally friendly, sustainable medical AI.
Identifying the location-dependent adipose tissue bacterial DNA signatures in obese patients that predict body weight loss
Authors: Matthieu Minty, Alberic Germain, Jiuwen Sun, Gracia Kaglan, Florence Servant, Benjamin Lelouvier, Emiri Misselis, Radu Mircea Neagoe, Menghini Rossella, Marina Cardellini, Rémy Burcelin, Massimo Federici, José Manuel Fernandez-Real, Vincent Blasco-Baque
Journal: Gut Microbes (2024)

Recent sets of evidence have described profiles of 16S rDNA sequences in host tissues, notably in fat pads that are significantly overrepresented and can serve as signatures of metabolic disease. However, these recent and original observations need to be further detailed and functionally defined. Here, using state-of-the-art targeted DNA sequencing and discriminant predictive approaches, we describe, from the longitudinal FLORINASH cohort of patients who underwent bariatric surgery, visceral, and subcutaneous fat pad-specific bacterial 16SrRNA signatures. The corresponding Porphyromonadaceae, Campylobacteraceae, Prevotellaceae, Actimomycetaceae, Veillonellaceae, Anaerivoracaceae, Fusobacteriaceae, and the Clostridium family XI 16SrRNA DNA segment profiles are signatures of the subcutaneous adipose depot while Pseudomonadaceae and Micrococcacecae, 16SrRNA DNA sequence profiles characterize the visceral adipose depot. In addition, we have further identified that a specific pre-bariatric surgery adipose tissue bacterial DNA signature predicts the efficacy of body weight loss in obese patients 5–10 years after the surgery. 16SrRNA signatures discriminate (ROC ~ 1) the patients who did not maintain bodyweight loss and those who did. Second, from the 16SrRNA sequences we infer potential pathways suggestive of catabolic biochemical activities that could be signatures of subcutaneous adipose depots that predict body weight loss.
VGLL-fusions define a new class of intraparenchymal CNS schwannoma
Authors: Simone Schmid, Kanish Mirchia, Anna Tietze, Ilon Liu, Christin Siewert, Jakob Nückles, Jens Schittenhelm, Felix Behling, Matija Snuderl, Christian Hartmann, Sebastian Brandner, Simon M L Paine, Andrey Korshunov, Martin Hasselblatt, Roland Coras, Sridhar Epari, Christine Stadelmann, Sabrina Zechel, Michèle Simon, Yelena Wilson, Francesca Gianno, G Lucas Calixto-Hope, Viktor Zherebitskiy, Vassil B Kaimaktchiev, Lorraina Robinson, Kenneth Aldape, Eelco W Hoving, Bastiaan B J Tops, Ashwyn Augustine Perera, Pauline Göller, Pablo Hernáiz Driever, Pieter Wesseling, Arend Koch, Arie Perry, Felix Sahm, David T W Jones, David Capper
Journal: Neuro-Oncology (2024)

Abstract Background Intracerebral schwannomas are rare tumors resembling their peripheral nerve sheath counterparts but localized in the CNS. They are not classified as a separate tumor type in the 2021 WHO classification. This study aimed to compile and characterize these rare neoplasms morphologically and molecularly. Methods We analyzed 20 tumor samples by histology, RNA Next-Generation Sequencing, DNA-methylation profiling, copy number analyses, and single nucleus RNA sequencing (snRNA-seq). Clinical data, including age, sex, and disease progression, were collected. MRI series were included when available. Results All cases with tissue available for histology review (n=13) were morphologically consistent with intracerebral schwannoma, but differed in their extent of GFAP staining. All (n=20) shared DNA-methylation profiles distinct from other CNS tumors, as well as from VGLL-altered peripheral nerve sheath tumors. Most cases (n=14/17) harbored fusions of either VGLL3 or VGLL1 (CHD7::VGLL3 (n=9/17) and EWSR1::VGLL1 (n=5/17)). In two cases the presence of a VGLL3 fusion was also confirmed by CNA analyses (n=2/17). MRI (n=4) showed well-defined, nodular tumors with strong, homogeneous enhancement and no diffusion restriction. Tumors were located throughout the neuroaxis [supratentorial (n=15), infratentorial (n=4), and spinal (n=1)]. snRNA-seq of a VGLL1-fused tumor indicated VGLL1 upregulation in 28.6% of tumor cells (n=1). During median follow-up of 1.8 years (range 3 months-9 years), none of the tumors recurred (n=10). Conclusions We identify and define a new benign tumor class, designated VGLL-altered intraparenchymal CNS schwannomas. These tumors feature VGLL alterations and a specific DNA-methylation profile, with schwannoma-like histopathology and CNS localization, akin to previously classified intracerebral schwannomas.
Controlled Release of Human Dental Pulp Stem Cell‐Derived Exosomes from Hydrogels Attenuates Temporomandibular Joint Osteoarthritis
Authors: Victor Diez‐Guardia, Yajing Tian, Yunzhe Guo, Jiaying Li, Shengjie Cui, Cécile A. Dreiss, Eileen Gentleman, Xuedong Wang
Journal: Advanced Healthcare Materials (2024)

Abstract Temporomandibular joint osteoarthritis (TMJOA) is a painful inflammatory condition that limits mouth opening. Cell‐derived exosomes, which have anti‐inflammatory effects, are emerging as a treatment for TMJOA. Injection of dental pulp stem cells (DPSCs), which secrete exosomes, can moderate tissue damage in a rat model of TMJOA. However, injected exosomes are quickly cleared, necessitating repeated injections for therapeutic efficacy. Here, vinyl sulfone‐modified hyaluronic acid (HA‐VS) hydrogels, suitable for encapsulating exosomes are formulated. HA‐VS hydrogels degrade in the presence of hyaluronidase and allow for the release of beads of similar size to exosomes over 3 to 6 days. In a rat model of TMJOA, injection of exosomes or exosomes within HA‐VS hydrogels significantly attenuated damage‐mediated subchondral bone loss as determined by micro‐computed tomography, and reduced inflammatory and tissue damage scores as assessed by histology. Overall, DPSCs‐derived exosomes attenuated joint damage, but treatment with exosomes within HA‐VS hydrogels shows additional protective effects on subchondral bone maintenance and integrity. These findings confirm the protective effects of DPSCs‐derived exosomes in moderating tissue damage in TMJOA and suggest that combining exosomes with HA hydrogels can further promote their therapeutic effects.
Structured Polymers Enable the Sustained Delivery of Glucocorticoids within the Intra‐Articular Space
Authors: Ana Crastin, Claire S. Martin, Sai Suresh, Scott P. Davies, Daniel Kearns, Ahsen Parlak, Holly Adcock, Andrew Filer, Simon W. Jones, Karim Raza, Richard JA Moakes, Liam M. Grover, Rowan S. Hardy
Journal: Advanced Healthcare Materials (2024)

Intra-articular glucocorticoid injections are effective in controlling inflammation and pain in arthritides but restricted by short duration of action and risk of joint degeneration. Controlled drug release using biocompatible hydrogels offers a unique solution, but limitations of in situ gelation restrict their application. Gellan sheared hydrogels (GSHs) retain the advantages of hydrogels, however their unique microstructures lend themselves to intra-articular application - capable of shear thinning under force but restructuring at rest to enhance residence. This study examined GSHs for extended intra-articular glucocorticoid delivery of prednisolone (10 mg mL-1); demonstrating links between material mechanics, steroid release, and preclinical assessment of efficacy in synoviocyte culture and transgenic(TNF)197Gkl (TNFtg) murine model of arthritis. GSHs demonstrated sustained release, with typical Fickian profiles over 18 days. Moreover, systems showed good stability under extended culture, with inherent cell-compatibility and suppression of inflammatory synoviocyte activation. In TNFtg animals, GSHs suppressed synovitis (70.08%, p < 0.05), pannus formation (45.01%, p < 0.05), and increased articular cartilage (82.23%, p < 0.05) relative to vehicle controls. The extended profile of steroid release from injectable GSH formulations holds promise in the treatment and management of inflammatory arthritides such as rheumatoid and osteoarthritis, representing a step-change in intra-articular drug delivery to suppress long-term joint inflammation.
The Epileptiogenic Modified Therapy: Regulating the Dynamic of Microglia via ROS‐Responsive Cascade Nano‐Formulation
Authors: Jiaxin Li, Shuai Liu, Chenghan Chen, Jiahong Deng, Zibo Du, Simin Yang, Hongying Deng, Zhixia Zhang, Yiyu Huang, Jingwen Fu, Wangming Zhang, Wai Sang Poon, Honghao Hou, Jun Wang
Journal: Advanced Healthcare Materials (2024)

Abstract Pharmacological treatment of epilepsy presents several challenges, particularly the ineffectiveness of antiseizure medicines (ASMs) in modifying disease. In fact, the removal of reactive oxygen species (ROS) and preconditioning with tolerable dose of nitric oxide (NO) can activate neuroprotective mechanisms during latency and enhance tolerance to oxidative stress during seizures. To address this, a ROS‐responsive cascade Nano‐formulation (RRCN) is developed, which will transform ROS into NO. Remarkably, RRCN significantly reduces seizure severity, prolongs seizure latency, and extends inter‐seizure intervals, though it does not increase the latency of generalized seizures. Microglia, the primary immune cells of the brain, play a crucial role in the initiation and progression of epilepsy. In the kainic acid (KA) epilepsy model, microglial processes elongate, branching increases, and interactions between microglia and neurons are strengthened in the CA1 and CA3 regions of the hippocampus compared to the Vehicle group. RRCN reverses these dynamic changes in microglia and their interactions with neurons, which are mediated by the NO/HIF/ErBb2 pathway. Thus, RRCN can inhibit seizures generalization by preconditioning the dynamic changes of microglia.
PEGylated Nanoliposomal Doxorubicin Conjugated with Specific TREM2 Peptides for Glioma‐Targeting Therapy
Authors: Hongyan Li, Duling Xu, Weihua Cai, Jiadi Liu, Zhitong Bing, Qiyue Zhang
Journal: Advanced Healthcare Materials (2024)

PEGylated liposomes can deliver anti-cancer drugs to brain tumors, and achieve enhanced permeability and retention effects. Triggering receptor expressed on myeloid cells 2 (TREM2) is an excellent biomarker for precise therapy of glioma. The present study is aimed at designing PEGylated nanoliposomal doxorubicin (PLD) conjugated with peptides targeting TREM2 for glioma-targeting therapy. The specific peptides are designed with the Rosetta Peptiderive Protocol. Schrodinger's peptide-specific version of Glide is used for molecular docking. PLD modified with peptides (peptide-PLD) are engineered and prepared. Cell cycle, apoptosis, cell invasion and migration, cell viability, and colony-formation assays are performed to analyze glioma cell functions. The anti-tumor effects of peptide-PLD are validated in an intracranial U87-MG cells orthotopic glioma model. The targeting peptides HLRKLRKR and LRKLRLRL showed specific affinity for TREM2 and better cellular uptake in U87-MG cells. PLD with peptide modification demonstrated stable doxorubicin loading, small sizes (<60 nm), and enrichment in the mouse brain. Peptide-PLD treatment inhibited the Akt/GSK3β/β-catenin pathway, thereby inhibiting cell invasion and migration, and colony-forming ability in U87-MG cells. The peptide modification of PLD achieved better suppression of glioma development than PLD. Overall, TREM2-targeting peptides are successfully designed, and peptide-PLD served as a potent drug delivery carrier for glioma-targeting therapy.
Rethinking Biomedical Titanium Alloy Design: A Review of Challenges from Biological and Manufacturing Perspectives
Authors: Daisy Rabbitt, Victor M. Villapún, Luke N. Carter, Kenny Man, Morgan Lowther, Paraic O'Kelly, Alexander J. Knowles, Alessandro Mottura, Yuanbo T. Tang, Lorenzo Luerti, Roger C. Reed, Sophie C. Cox
Journal: Advanced Healthcare Materials (2024)

Current biomedical titanium alloys have been repurposed from other industries, which has contributed to several biologically driven implant failure mechanisms. This review highlights the added value that may be gained by building an appreciation of implant biological responses at the onset of alloy design. Specifically, the fundamental mechanisms associated with immune response, angiogenesis, osseointegration and the potential threat of infection are discussed, including how elemental selection can modulate these pivotal systems. With a view to expedite inclusion of these interactions in alloy design criteria, methods to analyze these performance characteristics are also summarized. While machine learning techniques are being increasingly used to unearth complex relationships between alloying elements and material properties, much is still unknown about the correlation between composition and some bio-related properties. To bridge this gap, high-throughput methods are also reviewed to validate biological response along with cutting edge manufacturing approaches that may support rapid discovery. Taken together, this review encourages the alloy development community to rethink their approach to enable a new generation of biomedical implants intrinsically designed for a life in the body, including functionality to tackle biological challenges thereby offering improved patient outcomes.
Re: Muayad et al.: Comparative effects of GLP-1 receptor agonists and metformin on glaucoma risk in patients with type 2 diabetes (Ophthalmology. 2024 Aug 23:S0161-6420(24)00515-3)
Authors: Wei-Hsuan Bai, Yi-Chiao Bai, James Cheng-Chung Wei
Journal: Ophthalmology (2024)
Enhanced Vascular Smooth Muscle Cell and Extracellular Matrix Repair Using a Metal‐Organic Framework‐Based Co‐Delivery System for Abdominal Aortic Aneurysm Therapy
Authors: Jiahao Lei, Xunzhong Dong, Yong Huang, Zhaoyu Wu, Zhiyou Peng, Bo Li, Ruihua Wang, Ying Pan, Xiangtao Zheng, Zhen Zhao, Xinwu Lu
Journal: Advanced Healthcare Materials (2024)

The abdominal aortic aneurysm (AAA) is a severe and complex condition characterized by the pathological dilation of the abdominal aorta. Current therapeutic strategies are limited, with surgical repair being the most effective intervention due to the lack of medications that can slow aneurysmal expansion or prevent adverse events. In this study, an innovative nanoplatform, Mn-UiO-66-NH
Carboxymethyl Chitosan‐Based Antioxidant Hydrogel Accelerates Diabetic Wound Healing
Authors: Jiaying Zhang, Sifang Zhao, Yifan Zhou, Hongze Liang, Lingling Zhao, Hui Tan
Journal: Advanced Healthcare Materials (2024)

Diabetic wound healing is hampered due to oxidative stress, exacerbated inflammation, and impaired angiogenesis in the wounds. A pH-sensitive antioxidant hydrogel based on carboxymethyl chitosan (CMCS), oligoprocyanidins (OPC), and oxide dextran (Oxd) is prepared to accelerate diabetic wound healing. The hydrogel network is formed via imine and hydrogen bonding interactions in the presence of hydroxyl, amino, and aldehyde groups, and deferoxamine (DFO) is incorporated into the hydrogel. The hydrogel shows pH-triggered drug release, a good antioxidant, and anti-inflammatory properties, and can promote tube formation and cell migration in vitro. Moreover, the hydrogel can accelerate wound healing in streptozotocin (STZ)-induced diabetic mice by regulating the inflammation environment with up-regulation of anti-inflammatory factors (IL-4 and IL-10) and down-regulation of pro-inflammatory factors (TNF-α and IL-6), and promoting angiogenesis with up-regulation of HIF-1α, VEGF, and CD31. Thus, the pH-sensitive antioxidant hydrogel provides a promising therapeutic strategy for diabetic wound healing.
Thermal Transfer Printed Flexible and Wearable Bionic Skin with Bilayer Nanofiber for Comfortable Multimodal Health Management
Authors: Xinshuo Liang, Shuo Meng, Chuanwei Zhi, Shuai Zhang, Renjie Tan, Xingyuan Xu, Kaisong Huang, Leqi Lei, Jinlian Hu
Journal: Advanced Healthcare Materials (2024)

Abstract The advent of bionic skin sensors represents a significant leap forward in the realm of wearable health monitoring technologies. Existing bionic skin technologies face several limitations, including complex and expensive manufacturing processes, low wearing comfort, and challenges in achieving comfortable real‐time health monitoring. These shortcomings hinder the widespread adoption and practical utility of bionic skin in various applications. The bionic skin invention presented in this article addresses these issues by introducing a novel thermal transfer manufacturing process that is low‐cost and easy to operate. This method is particularly suitable for the small‐scale mass production required for bionic skin applications. Additionally, the innovative bilayer unidirectional moisture transport nanomembrane incorporated into the bionic skin offers high extensibility and breathability. This feature enhances the ability of the skin to absorb sweat, thereby facilitating comfortable real‐time health monitoring. The specially designed bionic skin sensor embedded within this system can monitor various biomarkers in sweat, including glucose, lactic acid, uric acid, pH, temperature, and skin impedance. When combined with the CARE(Continuous Analyte Monitoring with Real‐time Engagement) system, it enables real‐time data transmission and processing, offering a comprehensive approach to health monitoring that is both comfortable and reliable.
Building a modular and multi-cellular virtual twin of the synovial joint in Rheumatoid Arthritis
Authors: Naouel Zerrouk, Franck Augé, Anna Niarakis
Journal: npj Digital Medicine (2024)

Abstract Rheumatoid arthritis is a complex disease marked by joint pain, stiffness, swelling, and chronic synovitis, arising from the dysregulated interaction between synoviocytes and immune cells. Its unclear etiology makes finding a cure challenging. The concept of digital twins, used in engineering, can be applied to healthcare to improve diagnosis and treatment for complex diseases like rheumatoid arthritis. In this work, we pave the path towards a digital twin of the arthritic joint by building a large, modular biochemical reaction map of intra- and intercellular interactions. This network, featuring over 1000 biomolecules, is then converted to one of the largest executable Boolean models for biological systems to date. Validated through existing knowledge and gene expression data, our model is used to explore current treatments and identify new therapeutic targets for rheumatoid arthritis.
In vivo hyperphosphorylation of tau is associated with synaptic loss and behavioral abnormalities in the absence of tau seeds
Authors: Naoto Watamura, Martha S. Foiani, Sumi Bez, Mathieu Bourdenx, Alessia Santambrogio, Claire Frodsham, Elena Camporesi, Gunnar Brinkmalm, Henrik Zetterberg, Saisha Patel, Naoko Kamano, Mika Takahashi, Javier Rueda-Carrasco, Loukia Katsouri, Stephanie Fowler, Emir Turkes, Shoko Hashimoto, Hiroki Sasaguri, Takashi Saito, AFM Saiful Islam, Seico Benner, Toshihiro Endo, Katsuji Kobayashi, Chiho Ishida, Michele Vendruscolo, Masahito Yamada, Karen E. Duff, Takaomi C. Saido
Journal: Nature Neuroscience (2024)

Abstract Tau pathology is a hallmark of several neurodegenerative diseases, including frontotemporal dementia and Alzheimer’s disease. However, the sequence of events and the form of tau that confers toxicity are still unclear, due in large part to the lack of physiological models of tauopathy initiation and progression in which to test hypotheses. We have developed a series of targeted mice expressing frontotemporal-dementia-causing mutations in the humanized MAPT gene to investigate the earliest stages of tauopathy. MAPT Int10+3G&gt;A and MAPT S305N;Int10+3G&gt;A lines show abundant hyperphosphorylated tau in the hippocampus and entorhinal cortex, but they do not develop seed-competent fibrillar structures. Accumulation of hyperphosphorylated tau was accompanied by neurite degeneration, loss of viable synapses and indicators of behavioral abnormalities. Our results demonstrate that neuronal toxicity can occur in the absence of fibrillar, higher-order structures and that tau hyperphosphorylation is probably involved in the earliest etiological events in tauopathies showing isoform ratio imbalance.
Corrigendum to ‘Application of a microfluidic chip-based 3D co-culture to test drug sensitivity for individualized treatment of lung cancer’ [Biomaterials 34 (2013) 14772]
Authors: Zhiyun Xu, Yanghui Gao, Yuanyuan Hao, Encheng Li, Yan Wang, Jianing Zhang, Wenxin Wang, Zhancheng Gao, Qi Wang
Journal: Biomaterials (2024)
Dermatology response to the Hyperinflammation and HLH Across Specialty Collaboration consensus guideline – Authors' reply
Authors: Aisling S Carr, Ben Carpenter, Ian Proctor, Bethany Brockbank, Evangelia Panagou, Rachel Tattersall, Satyen Gohil, Jessica J Manson
Journal: The Lancet Rheumatology (2024)
Retraction notice “to Loss of mitochondrial adaptation associates with deterioration of mitochondrial turnover and structure in metabolic dysfunction-associated steatotic liver disease” [Metabolism 151 (2024) 155762]
Authors: Theresia Sarabhai, Sabine Kahl, Sofiya Gancheva, Lucia Mastrototaro, Bedair Dewidar, Dominik Pesta, Jacqueline M Ratter-Rieck, Pavel Bobrov, Kay Jeruschke, Irene Esposito, Matthias Schlensak, Michael Roden
Journal: Metabolism (2024)
Pooling Biospecimens for Efficient Exposure Assessment When Using Case–Cohort Analysis in Cohort Studies
Authors: Min Shi, David M. Umbach, Clarice R. Weinberg
Journal: Environmental Health Perspectives (2024)

Large prospective cohort studies have been fruitful for identifying exposure-disease associations. In a cohort where biospecimens (e.g., blood, urine) were collected at enrollment, analysts can exploit a case-cohort approach: Biospecimens from a random sample of cohort participants, called the "subcohort," plus a sample of incident cases that were not part of the subcohort are assayed. Reusing subcohort data for multiple disease outcomes can reduce costs and conserve specimen archives. Pooling biospecimen samples before assay could both save money and reduce depletion of the archive but has not been studied for cohort studies.