tbuckley/cabot-search huggingface dataset:
Lactobacillus casei Cell Wall Extract and Production of Galactose-Deficient IgA1 in a Humanized IGHA1 Mouse Model
Authors: Run Li, Manliu Wang, Jingyi Li, Li Zhu, Xinfang Xie, Hui Wang, Xu Zhang, Wenmin Tian, Yong Zhang, Yaping Dong, Jincan Zan, Hongyu Li, Yuemiao Zhang, Xujie Zhou, Sufang Shi, Chutian Shu, Lijun Liu, Jing Jin, Jicheng Lv, Hong Zhang
Journal: Journal of the American Society of Nephrology (2024)

Key Points We generated a transgenic mouse model expressing the human IgA1 heavy chain, which has a hinge region with rich O -linked glycosylation. After inflammatory stimulation, the mouse model showed elevated galactose-deficient IgA1 levels in the serum. Coupled with complement H factor mutant, the mice model exhibited glomerular lesions, associated with hematuria and albuminuria like IgA nephropathy. Background IgA nephropathy is the most common primary glomerulonephritis worldwide, and there is emerging evidence linking galactose-deficient IgA1 (Gd-IgA1) to the pathogenesis of the disease. However, mouse models that can be used to study Gd-IgA1's origin of production, biochemical characteristics, and immune reactivity are lacking. Methods We generated a humanized IgA1 mouse model with transgenic expression of the human IGHA1 gene from the mouse chromosomal locus of IgA heavy chain. The IGHA1 +/+ mice were crossed with complement factor H heterozygous mutant (FH W/R ) to generate IGHA1 +/+ FH W /R mice. IGHA1 +/+ mice were exposed to different levels of environmental pathogens in the first 4 months, as housed in germ-free, specific pathogen–free, or conventional environments. In addition, wild-type C57BL/6J mice, IGHA1 +/+ mice, and IGHA1 +/+ FH W/R mice were inoculated with Lactobacillus casei cell wall extract (LCWE) mixed with complete Freund's adjuvant (CFA) at 2 months of age to develop a mouse model of IgA nephropathy. Results Elevated levels of human IgA1 in blood circulation and mucosal sites were observed in IGHA1 +/+ mice from exposure to pathogens. Compared with buffer-treated control mice, LCWE plus CFA-treated mice had moderately elevated levels of circulating human IgA1 (by one-fold) and human IgA1 immune complexes (by two-fold). Serum Gd-IgA1 levels increased four-fold after LCWE treatments. Analyses of the O -glycopeptides of the IgA1 hinge region confirmed hypogalactosylation of IgA1, with the variety of the glycoforms matching those seen in clinical samples. Furthermore, LCWE induced persistent IgA1 and C3 deposition in the glomerular mesangial areas in association with mesangial expansion and hypercellularity, which are frequently observed in IgA nephropathy biopsies. The IGHA1 +/+ FH W/R mice stimulated with LCWE and CFA developed albuminuria and hematuria. Conclusions We observed elevated plasma Gd-IgA1 levels with kidney deposition of IgA1 in the IGHA1 +/+ mice after LCWE and CFA. In conjunction with factor H mutation, the mice exhibited severe glomerular alterations, associated with hematuria and albuminuria in resemblance of clinical IgA nephropathy.
Development and validation of a CT-based radiomics model to predict survival-graded fibrosis in pancreatic ductal adenocarcinoma
Authors: Siya Shi, Ruihao Liu, Jian Zhou, Jiawei Liu, Hongxin Lin, Junyang Mo, Jian Zhang, Xianfen Diao, Yanji Luo, Bingsheng Huang, Shi-Ting Feng
Journal: International Journal of Surgery (2024)

Tumor fibrosis plays an important role in chemotherapy resistance in pancreatic ductal adenocarcinoma (PDAC), however there remains a contradiction in the prognostic value of fibrosis. We aimed to investigate the relationship between tumor fibrosis and survival in patients with PDAC, classify patients into high- and low-fibrosis groups, and develop and validate a CT-based radiomics model to non-invasively predict fibrosis before treatment.
Neutrophil-targeted liposomal platform: A shift in novel approach for early detection and treatment of cancer metastasis
Authors: Cong Li, Kexin Zhang, Zehua Cheng, Lihong Wang, Zehao Li, Chao Shen, Zhihang Li, Zeyu Wang, Lianrui Cao, Lijiang Chen
Journal: Asian Journal of Pharmaceutical Sciences (2024)

Tumor metastasis is responsible for 90% of cancer-associated deaths, and its early detection may decrease the likelihood of mortality. Studies have demonstrated that metastasis results from the interaction between "seeds" (tumor cells) and "soil" (pre-metastatic niche, PMN). As the first and most abundant immune cells to be recruited to PMN, neutrophils play a key role in the ultimate formation of metastatic foci through mechanisms such as supporting tumor cell growth, promoting angiogenesis, and shaping an immune-suppressive microenvironment. In this study, two distinct types of sialic acid (SA)-modified liposomes were prepared to target and regulate pro-metastatic neutrophils through the l-selectin receptor. One of these liposomes, named ICG@SAL, was used to encapsulate indocyanine green (ICG) and was specifically designed for the early detection of cancer metastasis. The other liposome, referred to as ABE/Cur@SAL, co-loaded abemaciclib (ABE) and curcumin (Cur), with the intention of suppressing the progression of metastatic tumor. Fluorescence imaging results from the mouse spontaneous metastasis model indicated that ICG@SAL demonstrated faster targeting and stronger accumulation in the metastatic organs than unmodified ICG liposomes (ICG@CL). This suggested that ICG@SAL could detect tumor metastasis at an early stage. The therapy with co-loaded liposomes in the mouse experimental lung metastasis model indicated that ABE/Cur@SAL could inhibit regulatory T (Treg) cell proliferation, enhance effector T cell activity and reduce tumorigenic factor release, implying that ABE/Cur@SAL could inhibit tumor metastasis. Overall, our work provided a sensitive and convenient approach to early diagnosis and treatment of tumor metastasis. ICG@SAL could be employed for the early detection of tumor metastasis, while ABE/Cur@SAL could be used to inhibit the development of tumor metastasis when early metastasis was identified.
Persistence of Lugol-unstaining is associated with an increased risk of progression to malignancy in the esophagus
Authors: Mengfei Liu, Zeyu Yan, Zifan Qi, Ren Zhou, Chuanhai Guo, Anxiang Liu, Haijun Yang, Fenglei Li, Liping Duan, Lin Shen, Qi Wu, Zhen Liu, Yaqi Pan, Ying Liu, Fangfang Liu, Hong Cai, Zhonghu He, Yang Ke
Journal: Clinical Gastroenterology and Hepatology (2024)
Electrostatic spraying for fine-tuning particle dimensions to enhance oral bioavailability of poorly water-soluble drugs
Authors: Jung Suk Kim, Seunghyun Cheon, Mi Ran Woo, Sanghyun Woo, Jee-Eun Chung, Yu Seok Youn, Kyung Taek Oh, Soo-Jeong Lim, Sae Kwang Ku, Bao Loc Nguyen, Jong Oh Kim, Sung Giu Jin, Han-Gon Choi
Journal: Asian Journal of Pharmaceutical Sciences (2024)

While spray-drying has been widely utilized to improve the bioavailability of poorly water-soluble drugs, the outcomes often exhibit suboptimal particle size distribution and large particle sizes, limiting their effectiveness. In this study, we introduce electrostatic spraying as an advanced technology tailored for poorly water-soluble drugs, enabling the fabrication of nanoparticles with fine and uniform particle size distribution. Regorafenib (1 g), as a model drug, copovidone (5 g), and sodium dodecyl sulfate (0.1 g) were dissolved in 200 ml ethanol and subjected to conventional-spray-dryer and electrostatic spray dryer. The electrostatic spray-dried nanoparticles (ESDN) showed smaller particle sizes with better uniformity compared to conventional spray-dried nanoparticles (CSDN). ESDN demonstrated significantly enhanced solubility and rapid release in water.
Misregulation of mitochondrial 6mA promotes the propagation of mutant mtDNA and causes aging in C. elegans
Authors: Anne Hahn, Grace Ching Ching Hung, Arnaud Ahier, Chuan-Yang Dai, Ina Kirmes, Brian M Forde, Daniel Campbell, Rachel Shin Yie Lee, Josiah Sucic, Tessa Onraet, Steven Zuryn
Journal: Cell Metabolism (2024)
Mitochondrial membrane lipids in the regulation of bioenergetic flux
Authors: Stephen Thomas Decker, Katsuhiko Funai
Journal: Cell Metabolism (2024)

SummaryOxidative phosphorylation (OXPHOS) occurs through and across the inner mitochondrial membrane (IMM). Mitochondrial membranes contain a distinct lipid composition, aided by lipid biosynthetic machinery localized in the IMM and class-specific lipid transporters that limit lipid traffic in and out of mitochondria. This unique lipid composition appears to be essential for functions of mitochondria, particularly OXPHOS, by its effects on direct lipid-to-protein interactions, membrane properties, and cristae ultrastructure. This review highlights the biological significance of mitochondrial lipids, with a particular spotlight on the role of lipids in mitochondrial bioenergetics. We describe pathways for the biosynthesis of mitochondrial lipids and provide evidence for their roles in physiology, their implications in human disease, and the mechanisms by which they regulate mitochondrial bioenergetics.
Prevalence and clinical impact of topical corticosteroid phobia among patients with chronic hand eczema – findings from the Danish Skin Cohort
Authors: Maria O. Christensen, Johan Sieborg, Lea K. Nymand, Emma Guttman-Yassky, Khaled Ezzedine, Christoph Schlapbach, Sonja Molin, Jianzhong Zhang, Claus Zachariae, Simon F. Thomsen, Jacob P. Thyssen, Alexander Egeberg
Journal: Journal of the American Academy of Dermatology (2024)

BackgroundTopical corticosteroid phobia (TOPICOP) is associated with poor treatment adherence and is common among patients with skin disease. Knowledge about corticosteroid phobia and treatment adherence among patients with chronic hand eczema (CHE) is limited.ObjectivesTo investigate patient-reported outcomes regarding topical corticosteroids (TCSs), and their impact on treatment adherence in patients with CHE.MethodsPatients with CHE from the Danish Skin Cohort answered a questionnaire including the TOPICOP scale and Medication Adherence Report Scale. Response rate was 69.2%.ResultsOf 927 with CHE, 75.5% totally or almost agreed that TCS damage the skin, 48.9% totally or almost agreed that TCS would affect their future health and 36.3% reported some degree of fear of TCS although they were unaware of any TCS-associated risks. Most patients (77.9%) always or often stop treatment as soon as possible, whereas 54.8% always or often wait as long as possible before starting treatment. Overall, 38.8% reported that they had taken less medicine than prescribed and 54.0% had stopped treatment throughout a period. Treatment adherence decreased with increasing corticosteroid phobia (P = .004).LimitationsTOPICOP has not been validated in patients with CHE.ConclusionsCorticosteroid phobia is common among patients with CHE and negatively associated with treatment adherence.
Animals and the iterative natural kind strategy
Authors: Tim Bayne, Anil Seth, Marcello Massimini, Joshua Shepherd, Axel Cleeremans, Stephen M Fleming, Rafael Malach, Jason B Mattingley, David K Menon, Adrian M Owen, Megan A K Peters, Adeel Razi, Liad Mudrik
Journal: Trends in Cognitive Sciences (2024)
Sarcobesity: new paradigms for healthy aging related to taurine supplementation, gut microbiota and exercise
Authors: Gabriela Batitucci, Gabriela Ferreira Abud, Gabriela Ueta Ortiz, Lucas Fernandes Belisário, Sofia Germano Travieso, Marcela Coffacci de Lima Viliod, Ana Cláudia Rossini Venturini, Ellen Cristini de Freitas
Journal: Ageing Research Reviews (2024)
Value Proposition of Retinal Imaging in Alzheimer’s Disease Screening: A Review of Eight Evolving Trends
Authors: Victor T T Chan, An Ran Ran, Siegfried K Wagner, Herbert Y H Hui, Xiaoyan Hu, Ho Ko, Sharon Fekrat, Yaxing Wang, Cecilia S Lee, Alvin L Young, Clement C Tham, Yih Chung Tham, Pearse A Keane, Dan Milea, Christopher Chen, Tien Yin Wong, Vincent C T Mok, Carol Y Cheung
Journal: Progress in Retinal and Eye Research (2024)
Metal-organic frameworks in oral drug delivery
Authors: Aun Raza, Wei Wu
Journal: Asian Journal of Pharmaceutical Sciences (2024)

Metal-organic frameworks (MOFs) offer innovative solutions to the limitations of traditional oral drug delivery systems through their unique combination of metal ions and organic ligands. This review systematically examines the structural properties and principles of MOFs, setting the stage for their application in drug delivery. It discusses various classes of MOFs, including those based on zirconium, iron, zinc, copper, titanium, aluminum, potassium, and magnesium, assessing their drug-loading capacities, biocompatibility, and controlled release mechanisms. The effectiveness of MOFs is illustrated through case studies that highlight their capabilities in enhancing drug solubility, providing protection against the harsh gastrointestinal environment, and enabling precise drug release. The review addresses potential challenges, particularly the toxicity concerns associated with MOFs, and calls for further research into their biocompatibility and interactions with biological systems. It concludes by emphasizing the potential of MOFs in revolutionizing oral drug delivery, highlighting the critical need for comprehensive research to harness their full potential in clinical applications.
Transcription factor Twist1 drives fibroblast activation to promote kidney fibrosis via signaling proteins Prrx1/TNC.
Authors: Lianqin Sun, Lishan Liu, Juanjuan Jiang, Kang Liu, Jingfeng Zhu, Lin Wu, Xiaohan Lu, Zhimin Huang, Yanggang Yuan, Steven D Crowley, Huijuan Mao, Changying Xing, Jiafa Ren
Journal: Kidney International (2024)
ADAM10 isoforms: optimizing usage of antibodies based on protein regulation, structural features, biological activity and clinical relevance to Alzheimer’s disease
Authors: Sabrina Dorta, Vanessa Alexandre-Silva, Cecilia Patricia Popolin, Danilo Barroso de Sousa, Marina Mantellatto Grigoli, Lucas Nogueira de Carvalho Pelegrini, Patricia Regina Manzine, Antoni Camins, Elena Marcello, Kristina Endres, Marcia Regina Cominetti
Journal: Ageing Research Reviews (2024)

A Disintegrin and Metalloproteinase 10 (ADAM10) is a crucial transmembrane protein involved in diverse cellular processes, including cell adhesion, migration, and proteolysis. ADAM10's ability to cleave over 100 substrates underscores its significance in physiological and pathological contexts, particularly in Alzheimer's disease (AD). This review comprehensively examines ADAM10's multifaceted roles, highlighting its critical function in the non-amyloidogenic processing of the amyloid precursor protein (APP), which mitigates amyloid beta (Aβ) production, a critical factor in AD development. We summarize the regulation of ADAM10 at multiple levels: transcriptional, translational, and post-translational, revealing the complexity and responsiveness of its expression to various cellular signals. A standardized nomenclature for ADAM10 isoforms is proposed to improve clarity and consistency in research, facilitating better comparison and replication of findings across studies. We address the challenges in detecting ADAM10 isoforms using antibodies, advocating for standardized detection protocols to resolve discrepancies in results from different biological matrices. By highlighting these issues, this review underscores the potential of ADAM10 as a biomarker for early diagnosis and a therapeutic target in AD. By consolidating current knowledge on ADAM10's regulation and function, we aim to provide insights that will guide future research and therapeutic strategies in the AD context.
Community-based mpox and sexually transmitted disease surveillance using discarded condoms in the global south
Authors: Dhammika Leshan Wannigama, Mohan Amarasiri, Phatthranit Phattharapornjaroen, Cameron Hurst, Charin Modchang, John Jefferson V Besa, Kazuhiko Miyanaga, Longzhu Cui, Stefan Fernandez, Angkana T Huang, Puey Ounjai, Andrew C Singer, Naveen Kumar Devanga Ragupathi, Takashi Furukawa, Kazunari Sei, Asuka Nanbo, Asada Leelahavanichkul, Talerngsak Kanjanabuch, Tanittha Chatsuwan, Paul G Higgins, Daisuke Sano, Anthony Kicic, Jürgen Kurt Rockstroh, Richard Siow, Sam Trowsdale, Parichart Hongsing, Aisha Khatib, Kenji Shibuya, Shuichi Abe
Journal: The Lancet Infectious Diseases (2024)
Domain adaptation strategies for 3D reconstruction of the lumbar spine using real fluoroscopy data
Authors: Sascha Jecklin, Youyang Shen, Amandine Gout, Daniel Suter, Lilian Calvet, Lukas Zingg, Jennifer Straub, Nicola Alessandro Cavalcanti, Mazda Farshad, Philipp Fürnstahl, Hooman Esfandiari
Journal: Medical Image Analysis (2024)

In this study, we address critical barriers hindering the widespread adoption of surgical navigation in orthopedic surgeries due to limitations such as time constraints, cost implications, radiation concerns, and integration within the surgical workflow. Recently, our work X23D showed an approach for generating 3D anatomical models of the spine from only a few intraoperative fluoroscopic images. This approach negates the need for conventional registration-based surgical navigation by creating a direct intraoperative 3D reconstruction of the anatomy. Despite these strides, the practical application of X23D has been limited by a significant domain gap between synthetic training data and real intraoperative images. In response, we devised a novel data collection protocol to assemble a paired dataset consisting of synthetic and real fluoroscopic images captured from identical perspectives. Leveraging this unique dataset, we refined our deep learning model through transfer learning, effectively bridging the domain gap between synthetic and real X-ray data. We introduce an innovative approach combining style transfer with the curated paired dataset. This method transforms real X-ray images into the synthetic domain, enabling the in-silico-trained X23D model to achieve high accuracy in real-world settings. Our results demonstrated that the refined model can rapidly generate accurate 3D reconstructions of the entire lumbar spine from as few as three intraoperative fluoroscopic shots. The enhanced model reached a sufficient accuracy, achieving an 84% F1 score, equating to the benchmark set solely by synthetic data in previous research. Moreover, with an impressive computational time of just 81.1 ms, our approach offers real-time capabilities, vital for successful integration into active surgical procedures. By investigating optimal imaging setups and view angle dependencies, we have further validated the practicality and reliability of our system in a clinical environment. Our research represents a promising advancement in intraoperative 3D reconstruction. This innovation has the potential to enhance intraoperative surgical planning, navigation, and surgical robotics.
Effectiveness of rVSV-ZEBOV vaccination during the 2018–20 Ebola virus disease epidemic in the Democratic Republic of the Congo: a retrospective test-negative study
Authors: Sophie Meakin, Justus Nsio, Anton Camacho, Richard Kitenge, Rebecca M Coulborn, Etienne Gignoux, John Johnson, Esther Sterk, Elisabeth Mukamba Musenga, Stephane Hans Bateyi Mustafa, Flavio Finger, Steve Ahuka-Mundeke
Journal: The Lancet Infectious Diseases (2024)

The recombinant vesicular stomatitis virus-Zaire Ebola virus (rVSV-ZEBOV) vaccine is the only WHO prequalified vaccine recommended for use to respond to outbreaks of Ebola virus (species Zaire ebolavirus) by WHO's Strategic Advisory Group of Experts on Immunization. Despite the vaccine's widespread use during several outbreaks, no real-world effectiveness estimates are currently available in the literature.
Mast cell–derived BH4 and serotonin are critical mediators of postoperative pain
Authors: Philipp Starkl, Gustav Jonsson, Tyler Artner, Bruna Lenfers Turnes, Laura-Marie Gail, Tiago Oliveira, Aakanksha Jain, Nadine Serhan, Karel Stejskal, Karin Lakovits, Anastasiya Hladik, Meilin An, Keith M. Channon, Hail Kim, Thomas Köcher, Wolfgang Weninger, Georg Stary, Sylvia Knapp, Victoria Klang, Nicolas Gaudenzio, Clifford J. Woolf, Shweta Tikoo, Rohit Jain, Josef M. Penninger, Shane J. F. Cronin
Journal: Science Immunology (2024)

Postoperative pain affects most patients after major surgery and can transition to chronic pain. The considerable side effects and limited efficacy of current treatments underline the need for new therapeutic options. We observed increased amounts of the metabolites BH4 and serotonin after skin injury. Mast cells were primary postoperative sources of Gch1 , the rate-limiting enzyme in BH4 synthesis, itself an obligate cofactor in serotonin production by tryptophan hydroxylase (Tph1). Mice deficient in mast cells or in mast cell–specific Gch1 or Tph1 showed drastically decreased postoperative pain. We found that injury induced the nociceptive neuropeptide substance P, mast cell degranulation, and granule nerve colocalization. Substance P triggered serotonin release in mouse and human mast cells, and substance P receptor blockade substantially ameliorated pain hypersensitivity. Our findings highlight the importance of mast cells at the neuroimmune interface and substance P–driven mast cell BH4 and serotonin production as a therapeutic target for postoperative pain treatment.
PPARβ/δ-orchestrated metabolic reprogramming supports the formation and maintenance of memory CD8 <sup>+</sup> T cells
Authors: Alessio Bevilacqua, Fabien Franco, Ya-Ting Lu, Nabil Rahiman, Kung-Chi Kao, Yu-Ming Chuang, Yanan Zhu, Werner Held, Xin Xie, Kristin C. Gunsalus, Zhengtao Xiao, Shih-Yu Chen, Ping-Chih Ho
Journal: Science Immunology (2024)

The formation of memory T cells is a fundamental feature of adaptative immunity, allowing the establishment of long-term protection against pathogens. Although emerging evidence suggests that metabolic reprogramming is crucial for memory T cell differentiation and survival, the underlying mechanisms that drive metabolic rewiring in memory T cells remain unclear. Here, we found that up-regulation of the nuclear receptor peroxisome proliferator–activated receptor β/δ (PPARβ/δ) instructs the metabolic reprogramming that occurs during the establishment of central memory CD8 + T cells. PPARβ/δ-regulated changes included suppression of aerobic glycolysis and enhancement of oxidative metabolism and fatty acid oxidation. Mechanistically, exposure to interleukin-15 and expression of T cell factor 1 facilitated activation of the PPARβ/δ pathway, counteracting apoptosis induced by antigen clearance and metabolic stress. Together, our findings indicate that PPARβ/δ is a master metabolic regulator orchestrating a metabolic switch that may be favorable for T cell longevity.
Hematopoietic stem cell heterogeneity and age-associated platelet bias are evolutionarily conserved
Authors: Merve Aksöz, Grigore-Aristide Gafencu, Bilyana Stoilova, Mario Buono, Ying Zhang, Sven Turkalj, Yiran Meng, Niels Asger Jakobsen, Marlen Metzner, Sally-Ann Clark, Ryan Beveridge, Supat Thongjuea, Paresh Vyas, Claus Nerlov
Journal: Science Immunology (2024)

Hematopoietic stem cells (HSCs) reconstitute multilineage human hematopoiesis after clinical bone marrow (BM) transplantation and are the cells of origin of some hematological malignancies. Although HSCs provide multilineage engraftment, individual murine HSCs are lineage biased and contribute unequally to blood cell lineages. Here, we performed high-throughput single-cell RNA sequencing in mice after xenograft with molecularly barcoded adult human BM HSCs. We demonstrated that human individual BM HSCs are also functionally and transcriptionally lineage biased. Specifically, we identified platelet-biased and multilineage human HSCs. Quantitative comparison of transcriptomes from single HSCs from young and aged BM showed that both the proportion of platelet-biased HSCs and their level of transcriptional platelet priming increase with age. Therefore, platelet-biased HSCs and their increased prevalence and transcriptional platelet priming during aging are conserved features of mammalian evolution.