tbuckley/cabot-search huggingface dataset:
Type 1 innate lymphoid cells: a biomarker and therapeutic candidate in sarcoidosis
Authors: Inchul Cho, Andrew L. Ji
Journal: Journal of Clinical Investigation (2024)

Sarcoidosis is an inflammatory disease characterized by immune cell–rich granulomas that form in multiple organs. In this issue of the JCI, Sati and colleagues used scRNA-seq and spatial transcriptomics of skin samples from patients with sarcoidosis and non-sarcoidosis granulomatous disease to identify upregulation of a stromal-immune CXCL12/CXCR4 axis and accumulation of type 1 innate lymphoid cells (ILC1s) in sarcoidosis. The accumulation of ILC1s in skin and blood was specific to patients with sarcoidosis and not observed in other granulomatous diseases. The authors used a mouse model of lung granuloma to show that ILCs contribute to granuloma formation and that blockade of CXCR4 reduced the formation of granulomas, providing a proof of concept that sarcoidosis may be treated by CXCR4 blockade to prevent the progression of disease in patients. These results suggest ILC1s could serve as a diagnostic biomarker in sarcoidosis and a potential therapeutic target.
LAMTOR1 decreased exosomal PD-L1 to enhance immunotherapy efficacy in non-small cell lung cancer
Authors: Bo Wu, Xin Huang, Xiang Shi, Meixi Jiang, Hongxu Liu, Li Zhao
Journal: Molecular Cancer (2024)

Great progress has been made in utilizing immune checkpoint blockade (ICB) for the treatment of non-small-cell lung cancer (NSCLC). Therapies targeting programmed cell death protein 1 (PD-1) and its ligand PD-L1, expressed on tumor cells, have demonstrated potential in improving patient survival rates. An unresolved issue involves immune suppression induced by exosomal PD-L1 within the tumor microenvironment (TME), particularly regarding CD8+ T cells. Our study unveiled the crucial involvement of LAMTOR1 in suppressing the exosomes of PD-L1 and promoting CD8+ T cell infiltration in NSCLC. Through its interaction with HRS, LAMTOR1 facilitates PD-L1 lysosomal degradation, thereby reducing exosomal PD-L1 release. Notably, the ability of LAMTOR1 to promote PD-L1 lysosomal degradation relies on a specific ubiquitination site and an HRS binding sequence. The findings suggest that employing LAMTOR1 to construct peptides could serve as a promising strategy for bolstering the efficacy of immunotherapy in NSCLC. The discovery and comprehension of how LAMTOR1 inhibits the release of exosomal PD-L1 offer insights into potential therapeutic strategies for improving immunotherapy. It is imperative to conduct further research and clinical trials to investigate the feasibility and efficacy of targeting LAMTOR1 in NSCLC treatment.
Empowering new mothers in China: role of paediatric care in screening and management of postpartum depression
Authors: Yunting Zhang, Haiwa Wang, Saishuang Wu, Yuyin Xiao, Fan Jiang
Journal: BMJ (2024)

Though general paediatricians have traditionally been the gatekeepers of children's health, they can also work as part of a multidisciplinary team to tackle postpartum depression, argue <b>Fan Jiang and colleagues</b>
Solubilization techniques used for poorly water-soluble drugs
Authors: Bing Xie, Yaping Liu, Xiaotong Li, Pei Yang, Wei He
Journal: Acta Pharmaceutica Sinica B (2024)

About 40% of approved drugs and nearly 90% of drug candidates are poorly water-soluble drugs. Low solubility reduces the drugability. Effectively improving the solubility and bioavailability of poorly water-soluble drugs is a critical issue that needs to be urgently addressed in drug development and application. This review briefly introduces the conventional solubilization techniques such as solubilizers, hydrotropes, cosolvents, prodrugs, salt modification, micronization, cyclodextrin inclusion, solid dispersions, and details the crystallization strategies, ionic liquids, and polymer-based, lipid-based, and inorganic-based carriers in improving solubility and bioavailability. Some of the most commonly used approved carrier materials for solubilization techniques are presented. Several approved poorly water-soluble drugs using solubilization techniques are summarized. Furthermore, this review summarizes the solubilization mechanism of each solubilization technique, reviews the latest research advances and challenges, and evaluates the potential for clinical translation. This review could guide the selection of a solubilization approach, dosage form, and administration route for poorly water-soluble drugs. Moreover, we discuss several promising solubilization techniques attracting increasing attention worldwide.
Intrinsic ADRB2 inhibition improves CAR-T cell therapy efficacy against prostate cancer
Authors: Iqra Ajmal, Muhammad Asad Farooq, Yixin Duan, Jie Yao, Yaoxin Gao, Xinhui Hui, Yujia Ge, Yiran Chen, Yaojun Ren, Bingtan Du, Wenzheng Jiang
Journal: Molecular Therapy (2024)
Mammography classification with multi-view deep learning techniques: Investigating graph and transformer-based architectures
Authors: Francesco Manigrasso, Rosario Milazzo, Alessandro Sebastian Russo, Fabrizio Lamberti, Fredrik Strand, Andrea Pagnani, Lia Morra
Journal: Medical Image Analysis (2024)

The potential and promise of deep learning systems to provide an independent assessment and relieve radiologists' burden in screening mammography have been recognized in several studies. However, the low cancer prevalence, the need to process high-resolution images, and the need to combine information from multiple views and scales still pose technical challenges. Multi-view architectures that combine information from the four mammographic views to produce an exam-level classification score are a promising approach to the automated processing of screening mammography. However, training such architectures from exam-level labels, without relying on pixel-level supervision, requires very large datasets and may result in suboptimal accuracy. Emerging architectures such as Visual Transformers (ViT) and graph-based architectures can potentially integrate ipsi-lateral and contra-lateral breast views better than traditional convolutional neural networks, thanks to their stronger ability of modeling long-range dependencies. In this paper, we extensively evaluate novel transformer-based and graph-based architectures against state-of-the-art multi-view convolutional neural networks, trained in a weakly-supervised setting on a middle-scale dataset, both in terms of performance and interpretability. Extensive experiments on the CSAW dataset suggest that, while transformer-based architecture outperform other architectures, different inductive biases lead to complementary strengths and weaknesses, as each architecture is sensitive to different signs and mammographic features. Hence, an ensemble of different architectures should be preferred over a winner-takes-all approach to achieve more accurate and robust results. Overall, the findings highlight the potential of a wide range of multi-view architectures for breast cancer classification, even in datasets of relatively modest size, although the detection of small lesions remains challenging without pixel-wise supervision or ad-hoc networks.
Target modulation of glycolytic pathways as a new strategy for the treatment of neuroinflammatory diseases
Authors: Hanlong Wang, Shasha Liu, Yang Sun, Chen Chen, Ziyi Hu, Qinqin Li, Junpeng Long, Qian Yan, Jinping Liang, Yuting Lin, Songwei Yang, Meiyu Lin, Xuan Liu, Huiqin Wang, Jingbo Yu, Fan Yi, Yong Tan, Yantao Yang, Naihong Chen, Qidi Ai
Journal: Ageing Research Reviews (2024)
The gender congruences and life satisfaction scale for transgender and gender-diverse youth (GCLS-Y): a validation study with samples from the UK and US
Authors: Bethany A. Jones, Alisha. L. Nguyen, Gina M. Sequeira, Shane D. Morrison, Liam Cahill
Journal: International Journal of Transgender Health (2024)

Background There are currently no good quality psychometric tools available to assess multi-dimensional outcomes for trans and gender diverse youth. A tool is needed to develop a stronger evidence base regarding the evaluation of gender-affirming healthcare for the population.
Biomimetic nanoplatform with microbiome modulation and antioxidant functions ameliorating insulin resistance and pancreatic β-cell dysfunction for T2DM management
Authors: Xiudan Wang, Rui Tian, Chenghong Liang, Yifan Jia, Lingyun Zhao, Qinyuan Xie, Fenglian Huang, Huijuan Yuan
Journal: Biomaterials (2024)
Activation of pregnane X receptor sensitizes alcoholic steatohepatitis by transactivating fatty acid binding protein 4
Authors: Yiwen Zhang, Bingfang Hu, Shaoxing Guan, Pan Li, Yingjie Guo, Pengfei Xu, Yongdong Niu, Yujin Li, Ye Feng, Jiewen Du, Jun Xu, Xiuchen Guan, Jingkai Gu, Haiyan Sun, Min Huang
Journal: Acta Pharmaceutica Sinica B (2024)

Alcoholic steatohepatitis (ASH) is a liver disease characterized by steatosis, inflammation, and necrosis of the liver tissue as a result of excessive alcohol consumption. Pregnane X receptor (PXR) is a xenobiotic nuclear receptor best known for its function in the transcriptional regulation of drug metabolism and disposition. Clinical reports suggested that the antibiotic rifampicin, a potent human PXR activator, is a contraindication in alcoholics, but the mechanism was unclear. In this study, we showed that the hepatic expression of fatty acid binding protein 4 (FABP4) was uniquely elevated in ASH patients and a mouse model of ASH. Pharmacological inhibiting FABP4 attenuated ASH in mice. Furthermore, treatment of mice with the mouse PXR agonist pregnenolon-16
Antibodies and complement are key drivers of thrombosis
Authors: Konstantin Stark, Badr Kilani, Sven Stockhausen, Johanna Busse, Irene Schubert, Thuy-Duong Tran, Florian Gaertner, Alexander Leunig, Kami Pekayvaz, Leo Nicolai, Valeria Fumagalli, Julia Stermann, Felix Stephan, Christian David, Martin B Müller, Birgitta Heyman, Anja Lux, Alexandra da Palma Guerreiro, Lukas P Frenzel, Christoph Q Schmidt, Arthur Dopler, Markus Moser, Sue Chandraratne, Marie-Luise von Brühl, Michael Lorenz, Thomas Korff, Martina Rudelius, Oliver Popp, Marieluise Kirchner, Philipp Mertins, Falk Nimmerjahn, Matteo Iannacone, Markus Sperandio, Bernd Engelmann, Admar Verschoor, Steffen Massberg
Journal: Immunity (2024)
Hematopoietic Cell Transplantation for DOCK8 Deficiency: Results from a Prospective Clinical Trial
Authors: Alexandra F. Freeman, Corina E. Gonzalez, Bonnie Yates, Kristen Cole, Lauren Little, Erin Flannelly, Seth M. Steinberg, George Mo, Nicole Piette, Thomas E. Hughes, Jennifer Cuellar-Rodriguez, Juan Gea-Banacloche, Theo Heller, Dima A. Hammoud, Steve M. Holland, Heidi H. Kong, Fernanda D. Young, Huie Jing, Basak Kayaoglu, Helen C. Su, Sung-Yun Pai, Dennis D. Hickstein, Nirali N. Shah
Journal: Journal of Allergy and Clinical Immunology (2024)
Clinical-transcriptional prioritization of the circulating proteome in human heart failure
Authors: Andrew S Perry, Kaushik Amancherla, Xiaoning Huang, Michelle L Lance, Eric Farber-Eger, Priya Gajjar, Junedh Amrute, Lindsey Stolze, Shilin Zhao, Quanhu Sheng, Cassandra M Joynes, Zhongsheng Peng, Toshiko Tanaka, Stavros G Drakos, Kory J Lavine, Craig Selzman, Joseph R Visker, Thirupura S Shankar, Luigi Ferrucci, Saumya Das, Jane Wilcox, Ravi B Patel, Ravi Kalhan, Sanjiv J Shah, Keenan A Walker, Quinn Wells, Nathan Tucker, Matthew Nayor, Ravi V Shah, Sadiya S Khan
Journal: Cell Reports Medicine (2024)
Ultrasound-responsive Microfibers Promoted Infected Wound Healing with Neuro-vascularization by Segmented Sonodynamic Therapy and Electrical Stimulation
Authors: Xianli Wang, Ke Sun, Cheng Wang, Mengmeng Yang, Kun Qian, Bing Ye, Xiaodong Guo, Yi Shao, Chenglin Chu, Feng Xue, Jun Li, Jing Bai
Journal: Biomaterials (2024)
Autoantigen-specific CD4+ T cells acquire an exhausted phenotype and persist in human antigen-specific autoimmune diseases
Authors: Carina Saggau, Petra Bacher, Daniela Esser, Mahdi Rasa, Silja Meise, Nicola Mohr, Nora Kohlstedt, Andreas Hutloff, Sarah-Sophie Schacht, Justina Dargvainiene, Gabriela Rios Martini, Klarissa H Stürner, Ina Schröder, Robert Markewitz, Johannes Hartl, Maria Hastermann, Ankelien Duchow, Patrick Schindler, Mareike Becker, Carolin Bautista, Judith Gottfreund, Jörn Walter, Julia K Polansky, Mingxing Yang, Reza Naghavian, Mareike Wendorff, Ev-Marie Schuster, Andreas Dahl, Andreas Petzold, Susanne Reinhardt, Andre Franke, Marek Wieczorek, Lea Henschel, Daniel Berger, Guido Heine, Maike Holtsche, Vivien Häußler, Christian Peters, Enno Schmidt, Simon Fillatreau, Dirk H Busch, Klaus-Peter Wandinger, Kilian Schober, Roland Martin, Friedemann Paul, Frank Leypoldt, Alexander Scheffold
Journal: Immunity (2024)
Cancer drug-tolerant persister cells: from biological questions to clinical opportunities
Authors: Mariangela Russo, Mengnuo Chen, Elisa Mariella, Haoning Peng, Sumaiyah K. Rehman, Elena Sancho, Alberto Sogari, Tzen S. Toh, Nathalie Q. Balaban, Eduard Batlle, Rene Bernards, Mathew J. Garnett, Matthew Hangauer, Eleonora Leucci, Jean-Christophe Marine, Catherine A. O’Brien, Yaara Oren, E. Elizabeth Patton, Caroline Robert, Susan M. Rosenberg, Shensi Shen, Alberto Bardelli
Journal: Nature reviews. Cancer (2024)
Rare Genetic Variants in <i>LDLR</i> , <i>APOB</i> , and <i>PCSK9</i> are Associated with Aortic Stenosis
Authors: Joel Rämö, Sean J Jurgens, Shinwan Kany, Seung Hoan Choi, Xin Wang, Andrey N Smirnov, Sam Freesun Friedman, Mahnaz Maddah, Shaan Khurshid, Patrick T Ellinor, James Paul Pirruccello
Journal: Circulation (2024)

Background: Despite a proposed causal role for low-density lipoprotein cholesterol (LDL-C) in aortic stenosis (AS), randomized controlled trials of lipid-lowering therapy failed to prevent severe AS. We aimed to assess the impact on AS and peak velocity across the aortic valve conferred by lifelong alterations in LDL-C levels mediated by protein-disrupting variants in three clinically significant genes for LDL metabolism ( LDLR , APOB , PCSK9 ). Methods: We utilized sequencing data and electronic health records from UK Biobank (UKB) and All of Us and magnetic resonance imaging data from UKB. We identified predicted protein-disrupting variants with the LOFTEE and AlphaMissense algorithms and evaluated their associations with LDL-C and peak velocity across the aortic valve (UK Biobank), as well as diagnosed AS and aortic valve replacement (UK Biobank + All of Us). Results: We included 421,049 unrelated participants (5,621 with AS) in UKB and 195,519 unrelated participants (1,087 with AS) in All of Us. Carriers of protein-disrupting variants in LDLR had higher mean LDL-C (UKB: +42.6 mg/dl, P=4.4e-237) and greater risk of AS (meta-analysis: odds ratio [OR] =3.52 [95% CI 2.39−5.20], P=2.3e-10) and aortic valve replacement (meta-analysis: OR=3.78 [95% CI 2.26−6.32], P=4.0e-7). Carriers of protein-disrupting variants in APOB or PCSK9 had lower mean LDL-C (UKB: -32.3 mg/dl, P&lt;5e-324) and lower risk of AS (meta-analysis: OR=0.49 [0.31−0.75], P=0.001) and aortic valve replacement (meta-analysis: OR=0.54 [0.30−0.97], P=0.04). Among 57,371 UKB imaging substudy participants, peak velocities across the aortic valve were greater in carriers of protein-disrupting variants in LDLR (+12.2cm/s, P=1.6e-5) and lower in carriers of protein-disrupting variants in PCSK9 (-6.9cm/s, P=0.022). Conclusions: Rare genetic variants that confer lifelong higher or lower LDL-C levels are associated with substantially increased and decreased risk of AS, respectively. Early and sustained lipid-lowering therapy may slow or prevent AS development.
Understanding, assessing and treating immune, endothelial and haemostasis dysfunctions in bacterial sepsis
Authors: Massimo Girardis, Sascha David, Ricard Ferrer, Julie Helms, Nicole P. Juffermans, Ignacio Martin-Loeches, Pedro Povoa, Lene Russell, Manu Shankar-Hari, Toshiaki Iba, Irene Coloretti, Nicholas Parchim, Nathan D. Nielsen
Journal: Intensive Care Medicine (2024)
Crystallographic plane-induced selective mineralization of nanohydroxyapatite on fibrous-grained titanium promotes osteointegration and biocorrosion resistance
Authors: Ruohan Wang, Juan Li, Qunjie Bi, Binbin Yang, Ting He, Kaifeng Lin, Xiangdong Zhu, Kai Zhang, Rongrong Jin, Chongxiang Huang, Yu Nie, Xingdong Zhang
Journal: Biomaterials (2024)
Clinical Characteristics and Outcomes of Patients With Takotsubo Syndrome and Left Ventricular Outflow Tract Obstruction
Authors: Davide Di Vece, Michele Bellino, Angelo Silverio, Serena Migliarino, Eduardo Bossone, Fernando Scudiero, Giuseppina Novo, Matteo Cameli, Olga Vriz, Aneta Aleksova, Concetta Zito, Pasquale Innelli, Fausto Rigo, Mario Cristiano, Jorge Salerno-Uriarte, Tiziana Attisano, Gennaro Galasso, Guido Parodi, Gianfranco Sinagra, Carmine Vecchione, Rodolfo Citro
Journal: JACC. Cardiovascular imaging (2024)
Reduction of circulating IgE and allergens by a pH-sensitive antibody with enhanced FcγRIIb binding
Authors: Na Li, Nanxin Gong, Baoxin Duan, Yongyan Zhang, Yi Jian, Yanqin Xu, Jinming Liu, Xiaoqian Wang, Xiaoqi Zhang, Mingjuan Du, Feilong Zhou, Jiliang Zhao, Xiangchen Guan, Xiangda Peng, Sheng Wang, Hongkai Zhang, Xin Li
Journal: Molecular Therapy (2024)
Decoding the pathogenesis of spermatogenic failure in cryptorchidism through single-cell transcriptomic profiling
Authors: Xiaoyan Wang, Qiang Liu, Ziyan Zhuang, Jianxing Cheng, Wenxiu Zhang, Qiaoling Jiang, Yifei Guo, Ran Li, Xiaojian Lu, Lina Cui, Jiaming Weng, Yanlin Tang, Jingwei Yue, Songzhan Gao, Kai Hong, Jie Qiao, Hui Jiang, Jingtao Guo, Zhe Zhang
Journal: Cell Reports Medicine (2024)
In situ tumor cell engineering reverses immune escape to enhance immunotherapy effect
Authors: Shujun Liu, Shijun Yuan, Meichen Liu, Jinhu Liu, Shunli Fu, Tong Gao, Shuang Liang, Xinyan Huang, Xinke Zhang, Yongjun Liu, Zipeng Zhang, Na Zhang
Journal: Acta Pharmaceutica Sinica B (2024)

The underlying cause of low response rates to existing immunotherapies is that tumor cells dominate tumor immune escape through surface antigen deficiency and inducing tumor immunosuppressive microenvironment (TIME). Here, we proposed an in situ tumor cell engineering strategy to disrupt tumor immune escape at the root by restoring tumor cell MHC-I/tumor-specific antigen complex (MHC-I/TSA) expression to promote T-cell recognition and by silencing tumor cell CD55 to increase the ICOSL+ B-cell proportion and reverse the TIME. A doxorubicin (DOX) and dual-gene plasmid (MAC pDNA, encoding both MHC-I/ASMTNMELM and CD55-shRNA) coloaded drug delivery system (LCPN@ACD) with tumor targeting and charge/size dual-conversion properties was prepared. LCPN@ACD-induced ICD promoted DC maturation and enhanced T-cell activation and infiltration. LCPN@ACD enabled effective expression of MHC-I/TSA on tumor cells, increasing the ability of tumor cell recognition and killing. LCPN@ACD downregulated tumor cell CD55 expression, increased the proportion of ICOSL+ B cells and CTLs, and reversed the TIME, thus greatly improving the efficacy of αPD-1 and CAR-T therapies. The application of this in situ tumor cell engineering strategy eliminated the source of tumor immune escape, providing new ideas for solving the challenges of clinical immunotherapy.
Plasmid-borne tigecycline resistance gene tet(X4) in Salmonella enterica and Escherichia coli isolates from a pediatric patient with diarrhea
Authors: Zelin Yan, Yan Li, Yingling Ni, Xiaoni Xia, Yanyan Zhang, Yuchen Wu, Jing Zhang, Gongxiang Chen, Ruichao Li, Rong Zhang
Journal: Drug Resistance Updates (2024)
Phase III randomized trial comparing neoadjuvant paclitaxel+platinum to 5-fluorouracil+platinum in esophageal/GEJ squamous cell carcinoma
Authors: Vanita Noronha, Vijay Maruti Patil, Nandini Menon, Amit Joshi, Minit Jalan Shah, Ajaykumar Singh, Supriya Goud, Srushti Shah, Sucheta More, Kavita Nawale, Dipti Nakti, Akanksha Yadav, Shweta Jogdhankar, Rajiv Kumar Kaushal, Virendra Kumar Tiwari, Devayani Niyogi, Nilendu Purandare, Amit Janu, Nivedita Chakrabarty, Abhishek Mahajan, Anil Tibdewal, Jaiprakash Agarwal, Akash Pawar, Oindrila Roy Chowdhury, Vibhor Sharma, Venkatesh Kapu, Mehak Trikha, Srigadha Vivek Kumar, Manali Kolkur, Priyanka Bhagyavant, Zoya Peelay, Rutvij Khedkar, Medha Jain, Rajendra Achyut Badwe, Kumar Prabhash
Journal: JNCI Journal of the National Cancer Institute (2024)

Standard neoadjuvant chemotherapy (NACT) for locally advanced esophageal/gastroesophageal junction squamous cancer (LAEGSC), 5-fluorouracil (5FU)+platinum, is toxic and logistically challenging; alternative regimens are needed.
Cancer associated fibroblasts and metabolic reprogramming: unraveling the intricate crosstalk in tumor evolution
Authors: Fusheng Zhang, Yongsu Ma, Dongqi Li, Jianlei Wei, Kai Chen, Enkui Zhang, Guangnian Liu, Xiangyu Chu, Xinxin Liu, Weikang Liu, Xiaodong Tian, Yinmo Yang
Journal: Journal of Hematology & Oncology (2024)

Metabolic reprogramming provides tumors with an energy source and biofuel to support their survival in the malignant microenvironment. Extensive research into the intrinsic oncogenic mechanisms of the tumor microenvironment (TME) has established that cancer-associated fibroblast (CAFs) and metabolic reprogramming regulates tumor progression through numerous biological activities, including tumor immunosuppression, chronic inflammation, and ecological niche remodeling. Specifically, immunosuppressive TME formation is promoted and mediators released via CAFs and multiple immune cells that collectively support chronic inflammation, thereby inducing pre-metastatic ecological niche formation, and ultimately driving a vicious cycle of tumor proliferation and metastasis. This review comprehensively explores the process of CAFs and metabolic regulation of the dynamic evolution of tumor-adapted TME, with particular focus on the mechanisms by which CAFs promote the formation of an immunosuppressive microenvironment and support metastasis. Existing findings confirm that multiple components of the TME act cooperatively to accelerate the progression of tumor events. The potential applications and challenges of targeted therapies based on CAFs in the clinical setting are further discussed in the context of advancing research related to CAFs.