tbuckley/cabot-search huggingface dataset:
IFN-γ–producing T <sub>H</sub> 1 cells and dysfunctional regulatory T cells contribute to the pathogenesis of Sjögren’s disease
Authors: Yin-Hu Wang, Wenyi Li, Maxwell McDermott, Ga-Yeon Son, George Maiti, Fang Zhou, Anthony Y. Tao, Dimitrius Raphael, Andre L. Moreira, Boheng Shen, Martin Vaeth, Bettina Nadorp, Shukti Chakravarti, Rodrigo S. Lacruz, Stefan Feske
Journal: Science Translational Medicine (2024)

Sjögren’s disease (SjD) is an autoimmune disorder characterized by progressive salivary and lacrimal gland dysfunction, inflammation, and destruction, as well as extraglandular manifestations. SjD is associated with autoreactive B and T cells, but its pathophysiology remains incompletely understood. Abnormalities in regulatory T (T reg ) cells occur in several autoimmune diseases, but their role in SjD is ambiguous. We had previously shown that the function and development of T reg cells depend on store-operated Ca 2+ entry (SOCE), which is mediated by ORAI1 Ca 2+ channels and stromal interaction protein 1 (STIM1) and STIM2. Here, we show that mice with a Foxp3 + T reg cell–specific deletion of Stim1 and Stim2 develop a phenotype that fulfills all classification criteria of human SjD. Mutant mice have salivary and lacrimal gland inflammation characterized by strong lymphocyte infiltration and transcriptional signatures dominated by T helper 1 (T H 1) and interferon (IFN) signaling. CD4 + T cells from mutant mice are sufficient to induce SjD-like disease in an IFN-γ–dependent manner. Inhibition of IFN signaling with the JAK1/2 inhibitor baricitinib alleviated CD4 + T cell–induced SjD in mice. These findings are consistent with the transcriptional profiles of CD4 + T cells from patients with SjD, which indicate enhanced T H 1 but reduced memory T reg cell function. Together, our study provides evidence for a critical role of dysfunctional T reg cells and IFN-γ–producing T H 1 cells in the pathogenesis of SjD.
Reply: A positive step toward cost-effective and accessible HCC detection awaits further validation
Authors: Hashem B. El-Serag, Qingchun Jin, Tayob Nabihah
Journal: Hepatology (2024)

1Section of Gastroenterology and Hepatology, Department of Medicine, Michael E. DeBakey VA Medical Center and Baylor College of Medicine, Houston, Texas, USA 2Department of Data Science, Dana-Farber Cancer Institute, Boston, Massachusetts, USA This research was supported by grants from the NIH NCI (NCI U01 CA230997, U01 CA230694, U01 CA271887, R01 CA190776, P01 CA263025, R01 CA230503, R01 CA237659, and U24 CA230144) and NIDDK (P30 DK056338) and the Cancer Prevention and Research Institute of Texas (CPRIT RP220119, CPRIT RP200554, CPRIT RP190641, and CPRIT RP150587). Abbreviations: AFP, alpha-fetoprotein; AFP-L3, Lens culinaris agglutinin-reactive fraction of AFP; ALT, alanine aminotransferase; DCP, des-gamma-carboxy prothrombin; FPR, false-positive rate; HES, hepatocellular carcinoma early detection screening Correspondence Hashem B. El-Serag, Department of Medicine, Baylor College of Medicine, 7200 Cambridge St., Houston, TX 77030, USA. Email: [email protected]
Striatal stimulation enhances cognitive control and evidence processing in rodents and humans
Authors: Adriano E. Reimer, Evan M. Dastin-van Rijn, Jaejoong Kim, Megan E. Mensinger, Elizabeth M. Sachse, Aaron Wald, Eric Hoskins, Kartikeya Singh, Abigail Alpers, Dawson Cooper, Meng-Chen Lo, Amanda Ribeiro de Oliveira, Gregory Simandl, Nathaniel Stephenson, Alik S. Widge
Journal: Science Translational Medicine (2024)

Brain disorders, in particular mental disorders, might be effectively treated by direct electrical brain stimulation, but clinical progress requires understanding of therapeutic mechanisms. Animal models have not helped, because there are no direct animal models of mental illness. Here, we propose a potential path past this roadblock, by leveraging a common ingredient of most mental disorders: impaired cognitive control. We previously showed that deep brain stimulation (DBS) improves cognitive control in humans. We now reverse translate that result using a set-shifting task in rats. DBS-like stimulation of the midstriatum improved reaction times without affecting accuracy, mirroring our human findings. Impulsivity, motivation, locomotor, and learning effects were ruled out through companion tasks and model-based analyses. To identify the specific cognitive processes affected, we applied reinforcement learning drift-diffusion modeling. This approach revealed that DBS-like stimulation enhanced evidence accumulation rates and lowered decision thresholds, improving domain-general cognitive control. Reanalysis of prior human data showed that the same mechanism applies in humans. This reverse/forward translational model could have near-term implications for clinical DBS practice and future trial design.
Modeling craniopharyngioma for drug screening reveals a neuronal mechanism for tumor growth
Authors: Si Li, Wei Li, Yuqi Miao, Meixi Gao, Yanfei Jia, Zhenhua Chen, Xi Chen, Taotao Pan, Shuangfeng Zhang, Zhifang Xing, Shuping Han, Xue-Lian Sun, Xiaochan Wei, Zhiming Liu, Wentao Zhou, Wentao Wu, Fangzheng Liu, Lei Han, Hongmei Zhu, Hongying Ye, Longqi Liu, Yinqing Li, Peng Zhang, Jian Gong, Yongji Tian, Youwei Ai, Peng Cao, Di Wu, Xiangbing Qi, Songbai Gui, Qing-Feng Wu
Journal: Science Translational Medicine (2024)

Tumors occurring along the hypothalamus-pituitary axis receive axonal projection from neuroendocrine neurons, but it remains unclear whether neuroendocrine neuronal activity drives tumor expansion. Craniopharyngioma is a common suprasellar tumor with a propensity for invading the hypothalamus, leading to devastating endocrine and metabolic disorders. Here, we developed two autochthonous animal models that faithfully recapitulate the molecular pathology, clinical manifestations, and transcriptomic profiles of papillary craniopharyngioma. Using high-throughput drug screening, we identified 74 compounds with potent antitumor efficacy. The administration of (
Reply: Can plasma FSTL-1 levels serve as a reliable biomarker for advanced fibrosis?
Authors: Yongquan Chi, Xiaolong Qi, Jianhua Rao
Journal: Hepatology (2024)

1Hepatobiliary Center of The First Affiliated Hospital, Nanjing Medical University; Research Unit of Liver Transplantation and Transplant Immunology, Chinese Academy of Medical Sciences, Nanjing, Jiangsu 2Liver Disease Center of Integrated Traditional Chinese and Western Medicine, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nurturing Center of Jiangsu Province for State Laboratory of AI Imaging & Interventional Radiology (Southeast University), Nanjing, China; Basic Medicine Research and Innovation Center of Ministry of Education, Zhongda Hospital, Southeast University; State Key Laboratory of Digital Medical Engineering, Nanjing, China Letter to the Editor: How FSTL-1 will function in advanced liver fibrosis? Correspondence Jianhua Rao, Hepatobiliary Center of The First Affiliated Hospital, Nanjing Medical University; Research Unit of Liver Transplantation and Transplant Immunology, Chinese Academy of Medical Sciences, Nanjing, Jiangsu. Email: [email protected]
Blocking IL1RAP on cancer-associated fibroblasts in pancreatic ductal adenocarcinoma suppresses IL-1-induced neutrophil recruitment
Authors: Nils Hansen, Pablo Peña-Martínez, Petter Skoog, Katrin Reinbach, Finja C Hansen, Susanne Larsson Faria, Caitríona Grönberg, Kawther Abdilleh, Susanne Magnusson, Karin von Wachenfeldt, Camilla Rydberg Millrud, David Liberg, Marcus Järås
Journal: Journal for ImmunoTherapy of Cancer (2024)

Background Pancreatic ductal adenocarcinoma (PDAC) represents a major clinical challenge due to its tumor microenvironment, which exhibits immune-suppressive properties that facilitate cancer progression, metastasis, and therapy resistance. Interleukin 1 (IL-1) signaling has been implicated as a driver in this process. Mechanistically, both IL-1α and IL-1β bind to the IL-1 receptor type 1, forming a complex with IL-1-receptor accessory protein (IL1RAP), which triggers downstream signaling pathways. The IL1RAP blocking antibody nadunolimab is currently in clinical development, but the precise consequences of inhibiting IL-1 signaling in PDAC remains elusive. Methods To evaluate the biological relevance of blocking IL1RAP using nadunolimab in a PDAC animal model, human PDAC cells and cancer-associated fibroblasts (CAFs) were co-transplanted into mice. To study the underlying mechanisms of IL1RAP blockade ex vivo, co-cultured PDAC cells and CAFs were treated with nadunolimab prior to RNA sequencing. Migration assays were performed to assess how nadunolimab affects interactions between CAFs and myeloid immune cells. Finally, to establish a clinical correlation between IL1RAP expression and nadunolimab treatment effects, we analyzed tumor biopsies from a clinical phase I/II study in which nadunolimab was administered to patients. Results In the xenograft mouse model, nadunolimab exhibited antitumor effects only when human CAFs were co-transplanted with PDAC cells. IL-1 stimulation induced CAFs to secrete chemokines that recruited neutrophils and monocytes. The secretion of this chemokine and the migration of myeloid cells were inhibited by nadunolimab. Media conditioned by IL-1-stimulated CAFs sustained a neutrophil population with a tissue invasion phenotype, an effect that was reversed by nadunolimab. In a cohort of metastatic late-stage PDAC patients receiving nadunolimab as monotherapy, high IL1RAP expression in tumors was associated with extended progression-free survival. Conclusions Our study demonstrates that targeting IL1RAP on CAFs inhibits IL-1-induced chemokine secretion and recruitment of neutrophils and monocytes, thereby counteracting the immunosuppressive microenvironment in PDAC. These findings highlight the therapeutic potential of targeting IL1RAP in PDAC.
Reply to the commentary on “laparoscopic anatomical versus non-anatomical hepatectomy in the treatment of hepatocellular carcinoma: a randomised controlled trial”
Authors: Ke-Xi Liao, Li Cao, Shu-Guo Zheng
Journal: International Journal of Surgery (2024)

Institute of Hepatobiliary Surgery, First Affiliated Hospital, Army Medical University, Chongqing, China *Corresponding author. Address: Institute of Hepatobiliary Surgery, First Affiliated Hospital, Army Medical University, 30 Gaotanyan Main Street, Shapingba District, Chongqing 400038, China. Tel: +86 02368765707. E-mail address: [email protected] (S. Zheng). Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article. This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
Artificial intelligence in surgery: evolution, trends, and future directions
Authors: Huiyang Li, Zhuoqi Han, Haixiao Wu, Elmar R. Musaev, Yile Lin, Shu Li, Alexander D. Makatsariya, Vladimir P. Chekhonin, Wenjuan Ma, Chao Zhang
Journal: International Journal of Surgery (2024)

Artificial intelligence (AI) is significantly transforming surgery by enhancing precision, decision-making, and patient outcomes. This bibliometric analysis examines AI’s impact on surgery, highlighting research trends, key contributors, and evolving themes from 1998 to 2024. Utilizing data from the Web of Science Core Collection and analyzed through the Bibliometrix tool, the study reviews publication trends, author impact, institutional contributions, country-specific research activities, and keyword frequency. A total of 821 articles were examined, revealing a 14.53% annual growth rate in publications, increasing from one in 1998 to 328 in 2023. Influential contributors include 10,157 authors, notably HASHIMOTO DA and ITO M. Prominent institutions such as Harvard University and Stanford University, along with leading countries like the USA and China, play major roles in this field. High-frequency keywords identify core research areas: surgery, artificial intelligence, classification, diagnosis, and outcomes. Thematic evolution shows a shift from foundational concepts to advanced applications and interdisciplinary collaborations. AI integration into surgical practices is revolutionizing the field, driving advancements in precision, efficiency, and patient care. The study underscores significant research growth, influential contributors, and key trends, emphasizing the importance of continued interdisciplinary collaboration and innovation. Future research should focus on enhancing AI applications, addressing data quality and security challenges, and expanding into diverse surgical contexts to further improve surgical outcomes and patient care. AI in surgery is a rapidly evolving and promising field for innovation, with its full potential reliant on enhanced collaboration across disciplines.
Colonization of stenotrophomonas and its associated microbiome between paired primary colorectal cancers and their lung metastatic tumors. (experimental studies)
Authors: Xiaolan Zhang, Cheng Kong, Ke Chen, Jianqiang Liu
Journal: International Journal of Surgery (2024)

The role of gut microbiome in CRC lung metastases is still unclear. Herein, we collected primary colorectal tumors, matched lung metastasis, and adjacent normal colon from 7 patients for 16S rRNA sequencing to evaluate microbiome signature in distant site metastasis and analyze prognosis. Fecal samples from 19 non-metastases CRC patients and 11 CRC lung metastases patients were analyzed for validation. Our efforts led to a discovery of comprehensive microbiome in CRC lung metastatic tumors, characterized by a decreased microbial diversity and an increase bacterial interaction between gram-negative bacteria Stenotrophomonas and Brevundimonas . The primary-metastatic tumor pairs harbored highly similar microbial composition in both genus and species level, especially the high level of Stenotrophomonas maltophilia . Correspondingly, the S.maltophilia levels were positively associated with poor prognosis and cancer progression. Our work highlights the great potential of S.maltophilia and its associated microbiome as biomarkers in pathogenesis and prognosis of CRC lung metastases.
Adipose Stem Cells Prevent Esophageal Strictures After Extensive Endoscopic Submucosal Dissection-Experimental Research
Authors: Jie Liu, Yuting Jiang, Xianzeng Chen, Xujin Wei, Xiangyu Wang, Zeliang Yang, Jie Yang, Jianhui Zhang, Yunyi Peng, Caihao Lin, Qilin Chen, Genmiao Yu, Yangyang Chen, Qingqing Wei, Xiaoling Zheng, Shengwu Zheng
Journal: International Journal of Surgery (2024)

Background and aims: Endoscopic submucosal dissection (ESD) is a pivotal technique for excision of early-stage esophageal tumors. However, its primary complication, postoperative esophageal stricture, is a significant challenge owing to the absence of effective preventive measures. Adipose-derived stem cells (ADSCs) have emerged as a promising treatment modality to address this concern. In this study, we aimed to investigate, for the first time, the efficacy of allogenic ADSC injections in preventing esophageal stenosis after ESD. Methods: We administered allogeneic ADSC injections ((same-species but different individual)) to a porcine model of ESD as a way to observe the role of ADSC in preventing esophageal stricture. We also co-cultured rats ADSCs with rats esophageal fibroblasts and esophageal mucosal epithelial cells to investigate the mechanism. Results: ADSCs notably facilitated epithelial-mesenchymal transition (EMT) of epithelial cells. Furthermore, ADSC-conditioned medium exhibited a substantial inhibitory effect on fibroblast proliferation and migration, which was mediated by the transforming growth factor-beta pathway. Conclusions: Our findings underscore the potential of ADSC injections as a promising therapeutic intervention to enhance recovery and prevent post-ESD complications.
Quantification of valvular regurgitation by transthoracic 3D high pulse repetition frequency Doppler echocardiography
Authors: Erik Andreas Rye Berg, Stefano Fiorentini, Jørgen Avdal, Bjørnar Grenne, Knut Haakon Stensæth, Peter Thomas While, Torvald Espeland, Rune Wiseth, Hans Torp, Svend Aakhus
Journal:  (2024)

Abstract Aims To improve quantification of valvular regurgitation, a 3D high-pulse repetition frequency Doppler (3D HPRFD) method was developed for regurgitant volume (RVol) estimation from transthoracic echocardiography (TTE). Although successfully applied in vitro and in selected clinical cases, a systematic clinical validation of 3D HPRFD has not been published. Hence, our aims were to investigate (i) feasibility of 3D HPRFD and (ii) correlation between 3D HPRFD and RVol estimates obtained by the 2D proximal isovelocity surface area (PISA) method and cardiac magnetic resonance (CMR) in patients with either aortic regurgitation (AR) or mitral regurgitation (MR). Methods and results We included 45 patients with AR (42% mild, 40% moderate, and 18% severe) and 45 with MR (67% mild, 24% moderate, and 9% severe). Median time between start of TTE and start of CMR was 1.5 h, minimizing changes in load. Overall feasibility of 3D HPRFD was 56% in AR and 44% in MR. Feasibility was only 25% in patients with severe regurgitation. In AR, estimated RVol from 3D HPRF did not correlate with estimated RVol from PISA or CMR [Spearman rho = 0.06 (P = 0.78) and 0.04 (P = 0.4), respectively]. In MR, RVol estimates from 3D HPRFD correlated with PISA (rho = 0.72, P &amp;lt; 0.001) but not with CMR (rho = 0.31, P = 0.43). Conclusion Regurgitant volume estimation by 3D HPRFD had a low feasibility, especially in severe regurgitation, and in general correlated poorly with PISA and CMR estimates. In its current state, 3D HPRFD is not ready for clinical use.
Aberration correction – impact on image quality and chamber quantification in transthoracic echocardiography
Authors: Erik Andreas Rye Berg, Torvald Espeland, Håvard Dalen, Bjørnar Grenne, Tore Grüner Bjåstad, Espen Holte, Svein-Erik Måsøy
Journal:  (2024)

Abstract Aims To improve image quality (IQ) in echocardiography, an aberration correction (AC) algorithm has recently been implemented in commercial scanners. We aimed to study (i) the correlation of a subjective IQ-score and an objective IQ-metric [global image coherence (GIC)], (ii) if AC improved IQ; (iii) if AC affected average values and interobserver agreement of left ventricular (LV) size, LV longitudinal strain, and left atrial (LA) volume. Methods and results From 50 adult patients, where 45 (90%) had cardiovascular disease, unprocessed image data (channel data) were acquired from six standard transthoracic views. The data were processed with and without AC, resulting in 300 pairs of cine-loops. The cine-loops were randomly presented one-by-one to two blinded raters experienced in echocardiography. Both raters scored IQ subjectively from 1 (poor) to 4 (very good) and quantified LV dimensions, volumes and longitudinal strain, and LA volume. IQ-score correlated with GIC, Spearman rho 0.72, P &amp;lt; 0.001. AC improved median IQ-score from 2.5 to 3.0 (Wilcoxon signed rank: P &amp;lt; 0.001). The differences in average values of LV size, LV longitudinal strain, or LA volume with and without AC were not statistically significant and numerically minimal. Measured by intraclass correlation, interobserver agreement of these values was not significantly affected by AC. Conclusion Image quality-score strongly correlated with GIC. Aberration correction improved IQ. However, AC did not lead to statistically significant changes in average values or interobserver agreement of LV size, LV longitudinal strain or LA volume quantification. Likely, the major benefit of AC is enhanced visualization of anatomical details.
Left Ventricular Dimensions and Clinical Outcomes With a Fully Magnetically Levitated Left Ventricular Assist Device
Authors: Ezequiel J Molina, Mustafa M Ahmed, Farooq H Sheikh, Joseph C Cleveland, Daniel J Goldstein, Nir Y Uriel, AiJia Wang, Jordan J Revis, Mandeep R Mehra
Journal: JACC Heart Failure (2024)
Endpoint Selection in Randomized Clinical Trials for Hypertrophic Cardiomyopathy
Authors: Alberto Aimo, Iacopo Olivotto, Giancarlo Todiere, Andrea Barison, Giorgia Panichella, Mona Fiuzat, Cecilia Linde, Neal K. Lakdawala, Milind Desai, Faiez Zannad, Martin S. Maron
Journal: JACC Heart Failure (2024)
Bortezomib-releasing silica-collagen xerogels for local treatment of osteolytic bone- and minimal residual disease in multiple myeloma
Authors: Dirk Hose, Seemun Ray, Sina Rößler, Ulrich Thormann, Reinhard Schnettler, Kim de Veirman, Thaqif El Khassawna, Christian Heiss, Anne Hild, Daniel Zahner, Francisca Alagboso, Anja Henss, Susanne Beck, Martina Emde-Rajaratnam, Jürgen Burhenne, Juliane Bamberger, Eline Menu, Elke de Bruyne, Michael Gelinsky, Marian Kampschulte, Marcus Rohnke, Sabine Wenisch, Karin Vanderkerken, Thomas Hanke, Anja Seckinger, Volker Alt
Journal: Journal of Hematology & Oncology (2024)
Prognostic Impact of Diaphragm Thickness in Geriatric Patients With Heart Failure
Authors: Nobuyuki Kagiyama, Kentaro Kamiya, Misako Toki, Hiroshi Saito, Kentaro Iwata, Yuya Matsue, Kenji Yoshioka, Kazuya Saito, Takeshi Kitai, Emi Maekawa
Journal: JACC. Cardiovascular imaging (2024)
Clinical and Proteomic Risk Profiles of New-Onset Heart Failure in Men and Women
Authors: Hailun Qin, Jasper Tromp, Jozine M Ter Maaten, Geert H D Voordes, Bart J van Essen, Mark André de la Rambelje, Camilla C S van der Hoef, Bernadet T Santema, Carolyn S P Lam, Adriaan A Voors
Journal: JACC Heart Failure (2024)
Leslie Bow Bartlet
Authors: Cathy Hill, Victoria McGrigor, Josie Brown
Journal: BMJ (2024)

Chase D. Brownstein1,*, Thomas J. Near1,2 and Richard P. Dearden3,4Department of Ecology and Evolutionary Biology, Yale University, New Haven CT, USAYale Peabody Museum, New Haven CT, USAVertebrate Evolution, Development, and Ecology, Naturalis Biodiversity Center, Darwinweg 2, Leiden, 2333 CR, The NetherlandsSchool of Geography, Earth & Environmental Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK↵Corresponding author: chase.brownstein{at}yale.edu