tbuckley/cabot-search huggingface dataset:
68Ga-DOTATATE PET/CT Versus 18F-FDG PET/CT in TENIS Syndrome: A Head-to-Head Comparison With Elevated and Suppressed TSH Levels in Papillary Thyroid Carcinoma—A Pilot Study
Authors: Ludmila Santiago Almeida, Allan Santos, Lígia Assumpção, Tiago Oliveira Costa, Maidane Araujo, Mariana Lima, Denise Engelbrecht Zantut-Wittmann, Elba Etchebehere
Journal: Clinical Nuclear Medicine (2024)

Background TENIS syndrome is characterized by reduced expression of sodium-iodine symporter, rising serum thyroglobulin (Tg) levels, and negative whole-body 131 I scans. In such patients, somatostatin receptor imaging with 68 Ga-DOTATATE PET/CT (somatostatin receptor [SSR] PET/CT) and 18 F-FDG PET/CT (FDG PET/CT) can identify metastases and were compared under 2 conditions: elevated (eTSH) and suppressed (sTSH) TSH serum levels. Potential candidates for peptide receptor radionuclide therapy (PRRNT) were identified in 15 patients prospectively enrolled. All patients underwent 4 examinations. Images were blindly evaluated for differences in SUV max values and lesion detectability. Reference standard consisted of neck ultrasound, CT, MRI, PET/CT, biopsy, and follow-up. Three patients were received PRRNT. Results sTSH SSR PET/CT detected a greater number of cervical ( P = 0.0253 and P = 0.0176) and distant LNs ( P = 0.0253 and P = 0.0391) when compared with sTSH FDG PET/CT, respectively, in a per-patient and on a per-lesion based analysis. Likewise, eTSH SSR PET/CT detected a greater number of patients with local recurrences ( P = 0.0455) and distant LN metastases ( P = 0.0143). Per-lesion analysis revealed greater number of cervical and distant LNs ( P = 0.0337 and P = 0.0039, respectively) when compared with eTSH FDG PET/CT. There was no difference in detection of distant metastases by both tracers for lung and bone metastases (κ = 1). Both skeletal and pulmonary lesions were also detected by conventional CT part of FDG or DOTATATE PET/CT scans. TSH stimulation had no additional value in a per-patient analysis for both FDG and DOTATATE PET scans (κ varying from 0.6087 to 1). However, TSH stimulation led to more lesion identifications in DOTATATE PET/CT; most of those metastases were not confirmed by the reference standard leading to a decrease in specificity (84% vs 74%). One of 3 patients submitted to 3 cycles of PRRNT presented with a visual partial response, a 20% reduction in quantitative analyses, and stable disease regarding Tg and TgAb levels. Conclusions Patients with TENIS syndrome can be imaged with SSR PET/CT as well as FDG PET/CT with high overall accuracy regardless of TSH levels (86% to 92% and 92% to 85%, respectively, with eTSH and sTSH). SSR PET/CT detected a greater number of locoregional and distant LN metastases than FDG PET/CT with both sTSH and eTSH. One of 3 patients submitted to PRRNT presented a partial response to treatment. Our findings may impact in patient restaging, management, and theranostics strategies with radiolabeled somatostatin analogs.
Abdominal Noncontrast Computed Tomography Scanning to Screen for Kidney Cancer and Other Abdominal Pathology Within Community-based Computed Tomography Screening for Lung Cancer: Results of the Yorkshire Kidney Screening Trial
Authors: Grant D Stewart, Angela Godoy, Fiona Farquhar, Jessica Kitt, Jon Cartledge, Michael Kimuli, Sabrina H Rossi, Bethany Shinkins, Simon Burbidge, Sarah W Burge, Iztok Caglic, Emma Collins, Philip A J Crosbie, Claire Eckert, Sheila Fraser, Neil Hancock, Gareth R Iball, Catriona Marshall, Golnessa Masson, Richard D Neal, Suzanne Rogerson, Andrew Smith, Stephen J Sharp, Irene Simmonds, Tom Wallace, Matthew Ward, Matthew E J Callister, Juliet A Usher-Smith
Journal: European Urology (2024)
To PE or Not to PE
Authors: Aamir Ali, Akilan Gopal, Yang Lu
Journal: Clinical Nuclear Medicine (2024)

Abstract A 41-year-old woman with metastatic breast cancer presented with dyspnea, hypoxia, and elevated d -dimer. Perfusion planar imaging followed by SPECT/CT of the chest was performed due to the patient’s iodinated contrast allergy. Planar images showed multiple pleural-based wedge-shaped defects concerning for bilateral pulmonary embolism (PE). Perfusion SPECT/CT of the chest confirmed multiple areas of perfusion defects but was considered negative for PE and attributed the perfusion defects to the compressing of pulmonary vasculature from metastatic lymph nodes and pulmonary masses. Given the high pretest probability of PE, a CT pulmonary angiogram was performed after premedication for contrast allergy confirming absence of PE.
Erratum. A Multicenter Prospective Evaluation of the Benefits of Two Advanced Hybrid Closed-Loop Systems in Glucose Control and Patient-Reported Outcomes in a Real-world Setting. Diabetes Care 2024;47:216–224
Authors: Pilar Isabel Beato-Víbora, Ana Chico, Jesus Moreno-Fernandez, Virginia Bellido-Castañeda, Lia Nattero-Chávez, María José Picón-César, María Asunción Martínez-Brocca, Marga Giménez-Álvarez, Eva Aguilera-Hurtado, Elisenda Climent-Biescas, Sharona Azriel-Mir, Ángel Rebollo-Román, Carmen Yoldi-Vergara, Marcos Pazos-Couselo, Nuria Alonso-Carril, Carmen Quirós
Journal: Diabetes Care (2024)

In the article cited above, affiliation information for author Ana Chico was inadvertently omitted. The complete affiliation list for this author is below.Department of Endocrinology and Nutrition, Hospital Santa Creu i Sant Pau, Barcelona, SpainUniversitat Autònoma de Barcelona, Barcelona, SpainCIBER-BBN, Madrid, Spain The authors apologize for the omission. The online version of the article (https://doi.org/10.2337/dc23-1355) has been revised.
Hypofractionated Dose Escalation Radiotherapy for High-risk Prostate Cancer: The Survival Analysis of the Prostate Cancer Study 5, a Groupe de Radio-oncologie Génito-urinaire du Quebec–led Phase 3 Trial
Authors: Tamim Niazi, Abdenour Nabid, Talia Malagon, Steven Tisseverasinghe, Redouane Bettahar, Rafika Dahmane, Andre-Guy Martin, Marjory Jolicoeur, Michael Yassa, Maroie Barkati, Levon Igidbashian, Boris Bahoric, Robert Archambault, Hugo Villeneuve, Md Mohiuddin
Journal: European Urology (2024)
Beyond bacteria: the growing threat of antifungal resistance
Authors: Norman van Rhijn, Sevtap Arikan-Akdagli, Justin Beardsley, Felix Bongomin, Arunaloke Chakrabarti, Sharon C-A Chen, Tom Chiller, Arnaldo Lopes Colombo, Nelesh P Govender, Ana Alastruey-Izquierdo, Sarah E Kidd, Michaela Lackner, Ruoyu Li, Ferry Hagen
Journal: The Lancet (2024)
Distinct tumor architectures and microenvironments for the initiation of breast cancer metastasis in the brain
Authors: Siting Gan, Danilo G Macalinao, Sayyed Hamed Shahoei, Lin Tian, Xin Jin, Harihar Basnet, Catherine Bibby, James T Muller, Pranita Atri, Evan Seffar, Walid Chatila, Ali Karacay, Pharto Chanda, Anna-Katerina Hadjantonakis, Nikolaus Schultz, Edi Brogi, Tejus A Bale, Nelson S Moss, Rajmohan Murali, Dana Pe'er, Joan Massagué
Journal: Cancer Cell (2024)
B Cell Responses to the Placenta and Fetus
Authors: Gabrielle Rizzuto
Journal: Annual Review of Pathology Mechanisms of Disease (2024)

Pregnancy has fascinated immunologists ever since Peter Medawar's observation that reproduction runs contrary to the founding tenets of immunology. During healthy pregnancy, maternal B cells interact with antigens of the foreign conceptus (placenta and fetus) yet do not elicit rejection. Instead, robust, and redundant fetomaternal tolerance pathways generally prevent maternal B cells and antibodies from harming the placenta and fetus. Fetomaternal tolerance is not absolute, and unfortunately there exist several pregnancy complications that arise from breaks therein. Here, important historic and recent developments in the field of fetomaternal tolerance pertaining to maternal B cells and antibodies are reviewed. General rules from which to conceptualize humoral tolerance to the placenta and fetus are proposed. Significant but underexplored ideas are highlighted and topics for future research are suggested, findings from which are predicted to provide insight into the fundamental nature of tolerance and bolster efforts to combat immune-mediated pregnancy complications.
HEAR-MHE study: Automated speech analysis identifies minimal hepatic encephalopathy and may predict future overt hepatic encephalopathy
Authors: Patricia P. Bloom, Caitlyn J. Fisher, Nicholas Tedesco, Neil Kamdar, Luis Garrido-Trevino, Jessica Robin, Sumeet K. Asrani, Anna S. Lok
Journal: Hepatology (2024)

Background &amp; Aims: Hepatic encephalopathy (HE) is a major cause of poor quality of life in patients with cirrhosis. A simple diagnostic test to identify minimal HE (MHE) and predict future overt HE (OHE) is lacking. We aimed to evaluate if analysis of speech patterns using a modern speech platform: 1) correlates with validated HE tests, 2) correlates with MHE, and 3) predicts future OHE. Approach &amp; Results: In a two-center prospective cohort study of 200 outpatients with cirrhosis and 50 controls, patients underwent baseline speech recording and validated HE diagnostic testing with psychometric HE score (PHES). Patients were followed for 6 months to identify episodes of OHE. 752 speech variables were extracted using an automated speech analysis platform, reflecting the acoustic, lexical, and semantic aspects of speech. Patients with cirrhosis were median 63 years old (IQR 54, 68), 49.5% (99) were female. Over 100 speech variables were significantly associated with PHES ( p &lt;0.05 with FDR adjustment). A three-variable speech model (two acoustic, one speech tempo variable) was similar to animal naming test in predicting MHE (AUC 0.76 vs. 0.69; p =0.11). Adding age and MELD-Na improved accuracy of the speech model (AUC: 0.82). A combined clinical-speech model (“HEAR-MHE model”) predicted time to OHE with a concordance of 0.74 ( p =0.06). Conclusions: Automated speech analysis highly correlated with validated HE tests, associated with MHE, and may predict future OHE. Future research is needed to validate this tool and to understand how it can be implemented in clinical practice.
Circumventing resistance within the Ewing sarcoma microenvironment by combinatorial innate immunotherapy
Authors: Wen Luo, Hai Hoang, Hongwen Zhu, Katherine Miller, Xiaokui Mo, Shiori Eguchi, Meijuan Tian, Yanling Liao, Janet Ayello, Jeremy M Rosenblum, Mario Marcondes, Mark Currier, Elaine Mardis, Timothy Cripe, Dean Lee, Mitchell S Cairo
Journal: Journal for ImmunoTherapy of Cancer (2024)

Background Pediatric patients with recurrent/metastatic Ewing sarcoma (ES) have a dismal 5-year survival. Novel therapeutic approaches are desperately needed. Natural killer (NK) cell number and function are low in ES patient tumors, in large part due to the immunosuppressive tumor microenvironment (TME). Melanoma cell adhesion molecule (MCAM) is highly expressed on ES and associated with ES metastasis. NKTR-255 is a polymer-conjugated recombinant human interleukin-15 (IL-15) agonist improving NK cell activity and persistence. Magrolimab (MAG) is a CD47 blockade that reactivates the phagocytic activity of macrophages. Methods Transcriptome profiling coupled with CIBERSORT analyses in both ES mouse xenografts and human patient tumors were performed to identify mechanisms of NK resistance in ES TME. A chimeric antigen receptor (CAR) NK cell targeting MCAM was engineered by CAR mRNA electroporation into ex vivo expanded NK cells. In vitro cytotoxicity assays were performed to investigate the efficacy of anti-MCAM-CAR-NK cell alone or combined with NKTR-255 against ES cells. Interferon-γ and perforin levels were measured by ELISA. The effect of MAG on macrophage phagocytosis of ES cells was evaluated by in vitro phagocytosis assays. Cell-based and patient-derived xenograft (PDX)-based xenograft mouse models of ES were used to investigate the antitumor efficacy of CAR-NK alone and combined with NKTR-255 and MAG in vivo. Results We found that NK cell infiltration and activity were negatively regulated by tumor-associated macrophages (TAM) in ES TME. Expression of anti-MCAM CAR significantly and specifically enhanced NK cytotoxic activity against MCAM high but not MCAM-knockout ES cells in vitro, and significantly reduced lung metastasis and extended animal survival in vivo. NKTR-255 and MAG significantly enhanced in vitro CAR-NK cytotoxicity and macrophage phagocytic activity against ES cells, respectively. By combining with NKTR-255 and MAG, the anti-MCAM-CAR-NK cell significantly decreased primary tumor growth and prolonged animal survival in both cell- and PDX-based ES xenograft mouse models. Conclusions Our preclinical studies demonstrate that immunotherapy via the innate immune system by combining tumor-targeting CAR-NK cells with an IL-15 agonist and a CD47 blockade is a promising novel therapeutic approach to targeting MCAM high malignant metastatic ES.
Long-term hepatitis B surface antigen response after finite treatment of ARC-520 or JNJ-3989
Authors: Lung Yi Mak, Christine I Wooddell, Oliver Lenz, Thomas Schluep, James Hamilton, Heather L Davis, Xianhua Mao, Wai-Kay Seto, Michael Biermer, Man-Fung Yuen
Journal: Gut (2024)

Background and aims RNA interference has been extensively explored in patients with chronic hepatitis B (CHB) infection. We aimed to characterise the long-term efficacy of small interfering RNA (siRNA) on hepatitis B surface antigen (HBsAg) suppression. Methods We prospectively followed up participants with CHB who received siRNA, either ARC-520 or JNJ-73763989 (JNJ-3989), in combination with nucleoside analogue (NUC) in our centre. Participants enrolled included 15 receiving 4 monthly injections of ARC-520, 38 receiving 3 injections of JNJ-3989 at 1, 2 or 4 weekly intervals and 5 receiving placebo in previous clinical trials. Serial blood sampling was performed according to the original protocols and on completion every 24 weeks until last follow-up (LFU) with mean duration of 52.5 months. Results Among the 53 NUC+siRNA-treated participants (mean age 46.8, baseline HBsAg 3.08 log, 83% previously on NUC, 34% hepatitis B e antigen+), the proportion of patients achieving HBsAg seroclearance or &lt;100 IU/mL at LFU was 1.9% and 32.1%, respectively, compared with 0% and 0% for placebo. Among siRNA-recipients, 48.5% and 5.0% of those with HBsAg &lt;100 IU/mL and &gt;100 IU/mL at nadir or ≤24 weeks from last dose could maintain or achieve HBsAg &lt;100 IU/mL at LFU, respectively. Compared with placebo recipients, siRNA-recipients demonstrated faster overall annual decline of HBsAg (0.08 vs 0.21 log IU/mL/year) contributed predominantly by changes in the first year. Age was negatively correlated with HBsAg reduction at LFU (r=−0.427, p=0.001). Conclusion Short-duration siRNA treatment suppressed HBsAg expression with a prolonged effect for up to 6 years in some participants.
Functional dependence following intensive care unit-treated sepsis: three-year follow-up results from the prospective Mid-German Sepsis Cohort (MSC)
Authors: Carolin Fleischmann-Struzek, Sebastian Born, Miriam Kesselmeier, E Wesley Ely, Kristin Töpfer, Heike Romeike, Michael Bauer, Sven Bercker, Ulf Bodechtel, Sandra Fiedler, Heinrich V Groesdonk, Sirak Petros, Stefanie Platzer, Hendrik Rüddel, Torsten Schreiber, Konrad Reinhart, André Scherag
Journal: The Lancet Regional Health - Europe (2024)
Lactate supports Treg function and immune balance via MGAT1 effects on N-glycosylation in the mitochondria
Authors: Jinren Zhou, Jian Gu, Qufei Qian, Yigang Zhang, Tianning Huang, Xiangyu Li, Zhuoqun Liu, Qing Shao, Yuan Liang, Lei Qiao, Xiaozhang Xu, Qiuyang Chen, Zibo Xu, Yu Li, Ji Gao, Yufeng Pan, Yiming Wang, Roddy O'Connor, Keli L Hippen, Ling Lu, Bruce R Blazar
Journal: Journal of Clinical Investigation (2024)

Current research reports that lactate affects Treg metabolism, although the precise mechanism has only been partially elucidated. In this study, we presented evidence demonstrating that elevated lactate levels enhanced cell proliferation, suppressive capabilities, and oxidative phosphorylation (OXPHOS) in human Tregs. The expression levels of Monocarboxylate Transporters 1/2/4 (MCT1/2/4) regulate intracellular lactate concentration, thereby influencing the varying responses observed in naive Tregs and memory Tregs. Through mitochondrial isolation, sequencing, and analysis of human Tregs, we determined that Alpha-1,3-Mannosyl-Glycoprotein 2-Beta-N-Acetylglucosaminyltransferase (MGAT1) served as the pivotal driver initiating downstream N-glycosylation events involving progranulin (GRN) and hypoxia-upregulated 1 (HYOU1), consequently enhancing Treg OXPHOS. The mechanism by which MGAT1 was upregulated in mitochondria depended on elevated intracellular lactate that promoted the activation of XBP1s, which, in turn, supported MGAT1 transcription as well as the interaction of lactate with the translocase of the mitochondrial outer membrane 70 (TOM70) import receptor, facilitating MGAT1 translocation into mitochondria. Pre-treatment of Tregs with lactate reduced mortality in a xenogeneic graft-versus-host disease (GvHD) model. Together, these findings underscored the active regulatory role of lactate in human Treg metabolism through the upregulation of MGAT1 transcription and its facilitated translocation into the mitochondria.
Gut microbiota-mediated C-sulfonate metabolism impairs the bioavailability and anti-cholestatic efficacy of andrographolide
Authors: Dafu Tang, Wanyu Hu, Bingxuan Fu, Xiaojie Zhao, Guoquan You, Cong Xie, Hong Yu Wang, Xueni Guo, Qianbing Zhang, Zhongqiu Liu, Ling Ye
Journal: Gut Microbes (2024)

Cholestatic liver injury results from the accumulation of toxic bile acids in the liver, presenting a therapeutic challenge with no effective treatment available to date. Andrographolide (AP) has exhibited potential as a treatment for cholestatic liver disease. However, its limited oral bioavailability poses a significant obstacle to harnessing its potent therapeutic properties and restricts its clinical utility. This limitation is potentially attributed to the involvement of gut microbiota in AP metabolism. In our study, employing pseudo-germ-free, germ-free and strain colonization animal models, along with 16S rRNA and shotgun metagenomic sequencing analysis, we elucidate the pivotal role played by gut microbiota in the C-sulfonate metabolism of AP, a process profoundly affecting its bioavailability and anti-cholestatic efficacy. Subsequent investigations pinpoint a specific enzyme, adenosine-5'-phosphosulfate (APS) reductase, predominantly produced by
c-Myc alone is enough to reprogram fibroblasts into functional macrophages
Authors: Shanshan Li, Guoyu Chen, Xia Huang, Yingwen Zhang, Shuhong Shen, Haizhong Feng, Yanxin Li
Journal: Journal of Hematology & Oncology (2024)

Macrophage-based cell therapy is promising in solid tumors, but the efficient acquisition of macrophages remains a challenge. Induced pluripotent stem cell (iPSC)-induced macrophages are a valuable source, but time-consuming and costly. The application of reprogramming technologies allows for the generation of macrophages from somatic cells, thereby facilitating the advancement of cell-based therapies for numerous malignant diseases.
Observational cohort study on safety and efficacy of robotic thyroidectomy with super-meticulous capsular dissection versus open surgery for thyroid cancer: Postoperative dynamic risk assessment of radioactive iodine therapy
Authors: Xiangquan Qin, Yufan Zhang, Jia Luo, Lingjuan Zeng, Xia Liu, Ting Zhang, Lin Ren, Linjun Fan, Dingde Huang
Journal: International Journal of Surgery (2024)
Depth of radiographic response as an independent prognostic factor for patients with initially unresectable hepatocellular carcinoma receiving hepatectomy following targeted therapy plus immunotherapy
Authors: Bin Xu, Lu-Na Wang, Zi-Yi Wang, Tian He, Xiao-Dong Zhu, Ying-Hao Shen, Jian Zhou, Jia Fan, Hui-Chuan Sun, Cheng Huang
Journal: Liver Cancer (2024)

Introduction: Surgical resection following systemic therapy is feasible in patients with initially unresectable hepatocellular carcinoma (HCC). However, postoperative tumor recurrence is common after surgery, and the factors affecting this recurrence remain unclear. This study aimed to assess factors influencing postoperative outcomes in patients with initially unresectable HCC undergoing hepatectomy after systemic therapy. Methods: This study retrospectively enrolled patients with initially unresectable HCC who underwent hepatectomy after targeted therapy plus immunotherapy (with or without locoregional therapy). Multivariate Cox regression analyses were used to identify the independent prognostic factors for recurrence-free survival (RFS) and overall survival (OS). Machine learning was used to determine the RFS rates at different intervals for different radiographic responses. Results: Eighty-one patients who underwent R0 hepatectomy after systemic therapy were included. With a median follow-up of 17.4 (interquartile range: 7.2–22.3) months, median RFS and OS were not reached. Preoperative tumor downstaging and achieving pathological complete response were associated with improved RFS and OS. Multivariate Cox analyses identified radiographic response as an independent prognostic factor for RFS and OS. Furthermore, a radiographic response &gt;40% (assessed using the Response Evaluation Criteria in Solid Tumors, version 1.1) or &gt;50% (assessed using the modified Response Evaluation Criteria in Solid Tumors) was associated with a longer RFS (p = 0.006 and 0.003, respectively). Conclusion: Radiographic response depth was an independent prognostic factor in patients with initially unresectable HCC who underwent hepatectomy following targeted therapy plus immunotherapy, and the response to systemic therapy may be the determining factor for patient prognosis after surgery.
Exploring the feasibility of preoperative tumor-bed boost, oncoplastic surgery, and adjuvant radiotherapy schedule in early-stage breast cancer: A phase II clinical trial
Authors: Hao Dong, Hao Jing, Xiang-Yu Wang, Xiang-Yi Kong, Yi-Peng Wang, Yi-Rui Zhai, Shu-Nan Che, Yi Fang, Shu-Lian Wang, Jing Wang
Journal: International Journal of Surgery (2024)
Targeting Fatty Acid Metabolism Abrogates the Differentiation Blockade in Pre-leukemic Cells
Authors: Xiaoyu Liu, Yu Liu, Qing Rao, Yihan Mei, Haiyan Xing, Runxia Gu, Junli Mou, Manling Chen, Fan Ding, Wanqing Xie, Kejing Tang, Zheng Tian, Min Wang, Shaowei Qiu, Jianxiang Wang
Journal: Cancer Research (2024)

Abstract Metabolism plays a key role in the maintenance of normal hematopoietic stem cells (HSCs) and in the development of leukemia. A better understanding of the metabolic characteristics and dependencies of pre-leukemic cells could help identify potential therapeutic targets to prevent leukemic transformation. As AML1-ETO, one of the most frequent fusion proteins in acute myeloid leukemia that is encoded by a RUNX1::RUNX1T1 fusion gene, is capable of generating pre-leukemic clones, here we used a conditional Runx1::Runx1t1 knock-in mouse model to evaluate pre-leukemic cell metabolism. AML1-ETO expression resulted in impaired hematopoietic reconstitution and increased self-renewal ability. Oxidative phosphorylation and glycolysis decreased significantly in these pre-leukemic cells accompanied by increased HSC quiescence and reduced cell cycling. Furthermore, HSCs expressing AML1-ETO exhibited an increased requirement for fatty acids through metabolic flux. Dietary lipid deprivation or loss of the fatty acid transporter FATP3 by targeted deletion using CRISPR/Cas9 partially restored differentiation. These findings reveal the unique metabolic profile of pre-leukemic cells and propose FATP3 as a potential target for disrupting leukemogenesis.