tbuckley/cabot-search huggingface dataset:
Decoding the complexity: mechanistic insights into comorbidities in idiopathic pulmonary fibrosis
Authors: Moisés Selman, Ivette Buendía Roldán, Annie Pardo
Journal: European Respiratory Journal (2025)

The complex pathogenic relationships between idiopathic pulmonary fibrosis (IPF) and its usually associated comorbidities remain poorly understood. While evidence suggests that some comorbidities may directly influence the development or progression of IPF or vice versa, whether these associations are causal or arise independently due to shared risk factors, such as aging, smoking, lifestyle, and genetic susceptibility, is still uncertain. Some comorbidities, such as metabolic syndromes, gastro-esophageal reflux disease, and obstructive sleep apnea, precede the development of IPF. In contrast, others, like pulmonary hypertension or lung cancer, often become apparent after its onset or during its progression. These timing patterns suggest a directional relationship in their associations. The issue is further complicated by the fact that patients often have multiple comorbidities, which may interact and exacerbate one another, creating a vicious cycle. To clarify these correlations, some studies have used causal inference methods ( e.g. , Mendelian randomisation) and exploration of underlying mechanisms; however, these efforts have not yet generated conclusive insights. In this review, we provide a general overview of the relationship between IPF and its comorbidities, emphasizing the pathogenic mechanisms underlying each comorbidity, potential shared pathobiology with IPF, and, when available, causal insights from Mendelian randomisation studies.
Purging of highly deleterious mutations through an extreme bottleneck
Authors: Oliver P Stuart, Rohan Cleave, Kate Pearce, Michael J L Magrath, Alexander S Mikheyev
Journal: Molecular Biology and Evolution (2025)

Abstract Transitions to captivity often produce population bottlenecks. On one hand, bottlenecks increase inbreeding and decrease effective population size, thus increasing extinction risk. On the other, elevated homozygosity associated with inbreeding may purge deleterious mutations. Previous empirical studies of purging in captive breeding programs have focused on phenotypic measurements. We test natural selection’s ability to purge deleterious mutations following an extreme population bottleneck by analysing patterns of genetic diversity in wild and captive-bred individuals of the Lord Howe Island stick insect, Dryococelus australis. Dryococelus australis has been bred in captivity for two decades, having passed through an extreme bottleneck – only two mating pairs with few new additions since then. The magnitude of the bottleneck together with high female fecundity but low offspring recruitment set up nearly ideal conditions for the purging of deleterious mutations. As expected, captive-bred individuals had a greater number of long runs-of-homozygosity compared to wild individuals, implying strong inbreeding in captivity which would facilitate purging in homozygous regions. Stop-codon mutations were preferentially depleted in captivity compared to other mutations in coding and non-coding regions. The more deleterious a mutation was predicted to be, the more likely it was found outside of runs-of-homozygosity, implying that inbreeding facilitates the expression and thus removal of deleterious mutations, even after such an extreme bottleneck and under the benign conditions of captivity. These data implicate inbreeding and recessive deleterious mutation load in fitness variation among captive and wild D. australis.
Hyaluronan network remodeling by ZEB1 and ITIH2 enhances the motility and invasiveness of cancer cells
Authors: Sieun Lee, Jihye Park, Seongran Cho, Eun Ju Kim, Seonyeong Oh, Younseo Lee, Sungsoo Park, Keunsoo Kang, Dong Hoon Shin, Song Yi Ko, Jonathan M Kurie, Young-Ho Ahn
Journal: Journal of Clinical Investigation (2025)

Hyaluronan (HA) in the extracellular matrix promotes epithelial-to-mesenchymal transition (EMT) and metastasis; however, the mechanism by which the HA network constructed by cancer cells regulates cancer progression and metastasis in the tumor microenvironment (TME) remains largely unknown. In this study, inter-alpha-trypsin inhibitor heavy chain 2 (ITIH2), an HA-binding protein, was confirmed to be secreted from mesenchymal-like lung cancer cells when co-cultured with cancer-associated fibroblasts. ITIH2 expression is transcriptionally upregulated by the EMT-inducing transcription factor ZEB1, along with HA synthase 2 (HAS2), which positively correlates with ZEB1 expression. Depletion of ITIH2 and HAS2 reduced HA matrix formation and the migration and invasion of lung cancer cells. Furthermore, ZEB1 facilitates alternative splicing and isoform expression of CD44, an HA receptor, and CD44 knockdown suppresses the motility and invasiveness of lung cancer cells. Using a deep learning-based drug-target interaction algorithm, we identified an ITIH2 inhibitor (sincalide) that inhibited HA matrix formation and migration of lung cancer cells, preventing metastatic colonization of lung cancer cells in mouse models. These findings suggest that ZEB1 remodels the HA network in the TME through the regulation of ITIH2, HAS2, and CD44, presenting a strategy for targeting this network to suppress lung cancer progression.
4-1BB stimulation with concomitant inactivation of adenosine A2B receptors enhances CD8+ T cell antitumor response
Authors: Jihae Ahn, Ping Xie, Siqi Chen, Guilan Shi, Jie Fan, Minghui Zhang, Hui Tang, Amanda R Zuckerman, Deyu Fang, Yong Wan, Timothy M Kuzel, Yi Zhang, Bin Zhang
Journal: Journal of Clinical Investigation (2025)

Activating the immune co-stimulatory receptor 4-1BB (CD137) with agonist antibody binding and crosslinking-inducing agents that elicit 4-1BB intracellular signaling potentiates the antitumor responses of CD8 T cells. However, the underlying in-depth mechanisms remain to be defined. Here, we show that agonistic 4-1BB treatment of activated CD8+ T cells under continuous antigenic stimulation are more metabolically vulnerable to redox perturbation by ablation of intracellular glutathione (GSH) and glutathione peroxidase 4 (GPX4) inhibition. Further, genetic deletion of adenosine A2B receptor (A2BR) induces superior survival and expansion advantage of competent CD8+ T cells with agonistic 4-1BB costimulation, leading to more effective antitumor efficacy of adoptive cell therapy (ACT). Mechanistically, A2BR deletion helps sustain the increased energy and biosynthetic requirements through the GSH-GPX4 axis upon 4-1BB costimulation. A2BR deletion in combination with agonistic 4-1BB costimulation displays a greater ability to promote antitumor CD8+ effector T cell survival and expansion while mitigating T cell exhaustion. Thus, the A2BR pathway plays an important role in metabolic reprogramming with potentiation of the GSH-GPX4 cascade upon agonistic 4-1BB costimulation that allows the fine-tuning of the antitumor responses of CD8+ T cells.
Multimodal Imaging Demonstrated a Case of Buccal Cancer Cardiac Metastases Treated With Immune Checkpoint Inhibitor Therapy
Authors: Chien-Cheng Wang, Hsueh-Ju Lu, Teng-Fu Tsao, Wun-Zhih Siao, Pan-Fu Kao
Journal: Clinical Nuclear Medicine (2025)

A 35-year-old man with recurrent oral cancer underwent restaging FDG PET/CT imaging, which revealed neck lymph node metastasis and multiple distant metastases, including involvement of the right atrium, right ventricle, and pericardium. Doppler echocardiography and cardiac MRI confirmed the cardiac metastases while demonstrating preserved left ventricular systolic function. Follow-up FDG PET/CT imaging at 3 and 6 months after immune checkpoint inhibitor therapy, initiated due to high PD-L1 expression in the primary tumor, showed complete remission.
Evaluation of Cerebrovascular Reserve Using Basal/Acetazolamide Stress Brain Perfusion SPECT to Confirm Surgery in a Pediatric Moyamoya Disease
Authors: Julien Todeschi, Guillaume Dannhoff, Agathe Chammas, Izzie Jacques Namer, Caroline Bund
Journal: Clinical Nuclear Medicine (2025)

We report the case of a 6-year-old girl with Moyamoya disease and Alagille syndrome (JAGGED1 mutation). She presented left hemiparesis and central left facial paralysis due to an ischemic stroke in the right middle cerebral artery territory. Basal/acetazolamide stress brain perfusion SPECT showed decreased cerebral perfusion and cerebrovascular reserve in all the carotid artery territory, which can be improved by indirect bypass surgery. Ten months after surgery, the child no longer had a stroke, general condition has improved significantly, as has her school performance. Control SPECT showed successful revascularization visualized by significant improvement in cerebral perfusion and cerebrovascular reserve.
Prenatal and childhood phthalate mixtures and adolescent sleep health in The HOME Study
Authors: Clara G. Sears, Jessie P. Buckley, Kim M. Cecil, Heidi J. Kalkwarf, Yingying Xu, Aimin Chen, Kimberly Yolton, Joseph M. Braun
Journal: Environmental Health Perspectives (2025)

The biological mechanisms linking early life phthalate exposure with adverse behaviors and cardiometabolic conditions also impact sleep health, but whether early-life exposure impacts adolescent sleep is unknown. We evaluated whether gestational and childhood urinary phthalate metabolite mixtures were associated with sleep characteristics during adolescence. We also examined periods of heightened susceptibility to individual phthalates. In the HOME Study (Cincinnati, Ohio; 2003-2006; n=156), we quantified urinary metabolites of 8 parent phthalate diesters during pregnancy (16- and 26-weeks) and childhood (ages 1-, 2-, 3-, 4-, 5-, 8-, and 12-years). Using regression-calibration approaches, we estimated average measurement-error corrected phthalate metabolite concentrations during pregnancy and childhood. We used wrist-actigraphy to assess sleep characteristics for one-week among participants at age 12. Using quantile-based g-computation, we estimated covariate-adjusted differences in sleep efficiency (%), sleep fragmentation index scores (%), and sleep duration (minutes) per quartile increase in all phthalate metabolite concentrations (Ψ), and weights indicating the contribution of each metabolite to Ψ. Using multiple informant models, we examined whether associations between individual phthalate metabolites and sleep characteristics varied by timing of exposure. Increasing all gestational phthalate metabolites by a quartile was associated with lower sleep efficiency (Ψ = -1.3%; 95%CI= -2.4, -0.3) and higher sleep fragmentation (Ψ =1.6%; 95%CI=0.3, 3.0); mono-n-butyl phthalate (MnBP) and di(2-ethylhexyl) phthalate (DEHP) metabolites contributed most to these relations. Higher childhood phthalate metabolite mixture quartiles were associated with shorter sleep duration (Ψ = -21 minutes; 95%CI= -34, -9); monoethyl phthalate (MEP) and monocarboxyoctyl phthalate (MCOP) contributed most to this association. We found that higher DEHP metabolite concentrations during pregnancy were more strongly related with higher sleep fragmentation than childhood concentrations. In contrast, higher MEP and MnBP concentrations during childhood, but not pregnancy, were consistently associated with shorter sleep duration. Phthalate metabolite concentrations during pregnancy and childhood were associated with poorer adolescent sleep health. https://doi.org/10.1289/EHP15221.
Time-Resolved T1 and T2 Contrast for Enhanced Accuracy in MRI Tumor Detection
Authors: Zhongzhong Lu, Jincong Yan, Jianxian Zeng, Ruihao Zhang, Mingsheng Xu, Jihuan Liu, Lina Sun, Guangyue Zu, Xiaomin Chen, Ye Zhang, Renjun Pei, Yi Cao
Journal: Biomaterials (2025)
Recommendations for cardiac screening and emergency action planning in youth football: a FIFA consensus statement
Authors: Aaron L Baggish, Mats Borjesson, Guido E Pieles, Christian Schmied, Clea Simone Sabino de Souza Colombo, Cecilia Gonzales Corcia, Jonathan A Drezner, Katharina Grimm, Gary Mak, André La Gerche, Ben Levine, Sabiha Gati, Andrew Massey, Prince Pambo, Antonio Pelliccia, Margot Putukian, Yasser Abdelrahman, Sanjay Sharma, Mathew G Wilson, Andreas Serner
Journal: British Journal of Sports Medicine (2025)

Sudden cardiac death is the leading medical cause of death among football players. Determining the optimal cardiac screening, the use of carefully selected medical assessments to detect underlying cardiovascular conditions associated with sudden cardiac arrest/death, is a desired objective of the Fédération Internationale de Football Association (FIFA) for football players of all ages. To date, cardiac screening recommendations in football have primarily focused on adult competitive players. Acknowledging its responsibility for player health worldwide, FIFA convened an international working group of cardiology and sports medicine experts to develop cardiac screening recommendations for youth football players. This group performed structured literature reviews and ultimately congregated in January of 2024, when recommendations were presented, scrutinised and judged using a systematic process. The final FIFA recommendations for youth cardiac screening include personal medical history, family medical history, focused physical examination and resting 12-lead electrocardiography. This document provides detailed rationale and clinical recommendations for youth cardiac screening and emphasises the importance of emergency action planning.
Correction: Portal versus peripheral circulating tumor cells as prognostic biomarkers in patients with stage I–III pancreatic ductal adenocarcinoma
Authors: Thaninee Prasoppokakorn, Roongruedee Chaiteerakij, Areeya Buntho, Praewphan Ingrungruanglert, Nipan Israsena, Wiriyaporn Rittitid, Phonthep Angsuwatcharakon, Parit Mekaroonkamol, Pradermchai Kongkam, Rungsun Rerknimitr
Journal: Endoscopy (2025)
Prognostic Impact of Quantitative Changes Between Baseline and Interim 18F-FDG PET/CT in Pediatric Classic Hodgkin Lymphoma
Authors: Mehmet Oğuz Kartal, Ayşenur Sinem Kartal, Burçak Kurucu, Derya Özyörük, Gürses Şahin, Nedim C.M. Gülaldi
Journal: Clinical Nuclear Medicine (2025)

Purpose: 18 F-FDG PET/CT plays a crucial role in the evaluation and management of pediatric classic Hodgkin lymphoma (cHL). In addition to visual assessment, quantitative parameters also have prognostic value. This study aimed to investigate the prognostic significance of PET parameters, with a particular focus on the changes observed in these parameters after 2 cycles of chemotherapy, in pediatric cHL patients. Patients and Methods: The study was designed as a single-center, retrospective. A total of 198 pediatric cHL patients who underwent baseline and post-2-cycle chemotherapy interim 18 F-FDG PET/CT imaging between January 2019 and October 2023 were included in the study. Four different segmentation methods (%41 SUVmax, %42 SUVmax, mediastinal SUVmax, and liver SUVmax) were applied. Quantitative parameters, including metabolic tumor volume (MTV), total lesion glycolysis (TLG), and their changes after 2 chemotherapy cycles (ΔMTV, ΔTLG), were evaluated for each segmentation method. The prognostic significance of these parameters for progression-free survival (PFS) was assessed using Cox regression analysis, while survival differences based on optimal cutoff values were evaluated using Kaplan-Meier analysis. Results: A total of 48 pediatric cHL patients (32 males, median age: 12 y) met the inclusion criteria. During a median follow-up of 21 months (range: 5–52 mo), disease progression was observed in 22.9% of the patients (n=11). Baseline 18 F-FDG PET/CT quantitative parameters did not show significant differences between progression and nonprogression groups. However, on interim 18 F-FDG PET/CT, higher values of quantitative parameters from 3 segmentation methods (%41 SUVmax, %42 SUVmax, and mediastinal SUVmax) and lower postchemotherapy reductions in ΔSUVmax, ΔMTV (41) , ΔMTV (42) , ΔTLG (41) , and ΔTLG (med) were associated with poor PFS. In multivariate Cox regression analysis, i-SUVmax (Hazard ratio, HR: 1.20, P &lt;0.001) and ΔMTV (41) (HR: 0.965, P =0.007) were identified as independent risk factors for PFS. Conclusions: Interim 18 F-FDG PET parameters and postchemotherapy changes demonstrated significant prognostic value. Quantitative evaluation beyond visual assessment may contribute to risk-adapted and personalized treatment approaches in pediatric cHL.
Head-to-Head Comparison of 68Ga-FAPI-04 and 18F-FDG PET/CT for the Assessment of Crohn’s Disease
Authors: Qingqing Pan, Hui Xu, Silu Liu, Hongzhe Zhang, Shengyu Zhang, Ji Li, Fang Li, Yaping Luo
Journal: Clinical Nuclear Medicine (2025)

Background: Crohn disease is a chronic granulomatous inflammatory disease of gastrointestinal tract. Previous studies showed Crohn disease strictures overexpress fibroblast activation protein and had active 68 Ga-FAPI-04 uptake. Our study was to compare the diagnostic performance of 68 Ga-FAPI-04 and 18 F-FDG PET/CT in Crohn disease. Patients and Methods: This is a prospective cohort study recruiting patients with newly diagnosed or relapsed Crohn disease. All the patients underwent 68 Ga-FAPI-04 and 18 F-FDG PET/CT. The diagnostic performance of the 2 PET/CT modalities and their uptake values were compared. The correlation of PET semiquantitative parameters [metabolic intestinal volume (MIV FDG and MIV FAPI ), total intestinal uptake (TIU FDG and TIU FAPI )] with clinical biomarkers were also analyzed. Results: Seventeen participants (13 men and 4 women, age 32.3 ± 15.9 y) were recruited. The sensitivity of 68 Ga-FAPI-04 and 18 F-FDG PET/CT in detecting Crohn lesions were 90.0% and 85.0%, and the specificities were 93.0% and 88.4%, respectively. In receiver operating characteristic curve analysis, 68 Ga-FAPI-04 PET/CT [area under the curve = 0.92 (95% CI: 0.83–0.97), P &lt; 0.001] showed better diagnostic performance compared with 18 F-FDG PET/CT [area under the curve = 0.87 (95% CI: 0.78–0.93), P &lt; 0.001; P = 0.043]. The SUVmax of 68 Ga-FAPI and 18 F-FDG in stricture/fistula lesions were significantly higher than those in non-stricture/fistula lesions ( 68 Ga-FAPI, 10.9 ± 6.7 vs 5.0 ± 3.5, P = 0.0002; 18 F-FDG, 9.5 ± 4.9 vs 5.3 ± 1.8, P = 0.0016). TIU FAPI and MIV FAPI of 68 Ga-FAPI-04 PET/CT were significantly correlated with high sensitivity C-reactive protein and simple endoscopic score for Crohn disease ( P &lt; 0.05). TIU FDG and MIV FDG of 18 F-FDG PET/CT were also correlated with simple endoscopic scores for Crohn disease ( P &lt; 0.05). Conclusions: 68 Ga-FAPI-04 PET/CT showed better diagnostic performance than 18 F-FDG PET/CT in Crohn disease.
Prediction of Cerebral Hyperperfusion Syndrome After Combined Bypass Surgery in Moyamoya Disease Using Hemodynamic and Clinical Data
Authors: Min-Kyung Jung, Eun Jin Ha, Jin Hyung Kim, Young Sill Kang, Yuwhan Chung, Jeong Eun Kim, Hakseung Kim, Dong-Joo Kim, Won-Sang Cho
Journal: Clinical Nuclear Medicine (2025)

Purpose: Cerebral hyperperfusion syndrome (CHS) is a postoperative complication in moyamoya disease (MMD). However, limited studies have investigated the association between preoperative hemodynamic features and postoperative CHS. In this study, we aimed to identify the predictors of postoperative CHS in MMD using preoperative hemodynamic and clinical data. Patients and Methods: In this retrospective study, we analyzed data from 72 hemispheres of 56 adult patients with MMD who underwent combined bypass surgery. Hemodynamic features were extracted from the region of interest on preoperative arterial spin-labeling magnetic resonance imaging and basal and acetazolamide-challenged single-photon emission computed tomography (SPECT). The predictive capacity of the hemodynamic features for postoperative CHS was analyzed using a generalized estimating equation. Multivariable analysis was performed using hemodynami﻿c and clinical data. Results: Postoperative CHS occurred in 35 operated hemispheres (48.61%). Univariable analysis revealed that the cerebrovascular reservoir capacity (CVR) in the temporal and frontal cortices on SPECT significantly predicted CHS, with a lower CVR observed in the CHS group ( P &lt;0.050). In multivariable analysis, a lower CVR in the temporal cortex [odds ratio (95% CI), 0.99 [0.98–0.99]; P =0.034], higher preoperative modified Rankin scale score [1.18 (1.05–1.33); P =0.008], and anastomosis at the left hemisphere [1.25 (1.05–1.47); P =0.010] were associated with an increased CHS risk. Conclusions: Low preoperative CVR in the temporal cortex, poor preoperative neurological status, and surgery at dominant hemisphere are potential risk factors for postoperative CHS in MMD.
177Lu-FAPI-2286 Therapy in a Patient With Radio-iodine Refractory Papillary Thyroid Carcinoma: A Favorable Clinical and Biochemical Response
Authors: Nasrin Raeisi, Amin Saber Tanha, Mohammad Hossein Gozashti, Zahra Kiamanesh, Kamran Aryana
Journal: Clinical Nuclear Medicine (2025)

We report a 38-year-old man with radio-iodine refractory papillary thyroid carcinoma (RAIR PTC) who experienced significant relief from symptoms and showed a positive biochemical response after undergoing a single cycle of 177 Lu-FAPI-2286 therapy. A pretreatment 99m Tc-FAPI-46 scan showed diffuse uptake throughout both lungs and subsequent serial post-treatment scans demonstrated sustained uptake in pulmonary metastases. After treatment, there was a significant decline in serum thyroglobulin levels, accompanied by a remarkable improvement in symptoms, leading to near-complete resolution. This case highlights the potential of 177 Lu-FAPI-2286 therapy as an effective treatment option for RAIR PTC patients.
18F-FDG Brain PET/MRI in Postischemic Hyperperfusion
Authors: Faizullah Mashriqi, James Kim, Ana M Franceschi
Journal: Clinical Nuclear Medicine (2025)

A 58-year-old man with a past medical history of myocardial infarction and ventricular thrombus presented with successive stroke codes, initially for left arm weakness, then for dysarthria and right-sided weakness. Structural imaging showed an acute/subacute ischemic stroke in the right frontal and right parietal lobes. During the hospitalization, the patient suffered from impaired memory not attributable to the areas of ischemia, prompting a dementia workup. 18 F-FDG brain PET/MRI showed no evidence of neurodegenerative disease, but instead demonstrated focal hypermetabolism in the areas of acute/subacute infarcts, which was favored to represent luxury perfusion (postischemic hyperperfusion).
Extrarenal Uptake of 99mTc-DMSA in Uterine Leiomyoma
Authors: Mohammad Hadi Samadi, Pegah Sahafi, Haniye Elahifard, Bahram Memar, Somaye Barashki
Journal: Clinical Nuclear Medicine (2025)

We present a DMSA renal scan finding in a 42-year-old woman with new flank pain. Ultrasonography revealed hydronephrosis and renal stones. A 99m Tc-DMSA renal scan showed global cortical loss and multiple cortical defects in the left kidney, with an incidental large zone of uptake in the abdominopelvic region initially suspected as bladder. SPECT/CT imaging clarified this as a large leiomyoma which is proved in permanent pathology. This case highlights the importance of advanced imaging to distinguish physiological organs from tumoral masses and avoid misdiagnosis.
Unilateral Parotid Gland Involvement of Relapsed Acute Lymphoblastic Leukemia Demonstrated by 18F-FDG PET/CT
Authors: Xilan Yao, Hongrong Wang, Xiao Lei, Jigang Yang
Journal: Clinical Nuclear Medicine (2025)

The involvement of the parotid gland by acute lymphoblastic leukemia in extramedullary relapse is considered a rare occurrence. A 5-year-old girl with acute lymphoblastic leukemia presented with peripheral facial paralysis, and her symptoms remained unrelieved despite symptomatic treatment. 18 F-FDG PET/CT showed hypermetabolic activity not only in the left parotid gland but also in multiple cervical lymph nodes, confirming a relapse of T-cell acute lymphoblastic leukemia.