tbuckley/cabot-search huggingface dataset:
Proinflammatory phenotype of B10 and B10pro cells elicited by TNF-α in rheumatoid arthritis
Authors: Fanlei Hu, Lianjie Shi, Xiaohang Liu, Yingjia Chen, Xia Zhang, Yuan Jia, Xu Liu, Jianping Guo, Huaqun Zhu, Hongjiang Liu, Liling Xu, Yingni Li, Ping Wang, Xiangyu Fang, Jimeng Xue, Yang Xie, Chaonan Wei, Jing Song, Xi Zheng, Yan-Ying Liu, Yuhui Li, Limin Ren, Dakang Xu, Liwei Lu, Xiaoyan Qiu, Rong Mu, Jing He, Min Wang, Xuan Zhang, Wanli Liu, Zhanguo Li
Journal: Annals of the Rheumatic Diseases (2024)

B10 and B10pro cells suppress immune responses via secreting interleukin (IL)-10. However, their regulators and underlying mechanisms, especially in human autoimmune diseases, are elusive. This study aimed to address these questions in rheumatoid arthritis (RA), one of the most common highly disabling autoimmune diseases.
Neuropathic Pain With and Without Diabetic Peripheral Neuropathy in Type 1 Diabetes
Authors: Barbara H. Braffett, Laure El ghormli, James W. Albers, Eva L. Feldman, William H. Herman, Rose A. Gubitosi-Klug, Catherine L. Martin, Trevor J. Orchard, Neil H. White, John M. Lachin, Bruce A. Perkins, Rodica Pop-Busui
Journal: Diabetes Care (2024)

Diabetic peripheral neuropathy (DPN) is common; however, the features and burden of neuropathic pain (NP) in type 1 diabetes (T1D) are poorly understood. We evaluated the incidence of first occurrence, annual prevalence, remission, and risk factors for NP during long-term follow-up of participants with T1D.
Characterised intron retention profiles in muscle tissue of idiopathic inflammatory myopathy subtypes
Authors: Yizhi Xiao, Shasha Xie, Hong-Dong Li, Yanjuan Liu, Huali Zhang, Xiaoxia Zuo, Honglin Zhu, Yisha Li, Hui Luo
Journal: Annals of the Rheumatic Diseases (2024)

Objectives Idiopathic inflammatory myopathies (IIMs) are a group of heterogeneous autoimmune diseases. Intron retention (IR) serves as an important post-transcriptional and translational regulatory mechanism. This study aims to identify changes in IR profiles in IIM subtypes, investigating their influence on proteins and their correlations with clinical features. Methods RNA sequencing and liquid chromatography-tandem mass spectrometry were performed on muscle tissues obtained from 174 patients with IIM and 19 controls, following QC procedures. GTFtools and iREAD software were used for IR identification. An analysis of differentially expressed IRs (DEIs), exons and proteins was carried out using edgeR or DEP. Functional analysis was performed with clusterProfiler, and SPIRON was used to assess splicing factors. Results A total of 6783 IRs located in 3111 unique genes were identified in all IIM subtypes compared with controls. IIM subtype-specific DEIs were associated with the pathogenesis of respective IIM subtypes. Splicing factors YBX1 and HSPA2 exhibited the most changes in dermatomyositis and immune-mediated necrotising myopathy. Increased IR was associated with reduced protein expression. Some of the IIM-specific DEIs were correlated with clinical parameters (skin rash, MMT-8 scores and muscle enzymes) and muscle histopathological features (myofiber necrosis, regeneration and inflammation). IRs in IFIH1 and TRIM21 were strongly correlated with anti-MDA5+ antibody, while IRs in SRP14 were associated with anti-SRP+ antibody. Conclusion This study revealed distinct IRs and specific splicing factors associated with IIM subtypes, which might be contributing to the pathogenesis of IIM. We also emphasised the potential impact of IR on protein expression in IIM muscles.
IgG glycosylation associates with risk of progression from latent to active tuberculosis
Authors: Julie G. Burel, Wenjun Wang, Manfred Wuhrer, Martin Dedicoat, Thomas E. Fletcher, Adam F. Cunningham, Matthew K. O’Shea
Journal: Journal of Infection (2024)

Glycosylation motifs shape antibody structure, stability and antigen affinity and play an important role in antibody localization and function. Serum IgG glycosylation profiles are significantly altered in infectious diseases, including tuberculosis (TB), but have not been studied in the context of progression from latent to active TB.
Reply to: Additional Thoughts on Intrinsic Dysanapsis
Authors: Elizabeth A. McGinn, Erica W. Mandell, Bradford J. Smith, Joseph W. Duke, Andrew Bush, Steven H. Abman
Journal: American Journal of Respiratory and Critical Care Medicine (2024)

"Reply to: Additional Thoughts on Intrinsic Dysanapsis ." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp.
Outcomes of Post-Immunotherapy Durable Responders of Advanced Hepatocellular Carcinoma– with Emphasis on Locoregional Therapy for Oligoprogression
Authors: Tsung-Hao Liu, San-Chi Chen, Kun-Ming Rau, Li-Chun Lu, Po-Ting Lin, Yung-Yeh Su, Wei Teng, Shiue-Wei Lai, Ren-Hua Yeh, Tsui-Mai Kao, Pei-Chang Lee, Chi-Jung Wu, Chien-Hung Chen, Chih-Hung Hsu, Shi-Ming Lin, Yi-Hsiang Huang, Li-Tzong Chen, Ann-Lii Cheng, Ying-Chun Shen
Journal: Liver Cancer (2024)

Introduction: The progression patterns, dispositions, and outcomes of patients with advanced hepatocellular carcinoma (HCC) who achieved durable responses with immunotherapy remain poorly characterized. Methods: Patients with advanced HCC who received immune checkpoint inhibitor (ICI)-based immunotherapy and achieved durable responses were retrospectively included. A durable response was defined as partial response (PR) or stable disease (SD) per RECIST 1.1 for more than 8 months after initiation of immunotherapy. Oligoprogression and polyprogression were defined as progression at ≤3 and &gt;3 lesions, respectively. Results: A total of 91 durable responders (63 PR and 28 SD) were identified. The majority had chronic viral hepatitis (n = 69, 75.8%). Forty-seven (51.6%) and 44 (48.4%) patients received the index immunotherapy as first-line and second- or beyond-line therapy, respectively. Fifty-four (59.3%) patients subsequently developed progression, with a predominant pattern of oligoprogression (66.7%). The median overall survival (OS) was 46.2 months (95% CI: 34.1–58.3). For patients with subsequent progression, employment of locoregional therapy (LRT) for progression was associated with prolonged OS (univariate analysis: hazard ratio [HR] 0.397, p = 0.009; multivariate analysis: HR 0.363, p = 0.050). Patients with oligoprogression who received LRT showed longer median OS than those who did not (48.4 vs. 20.5 months, p &lt; 0.001). In contrast, the median OS of patients with polyprogression who received LRT was not different from those without LRT (27.7 vs. 25.5 months, p = 0.794). Conclusion: Approximately 60% of the post-immunotherapy durable responders of HCC subsequently develop progression. Proactive LRT may further rescue patients who develop subsequent oligoprogression. Prospective studies are mandatory to clarify the proper management of durable responders with subsequent progression.
Breaking the links between ageism and health: An integrated perspective
Authors: Julie D. Henry, Sarah P. Coundouris, Matthew R. Nangle
Journal: Ageing Research Reviews (2024)

Ageism refers to prejudice, stereotypes or discrimination based on a person's actual or perceived chronological age. While ageism can affect people at all stages of the human lifespan, ageism against older adults has emerged as the most pervasive and potentially harmful. Much is now understood about how ageism can impact older people's health and wellbeing via structural, organisational, and provider level biases that threaten the provision of equitable and ethical healthcare. Negative attitudes about age and ageing also contribute to workforce shortages in aged care sectors, such as residential aged care and nursing. However, often underappreciated is how self-directed ageism, which refers to ageism turned against oneself, can also be an important determinant of health and wellbeing. Relative to external sources of ageism, negative internalised ageist beliefs are not only experienced more frequently in older adults' everyday lives, but are also more strongly linked to their health and wellbeing. Here we highlight how this understanding means that eliminating ageism requires a multifaceted approach that targets not only health care systems and aged care professionals, but older people themselves. Because normal age-related cognitive changes in how we think, perceive and reason increase the risk of older people viewing themselves through a negative and ageist lens, we provide a novel discussion of how broader insights from cognitive ageing literature must play a central role in any agenda focused on breaking the links between ageism and health.
Cough Severity Visual Analog Scale Assesses Cough Burden and Predicts Survival in Idiopathic Pulmonary Fibrosis
Authors: Zhe Wu, David J. F. Smith, Leda Yazbeck, Peter Saunders, Jaclyn A. Smith, Toby M. Maher, Philip L. Molyneaux
Journal: American Journal of Respiratory and Critical Care Medicine (2024)

"Cough Severity Visual Analogue Scale Assesses Cough Burden and Predicts Survival in Idiopathic Pulmonary Fibrosis." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp.
Distinguishing community-acquired bacterial and viral meningitis: Microbes and biomarkers
Authors: Lauri Ivaska, Jethro Herberg, Manish Sadarangani
Journal: Journal of Infection (2024)

Diagnostic tools to differentiate between community-acquired bacterial and viral meningitis are essential to target the potentially lifesaving antibiotic treatment to those at greatest risk and concurrently spare patients with viral meningitis from the disadvantages of antibiotics. In addition, excluding bacterial meningitis and thus decreasing antibiotic consumption would be important to help reduce antimicrobial resistance and healthcare expenses. The available diagnostic laboratory tests for differentiating bacterial and viral meningitis can be divided microbiological pathogen-focussed methods and biomarkers of the host response. Bacterial culture-independent microbiological methods, such as highly multiplexed nucleic acid amplification tests, are rapidly making their way into the clinical practice. At the same time, more conventional host protein biomarkers, such as procalcitonin and C-reactive protein, are supplemented by newer proteomic and transcriptomic signatures. This review aims to summarise the current state and the recent advances in diagnostic methods to differentiate bacterial from viral meningitis.
Mn‐Based Artificial Mitochondrial Complex “VI” Acts as an Electron and Free Radical Conversion Factory to Suppress Macrophage Inflammatory Response
Authors: Mingxing Ren, Chongjing Zhou, Xinyi Li, Yining Zhang, Meng Li, Haoyue Song, Fengyi Liu, Tao Chen, Xinxin Xu, Sheng Yang
Journal: Advanced Healthcare Materials (2024)

Abstract Disturbance in the mitochondrial electron transport chain (ETC) is a key factor in the emerging discovery of immune cell activation in inflammatory diseases, yet specific regulation of ETC homeostasis is extremely challenging. In this paper, a mitochondrial complex biomimetic nanozyme (MCBN), which plays the role of an artificial “VI” complex and acts as an electron and free radical conversion factory to regulate ETC homeostasis is creatively developed. MCBN is composed of bovine serum albumin (BSA), polyethylene glycol (PEG), and triphenylphosphine (TPP) hierarchically encapsulating MnO 2 polycrystalline particles. It has nanoscale size and biological properties like natural complexes. In vivo and in vitro experiments confirm that MCBN can target the mitochondrial complexes of inflammatory macrophages, absorb excess electrons in ETC, and convert the electrons to decompose H 2 O 2 . By reducing the ROS and ATP bursts and converting existing free radicals, inhibiting NLRP3 inflammatory vesicle activation and NF‐ κ B signaling pathway, MCBN effectively suppresses macrophage M1 activation and inflammatory factor secretion. It also demonstrates good inflammation control and significantly alleviates alveolar bone loss in a mouse model of ligation‐induced periodontitis. This is the first nanozyme that mimics the mitochondrial complex and regulates ETC, demonstrating the potential application of MCBN in immune diseases.
Circulating Tumour DNA Detection By The Urine-Informed Analysis Of Archival Serum Samples From Muscle-Invasive Bladder Cancer Patients
Authors: Faisal S. BinHumaid, Anshita Goel, Naheema S. Gordon, Ben Abbotts, K.K. Cheng, Maurice P. Zeegers, Nicholas D. James, Waleed M. Altaweel, Raouf M. Seyam, Brian F. Meyer, Roland Arnold, Douglas G. Ward, Richard T. Bryan
Journal: European Urology (2024)
PIVOT-006: A phase 3, randomized study of cretostimogene grenadenorepvec versus observation for the treatment of intermediate risk non-muscle invasive bladder cancer (IR-NMIBC) following transurethral resection of bladder tumor (TURBT).
Authors: Robert S. Svatek, Trinity Bivalacqua, Kirk A. Keegan, Siamak Daneshmand
Journal: Journal of Clinical Oncology (2024)

TPS715 Background: Guidelines for Intermediate Risk Non-Muscle Invasive Bladder Cancer (IR-NMIBC) recommend adjuvant intravesical (IVE) therapy or surveillance. Despite this, 30–60% of patients still recur, and these Guideline recommendations are lacking level-1 evidence. Thus, there is a considerable gap in knowledge and an unmet medical need for improved therapies in the adjuvant setting. Cretostimogene Grenadenorepvec is an oncolytic adenovirus designed to preferentially replicate in and kill cancer cells. The vector is transcriptionally regulated by the E2F promoter that is up-regulated in retinoblastoma (Rb) pathway-defective tumor cells, common in most IR-NMIBC bladder tumors. Additionally, the virus is engineered to selectively express GM-CSF, in order to induce a robust systemic anti-tumor immune response. PIVOT-006 is an open-label, multi-center, randomized Phase 3 study designed to assess the efficacy and safety of intravesical Cretostimogene after TURBT versus TURBT alone. Methods: Eligibility criteria: age ≥18 years, Eastern Cooperative Oncology Group performance status of 0-2, histologically confirmed IR-NMIBC with absence of nodal or metastatic disease at screening. IR-NMIBC, as defined by American Urologic Association-Society of Urologic Oncology Guidelines on NMIBC, is either a Low Grade (LG) stage Ta tumor that recurs within 12 months of prior LG or High Grade (HG) bladder cancer, a solitary LGTa tumor &gt;3cm in size, multifocal LGTa tumors, primary HGTa lesion &lt; 3cm in size, or a LGT1 tumor. Participants will be stratified by receipt of perioperative chemotherapy and tumor grade. Pts (N~450) will be randomized 1:1 to receive intravesical Cretostimogene (Cohort 1) adjuvant to TURBT or TURBT alone (Cohort 2). Single dose perioperative intravesical chemotherapy at the time of TURBT is permitted. If intravesical NMIBC recurrence is noted in Cohort 2, participants will be eligible to receive intravesical Cretostimogene. In Cohort 1, intravesical Cretostimogene will be instilled in combination with n-dodecyl-B-D-maltoside (DDM, an inactive detergent) for 6 weekly doses during the induction phase, followed by 3 weekly maintenance cycles at months 3 and 6, and culminating in single intravesical doses at months 9 and 12. Primary disease assessments include serial cystoscopy, urine cytology, axial imaging, and centralized review of pathologic samples. The primary outcome measure is recurrence free survival. Secondary outcome measures include safety, tolerability, progression free survival, and time to next intervention. Exploratory outcome measures include patient-reported quality of life, biomarker analyses, coxsackie adenovirus receptor and E2F promoter expression, neutralizing antibodies, and markers of immunogenicity. Clinical trial information: Pending.
Phase II study of pembrolizumab in combination with radiation with or without olaparib in localized high-risk prostate cancer.
Authors: Zin Myint, William H St. Clair, Stephen Strup, Patrick J. Hensley, Donglin Yan, Jonathan David Tward, Benjamin L. Maughan
Journal: Journal of Clinical Oncology (2024)

TPS351 Background: Definitive radiation therapy (DRT) combined with androgen deprivation therapy (ADT) remains the standard of care in patients with high-risk prostate cancer (HRPC) who do not want surgery. However, up to 50% experience biochemical recurrence (BCR) within 5 years. A phase 3 NCIC group reported the 10-year biochemical recurrence free survival was 63% in ADT plus DRT vs. 27% in ADT alone. There is an urgent need for effective novel combination strategies. We hypothesize combined immune sensitizing effects of PARPi and radiation will result in significant activity of immunotherapy in men with HRPC. Methods: This is a multicenter phase II randomized study to assess biochemical response rates, safety and tolerability of combined therapy in pts with localized HRPC who elected for concurrent DRT. A total of 64 pts will be randomized 1:1 to receive either pembrolizumab (P) combined with olaparib or single agent P in addition to the standard of care ADT with DRT. Hypofractionated IMRT (2.4 to 4 Gy per fraction over 4-6 weeks) will be delivered and all pts will receive adjuvant P for one year and ADT for at least 18 months. All pts will undergo germline testing. Key eligible criteria include biopsy confirmed prostate adenocarcinoma who meets at least one of the four high-risk features: 1) clinical T3a, T3b or T4, 2) N1, 3) Gleason grade group 4 or 5, and 4) PSA &gt;20 ng/ml. Patients with less than 2 cm pelvic nodes and received ADT therapy within 3months prior to study enrollment are allowed. PSA &gt;150 ng/ml and patients with distant metastases will be excluded. The primary endpoint is to assess the proportion of patients who achieve a PSA nadir level of ≤ 0.06 ng/ml within six months after completion of radiation therapy in each arm. The secondary objectives include safety/tolerability, BCR and metastasis-free survival at 3 years. BCR is defined by the Phoenix definition. The study is designed to detect a 15% improvement in PSA nadir ≤ 0.06 ng/mL within 6 months after completion of the combined therapy versus historical control group data Geara FB et al., 2017. Enrollment began in August 2023. Clinical trial information: NCT05568550 .
Relugolix versus leuprolide in combination with radiotherapy for localized prostate cancer (REVELUTION trial): An initial analysis of patient treatment preferences and quality of life.
Authors: Sagar A. Patel, Subir Goyal, Yuan Liu, Bruce W. Hershatter, Pretesh R. Patel, Vishal Ramesh Dhere, Nikhil Sebastian, Ashesh B. Jani, Anant Mandawat
Journal: Journal of Clinical Oncology (2024)

301 Background: Relugolix, an oral gonadotropin releasing hormone (GnRH) antagonist, has superior testosterone suppression and may lower cardiovascular (CV) toxicity compared with more commonly used injectable GnRH agonists, such as leuprolide. The Relugolix Versus Leuprolide Trial (REVELUTION, NCT 05320406) is an ongoing, investigator-initiated, randomized trial comparing radiotherapy (XRT) plus relugolix versus XRT plus leuprolide for men with localized prostate cancer (PCa). Primary endpoint is change in coronary plaque on cardiac computed tomography from baseline to 12 months following treatment. Secondary endpoints include patient-reported outcomes (PRO). Herein, we report patient-specific treatment preferences prior to randomization and acute treatment-associated toxicity. Methods: Men with non-metastatic intact or biochemically recurrent PCa pursuing pelvic XRT (1.8-2.5 Gy per fraction) with ≥ 6 months of androgen deprivation therapy (ADT) were enrolled and randomized 1:1 to leuprolide (IM/SC 45 mg q6mo) or relugolix (PO 360 mg day 1, 120 mg daily thereafter). Prior to randomization, each patient completed an ADT preference questionnaire after reviewing an education brochure describing both drugs’ administration, testosterone kinetics, and common toxicities. PROs were assessed by International Prostate Symptom Score (IPSS) and Expanded Prostate Index Composite (EPIC-CP) at baseline and 3-/6-months after XRT initiation, with higher scores indicating more severe toxicity. Scores were compared using linear mixed-effects models accounting for within-subject correlations. Results: Between 06/2022 and 07/2023, 65 men were randomized (34 leuprolide, 31 relugolix). Median follow-up was 5 months (IQR 4-8). Prior to randomization, 61 (94%) preferred relugolix over leuprolide, due to faster testosterone recovery (n=36, 59%), lower CV risk (n=23, 38%), or oral administration (n=2, 3%); the four patients who preferred leuprolide all had compliance concerns with a daily oral pill. Compared with XRT+leuprolide, XRT+relugolix was associated with less impact on IPSS urinary score (mean difference [MD] -3.68, p=0.04). There was no difference in EPIC-CP incontinence (MD +0.07, p=0.91), bowel (MD +0.39, p=0.44), sexual (MD -0.74, p=0.43), or vitality (MD +0.17, p=0.80). Conclusions: In this trial of men with localized PCa treated with XRT plus ADT, most preferred relugolix over leuprolide. Relugolix, compared with leuprolide, mitigated acute urinary toxicity from XRT, perhaps due to superior castration resulting in greater prostate gland downsizing and less obstructive uropathy. Longer-term follow up is ongoing, and primary CV toxicity endpoint is expected to be complete in 2024. Clinical trial information: NCT05320406 .
The efficacy and safety of tinengotinib in patients with heavily pretreated metastatic castration-resistant prostate cancer (mCRPC).
Authors: Guo Hongqian, Sumit Kumar Subudhi, Weiqing Han, Chih-Yi Liao, Shun Zhang, Tao Dai, Peng Peng, Caixia Sun, Hui Wang, Katie Hennessy, Ximei Fu, Yingying Yu, Yingtong Wu, Qing Li, Ruolan Xu, Peng Huang, Levin Neo, Frank Wu, Jean Fan, Sarina A. Piha-Paul
Journal: Journal of Clinical Oncology (2024)

133 Background: Tinengotinib is a spectrum-selective multi-kinase inhibitor that targets cell proliferation, angiogenesis, and immune-oncology pathways by inhibiting Aurora kinases A/B, Janus kinases (JAK), and receptor tyrosine kinases (FGFRs, VEGFRs). It has been reported that the activation of JAK/STAT and fibroblast growth factor receptor (FGFR) signaling drives prostate tumor plasticity. Here we present the preliminary safety and efficacy data of tinengotinib in patients with mCRPC from three early phase clinical trials conducted in the US and China. Methods: Eligible mCRPC patients who have no available standard therapeutic treatment options were enrolled to the three studies. Tinengotinib was given as monotherapy at 8 mg QD, 10 mg QD and 12 mg QD. Efficacy tumor assessments were based on RECIST v1.1 for measurable disease and Prostate Cancer Working Group 3 criteria for non-measurable (bone) disease. PSA50 response was also evaluated. CTCAE v5.0 was used for safety assessments. Results: As of 28AUG2023, 30 patients with mCRPC were treated at dose levels of 8 mg QD (n=1), 10 mg QD (n=19) and 12 mg QD (n=10). Median age was 67 years (range 52-82) with ECOG performance status of 1 in 93% of patients. All patients had at least 2 prior therapies including 77% prior docetaxel, 87% prior abiraterone, and 30% prior enzalutamide. The median follow-up time is 5.4 months. Twenty-two (22) patients were efficacy evaluable, of which 13 were evaluable per RECIST v1.1. Fourteen (14) patients were PSA evaluable. The median radiographic progression-free survival (rPFS) was 5.6 months (95% CI, 3.3-7.3). Overall response rate (ORR) was 46% (6/13) and the disease control rate (DCR) was 85% (11/13). Median duration of response (DoR) was 3.0 months. The PSA50 response rate was 50% (7/14). Treatment-related adverse events (TRAEs) occurred in 28 patients (93%). The most common TRAEs (≥20%) included blood thyroid stimulating hormone increase (43%), anemia (37%), hypertension (27%), aspartate aminotransferase increase (23%), electrocardiogram QT prolongation (20%) and white blood cell count decrease (20%). Conclusions: Tinengotinib safety profile was tolerable and manageable. The preliminary efficacy data showed promising clinical benefit of tinengotinib monotherapy in patients with heavily pretreated mCRPC. Further study of tinengotinib in this disease is warranted. Clinical trial information: NCT03654547 , NCT04742959 , NCT05253053 .