tbuckley/cabot-search huggingface dataset:
Blood-based cardiometabolic phenotypes in atrial fibrillation and their associated risk: EAST-AFNET 4 biomolecule study
Authors: Larissa Fabritz, Winnie Chua, Victor R Cardoso, Christoph Al-Taie, Katrin Borof, Anna Suling, Linda Krause, Shinwan Kany, Christina Magnussen, Karl Wegscheider, Guenter Breithardt, Harry J G M Crijns, A John Camm, George Gkoutos, Patrick T Ellinor, Andreas Goette, Ulrich Schotten, Ursula-Henrike Wienhues-Thelen, Tanja Zeller, Renate B Schnabel, Antonia Zapf, Paulus Kirchhof
Journal: Cardiovascular Research (2024)

Abstract Aims Atrial fibrillation (AF) and concomitant cardiometabolic disease processes interact and combine to lead to adverse events, such as stroke, heart failure, myocardial infarction, and cardiovascular death. Circulating biomolecules provide quantifiable proxies for cardiometabolic disease processes. The aim of this study was to test whether biomolecule combinations can define phenotypes in patients with AF. Methods and results This pre-specified analysis of the EAST-AFNET 4 biomolecule study assigned patients to clusters using polytomous variable latent-class analysis based on baseline concentrations of 13 precisely quantified biomolecules potentially reflecting ageing, cardiac fibrosis, metabolic dysfunction, oxidative stress, cardiac load, endothelial dysfunction, and inflammation. In each cluster, rates of cardiovascular death, stroke, or hospitalization for heart failure or acute coronary syndrome, the primary outcome of EAST-AFNET 4, were calculated and compared between clusters over median 5.1 years follow-up. Findings were independently validated in a prospective cohort of 748 patients with AF (BBC-AF; median follow-up 2.9 years). Unsupervised biomolecule analysis assigned 1586 patients (71 years old, 46% women) into four clusters. The highest risk cluster was dominated by elevated bone morphogenetic protein 10, insulin-like growth factor–binding protein 7, N-terminal pro-B-type natriuretic peptide, angiopoietin 2, and growth differentiation factor 15. Patients in the lowest risk cluster showed low concentrations of these biomolecules. Two intermediate-risk clusters differed by high or low concentrations of C-reactive protein, interleukin-6, and D-dimer. Patients in the highest risk cluster had a five-fold higher cardiovascular event rate than patients in the low-risk cluster. Early rhythm control was effective across clusters (Pinteraction = 0.63). Sensitivity analyses and external validation in BBC-AF replicated clusters and risk gradients. Conclusion Biomolecule concentrations identify cardiometabolic subphenotypes in patients with AF at high and low cardiovascular risk.
Recent advances in living cell nucleic acid probes based on nanomaterials for early cancer diagnosis
Authors: Xuyao Liu, Qi Shi, Peng Qi, Ziming Wang, Tongyue Zhang, Sijia Zhang, Jiayan Wu, Zhaopei Guo, Jie Chen, Qiang Zhang
Journal: Asian Journal of Pharmaceutical Sciences (2024)

The early diagnosis of cancer is vital for effective treatment and improved prognosis. Tumor biomarkers, which can be used for the early diagnosis, treatment, and prognostic evaluation of cancer, have emerged as a topic of intense research interest in recent years. Nucleic acid, as a type of tumor biomarker, contains vital genetic information, which is of great significance for the occurrence and development of cancer. Currently, living cell nucleic acid probes, which enable the
Phase 1 study combining elotuzumab with autologous stem cell transplant and lenalidomide for multiple myeloma
Authors: David G Coffey, Keren Osman, Adolfo Aleman, Selma Bekri, Simone Kats, Amishi Dhadwal, Donna Catamero, Seunghee Kim-Schulze, Sacha Gnjatic, Ajai Chari, Samir Parekh, Sundar Jagannath, Hearn Jay Cho
Journal: Journal for ImmunoTherapy of Cancer (2024)

Background Autologous stem cell transplantation (ASCT) after induction therapy improves disease-free survival for patients with multiple myeloma (MM). While the goal of ASCT is to render a minimal disease state, it is also associated with eradication of immunosuppressive cells, and we hypothesize that early introduction of immunotherapy post-ASCT may provide a window of opportunity to boost treatment efficacy. Methods We conducted a phase 1 clinical trial to investigate the application of autologous lymphocyte infusion and anti-SLAMF7 monoclonal antibody, elotuzumab, after ASCT in patients with newly diagnosed MM previously treated with induction therapy. In addition to CD34+ stem cells, peripheral blood mononuclear cells were harvested prior to transplant and infused on day 3 after stem cell infusion to accelerate immune reconstitution and provide autologous natural killer (NK) cells that are essential to the mechanism of elotuzumab. Elotuzumab was administered starting on day 4 and then every 28 days after until 1 year post-ASCT. Cycles 4–12 were administered with standard-of-care lenalidomide maintenance. Results All subjects were evaluated for safety, and 13 of 15 subjects completed the treatment protocol. At 1 year post-ASCT, the disease status of enrolled subjects was as follows: five stringent complete responses, one complete response, six very good partial responses, one partial response, and two progressive diseases. The treatment plan was well tolerated, with most grade 3 and 4 AEs being expected hematologic toxicities associated with ASCT. Correlative analysis of the immune microenvironment demonstrated a trend toward reduced regulatory T cells during the first 3 months post-transplant followed by an increase in NK cells and monocytes in patients achieving a complete remission. Conclusions This phase 1 clinical trial demonstrates that early introduction of immunotherapy after ASCT is well tolerated and shows promising disease control in patients with MM, accompanied by favorable changes in the immune microenvironment. Trial registration number NCT02655458 .
Armored TGFβRIIDN ROR1-CAR T cells reject solid tumors and resist suppression by constitutively-expressed and treatment-induced TGFβ1
Authors: Tri Minh Tran, Bal Krishna Chand Thakuri, Saule Nurmukhambetova, Jia-Jye Lee, Peirong Hu, Ngoc Q Tran, Brittany Steimle, Pradyot Dash, Dina Schneider
Journal: Journal for ImmunoTherapy of Cancer (2024)

Background Chimeric antigen receptor (CAR) T-cell therapy target receptor tyrosine kinase-like orphan receptor 1 (ROR1) is broadly expressed in hematologic and solid tumors, however clinically-characterized ROR1-CAR T cells with single chain variable fragment (scFv)-R12 targeting domain failed to induce durable remissions, in part due to the immunosuppressive tumor microenvironment (TME). Herein, we describe the development of an improved ROR1-CAR with a novel, fully human scFv9 targeting domain, and augmented with TGFβRIIDN armor protective against a major TME factor, transforming growth factor beta (TGFβ). Methods CAR T cells were generated by lentiviral transduction of enriched CD4 + and CD8 + T cells, and the novel scFv9-based ROR1-CAR-1 was compared with the clinically-characterized ROR1-R12-scFv-based CAR-2 in vitro and in vivo. Results CAR-1 T cells exhibited greater CAR surface density than CAR-2 when normalized for %CAR + , and produced more interferon (IFN)-γ tumor necrosis factor (TNF)-α and interleukin (IL)-2 in response to hematologic (Jeko-1, RPMI-8226) and solid (OVCAR-3, Capan-2, NCI-H226) tumor cell lines in vitro. In vivo, CAR-1 and CAR-2 both cleared hematologic Jeko-1 lymphoma xenografts, however only CAR-1 fully rejected ovarian solid OVCAR-3 tumors, concordantly with greater expansion of CD8 + and CD4 + CAR T cells, and enrichment for central and effector memory phenotype. When equipped with TGFβ-protective armor TGFβRIIDN, CAR-1 T cells resisted TGFβ-mediated pSmad2/3 phosphorylation, as compared with CAR-1 alone. When co-cultured with ROR-1 + AsPC-1 pancreatic cancer line in the presence of TGFβ1, armored CAR-1 demonstrated improved recovery of killing function, IFN-γ, TNF-α and IL-2 secretion. In mouse AsPC-1 pancreatic tumor xenografts overexpressing TGFβ1, armored CAR-1, in contrast to CAR-1 alone, achieved complete tumor remissions, and yielded accelerated expansion of CAR + T cells, diminished circulating active TGFβ1, and no apparent toxicity or weight loss. Unexpectedly, in AsPC-1 xenografts without TGFβ overexpression, TGFβ1 production was specifically induced by ROR-1-CAR T cells interaction with ROR-1 positive tumor cells, and the TGFβRIIDN armor conferred accelerated tumor clearance. Conclusions The novel fully human TGFßRIIDN-armored ROR1-CAR-1 T cells are highly potent against ROR1-positive tumors, and withstand the inhibitory effects of TGFß in solid TME. Moreover, TGFβ1 induction represents a novel, CAR-induced checkpoint in the solid TME, which can be circumvented by co-expressing the TGβRIIDN armor on T cells.
One-Year Outcomes Among Children Identified With Celiac Disease Through a Mass Screening Program
Authors: Marisa G. Stahl, Zhaoxing Pan, Monique Germone, Sadie Nagle, Pooja Mehta, Mary Shull, Isabel Griffith, Brianne Shuler, Edward Hoffenberg, Iman Taki, Cristy Geno-Rasmussen, Marian J. Rewers, Jill M. Norris, Edwin Liu
Journal: Clinical Gastroenterology and Hepatology (2024)
Factors Affecting Nonfunctioning Small Pancreatic Neuroendocrine Neoplasms and Proposed New Treatment Strategies
Authors: Susumu Hijioka, Daiki Yamashige, Minoru Esaki, Goro Honda, Ryota Higuchi, Toshihiko Masui, Yasuhiro Shimizu, Masayuki Ohtsuka, Yusuke Kumamoto, Akio Katanuma, Naoto Gotohda, Hirofumi Akita, Michiaki Unno, Itaru Endo, Yukihiro Yokoyama, Suguru Yamada, Ippei Matsumoto, Takao Ohtsuka, Satoshi Hirano, Hiroaki Yasuda, Manabu Kawai, Taku Aoki, Masafumi Nakamura, Daisuke Hashimoto, Toshiki Rikiyama, Akihiko Horiguchi, Tsutomu Fujii, Shugo Mizuno, Keiji Hanada, Masaji Tani, Takashi Hatori, Tetsuhide Ito, Masataka Okuno, Shingo Kagawa, Hiroshi Tajima, Tatsuya Ishii, Motokazu Sugimoto, Shunsuke Onoe, Hideki Takami, Ryoji Takada, Takayuki Miura, Yusuke Kurita, Keiko Kamei, Yuko Mataki, Kazuichi Okazaki, Yoshifumi Takeyama, Hiroki Yamaue, Sohei Satoi
Journal: Clinical Gastroenterology and Hepatology (2024)

Despite previously reported treatment strategies for nonfunctioning small (≤20 mm) pancreatic neuroendocrine neoplasms (pNENs), uncertainties persist. We aimed to evaluate the surgically resected cases of nonfunctioning small pNENs (NF-spNENs) in a large Japanese cohort to elucidate an optimal treatment strategy for NF-spNENs.
EAU-EANM-ESTRO-ESUR-ISUP-SIOG Guidelines on Prostate Cancer—2024 Update. Part I: Screening, Diagnosis, and Local Treatment with Curative Intent
Authors: Philip Cornford, Roderick C.N. van den Bergh, Erik Briers, Thomas Van den Broeck, Oliver Brunckhorst, Julie Darraugh, Daniel Eberli, Gert De Meerleer, Maria De Santis, Andrea Farolfi, Giorgio Gandaglia, Silke Gillessen, Nikolaos Grivas, Ann M. Henry, Michael Lardas, Geert J.L.H. van Leenders, Matthew Liew, Estefania Linares Espinos, Jan Oldenburg, Inge M. van Oort, Daniela E. Oprea-Lager, Guillaume Ploussard, Matthew J. Roberts, Olivier Rouvière, Ivo G. Schoots, Natasha Schouten, Emma J. Smith, Johan Stranne, Thomas Wiegel, Peter-Paul M. Willemse, Derya Tilki
Journal: European Urology (2024)
Personalised follow-up and management schema for patients with screen-detected pulmonary nodules: A dynamic modelling study
Authors: Z. Wang, F. Xue, X. Sui, W. Han, W. Song, J. Jiang
Journal: Pulmonology (2024)

Selecting the time target for follow-up testing in lung cancer screening is challenging. We aim to devise dynamic, personalized lung cancer screening schema for patients with pulmonary nodules detected through low-dose computed tomography. We developed and validated dynamic models using data of pulmonary nodule patients (aged 55–74 years) from the National Lung Screening Trial. We predicted patient-specific risk profiles at baseline (R0) and updated the risk evaluation results in repeated screening rounds (R1 and R2). We used risk cutoffs to optimize time-dependent sensitivity at an early decision point (3 months) and time-dependent specificity at a late decision point (1 year). In validation, area under receiver operating characteristic curve for predicting 12-month lung cancer onset was 0.867 (95 % confidence interval: 0.827–0.894) and 0.807 (0.765–0.948) at R0 and R1-R2, respectively. The personalized schema, compared with National Comprehensive Cancer Network (NCCN) guideline and Lung-RADS, yielded lower rates of delayed diagnosis (1.7% vs. 1.7% vs. 6.9 %) and over-testing (4.9% vs. 5.6% vs. 5.6 %) at R0, and lower rates of delayed diagnosis (0.0% vs. 18.2% vs. 18.2 %) and over-testing (2.6% vs. 8.3% vs. 7.3 %) at R2. Earlier test recommendation among cancer patients was more frequent using the personalized schema (vs. NCCN: 29.8% vs. 20.9 %, p = 0.0065; vs. Lung-RADS: 33.2% vs. 22.8 %, p = 0.0025), especially for women, patients aged ≥65 years, and part-solid or non-solid nodules. The personalized schema is easy-to-implement and more accurate compared with rule-based protocols. The results highlight value of personalized approaches in realizing efficient nodule management.
Low tumor interleukin-1β expression predicts a limited effect of adjuvant platinum-based chemotherapy for patients with completely resected lung adenocarcinoma: An identification and validation study
Authors: S. Safi, J. Krzykalla, H. Hoffmann, A. Benner, H. Bischoff, M. Eichhorn, M. Kriegsmann, I. Poschke, F. Stögbauer, L. Umansky, C. Mogler, W. Weichert, H. Winter, P. Beckhove, T. Muley
Journal: Pulmonology (2024)

Adjuvant platinum-based chemotherapy for completely resected non-small cell lung cancer is associated with modest improvement in survival; nevertheless, no validated biomarker exists for predicting the benefit or harm of adjuvant platinum-based chemotherapy. We simultaneously measured 27 cytokines in operative tumor specimens from a discovery cohort (n = 97) by multiplex immunoassay; half of the patients received adjuvant platinum-based chemotherapy, and the other half were observed. We tested possible prognostic and predictive factors in multivariate Cox models for overall survival (OS) and relapse-free survival (RFS), and a tree-based method was applied to detect predictive factors with respect to RFS. The results were validated in an independent validation cohort (n = 93). Fifty-two of 97 (54 %) patients in the discovery cohort and 50 of 93 (54 %) in the validation cohort received adjuvant chemotherapy; forty-four (85 %) patients in the discovery cohort and 37 (74 %) in the validation cohort received four cycles as planned. In patients with low IL-1β-expressing tumors, RFS and OS were worse after adjuvant chemotherapy than after observation. The limited effect of adjuvant chemotherapy for patients with low IL-1β-expressing tumors was confirmed in the validation cohort. Additionally, RFS and OS were prolonged by adjuvant chemotherapy only in patients with high IL-1β-expressing tumors in the validation cohort. This study identified and validated low tumor IL-1β expression as a potential biomarker of a limited response to adjuvant platinum-based chemotherapy after complete resection of pulmonary adenocarcinoma. This finding has the potential to inform adjuvant treatment decisions.
Association between lung function and dyspnoea and its variation in the multinational Burden of Obstructive Lung Disease (BOLD) study
Authors: A. Müller, E.F. Wouters, P. Koul, T. Welte, I. Harrabi, A. Rashid, L.C. Loh, M. Al Ghobain, A. Elsony, R. Ahmed, J. Potts, K. Mortimer, F. Rodrigues, S.N. Paraguas, S. Juvekar, D. Agarwal, D. Obaseki, T. Gislason, T. Seemungal, A.A. Nafees, C. Jenkins, H.B. Dias, F.M.E. Franssen, M. Studnicka, C. Janson, H.H. Cherkaski, M. El Biaze, P.A. Mahesh, J. Cardoso, P. Burney, S. Hartl, D.J.A. Janssen, A.F.S. Amaral
Journal: Pulmonology (2024)

Dyspnoea is a common symptom of respiratory disease. However, data on its prevalence in general populations and its association with lung function are limited and are mainly from high-income countries. The aims of this study were to estimate the prevalence of dyspnoea across several world regions, and to investigate the association of dyspnoea with lung function.
Corrigendum to ‘Long-term outcomes to neoadjuvant pembrolizumab based on pathological response for patients with resectable stage III/IV cutaneous melanoma’
Authors: C.E. Sharon, G.N. Tortorello, K.L. Ma, A.C. Huang, X. Xu, L.R. Giles, S. McGettigan, K. Kreider, L.M. Schuchter, A.J. Mathew, R.K. Amaravadi, P.A. Gimotty, J.T. Miura, G.C. Karakousis, T.C. Mitchell
Journal: Annals of Oncology (2024)

The authors regret that in the original publication figures 1 (OS) and 2 (RFS) were the same; both figures used the RFS curve. The correct figure 1 is now given below. The authors further note that they did not include three early recurrences. These three recurrences were in patients without a major pathological response (MPR) to neoadjuvant therapy (poor response patients). The omission of these recurrences does not change the overall survival data (all three remain alive and well), nor does it impact any of the conclusions about the patients with major pathological responses (MPR, the focus of the paper), since the three omitted recurrences were in the group without MPRs/poor risk group, and there was less focus on this group in this publication. There were no changes in statistical significance in the updated RFS curves. The authors would like to apologise for any inconvenience caused. Long-term outcomes to neoadjuvant pembrolizumab based on pathological response for patients with resectable stage III/IV cutaneous melanomaAnnals of OncologyVol. 34Issue 9PreviewWhile neoadjuvant immunotherapy for melanoma has shown promising results, the data have been limited by a relatively short follow-up time, with most studies reporting 2-year outcomes. The goal of this study was to determine long-term outcomes for stage III/IV melanoma patients treated with neoadjuvant and adjuvant programmed cell death receptor 1 (PD-1) inhibition. Full-Text PDF
The use of faecal microbiota transplant as treatment for recurrent or refractory <i>Clostridioides difficile</i> infection and other potential indications: second edition of joint British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS) guidelines
Authors: Benjamin H Mullish, Blair Merrick, Mohammed Nabil Quraishi, Aggie Bak, Christopher A Green, David J Moore, Robert J Porter, Ngozi T Elumogo, Jonathan P Segal, Naveen Sharma, Belinda Marsh, Graziella Kontkowski, Susan E Manzoor, Ailsa L Hart, Christopher Settle, Josbert J Keller, Peter Hawkey, Tariq H Iqbal, Simon D Goldenberg, Horace R T Williams
Journal: Gut (2024)

The first British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS)-endorsed faecal microbiota transplant (FMT) guidelines were published in 2018. Over the past 5 years, there has been considerable growth in the evidence base (including publication of outcomes from large national FMT registries), necessitating an updated critical review of the literature and a second edition of the BSG/HIS FMT guidelines. These have been produced in accordance with National Institute for Health and Care Excellence-accredited methodology, thus have particular relevance for UK-based clinicians, but are intended to be of pertinence internationally. This second edition of the guidelines have been divided into recommendations, good practice points and recommendations against certain practices. With respect to FMT for
Survival outcome after surgery in patients with thymoma distant recurrence.
Authors: Marco Chiappetta, Carolina Sassorossi, Dania Nachira, Filippo Lococo, Elisa Meacci, Enrico Ruffini, Francesco Guerrera, Paraskevas Lyberis, Vittorio Aprile, Marco Lucchi, Marcello Carlo Ambrogi, Diana Bacchin, Andrea Dell’Amore, Carlotta Marino, Giovannimaria Comacchio, Gabriella Roca, Federico Rea, Stefano Margaritora
Journal: Journal of Thoracic Oncology (2024)
Targeting the Cdc2‐like kinase 2 for overcoming platinum resistance in ovarian cancer
Authors: Yinan Jiang, Shuting Huang, Lan Zhang, Yun Zhou, Wei Zhang, Ting Wan, Haifeng Gu, Yi Ouyang, Xiaojing Zheng, Pingping Liu, Baoyue Pan, Huiling Xiang, Mingxiu Ju, Rongzhen Luo, Weihua Jia, Shenjiao Huang, Jundong Li, Min Zheng
Journal: MedComm (2024)

Abstract Platinum resistance represents a major barrier to the survival of patients with ovarian cancer (OC). Cdc2‐like kinase 2 (CLK2) is a major protein kinase associated with oncogenic phenotype and development in some solid tumors. However, the exact role and underlying mechanism of CLK2 in the progression of OC is currently unknown. Using microarray gene expression profiling and immunostaining on OC tissues, we found that CLK2 was upregulated in OC tissues and was associated with a short platinum‐free interval in patients. Functional assays showed that CLK2 protected OC cells from platinum‐induced apoptosis and allowed tumor xenografts to be more resistant to platinum. Mechanistically, CLK2 phosphorylated breast cancer gene 1 (BRCA1) at serine 1423 (Ser1423) to enhance DNA damage repair, resulting in platinum resistance in OC cells. Meanwhile, in OC cells treated with platinum, p38 stabilized CLK2 protein through phosphorylating at threonine 343 of CLK2. Consequently, the combination of CLK2 and poly ADP‐ribose polymerase inhibitors achieved synergistic lethal effect to overcome platinum resistance in patient‐derived xenografts, especially those with wild‐type BRCA1. These findings provide evidence for a potential strategy to overcome platinum resistance in OC patients by targeting CLK2.
Recent advances on thermosensitive hydrogels-mediated precision therapy
Authors: Hao Chen, Jiangmei Xu, Jiangwei Sun, Yongxin Jiang, Wang Zheng, Wei Hu, Haisheng Qian
Journal: Asian Journal of Pharmaceutical Sciences (2024)

Precision therapy has become the preferred choice attributed to the optimal drug concentration in target sites, increased therapeutic efficacy, and reduced adverse effects. Over the past few years, sprayable or injectable thermosensitive hydrogels have exhibited high therapeutic potential. These can be applied as cell-growing scaffolds or drug-releasing reservoirs by simply mixing in a free-flowing sol phase at room temperature. Inspired by their unique properties, thermosensitive hydrogels have been widely applied as drug delivery and treatment platforms for precision medicine. In this review, the state-of-the-art developments in thermosensitive hydrogels for precision therapy are investigated, which covers from the thermo-gelling mechanisms and main components to biomedical applications, including wound healing, anti-tumor activity, osteogenesis, and periodontal, sinonasal and ophthalmic diseases. The most promising applications and trends of thermosensitive hydrogels for precision therapy are also discussed in light of their unique features.
Polyomavirus-positive Merkel cell carcinoma: the beginning of the beginning
Authors: Michael K. Wong, Cassian Yee
Journal: Journal of Clinical Investigation (2024)

Merkel cell carcinoma (MCC) is an aggressive, fast-growing, highly metastatic neuroendocrine skin cancer. The Merkel cell polyomavirus (MCPyV) is an oncogenic driver in the majority of MCC tumors. In this issue of the JCI, Hansen and authors report on their tracking of CD8+ T cells reactive to MCPyV T antigen (T-Ag) in the peripheral blood of 26 patients with MCC who were undergoing frontline anti-programmed cell death protein-1 (anti-PD-1) immunotherapy. They discovered unique T cell epitopes and used the power of bar-coded tetramers to portray immune checkpoint inhibitor-induced immunogenicity as a predictor of clinical response. These findings provide the foundation for therapeutic possibilities for MCC, including vaccines and adoptive T cell- and T cell receptor-driven (TCR-driven) treatments.