tbuckley/cabot-search huggingface dataset:
An electroencephalographic signature predicts craving for methamphetamine
Authors: Weiwen Tian, Di Zhao, Jinjun Ding, Shulu Zhan, Yi Zhang, Amit Etkin, Wei Wu, Ti-Fei Yuan
Journal: Cell Reports Medicine (2023)

Craving is central to methamphetamine use disorder (MUD) and both characterizes the disease and predicts relapse. However, there is currently a lack of robust and reliable biomarkers for monitoring craving and diagnosing MUD. Here, we seek to identify a neurobiological signature of craving based on individual-level functional connectivity pattern differences between healthy control and MUD subjects. We train high-density electroencephalography (EEG)-based models using data recorded during the resting state and then calculate imaginary coherence features between the band-limited time series across different brain regions of interest. Our prediction model demonstrates that eyes-open beta functional connectivity networks have significant predictive value for craving at the individual level and can also identify individuals with MUD. These findings advance the neurobiological understanding of craving through an EEG-tailored computational model of the brain connectome. Dissecting neurophysiological features provides a clinical avenue for personalized treatment of MUD.
Exercise-induced crosstalk between immune cells and adipocytes in humans: Role of oncostatin-M
Authors: Lucile Dollet, Leonidas S. Lundell, Alexander V. Chibalin, Logan A. Pendergrast, Nicolas J. Pillon, Elizabeth L. Lansbury, Merve Elmastas, Scott Frendo-Cumbo, Jutta Jalkanen, Thais de Castro Barbosa, Daniel T. Cervone, Kenneth Caidahl, Oksana Dmytriyeva, Atul S. Deshmukh, Romain Barrès, Mikael Rydén, Harriet Wallberg-Henriksson, Juleen R. Zierath, Anna Krook
Journal: Cell Reports Medicine (2023)

The discovery of exercise-regulated circulatory factors has fueled interest in organ crosstalk, especially between skeletal muscle and adipose tissue, and the role in mediating beneficial effects of exercise. We studied the adipose tissue transcriptome in men and women with normal glucose tolerance or type 2 diabetes following an acute exercise bout, revealing substantial exercise- and time-dependent changes, with sustained increase in inflammatory genes in type 2 diabetes. We identify oncostatin-M as one of the most upregulated adipose-tissue-secreted factors post-exercise. In cultured human adipocytes, oncostatin-M enhances MAPK signaling and regulates lipolysis. Oncostatin-M expression arises predominantly from adipose tissue immune cell fractions, while the corresponding receptors are expressed in adipocytes. Oncostatin-M expression increases in cultured human Thp1 macrophages following exercise-like stimuli. Our results suggest that immune cells, via secreted factors such as oncostatin-M, mediate a crosstalk between skeletal muscle and adipose tissue during exercise to regulate adipocyte metabolism and adaptation.
Manchester Procedure vs Sacrospinous Hysteropexy for Pelvic Organ Prolapse
Authors: Yang Ye, John S. Ji, Lan Zhu
Journal: JAMA (2023)

To the Editor A recent study1 compared the outcomes of 2 surgeries for pelvic organ prolapse: the Manchester procedure and sacrospinous hysteropexy. Two years after surgery, the Manchester procedure, which preserved the uterus, showed a higher success rate (87.3% vs 77.0%).
Misclassification of Both Influenza Infection and Oseltamivir Exposure Status in Administrative Data
Authors: Hannah K. Bassett, Eric R. Coon, Jonathan M. Mansbach, Kathleen Snow, Maya Wheeler, Alan R. Schroeder
Journal: JAMA Pediatrics (2023)

This cross-sectional study examines documented hospitalization for influenza and administration of neuraminidase inhibitors in US children.
Metabolomics at the tumor microenvironment interface: Decoding cellular conversations
Authors: Naomi Berrell, Habib Sadeghirad, Tony Blick, Charles Bidgood, Graham R. Leggatt, Ken O'Byrne, Arutha Kulasinghe
Journal: Medicinal Research Reviews (2023)

Cancer heterogeneity remains a significant challenge for effective cancer treatments. Altered energetics is one of the hallmarks of cancer and influences tumor growth and drug resistance. Studies have shown that heterogeneity exists within the metabolic profile of tumors, and personalized-combination therapy with relevant metabolic interventions could improve patient response. Metabolomic studies are identifying novel biomarkers and therapeutic targets that have improved treatment response. The spatial location of elements in the tumor microenvironment are becoming increasingly important for understanding disease progression. The evolution of spatial metabolomics analysis now allows scientists to deeply understand how metabolite distribution contributes to cancer biology. Recently, these techniques have spatially resolved metabolite distribution to a subcellular level. It has been proposed that metabolite mapping could improve patient outcomes by improving precision medicine, enabling earlier diagnosis and intraoperatively identifying tumor margins. This review will discuss how altered metabolic pathways contribute to cancer progression and drug resistance and will explore the current capabilities of spatial metabolomics technologies and how these could be integrated into clinical practice to improve patient outcomes.
Quantifying the benefits of early sublingual allergen immunotherapy tablet initiation in children
Authors: Eckard Hamelmann, Eva Hammerby, Katrine Skaarup Scharling, Mikkel Pedersen, Anna Okkels, Jochen Schmitt
Journal: Allergy (2023)

Abstract Background Allergic rhinitis (AR) is a chronic inflammatory disease of the upper airway, which progresses into allergic asthma (AA) in up to 45% of children. This analysis aimed to investigate clinical and economic benefits of sublingual allergen immunotherapy (SLIT tablets) initiated early in childhood for the treatment of AR by quantifying the long‐term reduction in new cases of AA. Methods A Markov model was developed to estimate the long‐term effects of SLIT tablets on the risk of developing asthma. Key parameters were primarily based on data from the GRAZAX® Asthma Prevention trial and included the age‐ and treatment‐dependent risk of developing AA as well as annual probabilities of progression/remission in AR severity. Healthcare costs were estimated using data from the REACT study. Results In a modelled cohort of children with moderate‐to‐severe seasonal AR initiated on SLIT tablets at ages 7 and 12, 24% and 29%, respectively, develop AA during a 20‐year period. In comparison, when initiated at age 5, 19% develop AA. Additionally, initiation of SLIT tablets at age 5 is associated with a total healthcare cost of EUR 20,429 per patient, whereas initiation at ages 7 and 12 is associated with, respectively, EUR 21,050 and EUR 22,379 per patient 20 years after AR diagnosis. Conclusion Initiation of SLIT tablets in early childhood is associated with a clinically meaningful and permanent reduction in new cases of AA and lower healthcare costs among children with AR. This finding supports the clinical relevance of initiating SLIT tablets early for children with AR to obtain long‐term clinical benefits.
Tezepelumab in patients with allergic and eosinophilic asthma
Authors: Marco Caminati, Roland Buhl, Jonathan Corren, Nicola A. Hanania, Harold Kim, Stephanie Korn, Marek Lommatzsch, Neil Martin, Andrea Matucci, Shuaib M. Nasser, Ian D. Pavord, Christian Domingo
Journal: Allergy (2023)

Abstract Asthma is a heterogeneous disease commonly driven by allergic and/or eosinophilic inflammation, both of which may be present in severe disease. Most approved biologics for severe asthma are indicated for specific phenotypes and target individual downstream type 2 components of the inflammatory cascade. Tezepelumab, a human monoclonal antibody (immunoglobulin G2λ), binds specifically to thymic stromal lymphopoietin (TSLP), an epithelial cytokine that initiates and sustains allergic and eosinophilic inflammation in asthma. By blocking TSLP, tezepelumab has demonstrated efficacy across known asthma phenotypes and acts upstream of all current clinically used biomarkers. In a pooled analysis of the phase 2b PATHWAY (NCT02054130) and phase 3 NAVIGATOR (NCT03347279) studies, compared with placebo, tezepelumab reduced the annualized asthma exacerbation rate over 52 weeks by 62% (95% confidence interval [CI]: 53, 70) in patients with perennial aeroallergen sensitization (allergic asthma); by 71% (95% CI: 62, 78) in patients with a baseline blood eosinophil count ≥300 cells/μL; and by 71% (95% CI: 59, 79) in patients with allergic asthma and a baseline blood eosinophil count ≥300 cells/μL. This review examines the efficacy and mode of action of tezepelumab in patients with allergic asthma, eosinophilic asthma and coexisting allergic and eosinophilic phenotypes.
Reduction of extramedullary erythropoiesis and amelioration of anemia in a β‐thalassemia patient treated with thalidomide
Authors: Valeria Maria Pinto, Nicola Romano, Manuela Balocco, Paola Carrara, Martina Lamagna, Sabrina Quintino, Antonio Castaldi, Gian Luca Forni
Journal: American Journal of Hematology (2023)

β-thalassemia patient treated with thalidomide: dimensional reduction of EMH foci (MRI evaluation) and reduction of hematological responce at follow-up. Nothing to disclose. The data are available from the corresponding author upon reasonable request.
Microenvironment-induced CREPT expression by cancer-derived small extracellular vesicles primes field cancerization
Authors: Yuting Lin, Hanguo Jiang, Jun Li, Fangli Ren, Yinyin Wang, Ying Qiu, Jianghua Li, Mengdi Li, Ying Wang, Liu Yang, Yunhao Song, Huihui Jia, Wanli Zhai, Yanshen Kuang, Hanyang Yu, Wenyuan Zhu, Suling Liu, Eiichi Morii, Christian Ensinger, Charles David, Hanqiu Zheng, Jianguo Ji, Hongxia Wang, Zhijie Chang
Journal: Theranostics (2023)

Rationale: Cancer local recurrence increases the mortality of patients, and might be caused by field cancerization, a pre-malignant alteration of normal epithelial cells.It has been suggested that cancer-derived small extracellular vesicles (CDEs) may contribute to field cancerization, but the underlying mechanisms remain poorly understood.In this study, we aim to identify the key regulatory factors within recipient cells under the instigation of CDEs.Methods: In vitro experiments were performed to demonstrate that CDEs promote the expression of CREPT in normal epithelial cells.TMT-based quantitative mass spectrometry was employed to investigate the proteomic differences between normal cells and tumor cells.Loss-of-function approaches by CRISPR-Cas9 system were used to assess the role of CREPT in CDEs-induced field cancerization.RNA-seq was performed to explore the genes regulated by CREPT during field cancerization.Results: CDEs promote field cancerization by inducing the expression of CREPT in non-malignant epithelial cells through activating the ERK signaling pathway.Intriguingly, CDEs failed to induce field cancerization when CREPT was deleted, highlighting the importance of CREPT.Transcriptomic analyses revealed that CDEs elicited inflammatory responses, primarily through activation of the TNF signaling pathway.CREPT, in turn, regulates the transduction of downstream signals of TNF by modulating the expression of TNFR2 and PI3K, thereby promoting inflammation-to-cancer transition. Conclusion:CREPT not only serves as a biomarker for field cancerization, but also emerges as a target for preventing the cancer local recurrence.
Combined BET and MEK Inhibition synergistically suppresses melanoma by targeting YAP1
Authors: Rui Hu, Huihui Hou, Yao Li, Minghui Zhang, Xin Li, Yanzhong Chen, Ying Guo, Hongyin Sun, Shuang Zhao, Mengting Liao, Dongsheng Cao, Qin Yan, Xiang Chen, Mingzhu Yin
Journal: Theranostics (2023)

Rationale:The response rate to the MEK inhibitor trametinib in BRAF-mutated melanoma patients is less than 30%, and drug resistance develops rapidly, but the mechanism is still unclear.Yes1-associated transcriptional regulator (YAP1) is highly expressed in melanoma and may be related to MEK inhibitor resistance.The purpose of this study was to investigate the mechanism of YAP1 in MEK inhibitor resistance in melanoma and to screen YAP1 inhibitors to further determine whether YAP1 inhibition reverses MEK inhibitor resistance.Methods: On the one hand, we analyzed paired melanoma and adjacent tissue samples using RNA-seq and found that the Hippo-YAP1 signaling pathway was the top upregulated pathway.On the other hand, we evaluated the transcriptomes of melanoma samples from patients before and after trametinib treatment and investigated the correlation between YAP1 expression and trametinib resistance.Then, we screened for inhibitors that repress YAP1 expression and investigated the mechanisms.Finally, we investigated the antitumor effect of YAP1 inhibition combined with MEK inhibition both in vitro and in vivo.Results: We found that YAP1 expression levels upon trametinib treatment in melanoma patients were correlated with resistance to trametinib.YAP1 was translocated into the nucleus after trametinib treatment in melanoma cells, which could render resistance to MEK inhibition.Thus, we screened for inhibitors that repress YAP1 expression and identified multiple bromodomain and extra-terminal (BET) inhibitors, including NHWD-870, as hits.BET inhibition repressed YAP1 expression by decreasing BRD4 binding to the YAP1 promoter.Consistently, YAP1 overexpression was sufficient to reverse the proliferation defect caused by BRD4 depletion.In addition, the BET inhibitor NHWD-870 acted synergistically with trametinib to suppress melanoma growth in vitro and in vivo.Conclusions: We identified a new vulnerability for MEK inhibitor-resistant melanomas, which activated Hippo pathway due to elevated YAP1 activity.Inhibition of BRD4 using BET inhibitors suppressed YAP1 expression and led to blunted melanoma growth when combined with treatment with the MEK inhibitor trametinib.
Pharmacological inhibition of MYC to mitigate chemoresistance in preclinical models of squamous cell carcinoma
Authors: Shuo Liu, Zhen Qin, Yaqing Mao, Ning Wang, Wenbo Zhang, Yujia Wang, Yiwen Chen, Lingfei Jia, Xin Peng
Journal: Theranostics (2023)

Cisplatin-based chemotherapy is the first-line treatment for late-stage head and neck squamous cell carcinoma (HNSCC). However, resistance to cisplatin has become a major obstacle for effective therapy. Cancer stem cells (CSCs) are critical for tumor initiation, growth, metastasis, and chemoresistance. How to effectively eliminate CSCs and overcome chemoresistance remains a key challenge. Herein, we confirmed that MYC plays critical roles in chemoresistance, and explored targeting MYC to overcome cisplatin resistance in preclinical models.
Inactivation of the NLRP3 inflammasome mediates exosome-based prevention of atrial fibrillation
Authors: Sandrine Parent, Ramana Vaka, Jennifer St Amant, Saad Kahn, Sophie Van Remortel, Christina Bi, David Courtman, Duncan John Stewart, Darryl Raymond Davis
Journal: Theranostics (2023)

Extracellular vesicles (EVs) from human explant-derived cells injected directly into the atria wall muscle at the time of open chest surgery reduce atrial fibrosis, atrial inflammation, and atrial fibrillation (AF) in a rat model of sterile pericarditis. Albeit a promising solution to prevent postoperative AF, the mechanism(s) underlying this effect are unknown and it is not clear if this benefit is dependent on EV dose.
Tumor-tropic Trojan horses: Using mesenchymal stem cells as cellular nanotheranostics
Authors: Ana Rosu, Behnaz Ghaemi, Jeff W.M. Bulte, Ali Shakeri-Zadeh
Journal: Theranostics (2023)

Various classes of nanotheranostics have been developed for enhanced tumor imaging and therapy. However, key limitations for a successful use of nanotheranostics include their targeting specificity with limited off-site tissue accumulation as well as their distribution and prolonged retention throughout the entire tumor. Due to their inherent tumor-tropic properties, the use of mesenchymal stem cells (MSCs) as a "Trojan horse" has recently been proposed to deliver nanotheranostics more effectively. This review discusses the current status of "cellular nanotheranostics" for combined (multimodal) imaging and therapy in preclinical cancer models. Emphasis is placed on the limited knowledge of the signaling pathways and molecular mechanisms of MSC tumor-tropism, and how such information may be exploited to engineer MSCs in order to further improve tumor homing and nanotheranostic delivery using image-guided procedures.
Current evidence and therapeutic implication of PANoptosis in cancer
Authors: Dickson Kofi Wiredu Ocansey, Fei Qian, Peipei Cai, Stephen Ocansey, Samuel Amoah, Yingchen Qian, Fei Mao
Journal: Theranostics (2023)

Regulated cell death (RCD) is considered a critical pathway in cancer therapy, contributing to eliminating cancer cells and influencing treatment outcomes. The application of RCD in cancer treatment is marked by its potential in targeted therapy and immunotherapy. As a type of RCD, PANoptosis has emerged as a unique form of programmed cell death (PCD) characterized by features of pyroptosis, apoptosis, and necroptosis but cannot be fully explained by any of these pathways alone. It is regulated by a multi-protein complex called the PANoptosome. As a relatively new concept first described in 2019, PANoptosis has been shown to play a role in many diseases, including cancer, infection, and inflammation. This study reviews the application of PCD in cancer, particularly the emergence and implication of PANoptosis in developing therapeutic strategies for cancer. Studies have shown that the characterization of PANoptosis patterns in cancer can predict survival and response to immunotherapy and chemotherapy, highlighting the potential for PANoptosis to be used as a therapeutic target in cancer treatment. It also plays a role in limiting the spread of cancer cells. PANoptosis allows for the elimination of cancer cells by multiple cell death pathways and has the potential to address various challenges in cancer treatment, including drug resistance and immune evasion. Moreover, active investigation of the mechanisms and potential therapeutic agents that can induce PANoptosis in cancer cells is likely to yield effective cancer treatments and improve patient outcomes. Research on PANoptosis is still ongoing, but it is a rapidly evolving field with the potential to lead to new treatments for various diseases, including cancer.
Prevalence and Therapeutic Targeting of High-Level ERBB2 Amplification in NSCLC
Authors: Igor Odintsov, Maisam Makarem, Mizuki Nishino, Sara Emily Bachert, Tom Zhang, Jaclyn LoPiccolo, Cloud P. Paweletz, Prafulla C. Gokhale, Elena Ivanova, Aisha Saldanha, Charles M. Rudin, William W. Lockwood, Marc Ladanyi, Romel Somwar, Pasi A. Jänne, Lynette M. Sholl
Journal: Journal of Thoracic Oncology (2023)

IntroductionERBB2 amplification in lung cancer remains poorly characterized. HER2 (encoded by ERBB2) is a transmembrane tyrosine kinase capable of ligand-independent dimerization and signaling when overexpressed, and a common cause of HER2 overexpression is ERBB2 amplification. Here, we evaluated the clinicopathologic and genomic characteristics of ERBB2-amplified NSCLC and explored a HER2 antibody–drug conjugate (ADC) therapeutic strategy.MethodsOur institutional next-generation DNA sequencing data (OncoPanel) from 5769 NSCLC samples (5075 patients) were queried for cases having high-level ERBB2 amplification (≥6 copies). Clinical and demographic characteristics were extracted from the electronic medical records. Efficacy of the pan-ERBB inhibitor afatinib or HER2 ADCs (trastuzumab deruxtecan and trastuzumab emtansine) was evaluated in NSCLC preclinical models and patients with ERBB2 amplification.ResultsHigh-level ERBB2 amplification was identified in 0.9% of lung adenocarcinomas and reliably predicted overexpression of HER2. ERBB2 amplification events are detected in two distinct clinicopathologic and genomic subsets of NSCLC: as the sole mitogenic driver in tumors arising in patients with a smoking history or as a concomitant alteration with other mitogenic drivers in patients with a light or never smoking history. We further reveal that trastuzumab deruxtecan is effective therapy in in vitro and in vivo preclinical models of NSCLC harboring ERBB2 amplification and report two cases of clinical activity of an anti-HER2 ADC in patients who acquired ERBB2 amplification after previous targeted therapy.ConclusionsHigh-level ERBB2 amplification reliably predicts HER2 overexpression in patients with NSCLC, and HER2 ADC is effective therapy in this population.
Comparative Effectiveness of Intensity-Modulated Proton Therapy Versus Intensity-Modulated Radiotherapy for Patients With Inoperable Esophageal Squamous Cell Carcinoma Undergoing Curative-Intent Concurrent Chemoradiotherapy
Authors: Chia-Lun Chang, Kuan-Chou Lin, Wan-Ming Chen, Ben-Chang Shia, Szu-Yuan Wu
Journal: Journal of Thoracic Oncology (2023)
Performance of DETECT Pulmonary Arterial Hypertension Algorithm According to the Hemodynamic Definition of Pulmonary Arterial Hypertension in the 2022 European Society of Cardiology and the European Respiratory Society Guidelines
Authors: Oliver Distler, Diana Bonderman, J. Gerry Coghlan, Christopher P. Denton, Ekkehard Grünig, Dinesh Khanna, Vallerie V. McLaughlin, Ulf Müller‐Ladner, Janet E. Pope, Madelon C. Vonk, Lilla Di Scala, Jean‐Christophe Lemarie, Loïc Perchenet, Éric Hachulla
Journal: Arthritis & Rheumatology (2023)

Objective The evidence‐based DETECT pulmonary arterial hypertension (PAH) algorithm is frequently used in patients with systemic sclerosis (SSc) to help clinicians screen for PAH by using noninvasive data to recommend patient referral to echocardiography and, if applicable, for a diagnostic right‐sided heart catheterization. However, the hemodynamic definition of PAH was recently updated in the 2022 European Society of Cardiology (ESC)/European Respiratory Society (ERS) guidelines. The performance of DETECT PAH in identifying patients with a high risk of PAH according to this new definition was assessed. Methods In this post hoc analysis of DETECT, which comprised 466 patients with SSc, the performance of the DETECT PAH algorithm in identifying patients with a high risk of PAH as defined in the 2022 ESC/ERS guidelines (mean pulmonary arterial pressure [mPAP] &gt;20 mm Hg, pulmonary capillary wedge pressure [PCWP] ≤15 mm Hg, and pulmonary vascular resistance &gt;2 Wood units) was assessed using summary statistics and was descriptively compared to the known performance of DETECT PAH as defined in 2014, when it was developed (mPAP ≥25 mm Hg and PCWP ≤15 mm Hg). Results The sensitivity of DETECT PAH in identifying patients with a high risk of PAH according to the 2022 ESC/ERS definition was lower (88.2%) compared to the 2014 definition (95.8%). Specificity improved from 47.8% to 50.8%. Conclusion The performance of the DETECT algorithm to screen for PAH in patients with SSc is maintained when PAH is defined according to the 2022 ESC/ERS hemodynamic definition, indicating that DETECT remains applicable to screen for PAH in patients with SSc. image
Prognostic Role of Interferon‐λ3 in Anti–Melanoma Differentiation–Associated Gene 5–Positive <scp>Dermatomyositis‐Associated</scp> Interstitial Lung Disease
Authors: Atsuki Fukada, Tomoyuki Fujisawa, Hironao Hozumi, Keigo Koda, Taisuke Akamatsu, Yoshiyuki Oyama, Yasuomi Satake, Mitsuru Niwa, Yusuke Kaida, Hiroyuki Matsuda, Koshi Yokomura, Naoki Koshimizu, Mikio Toyoshima, Shiro Imokawa, Dai Hashimoto, Akira Yoshida, Takahisa Gono, Masataka Kuwana, Yasuhiko Yamano, Yasuhiro Kondoh, Keita Yamashita, Masato Maekawa, Kazutaka Mori, Yusuke Inoue, Hideki Yasui, Yuzo Suzuki, Masato Karayama, Kazuki Furuhashi, Noriyuki Enomoto, Naoki Inui, Takafumi Suda
Journal: Arthritis & Rheumatology (2023)

Interferon-λ3 (IFNλ3) is a cytokine with antiviral functions on barrier surfaces, and it is associated with disease activity in autoimmune diseases. This study assessed the clinical significance of serum IFNλ3 levels in polymyositis/dermatomyositis (PM/DM)-associated interstitial lung disease (ILD).