tbuckley/cabot-search huggingface dataset:
TOX3 deficiency mitigates hyperglycemia by suppressing hepatic gluconeogenesis through FoxO1
Authors: Congcong Liu, Yuanwen Zheng, Shourui Hu, Xiaofan Liang, Yuxuan Li, Zhiheng Yu, Yue Liu, Yuehong Bian, Yuanyuan Man, Shigang Zhao, Xin Liu, Hongbin Liu, Tao Huang, Jinlong Ma, Zi-Jiang Chen, Han Zhao, Yuqing Zhang
Journal: Metabolism (2023)
Unusual Presentation of Solitary Penile Metastasis of Prostate Cancer on 68Ga-PSMA PET/CT
Authors: Noora Essa Bin Essa, Alaa Khalid Alderaibi, Francesco Fraioli
Journal: Clinical Nuclear Medicine (2023)

Abstract A 75-year-old patient was referred with biochemical recurrence for prostate cancer. The patient underwent 68 Ga-PSMA (prostate-specific membrane antigen) PET/CT scan, which revealed a focal PSMA activity in the proximal left lateral penile margin. Although a subsequent ultrasound did not identify the abnormality, MRI pelvis revealed a 10-mm lesion in the left proximal corpus cavernosum. This lesion was consistent with metastatic acinar adenocarcinoma of the prostate on postresection histopathology. This unusual presentation of asymptomatic, histopathology-proven, penile solitary metastases was documented 3 years after robotic-assisted laparoscopic prostatectomy and pelvic external beam radiotherapy.
68Ga-Citrate PET/CT Imaging in the Diagnosis of Skull Base Osteomyelitis and Its Usefulness in the Assessment of Treatment Response
Authors: Hanna Elizabeth Johnson, Saumya Sara Sunny, Julie Hephzibah, Regi Thomas, Rajan Sundaresan
Journal: Clinical Nuclear Medicine (2023)

Purpose 68 Ga-citrate PET/CT imaging in the diagnosis of skull base osteomyelitis (SBO) and its usefulness in the assessment of treatment response. Methods Eighteen patients underwent 68 Ga-citrate PET/CT scans for suspected SBO for diagnosis/assessment of treatment response. Results Of 18 patients, 16 patients had a positive study for SBO, and 2 patients had a negative study. Scan findings were correlated with clinical, biochemical, microbiological, and radiological parameters. Conclusion 68 Ga-citrate PET/CT is a promising tool in the diagnosis and management of skull base osteomyelitis.
Transformation From Atypical to Anaplastic Metastatic Meningioma
Authors: Robin Morcet-Delattre, Pierre Meneret, Olivier Coue, Elodie Vauleon, Kevin Prigent
Journal: Clinical Nuclear Medicine (2023)

Abstract World Health Organization (WHO) grade III anaplastic meningioma is scarce. In this way, most studies compared WHO grade I and II. Otherwise, some authors are uncertain about using 18 F-FDG as a diagnostic tool to estimate the WHO grade, especially high. We report the case from a man with a grading tumor evolution from WHO grade II atypical to grade III anaplastic metastatic meningioma. This turning point was imaged using 68 Ga-DOTATOC and 18 F-FDG. Diagnostic was confirmed by histology. The case underlines the unparalleled power of molecular imaging characterized by high sensitivity staging and spectacular avidity changing relationship with grading tumor evolution.
Community-Based Doulas — Can Clinicians Share Power to Improve Maternal and Infant Health Outcomes?
Authors: Dolly Pressley Byrd, Elizabeth Buys, Amanda Brickhouse Murphy, Crystal Cené
Journal: New England Journal of Medicine (2023)

Interview with Crystal Cené on the potential benefits, particularly for Black birthing people, of partnerships between perinatal care providers and community-based doulas. (14:57)Download Partnerships between perinatal care providers and community-based doulas are one way to improve health outcomes. Unfortunately, U.S. clinicians are often hesitant or unwilling to share power.
Incidence of healthcare utilization for allergic and respiratory infectious diseases in children with asthma before and during the COVID‐19 pandemic
Authors: Eun Lee, Eun Hee Rhee, Jinho Yu, Kyunghoon Kim, Hwan Soo Kim, Chae Hyun Im, Gitae Seo, Woo Kyung Kim, Dae Jin Song, Ji Soo Park, Young Yoo, Dong In Suh, Sungsu Jung, Jisun Yoon, Dae Hyun Lim, Hey Sung Baek, Meeyong Shin, Ji Won Kwon, Gwang Cheon Jang, Ju Hee Seo, Sung Il Woo, Youn Ho Shin, Ju Suk Lee, Seung Won Lee, Hyeon‐Jong Yang
Journal: Allergy (2023)

The data that support the findings of this study are available from the HIRA. Restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available due to personal information protection. Data are available at https://opendata.hira.or.kr/home.do. Appendix S1 Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Rescue of p53 functions by in vitro‐transcribed mRNA impedes the growth of high‐grade serous ovarian cancer
Authors: Monika Raab, Izabela Kostova, Samuel Peña‐Llopis, Daniela Fietz, Monika Kressin, Seyed Mohsen Aberoumandi, Evelyn Ullrich, Sven Becker, Mourad Sanhaji, Klaus Strebhardt
Journal: Cancer Communications (2023)

Abstract Background The cellular tumor protein p53 ( TP53 ) is a tumor suppressor gene that is frequently mutated in human cancers. Among various cancer types, the very aggressive high‐grade serous ovarian carcinoma (HGSOC) exhibits the highest prevalence of TP53 mutations, present in &gt;96% of cases. Despite intensive efforts to reactivate p53, no clinical drug has been approved to rescue p53 function. In this study, our primary objective was to administer in vitro‐transcribed (IVT) wild‐type (WT) p53‐mRNA to HGSOC cell lines, primary cells, and orthotopic mouse models, with the aim of exploring its impact on inhibiting tumor growth and dissemination, both in vitro and in vivo. Methods To restore the activity of p53, WT p53 was exogenously expressed in HGSOC cell lines using a mammalian vector system. Moreover, IVT WT p53 mRNA was delivered into different HGSOC model systems (primary cells and patient‐derived organoids) using liposomes and studied for proliferation, cell cycle progression, apoptosis, colony formation, and chromosomal instability. Transcriptomic alterations induced by p53 mRNA were analyzed using RNA sequencing in OVCAR‐8 and primary HGSOC cells, followed by ingenuity pathway analysis. In vivo effects on tumor growth and metastasis were studied using orthotopic xenografts and metastatic intraperitoneal mouse models. Results Reactivation of the TP53 tumor suppressor gene was explored in different HGSOC model systems using newly designed IVT mRNA‐based methods. The introduction of WT p53 mRNA triggered dose‐dependent apoptosis, cell cycle arrest, and potent long‐lasting inhibition of HGSOC cell proliferation. Transcriptome analysis of OVCAR‐8 cells upon mRNA‐based p53 reactivation revealed significant alterations in gene expression related to p53 signaling, such as apoptosis, cell cycle regulation, and DNA damage. Restoring p53 function concurrently reduces chromosomal instability within the HGSOC cells, underscoring its crucial contribution in safeguarding genomic integrity by moderating the baseline occurrence of double‐strand breaks arising from replication stress. Furthermore, in various mouse models, treatment with p53 mRNA reduced tumor growth and inhibited tumor cell dissemination in the peritoneal cavity in a dose‐dependent manner. Conclusions The IVT mRNA‐based reactivation of p53 holds promise as a potential therapeutic strategy for HGSOC, providing valuable insights into the molecular mechanisms underlying p53 function and its relevance in ovarian cancer treatment.
Glutathione‐triggered prodrugs: Design strategies, potential applications, and perspectives
Authors: Jintao Zhao, Xinming Li, Tao Ma, Bingbing Chang, Baoxin Zhang, Jianguo Fang
Journal: Medicinal Research Reviews (2023)

The burgeoning prodrug strategy offers a promising avenue toward improving the efficacy and specificity of cytotoxic drugs. Elevated intracellular levels of glutathione (GSH) have been regarded as a hallmark of tumor cells and characteristic feature of the tumor microenvironment. Considering the pivotal involvement of elevated GSH in the tumorigenic process, a diverse repertoire of GSH-triggered prodrugs has been developed for cancer therapy, facilitating the attenuation of deleterious side effects associated with conventional chemotherapeutic agents and/or the attainment of more efficacious therapeutic outcomes. These prodrug formulations encompass a spectrum of architectures, spanning from small molecules to polymer-based and organic-inorganic nanomaterial constructs. Although the GSH-triggered prodrugs have been gaining increasing interests, a comprehensive review of the advancements made in the field is still lacking. To fill the existing lacuna, this review undertakes a retrospective analysis of noteworthy research endeavors, based on a categorization of these molecules by their diverse recognition units (i.e., disulfides, diselenides, Michael acceptors, and sulfonamides/sulfonates). This review also focuses on explaining the distinct benefits of employing various chemical architecture strategies in the design of these prodrug agents. Furthermore, we highlight the potential for synergistic functionality by incorporating multiple-targeting conjugates, theranostic entities, and combinational treatment modalities, all of which rely on the GSH-triggering. Overall, an extensive overview of the emerging field is presented in this review, highlighting the obstacles and opportunities that lie ahead. Our overarching goal is to furnish methodological guidance for the development of more efficacious GSH-triggered prodrugs in the future. By assessing the pros and cons of current GSH-triggered prodrugs, we expect that this review will be a handful reference for prodrug design, and would provide a guidance for improving the properties of prodrugs and discovering novel trigger scaffolds for constructing GSH-triggered prodrugs.
Achieving Complete Tumor Clearance: A Minimalist Manganese Hydrogel for Magnetic Resonance Imaging‐Guided Synergetic Microwave Ablation and Chemodynamic Therapy
Authors: Yan Zhou, Gang Shu, Ying Luo, Fengmei Wang, Xiang Jing, Jinbin Pan, Shao‐Kai Sun
Journal: Advanced Healthcare Materials (2023)

The combination of microwave ablation (MWA) and chemodynamic therapy (CDT) presents a promising strategy for complete eradication of residual tumor after MWA. However, it remains challenging and urgent to develop a facile, biocompatible, and imaging-guided platform for the achievement of this goal. Herein, a minimalist manganese hydrogel (ALG-Mn hydrogel) is proposed for synergistic MWA and CDT to completely eradicate tumor in vivo. The ALG-Mn hydrogel is prepared using a simple mixing method and exhibits excellent syringeability, remarkable microwave sensitivity, and potent Fenton-like activity. By assisting in MWA procedures, the ALG-Mn hydrogel enables both elimination of primary tumor mass through enhanced MWA efficacy and eradication of potential residual tumor tissues via robust CDT. This approach achieves complete tumor clearance without additional drug loading. Furthermore, the paramagnetic Mn
Frequency of fungal pathogens in autopsy studies of people who died with HIV in Africa: a scoping review
Authors: Felix Bongomin, Winnie Kibone, Linda Atulinda, Bethan Morgan, Bright Ocansey, Isabelle S.R. Storer, Norman van Rhijn, Conrad Muzoora, David W. Denning, Davidson H. Hamer
Journal: Clinical Microbiology and Infection (2023)
A clinical perspective on ectopic Cushing’s syndrome
Authors: Oskar Ragnarsson, C. Christofer Juhlin, David J. Torpy, Henrik Falhammar
Journal: Trends in Endocrinology and Metabolism (2023)

Cushing's syndrome (CS) refers to the clinical features of prolonged pathological glucocorticoid excess. About 10–20% of individuals with CS have ectopic CS (ECS), that is, an adrenocorticotropin (ACTH)-producing tumour outside the pituitary gland. ACTH-secreting neuroendocrine neoplasia (NENs) can arise from many organs, although bronchial NEN, small cell lung cancer (SCLC), pancreatic NEN, thymic NEN, medullary thyroid cancer (MTC), and pheochromocytoma are the most common. Patients with ECS frequently present with severe hypercortisolism. The risk of life-threatening complications is high in severe cases, unless the hypercortisolism is effectively treated. A good outcome in ECS requires a methodical approach, incorporating prompt diagnosis, tumour localization, control of cortisol excess, and resection of the primary tumour when possible.
Current strategies of cell and gene therapy for solid tumors: results of the joint international ESMO and CTIWP-EBMT survey
Authors: P. Comoli, G. Pentheroudakis, A. Ruggeri, U. Koehl, F. Lordick, J.E. Mooyaart, J.D. Hoogenboom, A. Urbano-Ispizua, S. Peters, J. Kuball, N. Kröger, A. Sureda, C. Chabannon, J. Haanen, P. Pedrazzoli
Journal: Annals of Oncology (2023)
Liquid Biopsy Response Evaluation Criteria in Solid Tumors (LB-RECIST)
Authors: M.A. Gouda, F. Janku, A. Wahida, L. Buschhorn, A. Schneeweiss, N. Abdel Karim, D. De Miguel Perez, M. Del Re, A. Russo, G. Curigliano, C. Rolfo, V. Subbiah
Journal: Annals of Oncology (2023)

•Dynamic changes in ctDNA can be used to predict tumor response to therapeutic regimens in oncology.•LB-RECIST have been proposed and used in the context of clinical trials.•Several challenges exist for clinical applicability and need to be addressed for a more standardized approach. Current evaluation of treatment response in solid tumors depends on dynamic changes in tumor diameters as measured by imaging. However, these changes can only be detected when there are enough macroscopic changes in tumor volume, which limits the usability of radiological response criteria in evaluating earlier stages of disease response and necessitates much time to lapse for gross changes to be notable. One promising approach is to incorporate dynamic changes in circulating tumor DNA (ctDNA), which occur early in the course of therapy and can predict tumor responses weeks before gross size changes manifest. However, several issues need to be addressed before recommending the implementation of ctDNA response criteria in daily clinical practice such as clinical, biological, and regulatory challenges and, most importantly, the need to standardize/harmonize detection methods and ways to define ctDNA response and/or progression for precision oncology. Herein, we review the use of liquid biopsy (LB) to evaluate response in solid tumors and propose a plan toward standardization of LB-RECIST. Current evaluation of treatment response in solid tumors depends on dynamic changes in tumor diameters as measured by imaging. However, these changes can only be detected when there are enough macroscopic changes in tumor volume, which limits the usability of radiological response criteria in evaluating earlier stages of disease response and necessitates much time to lapse for gross changes to be notable. One promising approach is to incorporate dynamic changes in circulating tumor DNA (ctDNA), which occur early in the course of therapy and can predict tumor responses weeks before gross size changes manifest. However, several issues need to be addressed before recommending the implementation of ctDNA response criteria in daily clinical practice such as clinical, biological, and regulatory challenges and, most importantly, the need to standardize/harmonize detection methods and ways to define ctDNA response and/or progression for precision oncology. Herein, we review the use of liquid biopsy (LB) to evaluate response in solid tumors and propose a plan toward standardization of LB-RECIST.
Re: Michael Eppler, Conner Ganjavi, Lorenzo Storino Ramacciotti, et al. Awareness and Use of ChatGPT and Large Language Models: A Prospective Cross-sectional Global Survey in Urology. Eur Urol. 2024;85:146–53
Authors: Zhongwei Zhao, Zhenye Li, Nengwang Yu
Journal: European Urology (2023)
Age, BMI, and Type 2 Diabetes Modify the Relationship Between PNPLA3 and Advanced Fibrosis in Children and Adults With NAFLD
Authors: Chaowapong Jarasvaraparn, Eduardo Vilar-Gomez, Katherine P. Yates, Laura A. Wilson, Brent Neuschwander-Tetri, Rohit Loomba, Oscar Cummings, Miriam Vos, Stavra Xanthakos, Jeffrey Schwimmer, Jean P. Molleston, Arun Sanyal, James Tonascia, Naga Chalasani
Journal: Clinical Gastroenterology and Hepatology (2023)
Effects of nintedanib on symptoms in patients with progressive pulmonary fibrosis
Authors: Marlies Wijsenbeek, Jeffrey J. Swigris, Yoshikazu Inoue, Michael Kreuter, Toby M. Maher, Takafumi Suda, Michael Baldwin, Heiko Mueller, Klaus B. Rohr, Kevin R. Flaherty
Journal: European Respiratory Journal (2023)

Background Dyspnoea and cough can have a profound impact on the lives of patients with pulmonary fibrosis. We investigated the effects of nintedanib on the symptoms and impact of pulmonary fibrosis in patients with progressive pulmonary fibrosis (PPF) in the INBUILD trial using the Living with Pulmonary Fibrosis (L-PF) questionnaire. Methods Patients had a fibrosing interstitial lung disease (ILD) (other than idiopathic pulmonary fibrosis) of &gt;10% extent on high-resolution computed tomography (HRCT) and met criteria for ILD progression within the prior 24 months. Patients were randomised 1:1 to receive nintedanib or placebo. Changes in L-PF questionnaire scores from baseline to week 52 were assessed using mixed models for repeated measures. Results In total, 663 patients were treated. Compared with placebo, there were significantly smaller increases (worsenings) in adjusted mean L-PF questionnaire total (0.5 versus 5.1), symptoms (1.3 versus 5.3), dyspnoea (4.3 versus 7.8) and fatigue (0.7 versus 4.0) scores in the nintedanib group at week 52. L-PF questionnaire cough score decreased in the nintedanib group and increased in the placebo group (−1.8 versus 4.3). L-PF questionnaire impacts score decreased slightly in the nintedanib group and increased in the placebo group (−0.2 versus 4.6). Similar findings were observed in patients with a usual interstitial pneumonia-like fibrotic pattern on HRCT and in patients with other fibrotic patterns on HRCT. Conclusion Based on changes in L-PF questionnaire scores, nintedanib reduced worsening of dyspnoea, fatigue and cough and the impacts of ILD over 52 weeks in patients with PPF.
Exploring sexual health and risk of sexually transmitted infections among gender diverse individuals
Authors: Samuel A. Mickel, Cassie Sutten Coats, Sara Vargas, Brooke Rogers, Alexi Almonte, Philip A. Chan
Journal: International Journal of Transgender Health (2023)

Introduction: Transgender, non-binary, gender non-conforming, and other gender diverse individuals (TGN) may be at higher risk of sexually transmitted infections (STIs). Transgender women specifically bear a disproportionate burden of HIV and other STIs worldwide. This study describes STI knowledge, risks, and prevention practices among TGN to better characterize barriers to sexual health care and identify potential platforms for sexual health education focusing on STI prevention. Materials and Methods: Qualitative interviews were conducted with N = 14 TGN individuals until thematic saturation was reached. Transcripts were coded and analyzed using thematic analysis. Results: Four major themes emerged: (1) Sexual risk behaviors and STI prevention practices varied across participants; (2) individuals who demonstrated more knowledge about STIs either had a significant identifiable sexual educational experience or had a past personal experience with an STI; (3) individuals were interested in receiving information about STIs and sexual health from health care providers, school sexual education programs, and online resources based on a desire for accessible, private, factual, and inclusive content; and (4) public messaging around sexual health and STIs was seen both as potentially stigmatizing, but also important for increasing awareness of available services. Discussion: We found that while important, considering gender alone may not adequately characterize risk of STI infection for TGN populations, and more research is needed to better characterize risk profiles. Individuals were interested in learning about sexual health and STI prevention from school curricula, health care settings, online resources, and public messaging advertisements, and had recommendations to ensure that these forms of information sharing were relevant, inclusive, and non-stigmatizing.
<i>Jak2</i> <i>V617F</i> clonal hematopoiesis promotes arterial thrombosis via platelet activation and cross talk
Authors: Wenli Liu, Joachim Pircher, Art Schuermans, Qurrat Ul Ain, Zhe Zhang, Michael C. Honigberg, Mustafa Yalcinkaya, Tetsushi Nakao, Ashley Pournamadri, Tong Xiao, Mohammad Ali Hajebrahimi, Lisa Wasner, David Stegner, Tobias Petzold, Pradeep Natarajan, Steffen Massberg, Alan R. Tall, Christian Schulz, Nan Wang
Journal: Blood (2023)
Association between elevated white blood cell counts and thrombotic events in polycythemia vera: analysis from REVEAL
Authors: Aaron T. Gerds, Ruben Mesa, John M. Burke, Michael R. Grunwald, Brady L. Stein, Peg Squier, Jingbo Yu, J. E. Hamer-Maansson, Stephen T. Oh
Journal: Blood (2023)

Abstract Polycythemia vera (PV) is a myeloproliferative neoplasm characterized by clonal proliferation of hematopoietic progenitor cells and is associated with an increased risk of thrombotic events (TEs). Established risk factors for TEs in patients with PV include advanced age, TE history, and elevated hematocrit. Although an association of TE with elevated white blood cell (WBC) counts has been suggested by retrospective studies, this relationship needs further validation. The prospective observational study of patients with polycythemia vera in US clinical practices (REVEAL) study collected prospective clinical data from 2510 patients with PV with a median follow-up of 44.7 months (range, 2-59 months) from enrollment. Using time-dependent covariate Cox proportional hazards models, blood counts were individually modeled with sex, age, disease duration, TE history at enrollment (baseline covariates), and treatment (time-dependent covariate). Analysis of 2271 participants identified 142 TEs in 106 patients. Significant associations with initial TE occurrence during the study period were observed for hematocrit level &amp;gt;45% (hazard ratio [HR], 1.84; 95% confidence interval [95% CI], 1.234-2.749; P = .0028) and WBCs &amp;gt;11 × 109/L (HR, 2.35; 95% CI, 1.598-3.465; P &amp;lt; .0001). Elevated WBC count was significantly associated with initial TE occurrence in both low-risk and high-risk PV. When hematocrit was controlled at ≤45%, WBC count &amp;gt;12 × 109/L was significantly associated with TE occurrence (HR, 1.95; 95% CI, 1.066-3.554; P = .0300). The results support incorporation of WBC count into PV risk stratification and studies of treatment strategies, and indicate the importance of controlling both hematocrit and WBC count in disease management. This trial was registered at www.clinicaltrials.gov as #NCT02252159.
Targeting the tissue factor coagulation initiation complex prevents antiphospholipid antibody development
Authors: Nadine Müller-Calleja, Kristin Grunz, T. Son Nguyen, Jens Posma, Denise Pedrosa, Myriam Meineck, Anne Hollerbach, Johannes Braun, Sabine Muth, Hansjörg Schild, Kathrin Saar, Norbert Hübner, Sriram Krishnaswamy, Jennifer Royce, Luc Teyton, Niels Lemmermann, Julia Weinmann-Menke, Karl J. Lackner, Wolfram Ruf
Journal: Blood (2023)
Clearance of VWF by hepatic macrophages is critical for the protective effect of ADAMTS13 in sickle cell anemia mice
Authors: Huiping Shi, Liang Gao, Nicole Kirby, Bojing Shao, Xindi Shan, Mariko Kudo, Robert Silasi, John Michael McDaniel, Meixiang Zhou, Samuel McGee, Wei Jing, Florea Lupu, Audrey Cleuren, James N. George, Lijun Xia
Journal: Blood (2023)
Whole-genome CRISPR screening identifies molecular mechanisms of PD-L1 expression in adult T-cell leukemia/lymphoma
Authors: Masahiro Chiba, Joji Shimono, Keito Suto, Takashi Ishio, Tomoyuki Endo, Hideki Goto, Hiroo Hasegawa, Michiyuki Maeda, Takanori Teshima, Yibin Yang, Masao Nakagawa
Journal: Blood (2023)