tbuckley/cabot-search huggingface dataset:
Cascade Nanoreactor Employs Mitochondrial‐Directed Chemodynamic and δ‐ALA‐Mediated Photodynamic Synergy for Deep‐Seated Oral Cancer Therapy
Authors: Qiqi Yin, Jie Zhang, Handan Zhang, Jiamin Gao, Lin Weng, Tao Liu, Shuyang Sun, Yanli Yao, Xin Chen
Journal: Advanced Healthcare Materials (2024)

Abstract The management of oral squamous cell carcinoma (OSCC) poses significant challenges, leading to organ impairment and ineffective treatment of deep‐seated tumors, adversely affecting patient prognosis. A cascade nanoreactor that integrates photodynamic therapy (PDT) and chemodynamic therapy (CDT) for comprehensive multimodal OSCC treatment is introduced. Utilizing iron oxide and mesoporous silica, the FMMSH drug delivery system, encapsulating the photosensitizer prodrug δ‐aminolevulinic acid (δ‐ALA), is developed. Triphenylphosphine (TPP) modification facilitates mitochondrial targeting, while tumor cell membrane (TCM) coating provides homotypic targeting. The dual‐targeting δ‐ALA@FMMSH‐TPP‐TCM demonstrate efficacy in eradicating both superficial and deep tumors through synergistic PDT/CDT. Esterase overexpression in OSCC cells triggers δ‐ALA release, and excessive hydrogen peroxide in tumor mitochondria undergoes Fenton chemistry for CDT. The synergistic interaction of PDT and CDT increases cytotoxic ROS levels, intensifying oxidative stress and enhancing apoptotic mechanisms, ultimately leading to tumor cell death. PDT/CDT‐induced apoptosis generates δ‐ALA‐containing apoptotic bodies, enhancing antitumor efficacy in deep tumor cells. The anatomical accessibility of oral cancer emphasizes the potential of intratumoral injection for precise and localized treatment delivery, ensuring focused therapeutic agent delivery to maximize efficacy while minimizing side effects. Thus, δ‐ALA@FMMSH‐TPP‐TCM, tailored for intratumoral injection, emerges as a transformative modality in OSCC treatment.
Altered cardiac energetics in mice lacking <i>Scn1b</i>
Authors: Jessa L Aldridge, Emily Davis Alexander, Allison A Franklin, Chad R Frasier
Journal: Cardiovascular Research (2024)

Journal Article Accepted manuscript Altered cardiac energetics in mice lacking Scn1b Get access Jessa L Aldridge, Jessa L Aldridge East Tennessee State University, Quillen College of Medicine, Department of Biomedical Sciences, Johnson City, TN, United States of America Search for other works by this author on: Oxford Academic PubMed Google Scholar Emily Davis Alexander, Emily Davis Alexander East Tennessee State University, Quillen College of Medicine, Department of Biomedical Sciences, Johnson City, TN, United States of America Search for other works by this author on: Oxford Academic PubMed Google Scholar Allison A Franklin, Allison A Franklin East Tennessee State University, Quillen College of Medicine, Department of Biomedical Sciences, Johnson City, TN, United States of America Search for other works by this author on: Oxford Academic PubMed Google Scholar Chad R Frasier Chad R Frasier East Tennessee State University, Quillen College of Medicine, Department of Biomedical Sciences, Johnson City, TN, United States of America Corresponding Author: Chad R. Frasier, Ph.D., Assistant Professor, Department of Biomedical Sciences, Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, Telephone: (423) 439-2010, Email: frasierc@etsu.edu https://orcid.org/0000-0002-7496-2830 Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, cvae087, https://doi.org/10.1093/cvr/cvae087 Published: 20 April 2024 Article history Received: 21 December 2023 Revision received: 21 February 2024 Accepted: 29 February 2024 Published: 20 April 2024
Demographic bias in misdiagnosis by computational pathology models
Authors: Anurag Vaidya, Richard J. Chen, Drew F. K. Williamson, Andrew H. Song, Guillaume Jaume, Yuzhe Yang, Thomas Hartvigsen, Emma C. Dyer, Ming Y. Lu, Jana Lipkova, Muhammad Shaban, Tiffany Y. Chen, Faisal Mahmood
Journal: Nature Medicine (2024)
Metabolic-associated fatty liver voxel-based quantification on CT images using a contrast adapted automatic tool
Authors: Queralt Martín-Saladich, Juan M. Pericàs, Andreea Ciudin, Clara Ramirez-Serra, Manuel Escobar, Jesús Rivera-Esteban, Santiago Aguadé-Bruix, Miguel A. González Ballester, José Raul Herance
Journal: Medical Image Analysis (2024)
Clinicopathologic Features and Cytologic Correlation of ALK-Rearranged Papillary Thyroid Carcinoma: A Series of Eight Cases
Authors: Kun-Ping Shih, Yu-Cheng Lee, Jia-Jiun Tsai, Shu-Hui Lin, Chih-Yi Liu, Wan-Shan Li, Chien-Feng Li, Jen-Fan Hang
Journal: Endocrine Pathology (2024)

Anaplastic lymphoma kinase (ALK) gene fusions are rare in papillary thyroid carcinoma (PTC) but may serve as a therapeutic target. This study aims to evaluate the preoperative cytologic findings and clinicopathologic features of a series of eight ALK-rearranged PTCs from our pathology archives and consultations. All cases were confirmed by ALK D5F3 immunohistochemistry and six with additional targeted RNA-based next-generation sequencing (NGS). The original fine-needle aspiration (FNA) cytology diagnosis included the Bethesda System (TBS) category II in three (37.5%), TBS III in two (25%), TBS V in two (25%), and TBS VI in one (12.5%). Six cases had available FNA cytology and were reviewed. The cytologic features showed microfollicular architecture as well as limited or reduced nuclear elongation and chromatin alterations in all six. Nuclear grooves and pseudoinclusions were absent in two cases, rarely or focally noted in three, and frequently found in one. Two cases initially diagnosed as TBS II, showing microfollicular architecture without well-developed nuclear features, were revised to TBS III (with architectural atypia only). For histologic correlations, four were infiltrative follicular variant PTCs, three as classic subtype PTC with predominant follicular growth, and one as solid/trabecular subtype PTC. All eight cases demonstrated reduced PTC nuclear features with respect to nuclear elongation and chromatin alterations compared to those typically identified in "BRAF-like" PTCs. The NGS testing revealed EML4::ALK fusion in three, STRN::ALK fusion in two, and ITSN2::ALK fusion in one. In conclusion, although ALK-rearranged PTCs have been associated with neutral gene expression profile from a BRAF-RAS scoring perspective, the "RAS-like" nuclear features were more commonly identified in this series, resulting in frequent indeterminate diagnosis of preoperative FNA.
Tackling the threat of antimicrobial resistance in neonates and children: outcomes from the first WHO-convened Paediatric Drug Optimisation exercise for antibiotics
Authors: Alasdair Bamford, Tiziana Masini, Phoebe Williams, Mike Sharland, Valeria Gigante, Devika Dixit, Hatim Sati, Benedikt Huttner, Yasir Bin Nisar, Bernadette Cappello, Wilson Were, Jennifer Cohn, Martina Penazzato
Journal: The Lancet Child & Adolescent Health (2024)
Estimated global and regional causes of deaths from diarrhoea in children younger than 5 years during 2000–21: a systematic review and Bayesian multinomial analysis
Authors: Robert E Black, Jamie Perin, Diana Yeung, Tushara Rajeev, Jacob Miller, Sarah E Elwood, James A Platts-Mills
Journal: The Lancet Global Health (2024)

Information on the causes of deaths from diarrhoea in children younger than 5 years is needed to design improved preventive and therapeutic approaches. We aimed to conduct a systematic analysis of studies to report estimates of the causes of deaths from diarrhoea in children younger than 5 years at global and regional levels during 2000-21.
Palliative procedures for malignant gastric outlet obstruction: a network meta-analysis
Authors: Khoi Van Tran, Nguyen-Phong Vo, Hung Song Nguyen, Nhi Thi Vo, Thi Bao Trang Thai, Vu Anh Pham, El-Wui Loh, Ka-Wai Tam
Journal: Endoscopy (2024)

The optimal treatment for malignant gastric outlet obstruction (GOO) remains uncertain. This systematic review aimed to comprehensively investigate the efficacy and safety of four palliative treatments for malignant GOO: gastrojejunostomy, endoscopic ultrasound-guided gastroenterostomy (EUS-GE), stomach-partitioning gastrojejunostomy (PGJ), and endoscopic stenting.
The role and impact of viruses on cancer development
Authors: Adolfo Contreras, Sandra Amaya Sánchez, Carolina Rodríguez‐Medina, Javier Enrique Botero
Journal: Periodontology 2000 (2024)

Abstract This review focuses on three major aspects of oncoviruses' role in cancer development. To begin, we discuss their geographic distribution, revealing that seven oncoviruses cause 20% of all human cancers worldwide. Second, we investigate the primary carcinogenic mechanisms, looking at how these oncogenic viruses can induce cellular transformation, angiogenesis, and local and systemic inflammation. Finally, we investigate the possibility of SARS‐CoV‐2 infection reactivating latent oncoviruses, which could increase the risk of further disease. The development of oncovirus vaccines holds great promise for reducing cancer burden. Many unanswered questions about the host and environmental cofactors that contribute to cancer development and prevention remain, which ongoing research is attempting to address.
Inhibition of RNase 7 by RNase inhibitor promotes inflammation and <i>Staphylococcus aureus</i> growth: Implications for atopic dermatitis
Authors: Franziska Rademacher, Annika Scheel, Regine Gläser, Lena Schröder, Nina Heinemann, Joachim Bartels, Sascha Gerdes, Dora Stölzl, Elke Rodriguez, Katinka Döhner, Stephan Weidinger, Thomas Werfel, Jürgen Harder
Journal: Allergy (2024)

The antimicrobial ribonuclease RNase 7 is abundantly expressed in the epidermis of lesional skin of atopic dermatitis (AD). Host RNase inhibitor (RI) binds to RNase 7 and blocks its ribonuclease activity. This study aimed to evaluate the impact of RNase 7-RI interactions on AD.
Oral immunotherapy in alpha‐gal red meat allergy: Could specific <scp>IgE</scp> be a potential biomarker in monitoring management?
Authors: D. Ünal, D. Eyice‐Karabacak, A. Kutlu, S. Demir, O. C. Tüzer, F. A. Arslan, S. R. Işık, A. Gelincik
Journal: Allergy (2024)

The data that support the findings of this study are available from the corresponding author upon reasonable request.
The role of acquired host immunity in periodontal diseases
Authors: Denis F. Kinane, David F. Lappin, Shauna Culshaw
Journal: Periodontology 2000 (2024)

Abstract The aim of this narrative review is to relate the contribution of European researchers to the complex topic of the host immune system in periodontal disease, focusing on acquired immunity. Other chapters in this volume will address the genetics and autoantibody responses and other forms of immunity to periodontal disease. While the contribution of European authors is the focus, global literature is included in this descriptive narrative for contextual clarity, albeit many with European co‐authors. The topic is relatively intense and is thus broken down into sections outlined below, tackled as descriptive narratives to enhance understanding. Any attempt at a systematic or scoping review was quickly abandoned given the descriptive nature and marked variation of approach in almost all publications. Even the most uniform area of this acquired periodontal immunology literature, antibody responses to putative pathogens in periodontal diseases, falls short of common structures and common primary outcome variables one would need and expect in clinical studies, where randomized controlled clinical trials (RCTs) abound. Addressing ‘the host's role’ in immunity immediately requires a discussion of host susceptibility, which necessitates consideration of genetic studies (covered elsewhere in the volume and superficially covered here).
Earth Day: time for transformational change
Authors: None The Lancet Diabetes & Endocrinology
Journal: The Lancet Diabetes & Endocrinology (2024)

On April 22, the 54th annual Earth Day will continue endeavours to "diversify, educate and activate the environmental movement worldwide". Part of Earth Day's ongoing work includes broadening the definition of environmental issues to include the health of both individuals and communities. This year's theme, Planet vs Plastics, which encapsulates one of many ways the environment shapes human health, hopes to galvanise businesses, governments, non-governmental organisations, and individuals to commit to call for the end of plastics.
Tranexamic acid versus placebo in individuals with intracerebral haemorrhage treated within 2 h of symptom onset (STOP-MSU): an international, double-blind, randomised, phase 2 trial
Authors: Nawaf Yassi, Henry Zhao, Leonid Churilov, Teddy Y Wu, Henry Ma, Huy-Thang Nguyen, Andrew Cheung, Atte Meretoja, Duy Ton Mai, Timothy Kleinig, Jiann-Shing Jeng, Philip M C Choi, Phuc Dang Duc, Helen Brown, Annemarei Ranta, Neil Spratt, Geoffrey C Cloud, Hao-Kuang Wang, Rohan Grimley, Karim Mahawish, Der-Yang Cho, Darshan Shah, Thai My Phuong Nguyen, Gagan Sharma, Vignan Yogendrakumar, Bernard Yan, Emma L Harrison, Michael Devlin, Dennis Cordato, Nicolas Martinez-Majander, Daniel Strbian, Vincent Thijs, Lauren M Sanders, David Anderson, Mark W Parsons, Bruce C V Campbell, Geoffrey A Donnan, Stephen M Davis
Journal: The Lancet Neurology (2024)
Correction to Lancet Rheumatol 2022; 4: e177–87
Journal: The Lancet Rheumatology (2024)

In figure 2A of this Article, the y axis label for the second healthy controls plot should have read "Anti-spike protein CD8 + IFNγ + TNF + T cells (%)".This correction has been made to the online version as of April 19, 2024.
Beyond misinformation: developing a public health prevention framework for managing information ecosystems
Authors: Atsuyoshi Ishizumi, Jessica Kolis, Neetu Abad, Dimitri Prybylski, Kathryn A Brookmeyer, Christopher Voegeli, Claire Wardle, Howard Chiou
Journal: The Lancet Public Health (2024)

The COVID-19 pandemic has highlighted how infodemics (defined as an overabundance of information, including misinformation and disinformation) pose a threat to public health and could hinder individuals from making informed health decisions. Although public health authorities and other stakeholders have implemented measures for managing infodemics, existing frameworks for infodemic management have been primarily focused on responding to acute health emergencies rather than integrated in routine service delivery. We review the evidence and propose a framework for infodemic management that encompasses upstream strategies and provides guidance on identifying different interventions, informed by the four levels of prevention in public health: primary, secondary, tertiary, and primordial prevention. On the basis of a narrative review of 54 documents (peer-reviewed and grey literature published from 1961 to 2023), we present examples of interventions that belong to each level of prevention. Adopting this framework requires proactive prevention and response through managing information ecosystems, beyond reacting to misinformation or disinformation.
Phase 1a dose escalation study of ivonescimab (AK112/SMT112), an anti-PD-1/VEGF-A bispecific antibody, in patients with advanced solid tumors
Authors: Sophia Frentzas, Anna Rachelle Austria Mislang, Charlotte Lemech, Adnan Nagrial, Craig Underhill, Wenjing Wang, Zhongmin Maxwell Wang, Baiyong Li, Yu Xia, Jermaine I G Coward
Journal: Journal for ImmunoTherapy of Cancer (2024)

Background Studies showed that vascular endothelial growth factor (VEGF) inhibitors could improve therapeutic efficacy of PD-1/PD-L1 antibodies by transforming the immunosuppressive tumor microenvironment (TME) into an immunoresponsive TME. Ivonescimab is a first-in-class, humanized tetravalent bispecific antibody targeting PD-1 and VEGF-A simultaneously. Here, we report the first-in-human, phase 1a study of ivonescimab in patients with advanced solid tumors. Methods Patients with advanced solid tumors were treated with ivonescimab 0.3, 1, 3, 10, 20 or 30 mg/kg intravenously every 2 weeks using a 3+3+3 dose escalation design. Dose expansion occurred at 10 and 20 mg/kg in selected tumor types. The primary objective was to assess the safety and tolerability, and to determine the maximum tolerated dose (MTD). The secondary objectives included pharmacokinetics, pharmacodynamics and preliminary antitumor activity based on Response Evaluation Criteria in Solid Tumors V.1.1. Results Between October 2, 2019 and January 14, 2021, a total of 51 patients were enrolled and received ivonescimab. Two dose-limiting toxicities were reported at 30 mg/kg. The MTD of ivonescimab was 20 mg/kg every 2 weeks. Grade≥3 treatment-related adverse events (TRAEs) occurred in 14 patients (27.5%). The most common TRAEs of any grade were rash (29.4%), arthralgia (19.6%), hypertension (19.6%), fatigue (17.6%), diarrhea (15.7%) and pruritus (11.8%). The most common grade≥3 TRAEs were hypertension (7/51, 13.7%), alanine aminotransferase increased (3/51, 5.2%), aspartate aminotransferase increased (2/51, 3.9%) and colitis (2/51, 3.9%). Of 47 patients who had at least one postbaseline assessment, the confirmed objective response rate was 25.5% (12/47) and disease control rate was 63.8% (30/47). Among 19 patients with platinum-resistant ovarian cancer, 5 patients (26.3%) achieved partial response (PR). Efficacy signals were also observed in patients with mismatch repair proficient (pMMR) colorectal cancer, non-small cell lung cancer, and both MMR deficient and pMMR endometrial cancer. Conclusions Ivonescimab demonstrated manageable safety profiles and promising efficacy signals in multiple solid tumors. Exploration of alternative dosing regimens of ivonescimab monotherapy and combination therapies is warranted. Trial registration number NCT04047290 .
Can in vitro/in silico tools improve colonic concentration estimations for oral extended-release formulations? A case study with upadacitinib
Authors: Alessia Favaron, Bart Hens, Maiara Camotti Montanha, Mark McAllister, Irena Tomaszewska, Shaimaa Moustafa, Marília Alvarenga de Oliveira, Abdul W. Basit, Mine Orlu
Journal: Journal of Controlled Release (2024)

Upadacitinib, classified as a highly soluble drug, is commercially marketed as RINVOQ®, a modified-release formulation incorporating hydroxypropyl methylcellulose as a matrix system to target extended release throughout the gastrointestinal (GI) tract. Our study aimed to explore how drug release will occur throughout the GI tract using a plethora of in vitro and in silico tools. We built a Physiologically-Based Pharmacokinetic (PBPK) model in GastroPlus™ to predict the systemic concentrations of the drug when administered using in vitro dissolution profiles as input to drive luminal dissolution. A series of in vitro dissolution experiments were gathered using the USP Apparatus I, III and IV in presence of biorelevant media, simulating both fasted and fed state conditions. A key outcome from the current study was to establish an in vitro-in vivo correlation (IVIVC) between (i) the dissolution profiles obtained from the USP I, III and IV methods and (ii) the fraction absorbed of drug as deconvoluted from the plasma concentration-time profile of the drug. When linking the fraction dissolved as measured in the USP IV model, a Level A IVIVC was established. Moreover, when using the different dissolution profiles as input for PBPK modeling, it was also observed that predictions for plasma C
Particulate bioaerogels for respiratory drug delivery
Authors: Hao-Ying Li, Charalampos Makatsoris, Ben Forbes
Journal: Journal of Controlled Release (2024)

The bioaerogel microparticles have been recently developed for respiratory drug delivery and attract fast increasing interests. These highly porous microparticles have ultralow density and hence possess much reduced aerodynamic diameter, which favour them with greatly enhanced dispersibility and improved aerosolisation behaviour. The adjustable particle geometric dimensions by varying preparation methods and controlling operation parameters make it possible to fabricate bioaerogel microparticles with accurate sizes for efficient delivery to the targeted regions of respiratory tract (i.e. intranasal and pulmonary). Additionally, the technical process can provide bioaerogel microparticles with the opportunities of accommodating polar, weak polar and non-polar drugs at sufficient amount to satisfy clinical needs, and the adsorbed drugs are primarily in the amorphous form that potentially can facilitate drug dissolution and improve bioavailability. Finally, the nature of biopolymers can further offer additional advantageous characteristics of improved mucoadhesion, sustained drug release and subsequently elongated time for continuous treatment on-site. These fascinating features strongly support bioaerogel microparticles to become a novel platform for effective delivery of a wide range of drugs to the targeted respiratory regions, with increased drug residence time on-site, sustained drug release, constant treatment for local and systemic diseases and anticipated better-quality of therapeutic effects.
Risk-based lung cancer screening performance in a universal healthcare setting
Authors: Martin C. Tammemägi, Gail E. Darling, Heidi Schmidt, Meghan J. Walker, Deanna Langer, Yvonne W. Leung, Kathy Nguyen, Beth Miller, Diego Llovet, William K. Evans, Daniel N. Buchanan, Gabriela Espino-Hernandez, Usman Aslam, Amanda Sheppard, Aisha Lofters, Micheal McInnis, Julian Dobranowski, Steven Habbous, Christian Finley, Marianne Luettschwager, Erin Cameron, Caroline Bravo, Anna Banaszewska, Katherin Creighton-Taylor, Brenda Fernandes, Julia Gao, Alex Lee, Van Lee, Bogdan Pylypenko, Monica Yu, Erin Svara, Shivali Kaushal, Lynda MacNiven, Caitlin McGarry, Lauren Della Mora, Liz Koen, Jessica Moffatt, Michelle Rey, Marta Yurcan, Laurie Bourne, Gillian Bromfield, Melissa Coulson, Rebecca Truscott, Linda Rabeneck
Journal: Nature Medicine (2024)
Treatment of Noninfectious Uveitic Macular Edema with Periocular and Intraocular Corticosteroid Therapies
Authors: Justine R Smith, Jennifer E Thorne, Christina J Flaxel, Nieraj Jain, Stephen J Kim, Maureen G Maguire, Shriji Patel, Christina Y Weng, Steven Yeh, Leo A Kim
Journal: Ophthalmology (2024)
A ferroptosis amplifier based on triple-enhanced lipid peroxides accumulation strategy for effective pancreatic cancer therapy
Authors: Mengyao Chen, Xiaohan Tong, Yanting Sun, Chunyan Dong, Chen Li, Chunhui Wang, Minyi Zhang, Yixuan Wen, Pinting Ye, Ruihao Li, Jie Wan, Shujing Liang, Shuo Shi
Journal: Biomaterials (2024)
NLRP3 inflammasome-mediated premature immunosenescence drives diabetic vascular aging dependent on the induction of perivascular adipose tissue dysfunction
Authors: Guang-Jie Tai, Yan-Jie Ma, Jun-Lin Feng, Jia-Peng Li, Shu Qiu, Qing-Qing Yu, Ren-Hua Liu, Silumbwe Ceaser Wankumbu, Xin Wang, Xiao-Xue Li, Ming Xu
Journal: Cardiovascular Research (2024)

The vascular aging process accelerated by type 2 diabetes mellitus (T2DM) is responsible for the elevated risk of associated cardiovascular diseases (CVDs). Metabolic disorder-induced immune senescence has been implicated in multi-organ/tissue damage. Herein, we sought to determine the role of immunosenescence in diabetic vascular aging and to investigate the underlying mechanisms.