tbuckley/cabot-search huggingface dataset:
Occupational exposure to diesel exhausts and pancreatic cancer
Authors: Peng Ge, Yalan Luo, Hailong Chen
Journal: International Journal of Surgery (2024)

aDepartment of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, 116011, China bInstitute (College) of Integrative Medicine, Dalian Medical University, Dalian, Liaoning, 116044, China cLaboratory of Integrative Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, 116011, China dDepartment of Gastroenterology, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, 116011, China Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article. *Corresponding author. Address: (Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Zhongshan Road 222, Dalian, 116011, Liaoning, People's Republic of China. E-mail address: [email protected] (H. Chen). Supplemental Digital Content is available for this article. Direct URL citations are provided in the HTML and PDF versions of this article on the journal's website, www.lww.com/international-journal-of-surgery. Published online ■ ■ This is an open access article distributed under the Creative Commons Attribution-ShareAlike License 4.0, which allows others to remix, tweak, and build upon the work, even for commercial purposes, as long as the author is credited and the new creations are licensed under the identical terms. http://creativecommons.org/licenses/by-sa/4.0/
Association of glucagon-like peptide-1 receptor agonists with risk of cancers-evidence from a drug target Mendelian randomization and clinical trials
Authors: Yuming Sun, Yongjia Liu, Yating Dian, Furong Zeng, Guangtong Deng, Shaorong Lei
Journal: International Journal of Surgery (2024)

Glucagon-like peptide-1 receptor (GLP1R) agonists have been approved by Food and Drug Administration for management of obesity. However, the causal relationship of GLP1R agonists (GLP1RA) with cancers still unclear.
Trastuzumab deruxtecan in patients with solid tumours harbouring specific activating HER2 mutations (DESTINY-PanTumor01): an international, phase 2 study
Authors: Bob T Li, Funda Meric-Bernstam, Aditya Bardia, Yoichi Naito, Salvatore Siena, Philippe Aftimos, Ian Anderson, Giuseppe Curigliano, Maria de Miguel, Maitri Kalra, Do-Youn Oh, Joon Oh Park, Sophie Postel-Vinay, Sun Young Rha, Taroh Satoh, Iben Spanggaard, Flavia Michelini, Ann Smith, Karime Kalil Machado, Cristina Saura
Journal: The Lancet Oncology (2024)
Association of nirmatrelvir–ritonavir with post-acute sequelae and mortality in patients admitted to hospital with COVID-19: a retrospective cohort study
Authors: Huwen Wang, Yuchen Wei, Chi Tim Hung, Guozhang Lin, Xiaoting Jiang, Conglu Li, Katherine Min Jia, Carrie Ho Kwan Yam, Tsz Yu Chow, Janice Ying-en Ho, Yawen Wang, Shi Zhao, Zihao Guo, Kehang Li, Aimin Yang, Chris Ka Pun Mok, David S C Hui, Eng Kiong Yeoh, Ka Chun Chong
Journal: The Lancet Infectious Diseases (2024)

Studies have established the short-term efficacy of nirmatrelvir-ritonavir in managing COVID-19, yet its effect on post-COVID-19 condition, especially in patients admitted to hospital, remains understudied. This study aimed to examine the effect of nirmatrelvir-ritonavir on post-COVID-19 condition among patients admitted to hospital in Hong Kong.
Garadacimab for hereditary angioedema attack prevention: long-term efficacy, quality of life, and safety data from a phase 2, randomised, open-label extension study
Authors: Timothy J Craig, Donald S Levy, Avner Reshef, William R Lumry, Inmaculada Martinez-Saguer, Joshua S Jacobs, William H Yang, Bruce Ritchie, Emel Aygören-Pürsün, Paul K Keith, Paula Busse, Henrike Feuersenger, Mihai Alexandru Bica, Iris Jacobs, Ingo Pragst, Markus Magerl
Journal: The Lancet Haematology (2024)
Bioprinting in cardiovascular medicine: Possibilities, challenges, and future perspectives for low and middle-income countries
Authors: Amarveer Malhi, Inderbir Padda, Arun Mahtani, Daniel Fabian, Paul Karroum, Arpita M. Mathews, Tushar Ralhan, Yashendra Sethi, Talha B. Emran
Journal: International Journal of Surgery (2024)

Cardiovascular diseases (CVD) stemming from various factors significantly impact the quality of life (QoL) and are prevalent with high mortality rates in both developed and developing countries. In cases where pharmacotherapy proves insufficient and end-stage disease ensues, a heart transplant/surgical repair becomes the only feasible treatment option. However, challenges such as a limited supply of heart donors, complications associated with rejection, and issues related to medication compliance introduce an additional burden to healthcare services and adversely affect patient outcomes. The emergence of bioprinting has facilitated advancements in creating structures, including ventricles, valves, and blood vessels. Notably, the development of myocardial/cardiac patches through bioprinting has offered a promising avenue for revascularizing, strengthening, and regenerating ventricles. Employment loss in developing countries as a circumstance of disability or death can severely impact a family's well-being and means for sustainable living. Innovations by means of life sustaining treatment options can provide hope for the impoverished and help reduce disability burden on the economy of low- to middle-income countries (LMICs). Such developments can have a significant impact that can last for generations, especially in developing countries. In this review, the authors delve into various types of bioprinting techniques, exploring their possibilities, challenges, and potential future applications in treating various end-stage cardiovascular conditions in LMICs.
Letter to the editor: Some reflections on ‘Endonasal dacryocystorhinostomy in children: Our experience’
Authors: Zijian Chen, Shizhou Cheng, Zuhai Zhang
Journal: International Journal of Surgery (2024)

Department of Ophthalmology, The First Affiliated Hospital of Yangtze University, Jingzhou, Hubei Province, People's Republic of China Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article. Published online ■ ■ *Corresponding author. Address: Department of Ophthalmology, The First Affiliated Hospital of Yangtze University, Jingzhou 434000, Hubei Province, People's Republic of China. E-mail: [email protected] (Z. Zhang). This is an open access article distributed under the Creative Commons Attribution-ShareAlike License 4.0, which allows others to remix, tweak, and build upon the work, even for commercial purposes, as long as the author is credited and the new creations are licensed under the identical terms. http://creativecommons.org/licenses/by-sa/4.0/
CXCR6 expression correlates with radiotherapy response and immune context in triple-negative breast cancer (Experimental Studies)
Authors: Jin Meng, Yilan Yang, Jiaojie Lv, Hong Lv, Xu Zhao, Li Zhang, Wei Shi, Zhaozhi Yang, Xin Mei, Xingxing Chen, Jinli Ma, Zhen Zhang, Zhimin Shao, Xiaoli Yu, Xiaomao Guo
Journal: International Journal of Surgery (2024)

The chemokine receptor CXCR6 is critical for sustained tumor control mediated by CD8+ cytotoxic T cells (CTLs) in tumors. Previous studies have shown that ionizing radiation induces an inflamed immune contexture by upregulating CXCR6. However, the clinical significance of CXCR6 expression in triple-negative breast cancer (TNBC) and its correlation with radiotherapy remains unknown. This study aimed to clarify the prognostic value of CXCR6 and its role in the breast tumor microenvironment (TME).
Conversion surgery intervention versus continued systemic therapy in patients with a response after PD-1/PD-L1 inhibitor-based combination therapy for initially unresectable biliary tract cancer: a retrospective cohort study
Authors: Shanshan Wang, Yunchao Wang, Chengpei Zhu, Kai Liu, Jiashuo Chao, Nan Zhang, Mingjian Piao, Xu Yang, Longhao Zhang, Junyu Long, Ziyu Xun, Ting Zhang, Xinting Sang, Xiaobo Yang, Haitao Zhao
Journal: International Journal of Surgery (2024)

The role of conversion surgery in patients with unresectable biliary tract cancer who responded positively to PD-1/PD-L1 inhibitor-based therapy remains unclear. This study aimed to assess the outcomes in patients with or without conversion surgery.
Reengineering Addiction — The Tobacco Industry’s Potential Response to a Nicotine Standard for Cigarettes
Authors: Ahmad El-Hellani, Theodore L Wagener, Marielle C Brinkman
Journal: New England Journal of Medicine (2024)

The FDA is considering implementing a nicotine product standard, under which cigarettes could contain only very low levels of nicotine. Preparing for the tobacco industry's potential response is important.
Abstract Wrk2-01: Organoid Models of Cancer and the Tumor Microenvironment
Authors: C. Kuo
Journal: Cancer Research (2024)

Abstract Both cell-intrinsic and microenvironmental influences vitally govern tumor progression. Mutational, chromosomal and epigenetic alterations represent the former, while the latter is influenced by diverse stromal populations including fibroblasts, vasculature and immune cells. In vitro organoid culture provides an experimentally tractable platform for cancer research that is applicable to cell-autonomous and tumor microenvironmental studies. The first part of this lecture will describe our work using organoid culture to functionally validate tumor cell-intrinsic genomic alterations. Notably, cancer research has traditionally lacked in vitro methods where tumors can be holistically cultured in a non-reconstitutive manner that co-preserves neoplastic cells together with endogenous stromal components. Thus, the second part of this lecture will describe advances in 3D tumor organoid culture that allow growth of cancer cells in a manner that preserves their native interaction with diverse tumor-infiltrating immune cells and allows analysis of immune checkpoint inhibition. Citation Format: C. Kuo. Organoid Models of Cancer and the Tumor Microenvironment [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr Wrk2-01.
Alpha-galactosylceramide improves the potency of mRNA LNP vaccines against cancer and intracellular bacteria
Authors: Sofie Meulewaeter, Ilke Aernout, Joke Deprez, Yanou Engelen, Margo De Velder, Lorenzo Franceschini, Karine Breckpot, Serge Van Calenbergh, Caroline Asselman, Katie Boucher, Francis Impens, Stefaan C. De Smedt, Rein Verbeke, Ine Lentacker
Journal: Journal of Controlled Release (2024)

Although various types of mRNA-based vaccines have been explored, the optimal conditions for induction of both humoral and cellular immunity remain rather unknown. In this study, mRNA vaccines of nucleoside-modified mRNA in lipoplexes (LPXs) or lipid nanoparticles (LNPs) were evaluated after administration in mice through different routes, assessing mRNA delivery, tolerability and immunogenicity. In addition, we investigated whether mRNA vaccines could benefit from the inclusion of the adjuvant alpha-galactosylceramide (αGC), an invariant Natural Killer T (iNKT) cell ligand. Intramuscular (IM) vaccination with ovalbumin (OVA)-encoding mRNA encapsulated in LNPs adjuvanted with αGC showed the highest antibody- and CD8+ T cell responses. Furthermore, we observed that addition of signal peptides and endocytic sorting signals of either LAMP1 or HLA-B7 in the OVA-encoding mRNA sequence further enhanced CD8+ T cell activation although reducing the induction of IgG antibody responses. Moreover, mRNA LNPs with the ionizable lipidoid C12–200 exhibited higher pro-inflammatory- and reactogenic activity compared to mRNA LNPs with SM-102, correlating with increased T cell activation and antitumor potential. We also observed that αGC could further enhance the cellular immunity of clinically relevant mRNA LNP vaccines, thereby promoting therapeutic antitumor potential. Finally, a Listeria monocytogenes mRNA LNP vaccine supplemented with αGC showed synergistic protective effects against listeriosis, highlighting a key advantage of co-activating iNKT cells in antibacterial mRNA vaccines. Taken together, our study offers multiple insights for optimizing the design of mRNA vaccines for disease applications, such as cancer and intracellular bacterial infections.
Non-Poissonian bursts in the arrival of phenotypic variation can strongly affect the dynamics of adaptation
Authors: Nora S Martin, Steffen Schaper, Chico Q Camargo, Ard A Louis
Journal: Molecular Biology and Evolution (2024)

Modeling the rate at which adaptive phenotypes appear in a population is a key to predicting evolutionary processes. Given random mutations, should this rate be modeled by a simple Poisson process, or is a more complex dynamics needed? Here we use analytic calculations and simulations of evolving populations on explicit genotype-phenotype maps to show that the introduction of novel phenotypes can be "bursty" or overdispersed. In other words, a novel phenotype either appears multiple times in quick succession or not at all for many generations. These bursts are fundamentally caused by statistical fluctuations and other structure in the map from genotypes to phenotypes. Their strength depends on population parameters, being highest for "monomorphic" populations with low mutation rates. They can also be enhanced by additional inhomogeneities in the mapping from genotypes to phenotypes. We mainly investigate the effect of bursts using the well-studied genotype-phenotype map for RNA secondary structure, but find similar behavior in a lattice protein model and in Richard Dawkins's biomorphs model of morphological development. Bursts can profoundly affect adaptive dynamics. Most notably, they imply that fitness differences play a smaller role in determining which phenotype fixes than would be the case for a Poisson process without bursts.
EXPRESSION OF CONCERN: Efficacy of psilocybin for treating symptoms of depression: systematic review and meta-analysis
Journal: BMJ (2024)

The journal and the authors are investigating the problem.The study analysed data from randomised trials of psilocybin for the treatment of depression in adults.A methodological concern has been raised about an error in the calculation of standardised mean differences.This is likely to have overestimated the benefits of psilocybin.The authors are reviewing and responding to the error and its implications for the findings and conclusions of the paper.The authors' response will be reviewed by The BMJ who will decide what further action is needed.
Youth Experiencing Parental Death Due to Drug Poisoning and Firearm Violence in the US, 1999-2020
Authors: Benjamin-Samuel Schlüter, Diego Alburez-Gutierrez, Kirsten Bibbins-Domingo, Monica J. Alexander, Mathew V. Kiang
Journal: JAMA (2024)

Importance Youth (those aged &amp;amp;lt;18 years) parental death has been associated with negative health outcomes. Understanding the burden of parental death due to drug poisoning (herein, drugs) and firearms is essential for informing interventions. Objective To estimate the incidence of youth parental death due to drugs, firearms, and all other causes. Design, Setting, and Participants This cross-sectional observational study was conducted using vital registration, including all US decedents, and census data from January 1990 through December 2020. Data were analyzed from May 30, 2023, to March 28, 2024. Exposures Parental death due to drug poisoning or firearms. Main Outcomes and Measures A demographic matrix projection model was used to estimate the number and incidence of youth experiencing parental death, defined as the death of 1 or more parents, per 1000 population aged less than 18 years. Analyses evaluated parental deaths by drugs, firearms, and all other causes from 1999 through 2020 by race and ethnicity. Results Between 1999 and 2020, there were 931 785 drug poisoning deaths and 736 779 firearm-related deaths with a mean (SD) age of 42.6 (16.3) years. Most deaths occurred among males (73.8%) and White decedents (70.8%) followed by Black (17.5%) and Hispanic (9.5%) decedents. An estimated 759 000 (95% CI, 722 000-800 000) youth experienced parental death due to drugs and an estimated 434 000 (95% CI, 409 000-460 000) youth experienced parental death due to firearms, accounting for 17% of all parental deaths. From 1999 to 2020, the estimated number of youth who experienced parental death increased 345% (95% CI, 334%-361%) due to drugs and 39% (95% CI, 37%-41%) due to firearms compared with 24% (95% CI, 23%-25%) due to all other causes. Black youth experienced a disproportionate burden of parental deaths, based primarily on firearm deaths among fathers. In 2020, drugs and firearms accounted for 23% of all parental deaths, double the proportion in 1999 (12%). Conclusions and Relevance Results of this modeling study suggest that US youth are at high and increasing risk of experiencing parental death by drugs or firearms. Efforts to stem this problem should prioritize averting drug overdoses and firearm violence, especially among structurally marginalized groups.
Injury Prevention Science and Firearm Injury in Pediatric Health
Authors: Patrick M. Carter, Laura Seewald, Marc Zimmerman
Journal: JAMA (2024)

Elizabeth R. Wolf, MD, MPH; Frederick P. Rivara, MD, MPH; Colin J. Orr, MD, MPH; Anabeel Sen, MBBS, MPH; Derek A. Chapman, PhD; Steven H. Woolf, MD, MPH
miR-369-3p ameliorates diabetes-associated atherosclerosis by regulating macrophage succinate-GPR91 signalling
Authors: Shruti Rawal, Vinay Randhawa, Syed Husain Mustafa Rizvi, Madhur Sachan, Akm Khyrul Wara, Daniel Pérez-Cremades, Robert M Weisbrod, Naomi M Hamburg, Mark W Feinberg
Journal: Cardiovascular Research (2024)

Abstract Aims Diabetes leads to dysregulated macrophage immunometabolism, contributing to accelerated atherosclerosis progression. Identifying critical factors to restore metabolic alterations and promote resolution of inflammation remains an unmet goal. MicroRNAs orchestrate multiple signalling events in macrophages, yet their therapeutic potential in diabetes-associated atherosclerosis remains unclear. Methods and results miRNA profiling revealed significantly lower miR-369-3p expression in aortic intimal lesions from Ldlr–/– mice on a high-fat sucrose-containing (HFSC) diet for 12 weeks. miR-369-3p was also reduced in peripheral blood mononuclear cells from diabetic patients with coronary artery disease (CAD). Cell-type expression profiling showed miR-369-3p enrichment in aortic macrophages. In vitro, oxLDL treatment reduced miR-369-3p expression in mouse bone marrow-derived macrophages (BMDMs). Metabolic profiling in BMDMs revealed that miR-369-3p overexpression blocked the oxidized low density lipoprotein (oxLDL)-mediated increase in the cellular metabolite succinate and reduced mitochondrial respiration (OXPHOS) and inflammation [Interleukin (lL)-1β, TNF-α, and IL-6]. Mechanistically, miR-369-3p targeted the succinate receptor (GPR91) and alleviated the oxLDL-induced activation of inflammasome signalling pathways. Therapeutic administration of miR-369-3p mimics in HFSC-fed Ldlr−/− mice reduced GPR91 expression in lesional macrophages and diabetes-accelerated atherosclerosis, evident by a decrease in plaque size and pro-inflammatory Ly6Chi monocytes. RNA-Seq analyses showed more pro-resolving pathways in plaque macrophages from miR-369-3p-treated mice, consistent with an increase in macrophage efferocytosis in lesions. Finally, a GPR91 antagonist attenuated oxLDL-induced inflammation in primary monocytes from human subjects with diabetes. Conclusion These findings establish a therapeutic role for miR-369-3p in halting diabetes-associated atherosclerosis by regulating GPR91 and macrophage succinate metabolism.
Artificial intelligence in digital pathology: a systematic review and meta-analysis of diagnostic test accuracy
Authors: Clare McGenity, Emily L. Clarke, Charlotte Jennings, Gillian Matthews, Caroline Cartlidge, Henschel Freduah-Agyemang, Deborah D. Stocken, Darren Treanor
Journal: npj Digital Medicine (2024)

Abstract Ensuring diagnostic performance of artificial intelligence (AI) before introduction into clinical practice is essential. Growing numbers of studies using AI for digital pathology have been reported over recent years. The aim of this work is to examine the diagnostic accuracy of AI in digital pathology images for any disease. This systematic review and meta-analysis included diagnostic accuracy studies using any type of AI applied to whole slide images (WSIs) for any disease. The reference standard was diagnosis by histopathological assessment and/or immunohistochemistry. Searches were conducted in PubMed, EMBASE and CENTRAL in June 2022. Risk of bias and concerns of applicability were assessed using the QUADAS-2 tool. Data extraction was conducted by two investigators and meta-analysis was performed using a bivariate random effects model, with additional subgroup analyses also performed. Of 2976 identified studies, 100 were included in the review and 48 in the meta-analysis. Studies were from a range of countries, including over 152,000 whole slide images (WSIs), representing many diseases. These studies reported a mean sensitivity of 96.3% (CI 94.1–97.7) and mean specificity of 93.3% (CI 90.5–95.4). There was heterogeneity in study design and 99% of studies identified for inclusion had at least one area at high or unclear risk of bias or applicability concerns. Details on selection of cases, division of model development and validation data and raw performance data were frequently ambiguous or missing. AI is reported as having high diagnostic accuracy in the reported areas but requires more rigorous evaluation of its performance.
Optical coherence tomography choroidal enhancement using generative deep learning
Authors: Valentina Bellemo, Ankit Kumar Das, Syna Sreng, Jacqueline Chua, Damon Wong, Janika Shah, Rahul Jonas, Bingyao Tan, Xinyu Liu, Xinxing Xu, Gavin Siew Wei Tan, Rupesh Agrawal, Daniel Shu Wei Ting, Liu Yong, Leopold Schmetterer
Journal: npj Digital Medicine (2024)

Abstract Spectral-domain optical coherence tomography (SDOCT) is the gold standard of imaging the eye in clinics. Penetration depth with such devices is, however, limited and visualization of the choroid, which is essential for diagnosing chorioretinal disease, remains limited. Whereas swept-source OCT (SSOCT) devices allow for visualization of the choroid these instruments are expensive and availability in praxis is limited. We present an artificial intelligence (AI)-based solution to enhance the visualization of the choroid in OCT scans and allow for quantitative measurements of choroidal metrics using generative deep learning (DL). Synthetically enhanced SDOCT B-scans with improved choroidal visibility were generated, leveraging matching images to learn deep anatomical features during the training. Using a single-center tertiary eye care institution cohort comprising a total of 362 SDOCT-SSOCT paired subjects, we trained our model with 150,784 images from 410 healthy, 192 glaucoma, and 133 diabetic retinopathy eyes. An independent external test dataset of 37,376 images from 146 eyes was deployed to assess the authenticity and quality of the synthetically enhanced SDOCT images. Experts’ ability to differentiate real versus synthetic images was poor (47.5% accuracy). Measurements of choroidal thickness, area, volume, and vascularity index, from the reference SSOCT and synthetically enhanced SDOCT, showed high Pearson’s correlations of 0.97 [95% CI: 0.96–0.98], 0.97 [0.95–0.98], 0.95 [0.92–0.98], and 0.87 [0.83–0.91], with intra-class correlation values of 0.99 [0.98–0.99], 0.98 [0.98–0.99], and 0.95 [0.96–0.98], 0.93 [0.91–0.95], respectively. Thus, our DL generative model successfully generated realistic enhanced SDOCT data that is indistinguishable from SSOCT images providing improved visualization of the choroid. This technology enabled accurate measurements of choroidal metrics previously limited by the imaging depth constraints of SDOCT. The findings open new possibilities for utilizing affordable SDOCT devices in studying the choroid in both healthy and pathological conditions.