tbuckley/cabot-search huggingface dataset:
Postoperative Radiation Therapy Should Be Used for Completely Resected Stage III-N2 NSCLC in Select Patients
Authors: Jason Liu, Colton Ladbury, Jae Kim, Dan Raz, Loretta Erhunmwunsee, Howard (Jack) West, Terence Williams, Ravi Salgia, Erminia Massarelli, Arya Amini
Journal: Journal of Thoracic Oncology (2022)
Are urologists ready for interpretation of multiparametric MRI findings? A prospective multicentric evaluation
Authors: G. Mantica, N.R. Suardi, S. Smelzo, F. Esperto, R. Papalia, R. Larocca, L. Napolitano, M. Oderda, M. Ennas, A. Stabile, F. De Cobelli, A. Briganti, C. Introini, P. Gontero, F. Gaboardi, R.M. Scarpa, V. Mirone, F. Montorsi, C. Terrone, G. Cardone
Journal: European Urology (2021)
Renal Nano-drug delivery for acute kidney Injury: Current status and future perspectives
Authors: Hui Nee Geo, Dharmani Devi Murugan, Zamri Chik, Anwar Norazit, Yiing Yee Foo, Bey Fen Leo, Yin Yin Teo, Sharifah Zamiah Syed Binti Syed Abdul Kadir, Yinghan Chan, Hann Juang Chai, María Medel, Nor Azizan Abdullah, Edward J. Johns, María J. Vicent, Lip Yong Chung, Lik Voon Kiew
Journal: Journal of Controlled Release (2022)
Delivery of modified mRNA to damaged myocardium by systemic administration of lipid nanoparticles
Authors: Martijn J.W. Evers, Wenjuan Du, Qiangbing Yang, Sander A.A. Kooijmans, Aryan Vink, Mies van Steenbergen, Pieter Vader, Saskia C.A. de Jager, Sabine A. Fuchs, Enrico Mastrobattista, Joost P.G. Sluijter, Zhiyong Lei, Raymond Schiffelers
Journal: Journal of Controlled Release (2022)

Lipid Nanoparticles (LNPs) are a promising drug delivery vehicle for clinical siRNA delivery. Modified mRNA (modRNA) has recently gained great attention as a therapeutic molecule in cardiac regeneration. However, for mRNA to be functional, it must first reach the diseased myocardium, enter the target cell, escape from the endosomal compartment into the cytosol and be translated into a functional protein. However, it is unknown if LNPs can effectively deliver mRNA, which is much larger than siRNA, to the ischemic myocardium. Here, we evaluated the ability of LNPs to deliver mRNA to the myocardium upon ischemia-reperfusion injury functionally. By exploring the bio-distribution of fluorescently labeled LNPs, we observed that, upon reperfusion, LNPs accumulated in the infarct area of the heart. Subsequently, the functional delivery of modRNA was evaluated by the administration of firefly luciferase encoding modRNA. Concomitantly, a significant increase in firefly luciferase expression was observed in the heart upon myocardial reperfusion when compared to sham-operated animals. To characterize the targeted cells within the myocardium, we injected LNPs loaded with Cre modRNA into Cre-reporter mice. Upon LNP infusion, Tdtomato+ cells, derived from Cre mediated recombination, were observed in the infarct region as well as the epicardial layer upon LNP infusion. Within the infarct area, most targeted cells were cardiac fibroblasts but also some cardiomyocytes and macrophages were found. Although the expression levels were low compared to LNP-modRNA delivery into the liver, our data show the ability of LNPs to functionally deliver modRNA therapeutics to the damaged myocardium, which holds great promise for modRNA-based cardiac therapies.
Association of Genetic Ancestry and Molecular Signatures with Cancer Survival Disparities: A Pan-Cancer Analysis
Authors: Kara Keun Lee, Lavanya Rishishwar, Dongjo Ban, Shashwat Deepali Nagar, Leonardo Mariño-Ramírez, John F. McDonald, I. King Jordan
Journal: Cancer Research (2022)

Abstract While overall cancer mortality has steadily decreased in recent decades, cancer health disparities among racial and ethnic population groups persist. Here we studied the relationship between cancer survival disparities (CSD), genetic ancestry (GA), and tumor molecular signatures across 33 cancers in a cohort of 9,818 patients. GA correlated with race and ethnicity but showed observable differences in effects on CSD, with significant associations identified in four cancer types: breast invasive carcinoma (BRCA), head and neck squamous cell carcinoma (HNSCC), kidney renal clear cell carcinoma (KIRC), and skin cutaneous carcinoma (SKCM). Differential gene expression and methylation between ancestry groups associated cancer-related genes with CSD, of which, seven protein-coding genes [progestin and adipoQ receptor family member 6 (PAQR6), Lck-interacting transmembrane adaptor 1 (LIME1), Sin3A-associated protein 25 (SAP25), MAX dimerization protein 3 (MXD3), coiled-coil glutamate rich protein 2 (CCER2), refilin A (RFLNA), and cathepsin W (CTSW)] significantly interacted with GA and exacerbated observed survival disparities. These findings indicated that regulatory changes mediated by epigenetic mechanisms have a greater contribution to CSD than population-specific mutations. Overall, we uncovered various molecular mechanisms through which GA might impact CSD, revealing potential population-specific therapeutic targets for groups disproportionately burdened by cancer. Significance: This large-cohort, multicancer study identifies four cancer types with cancer survival disparities and seven cancer-related genes that interact with genetic ancestry and contribute to disparities.
Department of Error
Authors: Ioannis Katsoularis, Osvaldo Fonseca-Rodríguez, Paddy Farrington, Krister Lindmark, Anne-Marie Fors
Journal: The Lancet (2021)

of ischaemic stroke, which shares some of the same pathophysiological features as myocardial infarction.Furthermore, the increase in the risk of myocardial infarction was of the same magnitude as for ischaemic stroke, for which the risk of inaccurate diagnosis codification was low.Therefore, the case of a connection between COVID19 and cardiovascular events is strengthened.We declare no competing interests.
New Biomarkers With Prognostic Impact Based on Multitracer PET/CT Imaging in Neuroendocrine Neoplasms
Authors: Roberto C. Delgado Bolton, Adriana K. Calapaquí Terán, Stefano Fanti, Francesco Giammarile
Journal: Clinical Nuclear Medicine (2022)

The search for new biomarkers in cancer is currently one of the most widely sought end points in medical imaging, with the aim of improving the management decisions based on reliable indicators of prognosis, being neuroendocrine neoplasms a challenging group of tumors under investigation. Multitracer PET/CT imaging, in which different radiotracers supply information of different metabolic aspects of the tumor, can help classify and select the most appropriate therapy, providing basic aspects that will probably allow the generation of new imaging biomarkers useful in patient management.
Microbial signals, MyD88, and lymphotoxin drive TNF-independent intestinal epithelial tissue damage
Authors: Iulia Rusu, Elvira Mennillo, Jared L. Bain, Zhongmei Li, Xiaofei Sun, Kimberly M. Ly, Yenny Y. Rosli, Mohammad Naser, Zunqiu Wang, Rommel Advincula, Philip Achacoso, Ling Shao, Bahram Razani, Ophir D. Klein, Alexander Marson, Jessie A. Turnbaugh, Peter J. Turnbaugh, Barbara A. Malynn, Averil Ma, Michael G. Kattah
Journal: Journal of Clinical Investigation (2022)

Anti-TNF antibodies are effective for treating patients with inflammatory bowel disease (IBD), but many patients fail to respond to anti-TNF therapy, highlighting the importance of TNF-independent disease. We previously demonstrated that acute deletion of 2 IBD susceptibility genes, A20 (Tnfaip3) and Abin-1 (Tnip1), in intestinal epithelial cells (IECs) sensitized mice to both TNF-dependent and TNF-independent death. Here we show that TNF-independent IEC death after A20 and Abin-1 deletion was rescued by germ-free derivation or deletion of MyD88, while deletion of Trif provided only partial protection. Combined deletion of Ripk3 and Casp8, which inhibits both apoptotic and necroptotic death, completely protected against death after acute deletion of A20 and Abin-1 in IECs. A20- and Abin-1-deficient IECs were sensitized to TNF-independent, TNFR1-mediated death in response to lymphotoxin α (LTα) homotrimers. Blockade of LTα in vivo reduced weight loss and improved survival when combined with partial deletion of MyD88. Biopsies of inflamed colon mucosa from patients with IBD exhibited increased LTA and IL1B expression, including a subset of patients with active colitis on anti-TNF therapy. These data show that microbial signals, MyD88, and LTα all contribute to TNF-independent intestinal injury.
Engineering Multifunctional Hydrogel‐Integrated 3D Printed Bioactive Prosthetic Interfaces for Osteoporotic Osseointegration
Authors: Zuhao Li, Yue Zhao, Zhonghan Wang, Ming Ren, Xiangang Wang, He Liu, Quan Lin, Jincheng Wang
Journal: Advanced Healthcare Materials (2022)

3D printed porous titanium alloy implants is an advanced orthopedic material for joint replacement. However, the high risk of aseptic loosening and periprosthetic infection is difficult to avoid, and the declined autophagy of osteoporosis-derived bone marrow mesenchymal stem cells (OP-BMSCs) further severely impairs the osseointegration under the osteoporotic circumstance. It is thus becoming urgently significant to develop orthopedic materials with autophagy regulation and antibacterial bioactivity. In this regard, a novel class of multifunctional hydrogel-integrated 3D printed bioactive prosthetic interfaces is engineered for in situ osseointegration in osteoporosis. The hydrogel is fabricated from the dynamic crosslinking of synthetic polymers, natural polymers, and silver nanowires to deliver autophagy-regulated rapamycin. Therefore, the resultant soft material exhibits antibacterial ability, biocompatibility, degradability, conductive, self-healing, and stimuli-responsive abilities. In vitro experiments demonstrate that the hydrogel-integrated 3D printed bioactive prosthetic interfaces can restore the declined cellular activities of OP-BMSCs by upregulating the autophagy level and show excellent antibacterial activity against S. aureus and MRSA. More remarkably, the multifunctional 3D printed bioactive prosthetic interfaces significantly improve osseointegration and inhibit infection in osteoporotic environment in vivo. This study provides an efficient strategy to develop novel prosthetic interfaces to reduce complications after arthroplasty for patients with osteoporosis.
Adherence to the American Diabetes Association’s Glycemic Goals in the Treatment of Diabetes Among Older Americans, 2001–2018
Authors: Phuc Le, Gina Ayers, Anita D. Misra-Hebert, Shoshana J. Herzig, William H. Herman, Victoria A. Shaker, Michael B. Rothberg
Journal: Diabetes Care (2022)

OBJECTIVE To assess trends in HbA1c and appropriateness of diabetes medication use by patient health status. RESEARCH DESIGN AND METHODS We conducted cross-sectional analysis of 2001–2018 National Health and Nutrition Examination Survey (NHANES). We included older adults age ≥65 years who had ever been told they had diabetes, had HbA1c &amp;gt;6.4%, or had fasting plasma glucose &amp;gt;125 mg/dL. Health status was categorized as good, intermediate, or poor. Being below goal was defined as taking medication despite having HbA1c ≥1% below the glycemic goals of the American Diabetes Association (ADA), which varied by patient health status and time period. Drugs associated with hypoglycemia included sulfonylureas, insulin, and meglitinides. RESULTS We included 3,539 patients. Mean HbA1c increased over time and did not differ by health status. Medication use increased from 59% to 74% with metformin being the most common drug in patients with good or intermediate health and sulfonylureas and insulin most often prescribed to patients with poor health. Among patients taking medications, prevalence of patients below goal increased while prevalence of those above goal decreased from 2001 to 2018. One-half of patients with poor health and taking medications had below-goal HbA1c; two-thirds received drugs associated with hypoglycemia. Patients with poor health who were below goal had 4.9 (95% CI 2.3–10.4) times the adjusted odds of receiving drugs associated with hypoglycemia than healthy patients. CONCLUSIONS In accordance with ADA’s newer Standards of Medical Care in Diabetes, HbA1c goals were relaxed but did not differ by health status. Below-goal HbA1c was common among patients with poor health; many were prescribed medications associated with a higher risk of hypoglycemia.
RNA m6A methylation regulates dissemination of cancer cells by modulating expression and membrane localization of β-catenin
Authors: Jiexin Li, Guoyou Xie, Yifan Tian, Wanglin Li, Yingmin Wu, Feng Chen, Yu Lin, Xinyao Lin, Shannon Wing-Ngor Au, Jie Cao, Weiling He, Hongsheng Wang
Journal: Molecular Therapy (2022)

N6-methyladenosine (m6A) methylation, which is modified by the METTL3/METTL14 complex, is a dominant internal modification in mammalian RNA and tightly linked to cancer progression. Here we reveal that METTL3-promoted cell migration, invasion, and epithelial-to-mesenchymal transition (EMT) are associated with expression and membrane localization of β-catenin (encoded by CTNNB1), as opposed to Wnt signaling activation in various types of cancer cells, including cervical, lung, and liver cancer. Specifically, METTL3 regulates the transcription, mRNA decay, translation, and subcellular localization of β-catenin. For CTNNB1 expression, METTL3 indirectly suppresses CTNNB1 transcription by stabilizing its transcription suppressor E2F1 mRNA； deposition of 5'UTR m6A in CTNNB1 promotes its decay in a content-dependent manner via YTHDF2 recognition; 5'UTR m6A in CTNNB1 suppresses its translation efficiency, whereas the global METTL3 level controls the canonical and non-canonical translation of CTNNB1, which is probably associated with the interaction between YTHDF1 and eIF4E1/eIF4E3. For β-catenin translocation, METTL3 represses membrane localization of β-catenin and its interaction with E-cadherin by downregulating c-Met kinase, leading to inhibition of cell motility. In vitro, in vivo, and clinical analyses confirm the essential role of β-catenin and its expression regulators in cancer cell dissemination. The findings not only expand our understanding of m6A modification and its roles in gene expression and subcellular localization of targets but also suggest that the METTL3/β-catenin axis might be a potential target to inhibit cancer metastasis.
JAK and mTOR inhibitors prevent cytokine release while retaining T cell bispecific antibody in vivo efficacy
Authors: Gabrielle Leclercq, Hélène Haegel, Alberto Toso, Tina Zimmermann, Luke Green, Nathalie Steinhoff, Johannes Sam, Vesna Pulko, Anneliese Schneider, Anna Maria Giusti, John Challier, Anne Freimoser-Grundschober, Laurent Larivière, Alex Odermatt, Martin Stern, Pablo Umana, Marina Bacac, Christian Klein
Journal: Journal for ImmunoTherapy of Cancer (2022)

T cell engaging therapies, like chimeric antigen receptor T cells and T cell bispecific antibodies (TCBs), efficiently redirect T cells towards tumor cells, facilitating the formation of a cytotoxic synapse and resulting in subsequent tumor cell killing, a process that is accompanied by the release of cytokines. Despite their promising efficacy in the clinic, treatment with TCBs is associated with a risk of cytokine release syndrome (CRS). The aim of this study was to identify small molecules able to mitigate cytokine release while retaining T cell-mediated tumor killing.By screening a library of 52 Food and Drug Administration approved kinase inhibitors for their impact on T cell proliferation and cytokine release after CD3 stimulation, we identified mTOR, JAK and Src kinases inhibitors as potential candidates to modulate TCB-mediated cytokine release at pharmacologically active doses. Using an in vitro model of target cell killing by human peripheral blood mononuclear cells, we assessed the effects of mTOR, JAK and Src kinase inhibitors combined with 2+1 T cell bispecific antibodies (TCBs) including CEA-TCB and CD19-TCB on T cell activation, proliferation and target cell killing measured by flow cytometry and cytokine release measured by Luminex. The combination of mTOR, JAK and Src kinase inhibitors together with CD19-TCB was evaluated in vivo in non-tumor bearing stem cell humanized NSG mice in terms of B cell depletion and in a lymphoma patient-derived xenograft (PDX) model in humanized NSG mice in terms of antitumor efficacy.The effect of Src inhibitors differed from those of mTOR and JAK inhibitors with the suppression of CD19-TCB-induced tumor cell lysis in vitro, whereas mTOR and JAK inhibitors primarily affected TCB-mediated cytokine release. Importantly, we confirmed in vivo that Src, JAK and mTOR inhibitors strongly reduced CD19-TCB-induced cytokine release. In humanized NSG mice, continuous treatment with a Src inhibitor prevented CD19-TCB-mediated B cell depletion in contrast to mTOR and JAK inhibitors, which retained CD19-TCB efficacy. Ultimately, transient treatment with Src, mTOR and JAK inhibitors minimally interfered with antitumor efficacy in a lymphoma PDX model.Taken together, these data support further evaluation of the use of Src, JAK and mTOR inhibitors as prophylactic treatment to prevent occurrence of CRS.
Screening for Atrial Fibrillation
Authors: Jill Jin
Journal: JAMA (2022)

US Preventive Services Task Force; Karina W. Davidson, PhD, MASc; Michael J. Barry, MD; Carol M. Mangione, MD, MSPH; Michael Cabana, MD, MA, MPH; Aaron B. Caughey, MD, PhD; Esa M. Davis, MD, MPH; Katrina E. Donahue, MD, MPH; Chyke A. Doubeni, MD, MPH; John W. Epling Jr, MD, MSEd; Martha Kubik, PhD, RN; Li Li, MD, PhD, MPH; Gbenga Ogedegbe, MD, MPH; Lori Pbert, PhD; Michael Silverstein, MD, MPH; James Stevermer, MD, MSPH; Chien-Wen Tseng, MD, MPH, MSEE; John B. Wong, MD
Pathophysiology and therapy of Takotsubo syndrome. Letter regarding the article ‘Pathophysiology of Takotsubo syndrome – a joint scientific statement from the Heart Failure Association Takotsubo Syndrome Study Group and Myocardial Function Working Group of the European Society of Cardiology – Part 1: overview and the central role for catecholamines and sympathetic nervous system’
Authors: John E. Madias
Journal: European Journal of Heart Failure (2022)
Adrenocortical Carcinoma with venous tumor invasion. Is there a role for mini-invasive surgery?
Authors: A. Olivero, K. Liu, E. Checcucci, L. Lei, L. Ma, G. Wang, G. Mantica, S. Tappero, D. Amparore, M. Sica, C. Fiori, Q. Huang, S. Niu, B. Wang, X. Ma, X. Hou, F. Porpiglia, C. Terrone, X. Zhang
Journal: European Urology (2021)
The prevalence of non‐allergic rhinitis phenotypes in the general population: A cross‐sectional study
Authors: Klementina S. Avdeeva, Wytske J. Fokkens, Christine L. Segboer, Sietze Reitsma
Journal: Allergy (2022)

Non-allergic rhinitis (NAR) can be subdivided into several phenotypes: rhinorrhea of the elderly, rhinitis medicamentosa, smokers', occupational, hormonal, drug-induced, gustatory, and idiopathic rhinitis. There are two pathophysiological endotypes of NAR: inflammatory and neurogenic. Phenotypes may serve as an indicator of an underlying endotype and, therefore, help to guide the treatment. The prevalence of each phenotype in the general population is currently unknown.Cross-sectional questionnaire-based study in the general population of the Netherlands.The prevalence of chronic rhinitis in the general population was 40% (N = 558, of those, 65% had NAR and 28% AR, in 7% allergy status is unknown). Individuals with NAR (N = 363) had significantly more complaints in October-February. Those with AR (N = 159) had significantly more complaints in April-August. The most common NAR phenotypes were idiopathic (39%) and rhinitis medicamentosa (14%), followed by occupational (8%), smokers' (6%), hormonal (4%), gustatory (4%), and rhinorrhea of the elderly (4%). The least prevalent phenotype was drug induced (1%). Nineteen percent of the NAR group could not be classified into any of the phenotypes.This is the first study to describe the prevalences of NAR phenotypes in the general population. AR and NAR have a distinct seasonality pattern with NAR being more prevalent in autumn/winter and AR in spring/summer. Our data on the prevalence of phenotypes may help clinicians to anticipate the type of patients at their clinic and help guide a tailored treatment approach. The high prevalence of rhinitis medicamentosa is alarming, since this is a potentially preventable phenotype.
Editorial: Narcolepsy.
Journal: BMJ (1975)

NarcolepsyThe narcoleptic syndrome is not uncommon, though its prevalence in Britain is not known for certain.A recent con- servative estimate' puts the inumber of narcoleptics in the U.S.A. as 100 000.The apparent slight male preponderance may wellbe due to its more disabling nature in men than women, and the actual sex incidence is probably equal.A third of patients have one or more affected relatives, usually on 16 August
Accounting for missing data caused by drug cessation in observational comparative effectiveness research: a simulation study
Authors: Denis Mongin, Kim Lauper, Axel Finckh, Thomas Frisell, Delphine Sophie Courvoisier
Journal: Annals of the Rheumatic Diseases (2022)

Objectives To assess the performance of statistical methods used to compare the effectiveness between drugs in an observational setting in the presence of attrition. Methods In this simulation study, we compared the estimations of low disease activity (LDA) at 1 year produced by complete case analysis (CC), last observation carried forward (LOCF), LUNDEX, non-responder imputation (NRI), inverse probability weighting (IPW) and multiple imputations of the outcome. All methods were adjusted for confounders. The reasons to stop the treatments were included in the multiple imputation method (confounder-adjusted response rate with attrition correction, CARRAC) and were either included (IPW2) or not (IPW1) in the IPW method. A realistic simulation data set was generated from a real-world data collection. The amount of missing data caused by attrition and its dependence on the ‘true’ value of the data missing were varied to assess the robustness of each method to these changes. Results LUNDEX and NRI strongly underestimated the absolute LDA difference between two treatments, and their estimates were highly sensitive to the amount of attrition. IPW1 and CC overestimated the absolute LDA difference between the two treatments and the overestimation increased with increasing attrition or when missingness depended on disease activity at 1 year. IPW2 and CARRAC produced unbiased estimations, but IPW2 had a greater sensitivity to the missing pattern of data and the amount of attrition than CARRAC. Conclusions Only multiple imputation and IPW2, which considered both confounding and treatment cessation reasons, produced accurate comparative effectiveness estimates.
A systematic review on the impact of surgeon and hospital caseload volume on oncological and non-oncological outcomes after radical prostatectomy for non-metastatic prostate cancer
Authors: T. Van Den Broeck, D. Oprea-Lager, L. Moris, M. Kailavasan, E. Briers, P. Cornford, M. De Santis, G. Gandaglia, S. Gillessen Sommer, J.P. Grummet, N. Grivas, T.B. Lam, M. Lardas, M. Liew, M. Mason, S. O’Hanlon, G. Ploussard, O. Rouvière, I. Schoots, D. Tilki, R.C.N. Van Den Bergh, H. Van Der Poel, T. Wiegel, P. Willemse, N. Mottet
Journal: European Urology (2021)
Concomitant type 2 diabetes mellitus (T2DM) in metastatic melanoma patients could be related to lower level of LAG-3: a transcriptomic analysis of a retrospective cohort
Authors: D. Mallardo, A. Cortellini, M. Capone, G. Madonna, D.J. Pinato, S. Warren, E. Simeone, P.A. Ascierto
Journal: Annals of Oncology (2022)