tbuckley/cabot-search huggingface dataset:
Investigating the Evolution of <i>Drosophila</i> STING-Dependent Antiviral Innate Immunity by Multispecies Comparison of 2′3′-cGAMP Responses
Authors: Léna Hédelin, Antonin Thiébaut, Jingxian Huang, Xiaoyan Li, Aurélie Lemoine, Gabrielle Haas, Carine Meignin, Hua Cai, Robert M Waterhouse, Nelson Martins, Jean-Luc Imler
Journal: Molecular Biology and Evolution (2024)

Viruses represent a major threat to all animals, which defend themselves through induction of a large set of virus-stimulated genes that collectively control the infection. In vertebrates, these genes include interferons that play a critical role in the amplification of the response to infection. Virus- and interferon-stimulated genes include restriction factors targeting the different steps of the viral replication cycle, in addition to molecules associated with inflammation and adaptive immunity. Predictably, antiviral genes evolve dynamically in response to viral pressure. As a result, each animal has a unique arsenal of antiviral genes. Here, we exploit the capacity to experimentally activate the evolutionarily conserved stimulator of IFN genes (STING) signaling pathway by injection of the cyclic dinucleotide 2'3'-cyclic guanosine monophosphate-adenosine monophosphate into flies to define the repertoire of STING-regulated genes in 10 Drosophila species, spanning 40 million years of evolution. Our data reveal a set of conserved STING-regulated factors, including STING itself, a cGAS-like-receptor, the restriction factor pastel, and the antiviral protein Vago, but also 2 key components of the antiviral RNA interference pathway, Dicer-2, and Argonaute2. In addition, we identify unknown species- or lineage-specific genes that have not been previously associated with resistance to viruses. Our data provide insight into the core antiviral response in Drosophila flies and pave the way for the characterization of previously unknown antiviral effectors.
Incidental Detection of Myocardial Ischemia on Whole-Body PET/CT in a Patient With Carcinoma Lung
Authors: Parneet Singh, Girish Kumar Parida, Tejasvini Singhal, Jaydeep Gupta, Kanhaiyalal Agrawal
Journal: Clinical Nuclear Medicine (2024)

Abstract 18 F-FDG PET/CT being a whole-body technique can detect multiple other critical nononcological findings. Various cardiac disorders identified incidentally on 18 F-FDG have been reported to help in timely management and improve overall patient care. We hereby present one such case where 18 F-FDG PET/CT performed for a workup of carcinoma lung revealed abnormal myocardial FDG uptake in the anteroseptal and apical region, which raised suspicion of myocardial ischemia such as hot spot imaging. On coronary angiography, coronary artery disease was detected and subsequently managed.
E3MPH16: An efficient endosomolytic peptide for intracellular protein delivery
Authors: Yoshimasa Kawaguchi, Yuki Kawamura, Hisaaki Hirose, Megumi Kiyokawa, Momo Hirate, Tsuyoshi Hirata, Yuriko Higuchi, Shiroh Futaki
Journal: Journal of Controlled Release (2024)
Detection of metastatic lymph node and sentinel lymph node mapping ​using mannose receptor targeting in in vivo mouse and rabbit uterine cancer models
Authors: Sohyeon Jeong, Ok Hwa Jeon, Jin Hwa Hong, Kyungsu Kim, Beop-Min Kim, Ji Yong Park, Kweon Kim, Hyun-Woong Cho, Hyun Koo Kim
Journal: International Journal of Surgery (2024)

Background: This study aimed to evaluate the effectiveness of neo-mannosyl human serum albumin-indocyanine green (MSA-ICG) for detecting metastatic lymph node and mapping sentinel lymph node (SLN) using mouse footpad uterine tumor models. Additionally, we assessed the feasibility of MSA-ICG in SLN mapping in rabbit uterine cancer models. Materials and Methods: We compared the LN targeting ability of MSA-ICG with ICG. Six mouse footpad tumor models and two normal mice were each assigned to MSA-ICG and ICG, respectively. After the assigned tracers were injected, fluorescence images were taken, and we compared the signal-to-background ratio (SBR) of the tracers. A SLN biopsy was performed to confirm LN metastasis status and CD206 expression level. Finally, an intraoperative SLN biopsy was performed in rabbit uterine cancer models using MSA-ICG. Results: We detected 14 groin LNs out of 16 in the MSA-ICG and ICG groups. The SBR of the MSA-ICG group was significantly higher than that of the ICG group. The metastatic LN subgroup of MSA-ICG showed a significantly higher SBR than that of ICG. CD206 was expressed at a high level in metastatic LN, and the signal intensity difference increased as the CD206 expression level increased. SLN mapping was successfully performed in two of the three rabbit uterine cancer models. Conclusion: MSA-ICG was able to distinguish metastatic LN for an extended period due to its specific tumor-associated macrophage-targeting property. Therefore, it may be a more distinguishable tracer for identifying metastatic LNs and SLNs during uterine cancer surgery. Further research is needed to confirm these results.
CRISPR/Cas9: an overview of recent developments and applications in cancer research
Authors: Nandibala Devi Shamjetsabam, Rashmi Rana, Priyanka Malik, Nirmal Kumar Ganguly
Journal: International Journal of Surgery (2024)

Clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR associated protein 9 (Cas9) has risen as a potent gene editing method with vast potential across numerous domains, including its application in cancer research and therapy. This review article provides an extensive overview of the research that has been done so far on CRISPR-Cas9 with an emphasis on how it could be utilized in the treatment of cancer. The authors go into the underlying ideas behind CRISPR-Cas9, its mechanisms of action, and its application for the study of cancer biology. Furthermore, the authors investigate the various uses of CRISPR-Cas9 in cancer research, spanning from the discovery of genes and the disease to the creation of novel therapeutic approaches. The authors additionally discuss the challenges and limitations posed by CRISPR-Cas9 technology and offer insights into the potential applications and future directions of this cutting-edge field of research. The article intends to consolidate the present understanding and stimulate more research into CRISPR-Cas9’s promise as a game-changing tool for cancer research and therapy.
Dynamic Fluctuations of Metastatic Pulmonary Lesions
Authors: Weijie Dong, Yan You, Chunyi Liu, Qing Ma, Dan Wang, Xinlin Shi, Daoxin Wang, Changyi Li
Journal: American Journal of Respiratory and Critical Care Medicine (2024)

"Dynamic Fluctuations of Metastatic Pulmonary Lesions." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp.
The Immune Landscape of Pheochromocytoma and Paraganglioma: Current Advances and Perspectives
Authors: Ondrej Uher, Katerina Hadrava Vanova, David Taïeb, Bruna Calsina, Mercedes Robledo, Roderick Clifton-Bligh, Karel Pacak
Journal: Endocrine Reviews (2024)

Abstract Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors derived from neural crest cells from adrenal medullary chromaffin tissues and extra-adrenal paraganglia, respectively. Although the current treatment for PPGLs is surgery, optimal treatment options for advanced and metastatic cases have been limited. Hence, understanding the role of the immune system in PPGL tumorigenesis can provide essential knowledge for the development of better therapeutic and tumor management strategies, especially for those with advanced and metastatic PPGLs. The first part of this review outlines the fundamental principles of the immune system and tumor microenvironment, and their role in cancer immunoediting, particularly emphasizing PPGLs. We focus on how the unique pathophysiology of PPGLs, such as their high molecular, biochemical, and imaging heterogeneity and production of several oncometabolites, creates a tumor-specific microenvironment and immunologically “cold” tumors. Thereafter, we discuss recently published studies related to the reclustering of PPGLs based on their immune signature. The second part of this review discusses future perspectives in PPGL management, including immunodiagnostic and promising immunotherapeutic approaches for converting “cold” tumors into immunologically active or “hot” tumors known for their better immunotherapy response and patient outcomes. Special emphasis is placed on potent immune-related imaging strategies and immune signatures that could be used for the reclassification, prognostication, and management of these tumors to improve patient care and prognosis. Furthermore, we introduce currently available immunotherapies and their possible combinations with other available therapies as an emerging treatment for PPGLs that targets hostile tumor environments.
Estimating the impact of alternative programmatic cotrimoxazole strategies on mortality among children born to mothers with HIV: A modelling study
Authors: Shrey Mathur, Melanie Smuk, Ceri Evans, Catherine J. Wedderburn, Diana M. Gibb, Martina Penazzato, Andrew J. Prendergast
Journal: PLoS Medicine (2024)

Background World Health Organization (WHO) guidelines recommend cotrimoxazole prophylaxis for children who are HIV-exposed until infection is excluded and vertical transmission risk has ended. While cotrimoxazole has benefits for children with HIV, there is no mortality benefit for children who are HIV-exposed but uninfected, prompting a review of global guidelines. Here, we model the potential impact of alternative cotrimoxazole strategies on mortality in children who are HIV-exposed. Methods and findings Using a deterministic compartmental model, we estimated mortality in children who are HIV-exposed from 6 weeks to 2 years of age in 4 high-burden countries: Côte d’Ivoire, Mozambique, Uganda, and Zimbabwe. Vertical transmission rates, testing rates, and antiretroviral therapy (ART) uptake were derived from UNAIDS data, trial evidence, and meta-analyses. We explored 6 programmatic strategies: maintaining current recommendations; shorter cotrimoxazole provision for 3, 6, 9, or 12 months; and starting cotrimoxazole only for children diagnosed with HIV. Modelled alternatives to the current strategy increased mortality to varying degrees; countries with high vertical transmission had the greatest mortality. Compared to current recommendations, starting cotrimoxazole only after a positive HIV test had the greatest predicted increase in mortality: Mozambique (961 excess annual deaths; excess mortality 339 per 100,000 HIV-exposed children; risk ratio (RR) 1.06), Uganda (491; 221; RR 1.04), Zimbabwe (352; 260; RR 1.05), and Côte d’Ivoire (125; 322; RR 1.06). Similar effects were observed for 3-, 6-, 9-, and 12-month strategies. Increased mortality persisted but was attenuated when modelling lower cotrimoxazole uptake, smaller mortality benefits, higher testing coverage, and lower vertical transmission rates. The study is limited by uncertain estimates of cotrimoxazole coverage in programmatic settings; an inability to model increases in mortality arising from antimicrobial resistance due to limited surveillance data in sub-Saharan Africa; and lack of a formal health economic analysis. Conclusions Changing current guidelines from universal cotrimoxazole provision for children who are HIV-exposed increased predicted mortality across the 4 modelled high-burden countries, depending on test-to-treat cascade coverage and vertical transmission rates. These findings can help inform policymaker deliberations on cotrimoxazole strategies, recognising that the risks and benefits differ across settings.
Adult Presentation of Cutaneous Langerhans Cell Histiocytosis
Authors: Elizabeth Robinson, Ayah Nawwar, Julie Searle, Iain Lyburn
Journal: Clinical Nuclear Medicine (2024)

Abstract Langerhans cell histiocytosis (LCH) is a rare hematological disease, more common in pediatric populations. A 26-year-old man with biopsy-proven cutaneous LCH underwent 18 F-FDG PET/CT systemic staging. 18 F-FDG PET/CT highlighted multiple sites of avid cutaneous disease within the natal cleft. Additional characteristic cystic lung disease was seen on the CT component and focal uptake in the pituitary stalk/hypothalamic region noted, a common but occult site of disease in this patient. Because of the rarity of adult-onset cutaneous LCH, guidance on management and staging is lacking. 18 F-FDG PET/CT is critical to baseline evaluation of systemic disease, as illustrated here.
18F-FAPI for Imaging Metastatic Perivascular Epithelioid Cell Neoplasm
Authors: Jing Zhang, Miao Ke, Ruiyue Zhao, Peng Hou, Xinlu Wang
Journal: Clinical Nuclear Medicine (2024)

Abstract We compared 18 F-FAPI and 18 F-FDG PET/CT findings of metastatic perivacular epitheliod cell tumor in a 23-year-old woman. Apart from showing strong uptake of a left upper lung mass that showed moderate uptake on 18 F-FDG, 18 F-FAPI PET/CT additionally presented hypermetabolism in diffuse multifocal lesion throughout the body. This case suggests that 18 F-FAPI PET/CT might play a more beneficial role than 18 F-FDG PET/CT in identifying and assessing the extent of perivascular epithelioid cell tumors.
Small Cell Neuroendocrine Carcinoma of the Prostate on 18F-DCFPyL and 18F-FDG PET/CT
Authors: Edward Li, Andrew Russon, Jeffrey Chen, Victor Mansberg, Robert Mansberg
Journal: Clinical Nuclear Medicine (2024)

Abstract A 51-year-old man with newly diagnosed small cell neuroendocrine carcinoma of the prostate was referred for a staging 18 F-DCFPyL PET/CT, which showed a solitary metastasis in the left acetabulum. Subsequent 18 F-FDG PET/CT showed intense uptake throughout the prostate as well as extensive avid pelvic and thoracic nodal disease and redemonstration of the left acetabular metastasis. Despite initial metabolic response to treatment, subsequent 18 F-FDG PET 8 months later revealed significant progression of nodal disease above and below the diaphragm, as well as multiple new sites of metastases.
Cardiac Troponin in Patients With Light Chain and Transthyretin Cardiac Amyloidosis
Authors: Laura De Michieli, Alberto Cipriani, Sabino Iliceto, Angela Dispenzieri, Allan S. Jaffe
Journal: JACC CardioOncology (2024)

Cardiac amyloidosis (CA) is an infiltrative disease caused by amyloid fibril deposition in the myocardium; the 2 forms that most frequently involve the heart are amyloid light chain (AL) and amyloid transthyretin (ATTR) amyloidosis. Cardiac troponin (cTn) is the biomarker of choice for the detection of myocardial injury and is frequently found to be elevated in patients with CA, particularly with high-sensitivity assays. Multiple mechanisms of myocardial injury in CA have been proposed, including cytotoxic effect of amyloid precursors, interstitial amyloid fibril infiltration, coronary microvascular dysfunction, amyloid- and non-amyloid-related coronary artery disease, diastolic dysfunction, and heart failure. Regardless of the mechanisms, cTn values have relevant prognostic (and potentially diagnostic) implications in both AL and ATTR amyloidosis. In this review, the authors discuss the significant aspects of cTn biology and measurement methods, potential mechanisms of myocardial injury in CA, and the clinical application of cTn in the management of both AL and ATTR amyloidosis.
Real-life practice of reflectance confocal microscopy in France: A prospective multicenter study
Authors: Marion Stefanski, Aurore Le Guern, Laetitia Visseaux, Marine Ehret, Michel Colomb, Géraldine Jeudy, Florence Le Duff, Morgane Vourc'h, Barouyr Baroudjian, Rosa Perea-Villacorta, Charlotte Bernigaud, Stéphanie Mallet, Laurène Norberciak, Sébastien Debarbieux, Jean-Luc Perrot, Florent Grange, Philippe Modiano, Jilliana Monnier, Philippe Bahadoran
Journal: Journal of the American Academy of Dermatology (2024)
Negative impact of comorbidities on all-cause mortality of patients with psoriasis is partially alleviated by biologic treatment: A real-world case-control study
Authors: Saba Riaz, Sepideh Emam, Ting Wang, Robert Gniadecki
Journal: Journal of the American Academy of Dermatology (2024)

Background Cardiovascular comorbidities are believed to cause higher mortality in psoriasis patients. Conversely, systemic therapy may improve overall survival. Objective To evaluate the impact of different comorbidities and therapy on mortality risk of psoriasis patients in the entire population of Alberta, Canada (population 4.37 million). Methods Cohorts of psoriasis cases (n=18,618) and controls (ambulatory patients matched 1:3 by by age, and sex) were retrieved from Alberta Health Services Data Repository of Reporting database within the period 2012-2019. Cases were stratified according to Charlson Comorbidity Index (CCI), and the type of therapy. Results Mortality in psoriasis cohort was significantly higher than in the controls (median age of death 72.0 years vs 74.4 years, respectively). CCI and comorbidities were strong predictors of mortality, in particular drug induced liver injury (hazard ratio [HR] 1.8, affective bipolar disease, HR 1.6, and major cardiovascular diseases. Mortality was lower in patients treated with biologics (HR 0.54). Limitations Some factors (psoriasis type and severity, response to treatment, smoking, alcohol intake) could not be measured. Conclusions Hepatic injury, psychiatric affective disorders and cardiovascular disease were major determinants of overall survival in psoriasis. Biologic therapy was associated with a reduced mortality risk.
Coeliac disease: the paradox of diagnosing a food hypersensitivity disorder with autoantibodies
Authors: M Fleur du Pre, Rasmus Iversen, Ludvig M Sollid
Journal: Gut (2024)

Serum antibodies to the autoantigen transglutaminase 2 (TG2) are increasingly harnessed to diagnose coeliac disease. Diagnostic guidelines for children give recommendation for a no-biopsy-based diagnosis through detection of high amounts of IgA anti-TG2 antibodies in serum with confirmation of positivity in a separate blood sample by characteristic autoantibody-staining of tissue. While measurement of IgA anti-TG2 also is important in the diagnostic workup of adults, the adult guidelines still mandate examination of gut biopsies. This requirement might well change in the future, as might the necessity for confirming autoantibody positivity by tissue staining. The key role of autoantibody serology for diagnosis of coeliac disease is paradoxical. Coeliac disease was considered, and still can be considered, a food intolerance disorder where autoantibodies at face value are out of place. The immunological mechanisms underlying the formation of autoantibodies in response to gluten exposure have been dissected. This review presents the current insights demonstrating that the autoantibodies in coeliac disease are intimately integrated in the maladapted immune response to gluten.
Risk of long COVID and associated symptoms after acute SARS-COV-2 infection in ethnic minorities: A nationwide register-linked cohort study in Denmark
Authors: George Frederick Mkoma, Charles Agyemang, Thomas Benfield, Mikael Rostila, Agneta Cederström, Jørgen Holm Petersen, Marie Norredam
Journal: PLoS Medicine (2024)

Background Ethnic minorities living in high-income countries have been disproportionately affected by Coronavirus Disease 2019 (COVID-19) in terms of infection rates, hospitalisations, and deaths; however, less is known about long COVID in these populations. Our aim was to examine the risk of long COVID and associated symptoms among ethnic minorities. Methods and findings We used nationwide register-based cohort data on individuals diagnosed with COVID-19 aged ≥18 years (n = 2,287,175) between January 2020 and August 2022 in Denmark. We calculated the risk of long COVID diagnosis and long COVID symptoms among ethnic minorities compared with native Danes using multivariable Cox proportional hazard regression and logistic regression, respectively. Among individuals who were first time diagnosed with COVID-19 during the study period, 39,876 (1.7%) were hospitalised and 2,247,299 (98.3%) were nonhospitalised individuals. Of the diagnosed COVID-19 cases, 1,952,021 (85.3%) were native Danes and 335,154 (14.7%) were ethnic minorities. After adjustment for age, sex, civil status, education, family income, and Charlson comorbidity index, ethnic minorities from North Africa (adjusted hazard ratio [aHR] 1.41, 95% confidence interval [CI] [1.12,1.79], p = 0.003), Middle East (aHR 1.38, 95% CI [1.24,1.55], p &lt; 0.001), Eastern Europe (aHR 1.35, 95% CI [1.22,1.49], p &lt; 0.001), and Asia (aHR 1.23, 95% CI [1.09,1.40], p = 0.001) had significantly greater risk of long COVID diagnosis than native Danes. In the analysis by largest countries of origin, the greater risks of long COVID diagnosis were found in people of Iraqi origin (aHR 1.56, 95% CI [1.30,1.88], p &lt; 0.001), people of Turkish origin (aHR 1.42, 95% CI [1.24,1.63], p &lt; 0.001), and people of Somali origin (aHR 1.42, 95% CI [1.07,1.91], p = 0.016). A significant factor associated with an increased risk of long COVID diagnosis was COVID-19 hospitalisation. The risk of long COVID diagnosis among ethnic minorities was more pronounced between January 2020 and June 2021. Furthermore, the odds of reporting cardiopulmonary symptoms (including dyspnoea, cough, and chest pain) and any long COVID symptoms were higher among people of North African, Middle Eastern, Eastern European, and Asian origins than among native Danes in both unadjusted and adjusted models. Despite including the nationwide sample of individuals diagnosed with COVID-19, the precision of our estimates on long COVID was limited to the sample of patients with symptoms who had contacted the hospital. Conclusions Belonging to an ethnic minority group was significantly associated with an increased risk of long COVID, indicating the need to better understand long COVID drivers and address care and treatment strategies in these populations.
Time to consider oesophageal atresia as a life-long disease
Authors: Mélanie Leroy, Madeleine Aumar, David Seguy, Florent Vandamme, Anke Widenmann-Grolig, Rony Sfeir, Frédéric Gottrand
Journal: International Journal of Surgery (2024)

Leroy, Mélanie PhD; Aumar, Madeleine MD, PhD; Seguy, David MD, PhD; Vandamme, Florent MD; Widenmann-Grolig, Anke Engineer; Sfeir, Rony MD; Gottrand, Frédéric MD, PhD Author Information