tbuckley/cabot-search huggingface dataset:
Commentary
Authors: Cesare Hassan, Yuichi Mori, Alessandro Repici
Journal: Endoscopy (2022)

Some endoscopists might assume that computer-aided detection (CADe) used in colonoscopy can identify any type of polyp, regardless of its shape, size, and histology. Unfortunately, the differences amongst polyps are greater and much more various than, say, differences amongst cars, and the accuracy of CADe is extremely dependent on the prevalence of each polyp type in the training dataset. The training of CADe software is mainly based on subcentimetric adenomas, while sessile serrated lesions, nongranular laterally spreading lesions, or even advanced cancers are insufficiently represented in the dataset. Thus, endoscopists need to be aware of this potential limitation of CADe as well as of its benefits for increasing the adenoma detection rate [1] [2]. It is also noteworthy that most manufacturers are eager to improve the software by including more varieties of images to overcome this significant drawback of CADe in clinical practice.
Human Cerebellar Development and Transcriptomics: Implications for Neurodevelopmental Disorders
Authors: Parthiv Haldipur, Kathleen J. Millen, Kimberly A. Aldinger
Journal: Annual Review of Neuroscience (2022)

Developmental abnormalities of the cerebellum are among the most recognized structural brain malformations in human prenatal imaging. Yet reliable information regarding their cause in humans is sparse, and few outcome studies are available to inform prognosis. We know very little about human cerebellar development, in stark contrast to the wealth of knowledge from decades of research on cerebellar developmental biology of model organisms, especially mice. Recent studies show that multiple aspects of human cerebellar development significantly differ from mice and even rhesus macaques, a nonhuman primate. These discoveries challenge many current mouse-centric models of normal human cerebellar development and models regarding the pathogenesis of several neurodevelopmental phenotypes affecting the cerebellum, including Dandy-Walker malformation and medulloblastoma. Since we cannot model what we do not know, additional normative and pathological human developmental data are essential, and new models are needed.
Extracellular nucleoprotein exacerbates influenza virus pathogenesis by activating Toll-like receptor 4 and the NLRP3 inflammasome
Authors: Chang-Ung Kim, Yu-Jin Jeong, Pureum Lee, Moo-Seung Lee, Jong-Hwan Park, Young-Sang Kim, Doo-Jin Kim
Journal: Cellular and Molecular Immunology (2022)
The value of alleviating suffering and dignifying death in war and humanitarian crises
Authors: William E Rosa, Liz Grant, Felicia Marie Knaul, Joan Marston, Hector Arreola-Ornelas, Olena Riga, Roman Marabyan, Andriy Penkov, Libby Sallnow, M R Rajagopal
Journal: The Lancet (2022)
Disruption of dNTP homeostasis by ribonucleotide reductase hyperactivation overcomes AML differentiation blockade
Authors: Hanying Wang, Xin He, Lei Zhang, Haojie Dong, Feiteng Huang, Jie Xian, Min Li, Wei Chen, Xiyuan Lu, Khyatiben V. Pathak, Wenfeng Huang, Zheng Li, Lianjun Zhang, Le Xuan Truong Nguyen, Lu Yang, Lifeng Feng, David J. Gordon, Jing Zhang, Patrick Pirrotte, Chun-Wei Chen, Amandeep Salhotra, Ya-Huei Kuo, David Horne, Guido Marcucci, David B. Sykes, Stefano Tiziani, Hongchuan Jin, Xian Wang, Ling Li
Journal: Blood (2022)
Stimulation of the EP<sub>3</sub>receptor causes lung oedema by activation of TRPC6 in pulmonary endothelial cells
Authors: Tian Jiang, Rudi Samapati, Sergej Klassen, Disi Lei, Lasti Erfinanda, Vera Jankowski, Szandor Simmons, Jun Yin, Christoph Arenz, Alexander Dietrich, Thomas Gudermann, Dieter Adam, Michael Schaefer, Joachim Jankowski, Veit Flockerzi, Rolf Nüsing, Stefan Uhlig, Wolfgang M. Kuebler
Journal: European Respiratory Journal (2022)

Prostaglandin E2 (PGE2) increases pulmonary vascular permeability by activation of the PGE2 receptor 3 (EP3), which may explain adverse pulmonary effects of the EP1/EP3 receptor agonist sulprostone in patients. In addition, PGE2 contributes to pulmonary oedema in response to platelet-activating factor (PAF). PAF increases endothelial permeability by recruiting the cation channel transient receptor potential canonical 6 (TRPC6) to endothelial caveolae via acid sphingomyelinase (ASMase). Yet, the roles of PGE2 and EP3 in this pathway are unknown. We hypothesised that EP3 receptor activation may increase pulmonary vascular permeability by activation of TRPC6, and thus, synergise with ASMase-mediated TRPC6 recruitment in PAF-induced lung oedema.In isolated lungs, we measured increases in endothelial calcium (ΔCa2+) or lung weight (Δweight), and endothelial caveolar TRPC6 abundance as well as phosphorylation.PAF-induced ΔCa2+ and Δweight were attenuated in EP3-deficient mice. Sulprostone replicated PAF-induced ΔCa2+ and Δweight which were blocked by pharmacological/genetic inhibition of TRPC6, ASMase or Src-family kinases (SrcFK). PAF, but not sulprostone, increased TRPC6 abundance in endothelial caveolae. Immunoprecipitation revealed PAF- and sulprostone-induced tyrosine-phosphorylation of TRPC6 that was prevented by inhibition of phospholipase C (PLC) or SrcFK. PLC inhibition also blocked sulprostone-induced ΔCa2+ and Δweight, as did inhibition of SrcFK or inhibitory G-protein (Gi) signalling.EP3 activation triggers pulmonary oedema via Gi-dependent activation of PLC and subsequent SrcFK-dependent tyrosine phosphorylation of TRPC6. In PAF-induced lung oedema, this TRPC6 activation coincides with ASMase-dependent caveolar recruitment of TRPC6, resulting in rapid endothelial Ca2+ influx and barrier failure.
Caspase-3 mediated switch therapy of self-triggered and long-acting prodrugs for metastatic TNBC
Authors: Ha Rin Kim, Young Seok Cho, Seung Woo Chung, Jeong Uk Choi, Yoon Gun Ko, Seong Jin Park, Sang Yoon Kim, Youngro Byun
Journal: Journal of Controlled Release (2022)

Triple-negative breast cancer (TNBC) is characterized by its highly heterogeneous microenvironment and propensity for aggressive behavior, both of which represent, along with poor prognosis and high incidence of relapse, the main challenges of curing the disease. Although recent progress in targeted chemotherapy combinations has shown promising outcomes, conventional targeted chemotherapeutic approaches have relied on exploiting the expression of certain molecules or proteins overexpressed on cancer cells as drug targets, which have demonstrated limited clinical benefit against metastatic cancers. Here, we describe a tumoral caspase-3 mediated peptide-doxorubicin conjugates (PDC) switch therapy that adopts two different caspase-3 cleavable PDCs, RGDEVD-DOX (TPD1) and EMC-KGDEVD-DOX (MPD1), for targeting metastatic triple-negative breast cancer (mTNBC). First, using TPD1, an integrin αVβ3 based targeted strategy was utilized to target tumor cells or tumor vasculature associated with the highly malignant progression of mTNBC. TPD1 triggered the tumor cell-specific initial apoptosis and the induction of caspase-3 expression in the target tumor site. Then MPD1 was administered sequentially, which is an albumin-binding prodrug, and activated by induced caspase-3 in order to maintain the tumoral caspase-3 level and release the cytotoxic payload. The PDC switch therapy markedly accumulated doxorubicin in the tumor site and augmented tumor-specific in situ amplification of apoptosis. Importantly, the PDC switch therapy exerted a bystander killing effect on the neighboring cancer cells thus demonstrating potent therapeutic efficacy against both local and metastatic cancers. Given the limited therapeutic outcomes with conventional targeted therapies, our strategy of regulating the expression of caspase-3 level as a drug target could provide as a more durable and effective alternative in the treatment of highly heterogeneous mTNBC.
FDG PET/CT Features of Polysaccharide-Based Hemostatic Agent
Authors: Emine Bozkurtlar, Kevser Oksuzoglu, Korkut Bostanci, Sezer Aslan, Tugba Nergiz Kissa, Derya Kocakaya, Tunc Ones
Journal: Clinical Nuclear Medicine (2022)

Purpose To prevent hemorrhagic complications, hemostatic agents (HAs) have been widely used in recent years. The use of HAs can lead to false-positive results on postoperative imaging. There exists only 1 study in the literature evaluating these applications during surgical procedures. Therefore, we aimed to evaluate the postoperative imaging features of polysaccharide-based HAs in thoracic surgery patients who have had 18 F-FDG PET/CT scans. Patients and Methods Two hundred nine consecutive patients who underwent thoracic surgery were enrolled in this study. A topical polysaccharide-based HA was applied to the surgical bed for all of the patients. The patients diagnosed with cancer were followed up with subsequent thoracic CT scans, and 42 of these patients were also imaged with 18 F-FDG PET/CT, which then comprised the main study group. Due to suspicion of metastasis, 19/42 patients were reoperated or rebiopsied. The latest histopathological findings were accepted as criterion standard, and previous FDG PET/CT images were retrospectively reevaluated. Results Polysaccharide-based HAs that appear as amorphous basophilic material were identified in histopathological samples of 11/19 patients. Lymphocytes, plasma cells, and histiocytes, which formed foreign body reaction and/or foreign body granuloma, indicating the presence of chronic inflammation, were seen in all of the samples. 18 F-FDG PET/CT showed increased FDG uptake in all of these lesions. Conclusions Despite the inconsistency of the literature, polysaccharide-based HAs can be demonstrated in human surgical specimens as amorphous basophilic materials even after a long time from the initial surgical procedure. These agents almost always cause chronic inflammatory changes. In addition, these agents may mimic “false-positive” findings on postoperative FDG PET/CT scans.
Prognostic impact of<i>DDX41</i>germline mutations in intensively treated acute myeloid leukemia patients: an ALFA-FILO study
Authors: Nicolas Duployez, Laëtitia Largeaud, Matthieu Duchmann, Rathana Kim, Julie Rieunier, Juliette Lambert, Audrey Bidet, Lise Larcher, Jean Lemoine, François Delhommeau, Pierre Hirsch, Laurène Fenwarth, Olivier Kosmider, Justine Decroocq, Anne Bouvier, Yannick Le Bris, Marlène Ochmann, Alberto Santagostino, Lionel Adès, Pierre Fenaux, Xavier Thomas, Jean-Baptiste Micol, Claude Gardin, Raphael Itzykson, Jean Soulier, Emmanuelle Clappier, Christian Recher, Claude Preudhomme, Arnaud Pigneux, Hervé Dombret, Eric Delabesse, Marie Sébert
Journal: Blood (2022)
Exploring racial disparities in treatment patterns and outcomes for patients with multiple myeloma using real world data
Authors: Kathleen Maignan, Lola A. Fashoyin-Aje, Aracelis Z. Torres, Laura L. Fernandes, Thomas Gwise, Shrujal B. Baxi, James P. Roose, Donna R. Rivera, Yuan Li Shen, Paul G. Kluetz, Nicole J. Gormley
Journal: Blood Cancer Journal (2022)

Abstract This retrospective observational study evaluated racial disparities among Black and White patients with multiple myeloma (MM). We included patients from a longitudinal de-identified EHR-derived database who had ≥2 visits recorded on or after 1/1/2011, documented treatment, and race listed as White or Black. Black patients ( n = 1172) were more likely female (54.8%/42.9%) and younger (&lt;65 years, 40.8%/30.8%) than White patients ( n = 4637). Unadjusted median real-world overall survival (rwOS) indexed to first-line of therapy (LOT) was 64.6 months (95% CI: 57.8–74.0) for Blacks and 54.5 months (95% CI: 50.9–56.2) for Whites. Adjusted rwOS estimates (for sex, age at index date, and practice type) to either first- (aHR = 0.94; 95% CI: 0.84–1.06) or second-LOT (aHR = 0.90; 95% CI: 0.77–1.05) were similar. Unadjusted derived response rate (dRR) during first-LOT was 84.8% (95% CI: 80.7–88.1) for Blacks and 86.9% (95% CI: 85.0–88.5) for Whites (odds ratio [OR] = 0.78 [95% CI: 0.57–1.10]); in second-LOT, 67.2% (95% CI: 58.4–75.0) for Blacks and 72.4% (95% CI: 68.1–76.3) for Whites (OR = 0.72 [95% CI: 0.46–1.13]). High representation of Black patients enabled this robust analysis, albeit with limitations inherent to the observational data source, the retrospective design, and the analytic use of newly derived endpoints requiring further validation.
α-Gal present on both glycolipids and glycoproteins contributes to immune response in meat-allergic patients
Authors: Neera Chakrapani, Jörg Fischer, Kyra Swiontek, Françoise Codreanu-Morel, Farah Hannachi, Martine Morisset, Clément Mugemana, Dmitry Bulaev, Simon Blank, Carsten Bindslev-Jensen, Tilo Biedermann, Markus Ollert, Christiane Hilger
Journal: Journal of Allergy and Clinical Immunology (2022)
The Detection Performance of 18F–Prostate-Specific Membrane Antigen-1007 PET/CT in Primary Prostate Cancer
Authors: Ya-Ting Huang, Neng-Chuan Tseng, Yen-Kung Chen, Kuo-How Huang, Hsiu-Ying Lin, Ya-Yao Huang, Thomas I. S. Hwang, Yen-Chuan Ou
Journal: Clinical Nuclear Medicine (2022)

Background Multiple tools are now available to determine the requirement for a biopsy to diagnose prostate cancer, and PET/CT with radiolabeled prostate-specific membrane antigen (PSMA)–targeting radiotracers has been recommended for detecting primary prostate cancer. Particularly, the radiotracer 18 F-PSMA-1007 was found to be more favorable for primary tumors compared with other PSMA-targeting radiotracers because of its low clearance via the urinary tract and better image resolution. Thus, we performed a systematic review and meta-analysis to more accurately evaluate the detection performance of 18 F-PSMA-1007 PET/CT in primary prostate cancer patients. Methods An update on the databases of PubMed/MEDLINE, EMBASE, and Cochrane Library for comprehensive literature search was performed on September 30, 2021. The pooling detection rate was calculated on a per-patient basis. The pooling median of the SUV max was analyzed from the included studies. Furthermore, the positive predictive value of 18 F-PSMA-1007 PET/CT with pathologic lesions was analyzed using the criterion standard. Results Twelve studies (540 patients total) were included in the meta-analysis. The overall pooling detection rate of 18 F-PSMA-1007 per patient was 94%, and the pooling median of SUV max located at the intraprostate tumor was 16 (range, 3.7–77.7). The positive predictive value of 18 F-PSMA-1007 per lesion with histopathological validation was 0.90, detecting regional lymph node metastasis was 0.94, and detecting localized prostatic tumors was 0.84. Conclusions In the current meta-analysis, we revealed the excellent performance of 18 F-PSMA-1007 to detect localized prostatic tumor lesions and regional lymph node metastasis. Moreover, the uptake of localized tumors in primary prostate cancer was nearly liver uptake and may be considered a suspicious malignancy if it was equal to or greater than the liver uptake.
A challenge to the kidney community by a man-made crisis
Authors: P. Toby Coates, Germaine Wong, Brad H. Rovin, Pierre Ronco, Pierre Ronco, Brad Rovin, P. Toby Coates, Olivier Devuyst, Tilman B. Drueke, Iain Drummond, Jurgen Floege, Agnes B. Fogo, T. Alp Ikizler, Krzysztof Kiryluk, Masaomi Nangaku, Jai Radhakrishnan, Germaine Wong, Christina Wyatt, Jun Xia, Pat Morrissey, Susan Small, Christine Burgos-Clavel
Journal: Kidney International (2022)
Glutamatergic synapses from the insular cortex to the basolateral amygdala encode observational pain
Authors: Ming-Ming Zhang, An-Qi Geng, Kun Chen, Jian Wang, Pan Wang, Xin-Tong Qiu, Jun-Xiang Gu, Hong-Wei Fan, Da-Yu Zhu, Shan-Ming Yang, Qi-Yu Chen, Zhao-Xiang Zhou, Bo-Yuan Fan, Yang Bai, Ke-Ke Xing, Jia-Ming Feng, Jun-Da Wang, Yan Chen, Ya-Cheng Lu, Ying Liang, Peng Cao, Bong-Kiun Kaang, Min Zhuo, Yun-Qing Li, Tao Chen
Journal: Neuron (2022)
COVID-19 in patients with lymphoproliferative diseases during the Omicron variant surge
Authors: Yotam Bronstein, Roi Gat, Shai Levi, Yael C. Cohen, Efrat Luttwak, Noam Benyamini, Tamir Shragai, Roy Vitkon, Miriam Neaman, Nili Eilaty, Mor Levi, Svetlana Trestman, Chava Perry, Yair Herishanu, Irit Avivi
Journal: Cancer Cell (2022)
Rab44 regulates murine mast cell–driven anaphylaxis through kinesin-1–dependent secretory granule translocation
Authors: Cyril Longé, Manuela Bratti, Mathieu Kurowska, Shamila Vibhushan, Pierre David, Valère Desmeure, Jian-Dong Huang, Alain Fischer, Geneviève de Saint Basile, Fernando E. Sepulveda, Ulrich Blank, Gaël Ménasché
Journal: Journal of Allergy and Clinical Immunology (2022)

Mast cells (MCs) are key effectors of the allergic response. Following the cross-linking of IgE receptors (FcεRIs), they release crucial inflammatory mediators through degranulation. Although degranulation depends critically on secretory granule (SG) trafficking toward the plasma membrane, the molecular machinery underlying this transport has not been fully characterized.This study analyzed the function of Rab44, a large, atypical Rab guanosine triphosphatase highly expressed in MC, in the MC degranulation process.Murine knockout (KO) mouse models (KORab44 and DKOKif5b/Rab44) were used to perform passive cutaneous anaphylaxis experiments and analyze granule translocation in bone marrow-derived MCs during degranulation.This study demonstrate that mice lacking Rab44 (KORab44) in their bone marrow-derived MCs are impaired in their ability to translocate and degranulate SGs at the plasma membrane on FcεRI stimulation. Accordingly, KORab44 mice were less sensitive to IgE-mediated passive cutaneous anaphylaxis in vivo. A lack of Rab44 did not impair early FcεRI-stimulated signaling pathways, microtubule reorganization, lipid mediator release, or cytokine secretion. Mechanistically, Rab44 appears to interact with and function as part of the previously described kinesin-1-dependent transport pathway.These results highlight a novel role of Rab44 as a regulator of SG transport during degranulation and anaphylaxis acting through the kinesin-1-dependent microtubule transport machinery. Rab44 can thus be considered a potential target for modulating MC degranulation and inhibiting IgE-mediated allergic reactions.
Tempering Optimism Concerning the Recent Decline in US Suicide Deaths
Authors: Mark Olfson, Rajeev Ramchand, Michael Schoenbaum
Journal: JAMA Psychiatry (2022)

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Mothers’ Sources of Child Fluoride Information and Misinformation From Social Connections
Authors: Jacqueline M. Burgette, Zelda T. Dahl, Janice S. Yi, Robert J. Weyant, Daniel W. McNeil, Betsy Foxman, Mary L. Marazita
Journal: JAMA Network Open (2022)

<h3>Importance</h3> Fluoride delivered either topically (eg, fluoride varnish) or systemically (eg, water fluoridation, prescription fluoride supplements) is widely used as a caries preventive agent in children. The widespread existence of misinformation, including inaccurate information that attaches negative values or suspicion to fluoride treatments, raises concerns that misinformation will lead to underutilization of fluoride and contribute to avoidable increases in caries prevalence. <h3>Objective</h3> To describe the social relationships from which mothers obtain child fluoride information and misinformation. <h3>Design, Setting, and Participants</h3> This qualitative study analyzed 126 mothers with children aged 3 to 5 years to explore how their social networks were associated with their child's oral health. Mothers were recruited from community-based sites in Pittsburgh, Pennsylvania, and throughout the state of West Virginia from 2018 to 2020. In-person, semi-structured qualitative interviews were conducted. Data were transcribed, coded, and analyzed using Nvivo 12. Three investigators analyzed data using template analysis, a qualitative technique that combines inductive and deductive approaches to identify patterns until primary themes are identified. <h3>Main Outcomes and Measures</h3> Sources of information regarding fluoride from the mother's social relationships. <h3>Results</h3> Of the 126 mothers with children aged 3 to 5 years in Pittsburgh and West Virginia, 120 (95%) identified as non-Hispanic White and 5 (4%) identified as Hispanic White; 38 (30%) had a bachelor's degree, 77 (61%) had private dental insurance for their child, and 52 (41%) had an income less than $50 000; 82 (65%) reported that they discussed child fluoride information with members of their social network. Mothers described that they obtained fluoride information from family members, health care clinicians, and community members. The receipt of inconsistent child fluoride information from multiple sources resulted in confusion and difficulty assessing whether fluoride information was accurate. <h3>Conclusions and Relevance</h3> This qualitative study found that mothers received inconsistent child fluoride information from multiple sources, which resulted in confusion and difficulty assessing the accuracy of the fluoride information. These findings suggest that social relationships can be a potential target for interventions to communicate fluoride information related to children.
Narsoplimab, a Mannan-Binding Lectin-Associated Serine Protease-2 Inhibitor, for the Treatment of Adult Hematopoietic Stem-Cell Transplantation–Associated Thrombotic Microangiopathy
Authors: Samer K. Khaled, Kathleen Claes, Yeow Tee Goh, Yok Lam Kwong, Nelson Leung, Włodzimierz Mendrek, Ryotaro Nakamura, Jameela Sathar, Edmund Ng, Narinder Nangia, Steve Whitaker, Alessandro Rambaldi
Journal: Journal of Clinical Oncology (2022)

Hematopoietic stem-cell transplantation-associated thrombotic microangiopathy (HSCT-TMA) is a serious complication with significant mortality and no approved therapy. HSCT-TMA results from endothelial injury, which activates the lectin pathway of complement. Narsoplimab (OMS721), an inhibitor of mannan-binding lectin-associated serine protease-2 (MASP-2), was evaluated for safety and efficacy in adults with HSCT-TMA.In this single-arm open-label pivotal trial (NCT02222545), patients received intravenous narsoplimab once weekly for 4-8 weeks. The primary end point (response rate) required clinical improvement in two categories: (1) laboratory TMA markers (both platelet count and lactate dehydrogenase) and (2) organ function or freedom from transfusion. Patients receiving at least one dose (full analysis set [FAS]; N = 28) were analyzed.The response rate was 61% in the FAS population. Similar responses were observed across all patient subgroups defined by baseline features, HSCT characteristics, and HSCT complications. Improvement in organ function occurred in 74% of patients in the FAS population. One-hundred-day survival after HSCT-TMA diagnosis was 68% and 94% in FAS population and responders, respectively, whereas median overall survival was 274 days in the FAS population. Narsoplimab was well tolerated, and adverse events were typical of this population, with no apparent safety signal of concern.In this study, narsoplimab treatment was safe, significantly improved laboratory TMA markers, and resulted in clinical response and favorable overall survival.