tbuckley/cabot-search huggingface dataset:
<i>Helicobacter hepaticus</i> is required for immune targeting of bacterial heat shock protein 60 and fatal colitis in mice
Authors: Verena Friedrich, Ignasi Forné, Dana Matzek, Diana Ring, Bastian Popper, Lara Jochum, Stefanie Spriewald, Tobias Straub, Axel Imhof, Anne Krug, Bärbel Stecher, Thomas Brocker
Journal: Gut Microbes (2021)

Gut microbiota and the immune system are in constant exchange shaping both host immunity and microbial communities. Here, improper immune regulation can cause inflammatory bowel disease (IBD) and colitis. Antibody therapies blocking signaling through the CD40-CD40L axis showed promising results as these molecules are deregulated in certain IBD patients. To better understand the mechanism, we used transgenic DC-LMP1/CD40 animals with a constitutive CD40-signal in CD11c+ cells, causing a lack of intestinal CD103+ dendritic cells (DCs) and failure to induce regulatory T (iTreg) cells. These mice rapidly develop spontaneous fatal colitis, accompanied by dysbiosis and increased inflammatory IL-17+IFN-γ+ Th17/Th1 and IFN-γ + Th1 cells. In the present study, we analyzed the impact of the microbiota on disease development and detected elevated IgA- and IgG-levels in sera from DC-LMP1/CD40 animals. Their serum antibodies specifically bound intestinal bacteria, and by proteome analysis, we identified a 60 kDa chaperonin GroEL (Hsp60) from Helicobacter hepaticus (Hh) as the main specific antigen targeted in the absence of iTregs. When re-derived to a different Hh-free specific-pathogen-free (SPF) microbiota, mice showed few signs of disease, normal microbiota, and no fatality. Upon recolonization of mice with Hh, the disease developed rapidly. Thus, the present work identifies GroEL/Hsp60 as a major Hh-antigen and its role in disease onset, progression, and outcome in this colitis model. Our results highlight the importance of CD103+ DC- and iTreg-mediated immune tolerance to specific pathobionts to maintain healthy intestinal balance.
Accumulation of Allergen-specific CD4+ T cells in the Airways after Segmental Allergen Challenge is Associated with Reduced Expression of T2 Chemoattractant Receptors on Allergen-specific CD4+ T cells in Blood
Authors: Mark Larché, Elena Tonti, Jingyu Mu, MyLinh Duong, Terence Ho, Kieran Killian, Helen Neighbour, Deanna French, Desmond Murphy, Amani El-Gammal, Karen Howie, Lesley Wiltshire, Patrick Mitchell, Caroline Munoz, Caitlin Obminski, Cheryl Kipling, Peter Gergen, Paul O'Byrne, William Kwok, Gail Gauvreau
Journal: Journal of Allergy and Clinical Immunology (2021)
Roles for hENT1 and dCK in gemcitabine sensitivity and malignancy of meningioma
Authors: Masahiro Yamamoto, Tomomi Sanomachi, Shuhei Suzuki, Hiroyuki Uchida, Hajime Yonezawa, Nayuta Higa, Tomoko Takajo, Yuki Yamada, Asuka Sugai, Keita Togashi, Shizuka Seino, Masashi Okada, Yukihiko Sonoda, Hirofumi Hirano, Koji Yoshimoto, Chifumi Kitanaka
Journal: Neuro-Oncology (2021)

High-grade meningiomas are aggressive tumors with high morbidity and mortality rates that frequently recur even after surgery and adjuvant radiotherapy. However, limited information is currently available on the biology of these tumors, and no alternative adjuvant treatment options exist. Although we previously demonstrated that high-grade meningioma cells were highly sensitive to gemcitabine in vitro and in vivo, the underlying molecular mechanisms remain unknown.We examined the roles of hENT1 (human equilibrative nucleoside transporter 1) and dCK (deoxycytidine kinase) in the gemcitabine sensitivity and growth of meningioma cells in vitro. Tissue samples from meningiomas (26 WHO grade I and 21 WHO grade II/III meningiomas) were immunohistochemically analyzed for hENT1 and dCK as well as for Ki-67 as a marker of proliferative activity.hENT1 and dCK, which play critical roles in the intracellular transport and activation of gemcitabine, respectively, were responsible for the high gemcitabine sensitivity of high-grade meningioma cells and were strongly expressed in high-grade meningiomas. hENT1 expression was required for the proliferation and survival of high-grade meningioma cells and dCK expression. Furthermore, high hENT1 and dCK expression levels correlated with stronger tumor cell proliferative activity and shorter survival in meningioma patients.The present results suggest that hENT1 is a key molecular factor influencing the growth capacity and gemcitabine sensitivity of meningioma cells and also that hENT1, together with dCK, may be a viable prognostic marker for meningioma patients as well as a predictive marker of their responses to gemcitabine.
Association of Transanal Total Mesorectal Excision With Local Recurrence of Rectal Cancer
Authors: Antonio Caycedo-Marulanda, Lawrence Lee, Sami A. Chadi, Chris P. Verschoor, Jordan Crosina, Shady Ashamalla, Carl J. Brown
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Proponents of novel transanal total mesorectal excision (TME) suggest the procedure overcomes the technical and oncologic challenges of conventional approaches for treating rectal cancer. Recently, however, there has been controversy regarding the oncologic safety of the procedure. <h3>Objective</h3> To assess the association of transanal TME with the incidence of local recurrence (LR) of cancer and the probability of remaining free of LR during follow-up. <h3>Design, Setting, and Participants</h3> This multicenter cohort study used data from 8 high-volume rectal cancer academic institutions from across Canada on all consecutive patients with primary rectal cancer treated by transanal TME at the participating centers. The study was conducted between January 2014 and December 2018, and data were analyzed from April 1, 2020, to September 15, 2020. <h3>Exposure</h3> Transanal TME. <h3>Main Outcomes and Measures</h3> The incidence of LR was reported as a direct measure of quality of resection. The cumulative probability of LR- and systemic recurrence (SR)–free survival at 36 months was estimated. Local recurrence and SR were defined as radiologic or endoscopic evidence of 1 or more new lesions in or outside the pelvis, respectively, documented during surveillance after the removal of the primary tumor. <h3>Results</h3> Of 608 total patients included in the analysis, 423 (69.6%) were male; the median age was 63 years (interquartile range [IQR], 54-70 years). Local recurrence was identified in 22 patients (3.6%) after a median follow-up of 27 months (IQR, 18-38 months). The median time to LR was 13 months (IQR, 9-19 months). Sixteen of the 22 patients with LR (72.7%) were male, 14 (63.6%) received neoadjuvant chemoradiation, and 12 (54.5%) had American Joint Committee on Cancer stage III disease. Of those with LR, 16 (72.7%) had a negative circumferential radial margin and 20 (90.9%) had a negative distal resection margin, 2 (9.1%) experienced conversion to open surgery, and 15 (68.2%) also developed SR. The probability of LR-free survival at 36 months was 96% (95% CI, 94%-98%). According to the Cox proportional hazards regression model, the hazard ratio of LR was estimated to be 4.2 (95% CI, 2.9-6.2) times higher among patients with a positive circumferential radial margin than among those with a negative circumferential radial margin. <h3>Conclusions and Relevance</h3> In this cohort study, transanal TME performed by experienced surgeons was associated with an incidence of LR and SR that is in line with the published literature on open and laparoscopic TME, suggesting that transanal TME may be an acceptable approach for management of rectal cancer.
Transient Inhibition of the JAK1/3-STAT5 Pathway By Ruxolitinib Is Insufficient to Produce Clinical Benefit in Patients with Indolent Adult T-Cell Leukemia
Authors: Sigrid Dubois, Milos D. Miljkovic, Thomas Fleisher, Jennifer Hsu, Thomas A Waldmann, Kevin C Conlon
Journal: Blood (2017)
Pan-Cancer Analysis of Ligand–Receptor Cross-talk in the Tumor Microenvironment
Authors: Umesh Ghoshdastider, Neha Rohatgi, Marjan Mojtabavi Naeini, Probhonjon Baruah, Egor Revkov, Yu Amanda Guo, Simone Rizzetto, Angeline M.L. Wong, Sundar Solai, Tin T. Nguyen, Joe Poh Sheng Yeong, Jabed Iqbal, Puay Hoon Tan, Balram Chowbay, Ramanuj Dasgupta, Anders J. Skanderup
Journal: Cancer Research (2021)

Abstract Signaling between cancer and nonmalignant (stromal) cells in the tumor microenvironment (TME) is a key to tumor progression. Here, we deconvoluted bulk tumor transcriptomes to infer cross-talk between ligands and receptors on cancer and stromal cells in the TME of 20 solid tumor types. This approach recovered known transcriptional hallmarks of cancer and stromal cells and was concordant with single-cell, in situ hybridization and IHC data. Inferred autocrine cancer cell interactions varied between tissues but often converged on Ephrin, BMP, and FGFR-signaling pathways. Analysis of immune checkpoints nominated interactions with high levels of cancer-to-immune cross-talk across distinct tumor types. Strikingly, PD-L1 was found to be highly expressed in stromal rather than cancer cells. Overall, our study presents a new resource for hypothesis generation and exploration of cross-talk in the TME. Significance: This study provides deconvoluted bulk tumor transcriptomes across multiple cancer types to infer cross-talk in the tumor microenvironment.
Head and Neck Cancers, Version 2.2014
Authors: David G. Pfister, Sharon Spencer, David M. Brizel, Barbara Burtness, Paul M. Busse, Jimmy J. Caudell, Anthony J. Cmelak, A. Dimitrios Colevas, Frank Dunphy, David W. Eisele, Jill Gilbert, Maura L. Gillison, Robert I. Haddad, Bruce H. Haughey, Wesley L. Hicks, Ying J. Hitchcock, Antonio Jimeno, Merrill S. Kies, William M. Lydiatt, Ellie Maghami, Renato Martins, Thomas McCaffrey, Loren K. Mell, Bharat B. Mittal, Harlan A. Pinto, John A. Ridge, Cristina P. Rodriguez, Sandeep Samant, David E. Schuller, Jatin P. Shah, Randal S. Weber, Gregory T. Wolf, Frank Worden, Sue S. Yom, Nicole R. McMillian, Miranda Hughes
Journal: Journal of the National Comprehensive Cancer Network (2014)

This selection from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Head and Neck Cancers focuses on glottic laryngeal cancer, which is the most common type of laryngeal cancer and has an excellent cure rate. The lymphatic drainage of the glottis is sparse, and early stage primaries rarely spread to regional nodes. Because hoarseness is an early symptom, most glottic laryngeal cancer is early stage at diagnosis. Updates to these guidelines for 2014 include revisions to "Principles of Radiation Therapy" for each site and "Principles of Surgery," and the addition of a new section on "Principles of Dental Evaluation and Management."
FOXA3 induction under endoplasmic reticulum stress contributes to non-alcoholic fatty liver disease
Authors: Caizhi Liu, Bing Zhou, Meiyao Meng, Wenjun Zhao, Dongmei Wang, Youwen Yuan, Ying Zheng, Jin Qiu, Yu Li, Guoqiang Li, Xuelian Xiong, Hua Bian, Huijie Zhang, Hua Wang, Xinran Ma, Cheng Hu, Lingyan Xu, Yan Lu
Journal: Journal of Hepatology (2021)
How To Care For Errors of Innate Immunity (EII) Patients During The Pandemic In a Developing Country Without Telemedicine?
Authors: Raissa Roque, Fernanda Vaz, Rafael Saldanha, Caroline Ferreira, Nathalia Vital, Pedro Bubach, Mariana Pimentel, Rafaela Guimarães, Luiza Schmid, Candida Rizzo, Carolina Aranda, Dirceu Solé
Journal: Journal of Allergy and Clinical Immunology (2021)
SAM68 promotes tumorigenesis in lung adenocarcinoma by regulating metabolic conversion via PKM alternative splicing
Authors: Song Zhu, Weiping Chen, Jizhong Wang, Ling Qi, Huilin Pan, Zhengfu Feng, Dongbo Tian
Journal: Theranostics (2021)

Background: A metabolic "switch" from oxidative phosphorylation to glycolysis provides tumor cells with energy and biosynthetic substrates, thereby promoting tumorigenesis and malignant progression. However, the mechanisms controlling this metabolic switch in tumors is not entirely clear. Methods: Clinical specimens were used to determine the effect of SAM68 on lung adenocarcinoma (LUAD) tumorigenesis and metastasis, and mouse models and molecular biology assays were performed to elucidate the function and underlying mechanisms in vitro and in vivo. Results:SAM68 mRNA levels were higher in LUAD tissue than in normal lung tissue, indicating that SAM68 expression is upregulated in LUAD. Patients with LUAD with SAM68high (n = 257) had a higher frequency of tumor recurrence (p = 0.025) and recurrence-free survival (p = 0.013) than did those with SAM68low (n = 257). Patients with SAM68high mRNA levels (n = 257) were at a higher risk for cancer-related death (p = 0.006), and had shorter overall survival (p = 0.044) than did those with SAM68low. SAM68 promotes tumorigenesis and metastasis of LUAD cells in vitro and in vivo by regulating the cancer metabolic switch. SAM68 drives cancer metabolism by mediating alternative splicing of pyruvate kinase (PKM) pre-mRNAs, and promoting the formation of PKM2. Mechanistically, SAM68 increased the binding of the splicing repressor hnRNP A1 to exon 9 of PKM, thereby enhancing PKM2 isoform formation and PKM2-dependent aerobic glycolysis and tumorigenesis. Conclusions: SAM68 promotes LUAD cell tumorigenesis and cancer metabolic programming via binding of the 351-443 aa region of SAM68 to the RGG motif of hnRNP A1, driving hnRNP A1-dependent PKM splicing, contributing to increased oncogene PKM2 isoform formation and inhibition of PKM1 isoform formation. SAM68 is therefore a promising therapeutic target for the treatment of LUAD.
Abstract 9911: Hemodynamic Contributions of Computer Aided Designs and Surgeon’s Unconstrained Modelling to the Fontan Operation: A Computational Fluid Dynamic Simulation Study
Authors: Yue-hin Loke, Byeol Kim, Paige Mass, Justin Opfermann, Axel Krieger, Narutoshi Hibino, Laura Olivieri
Journal: Circulation (2019)

Introduction: Tissue-engineered vascular grafts guided by computer-aided designs (CAD) using computational fluid dynamic (CFD) simulation can create novel Fontan conduits unconstrained by available...
Diagnostic performance of artificial intelligence for histologic melanoma recognition compared to 18 international expert pathologists
Authors: Titus J. Brinker, Max Schmitt, Eva I. Krieghoff-Henning, Raymond Barnhill, Helmut Beltraminelli, Stephan A. Braun, Richard Carr, Maria-Teresa Fernandez-Figueras, Gerardo Ferrara, Sylvie Fraitag, Raffaele Gianotti, Mar Llamas-Velasco, Cornelia S.L. Müller, Antonio Perasole, Luis Requena, Omar P. Sangueza, Carlos Santonja, Hans Starz, Esmeralda Vale, Wolfgang Weyers, Achim Hekler, Jakob N. Kather, Stefan Fröhling, Dieter Krahl, Tim Holland-Letz, Jochen S. Utikal, Andrea Saggini, Heinz Kutzner
Journal: Journal of the American Academy of Dermatology (2021)
Multi-system Inflammatory syndrome in Children (MIS-C): an evolving presentation of COVID-19 in the pediatric population: A Florida State experience and our management approach
Authors: Farida Karim, Miry Makebish, Pallavi Agarwal, Callah Antonetti
Journal: Journal of Allergy and Clinical Immunology (2021)

Florida is among the states with the highest COVID-19 disease burden in the country. We have seen an emergence of multi-system inflammatory syndrome in children (MIS-C), associated with COVID-19 infection in our region and successfully treated three patients in our hospital. Here, we describe the diagnosis and management of MIS-C in one of these patients. COVID-19 associated MIS-C guidelines; A Western New York Approach (PMCID 7244417) criteria [Fever > 24 hours, illness requiring hospitalization, laboratory evidence of inflammation, > 2 organ system involvement and no alternative plausible diagnosis with COVID-19 positivity/exposure] and treatment recommendations were followed for the management of this patient. A 2-year-old African-American male presented with fever, rash, and bilateral eye redness for 5 days with prior SARS-COV-2 exposure confirmed by positive serum IgG. Clinical findings included features of a Kawasaki-disease (KD)-like illness with bilateral bulbar injection, pharyngitis, polymorphous rash, erythema of palms and soles, and unilateral cervical lymphadenopathy. He had elevated inflammatory markers, elevated D-dimer and fibrinogen, and hypoalbuminemia. He also had elevated brain natriuretic peptide with a normal echocardiogram, meeting MIS-C criteria of remote infection with predominant KD features. He was treated with low dose aspirin, IVIG, and intravenous methylprednisolone. He improved and was discharged after 7 days of hospitalization. Recognition of MIS-C in its early stages is very critical, however, in the absence of standardized management guidelines, the treatment gets very challenging. Therefore, global reporting of the detection and management of these cases is essential for developing a definitive management standard.
Increase in medical school applicants will not equal more doctors, says BMA
Authors: Nikki Nabavi
Journal: BMJ (2021)

Despite an increase in applicants to medical schools, the BMA has warned that the UK needs an increase in student places to have more doctors working in the NHS. The association said this increase needed to be coupled with support and funding for both medical schools and the NHS.

New data from UCAS,1 the university admissions service, shows an …
Remote Continuous Glucose Monitoring With a Computerized Insulin Infusion Protocol for Critically Ill Patients in a COVID-19 Medical ICU: Proof of Concept
Authors: Georgia M. Davis, Eileen Faulds, Tara Walker, Debbie Vigliotti, Marina Rabinovich, Joi Hester, Limin Peng, Barbara McLean, Patricia Hannon, Norma Poindexter, Petrena Saunders, Citlalli Perez-Guzman, Seema S. Tekwani, Greg S. Martin, Guillermo Umpierrez, Shivani Agarwal, Kathleen Dungan, Francisco J. Pasquel
Journal: Diabetes Care (2021)

OBJECTIVE The use of remote real-time continuous glucose monitoring (CGM) in the hospital has rapidly emerged to preserve personal protective equipment and reduce potential exposures during coronavirus disease 2019 (COVID-19). RESEARCH DESIGN AND METHODS We linked a hybrid CGM and point-of-care (POC) glucose testing protocol to a computerized decision support system for continuous insulin infusion and integrated a validation system for sensor glucose values into the electronic health record. We report our proof-of-concept experience in a COVID-19 intensive care unit. RESULTS All nine patients required mechanical ventilation and corticosteroids. During the protocol, 75.7% of sensor values were within 20% of the reference POC glucose with an associated average reduction in POC of 63%. Mean time in range (70–180 mg/dL) was 71.4 ± 13.9%. Sensor accuracy was impacted by mechanical interferences in four patients. CONCLUSIONS A hybrid protocol integrating real-time CGM and POC is helpful for managing critically ill patients with COVID-19 requiring insulin infusion.
Abstract 13425: Comparison Between Impella 5.0 and External Corporeal Left Ventricular Assist Device as a Bridge to Decision in Patients With Cardiogenic Shock
Authors: Toru Kondo, Naoki Shibata, shingo kazama, Yuki Kimura, Hideo Oishi, Tasuku Kuwayama, Ryota Morimoto, TAKAHIRO OKUMURA, Toyoaki Murohara
Journal: Circulation (2020)

Background: In cardiogenic shock refractory to medical treatment, choosing and changing mechanical circulatory support to stabilize hemodynamics until cardiac recovery or next treatment is a strategic cornerstone for improving the outcome. We aimed to clarify the differences in treatment course and outcome between Impella 5.0 and extracorporeal left ventricular assist device (eLVAD) in patients with cardiogenic shock refractory to medical therapy or other mechanical circulatory support. Methods: We performed a retrospective medical record review of consecutive patients who were treated with Impella 5.0 or eLVAD as a bridge to decision (BTD) at our medical center from December 2011 to January 2020. Results: A total of 26 patients (median age 40 years, 16 males) were analyzed. Of seven patients managed with Impella 5.0, one patients used Impella CP and four patients used peripheral veno-arterial extracorporeal membrane oxygenation (VA-ECMO) before Impella 5.0 implantation. On the other hand, of 19 patients managed with eLVAD, 11 patients used VA-ECMO before eLVAD implantation. In patients managed with Impella 5.0, Impella 5.0 was removed successfully in two patients (29%) and four patients (71%) underwent the operation for durable LVAD. In patients managed with eLVAD, eLVAD was successfully removed in three patients (16%), nine patients (47%) required durable LVAD, and seven patients (37%) died during eLVAD management. The period between implantation of Impella 5.0 or eLVAD to durable LVAD surgery was significantly shorter with Impella 5.0 (58 [38 - 95] vs. 235 [126 - 318] days, p=0.001). During durable LVAD implantation, cardiopulmonary bypass time was significantly shorter and a significantly smaller amount of red blood cells transfusion was required with Impella 5.0 (149 [125 - 182] vs. 192 [170 - 250] minutes, p=0.042; 7.0 [5.0 - 9.5] vs. 15.0 [10.0- 2.0] units, p=0.019, respectively). There were 4 massive stroke events in eLVAD, but no massive stroke events in Impella 5.0. In Impella 5.0. Conclusions: Impella 5.0 facilitates smoother management as a BTD and reduces surgical invasiveness during durable LVAD implantation. Impella 5.0 would be a more effective option for success to cardiac recovery or next therapy than eLVAD.
Biomimetic mineralized hybrid scaffolds with antimicrobial peptides
Authors: Zhou Ye, Xiao Zhu, Isha Mutreja, Sunil Kumar Boda, Nicholas G. Fischer, Anqi Zhang, Christine Lui, Yipin Qi, Conrado Aparicio
Journal: Bioactive Materials (2021)

Infection in hard tissue regeneration is a clinically-relevant challenge. Development of scaffolds with dual function for promoting bone/dental tissue growth and preventing bacterial infections is a critical need in the field. Here we fabricated hybrid scaffolds by intrafibrillar-mineralization of collagen using a biomimetic process and subsequently coating the scaffold with an antimicrobial designer peptide with cationic and amphipathic properties. The highly hydrophilic mineralized collagen scaffolds provided an ideal substrate to form a dense and stable coating of the antimicrobial peptides. The amount of hydroxyapatite in the mineralized fibers modulated the rheological behavior of the scaffolds with no influence on the amount of recruited peptides and the resulting increase in hydrophobicity. The developed scaffolds were potent by contact killing of Gram-negative Escherichia coli and Gram-positive Streptococcus gordonii as well as cytocompatible to human bone marrow-derived mesenchymal stromal cells. The process of scaffold fabrication is versatile and can be used to control mineral load and/or intrafibrillar-mineralized scaffolds made of other biopolymers.
SARS-CoV-2 infection induces EMT-like molecular changes, including ZEB1-mediated repression of the viral receptor ACE2, in lung cancer models
Authors: C. A. Stewart, K. Ramkumar, K. R. Cargill, R. Cardnell, M. Nilsson, S. Heeke, E. M. Park, S. Kundu, L. Diao, Q. Wang, L. Shen, Y. Xi, C. M. Della Corte, K. Kundu, D. L. Gibbons, J. Wang, J. V. Heymach, L. A. Byers
Journal: Annals of Oncology (2020)
Milestones and current achievements in development of multifunctional bioscaffolds for medical application
Authors: Jagoda Litowczenko, Marta J. Woźniak-Budych, Katarzyna Staszak, Karolina Wieszczycka, Stefan Jurga, Bartosz Tylkowski
Journal: Bioactive Materials (2021)

Tissue engineering (TE) is a rapidly growing interdisciplinary field, which aims to restore or improve lost tissue function. Despite that TE was introduced more than 20 years ago,
Abstract 14769: Real-Word Outcomes Following Left Atrial Appendage Occlusion Using the WatchmanTM Device: Analysis From the National Inpatient Sample
Authors: Antoine Addoumieh, Mohamed Khayata, Nour Tashtish, Sadeer Al-Kindi, Saqer Alkharabsheh, Beni R Verma, Muhammad M Furqan, Allan L Klein, David Majdalany, Khaldoun Tarakji, Oussama M Wazni
Journal: Circulation (2019)

Introduction: Left atrial appendage occlusion (LAAO) using WATCHMANTM device (WD) is used for stroke prevention in non-valvular atrial fibrillation (AF). Trials have shown that LAAO was non-inferio...