tbuckley/cabot-search huggingface dataset:
Functional Comparison of Interferon‐α Subtypes Reveals Potent Hepatitis B Virus Suppression by a Concerted Action of Interferon‐α and Interferon‐γ Signaling
Authors: Jieliang Chen, Yaming Li, Fritz Lai, Yang Wang, Kathrin Sutter, Ulf Dittmer, Jianyu Ye, Wenjing Zai, Min Liu, Fang Shen, Min Wu, Kongying Hu, Baocun Li, Mengji Lu, Xiaonan Zhang, Jiming Zhang, Jianhua Li, Qingfeng Chen, Zhenghong Yuan
Journal: Hepatology (2020)

Background and Aims Interferon (IFN)‐α, composed of numerous subtypes, plays a crucial role in immune defense. As the most studied subtype, IFN‐α2 has been used for treating chronic hepatitis B virus (HBV) infection, with advantages of finite treatment duration and sustained virologic response, but its efficacy remains relatively low. This study aimed to screen for IFN‐α subtypes with the highest anti‐HBV potency and to characterize mechanisms of IFN‐α–mediated HBV restriction. Approach and Results Using cell culture–based HBV infection systems and a human‐liver chimeric mouse model, IFN‐α subtype–mediated antiviral response and signaling activation were comprehensively analyzed. IFN‐α14 was identified as the most effective subtype in suppression of HBV covalently closed circular DNA transcription and HBV e antigen/HBV surface antigen production, with median inhibitory concentration values approximately 100‐fold lower than those of the conventional IFN‐α2. IFN‐α14 alone elicited IFN‐α and IFN‐γ signaling crosstalk in a manner similar to the combined use of IFN‐α2 and IFN‐γ, inducing multiple potent antiviral effectors, which synergistically restricted HBV replication. Guanylate binding protein 5, one of the most differentially expressed genes between IFN‐α14–treated and IFN‐α2–treated liver cells, was identified as an HBV restriction factor. A strong IFN‐α–IFN‐α receptor subunit 1 interaction determines the anti‐HBV activity of IFN‐α. The in vivo anti‐HBV activity of IFN‐α14 and treatment‐related transcriptional patterns were further confirmed, and few adverse effects were observed. Conclusions A concerted IFN‐α and IFN‐γ response in liver, which could be efficiently elicited by IFN‐α subtype 14, is associated with potent HBV suppression. These data deepen the understanding of the divergent activities of IFN‐α subtypes and the mechanism underlying the synergism between IFN‐α and IFN‐γ signaling, with implications for improved IFN therapy and HBV curative strategies.
Immune profiles provide insights into respiratory syncytial virus disease severity in young children
Authors: Santtu Heinonen, Victoria M. Velazquez, Fang Ye, Sara Mertz, Santiago Acero-Bedoya, Bennett Smith, Eleonora Bunsow, Cristina Garcia-Mauriño, Silvia Oliva, Daniel M. Cohen, Melissa Moore-Clingenpeel, Mark E. Peeples, Octavio Ramilo, Asuncion Mejias
Journal: Science Translational Medicine (2020)

The mild RSV disease phenotype is driven by robust IFN expression, adequate monocyte activation, and high viral loads.
Peroral endoscopic myotomy (POEM) for dysphagia and esophageal motor disorder after antireflux fundoplication
Authors: Jean-Michel Gonzalez, Laurent Monino, Philippe Ah-Soune, Véronique Vitton, Marc Barthet
Journal: Endoscopy (2020)

Abstract Introduction Laparoscopic fundoplication is the treatment of severe and refractory gastroesophageal reflux disease (GERD). It induces dysphagia in 5 % – 10 % owing to a tight valve ± esophageal motility disorders (EMD), with challenging management. We assessed the first case series assessing peroral endoscopic myotomy (POEM) in such a situation. Methods A retrospective case series including eight patients with severe dysphagia after laparoscopic fundoplication who were treated by POEM. They were assessed clinically by Eckardt and Mellow – Pinkas dysphagia scores, and by high resolution manometry (HRM). The procedure was a regular esophageal POEM, mainly posterior, including a myotomy of the wrap. The objectives were to evaluate the clinical efficacy, technical difficulties, and complications of this approach. Results HRM showed aperistalsis in 6 /8 patients and raised lower esophageal sphincter (LES) pressure in 5 /8. The median preoperative Eckardt and dysphagia scores were 5 and 3.5, respectively. The procedure was completed in 7 /8 patients, with a clinical efficacy rate (normalization of both scores) of 75 % (6 /8). Although the submucosa seemed more fibrotic and vascularized, no severe complications occurred. Conclusion POEM is a newly described therapeutic option to consider for managing dysphagia due to EMD after laparoscopic fundoplication.
Covid-19 management: it’s inappropriate to make judgments in hindsight that rely on information not available at the outset
Authors: Andrew N Bamji
Journal: BMJ (2020)

Critics of covid-19 management say that something should have been done weeks before it was,1 forgetting that most aspects of the infection were unknown before January. If tests haven’t been invented, you can’t test; if unreliable, they are useless. If infection is asymptomatic then testing only those with symptoms will miss many. Why are death rates in different countries markedly different? …
Abstract 1874: The Iroquois Homeobox 3 Transcription Factor Controls Impulse Propagation in the Ventricular Conduction System by Regulating Sodium Channel Function in Purkinje Cells
Authors: Robert A Rose, Shan-shan Zhang, Vasanth Vedantham, Rui Sakuma, Nathalie Gaborit, Tatyana Sukonnik, Lucile Miquerol, Deepak Srivastava, Chi-chung Hui, Benoit G Bruneau, Peter H Backx
Journal: Circulation (2008)
Inactivation of furin by its naturally occurring inhibitor pro-furin abolish breast cancer cells malignant phenotypes and tumorigenecity in mice.
Authors: Nathalie Scamuffa, Nabil Seidah, Ajoy Basak, Fabien Calvo, Abdel-Majid Khatib
Journal: Cancer Research (2006)

5269  Maturation of various cancer-related substrates by the ubiquitous proprotein convertase (PC) furin was reported to be a crucial step in various processes of tumor progression and metastasis. Like its substrates, the furin is also synthesized as inactive proenzyme and is auto-catalytically activated. Following signal sequence removal, furin undergo auto-proteolytic cleavage of its prosegment domain (pro-furin). The latter remains associated with the enzyme and functions as a potent auto-inhibitor. After this step, the inactive complex transits to late Trans-Golgi Network where a second auto-proteolytic cleavage of the prosegment occurs and activates the furin. In the present study we sought to determine whether the pro-furin mediated-loss of furin-activity might affect the malignant phenotypes of breast cancer cells. Overexpression of pro-furin cDNA in breast cancer cells in a stable manner resulted in processing blockade of various PC substrates including IGF-1 receptor, PDGF-A, PDGF-B and VEGF-C. Similarly, using the reverse transcription-polymerase chain reaction, we found that various genes involved in tumorigenesis such as MMPs were significantly downregulated in pro-furin overexpressing cells. In vitro and in vivo comparative studies revealed that these cells exhibited a reduced ability to proliferate and when subcutaneously inoculated in nude mice they induced delayed tumors with reduced size and incidence. Finally, using pro-furin derived synthetic peptides with various sequence lengths revealed that only the full length pro-furin peptide was able to mediate an inhibitory effect \. on breast cancer cells growth. These findings suggest that furin inhibition by its naturally occurring inhibitor pro-furin may be a useful strategy in breast cancer therapy.
Tenofovir Versus Entecavir on Recurrence of Hepatitis B Virus–Related Hepatocellular Carcinoma After Surgical Resection
Authors: Jonggi Choi, Chanyoung Jo, Young‐Suk Lim
Journal: Hepatology (2020)

Background and Aims Studies have suggested that tenofovir disoproxil fumarate (TDF) treatment is associated with a significantly lower risk of hepatocellular carcinoma (HCC) occurrence when compared with entecavir (ETV) therapy in patients with chronic hepatitis B. We aimed to compare HCC recurrence and survival of patients treated with TDF or ETV after surgical resection for hepatitis B virus (HBV)–related HCC. Approach and Results This historical cohort study included 1,695 consecutive patients treated with ETV (n = 813) or TDF (n = 882) after curative‐intent hepatectomy for HBV‐related HCC of Barcelona Clinic Liver Cancer stage 0 or A in Korea between 2010 and 2018. HCC recurrence and overall survival of patients were compared between ETV and TDF groups by propensity score–matched and multivariable‐adjusted Cox regression analyses from the date of hepatectomy for HCC. The mean age of the study patients was 54.8 years, and 1,294 patients (76.3%) were male. During the median follow‐up duration of 37.6 months with continued ETV or TDF therapy, 561 (33.1%) patients developed HCC recurrence, 144 (8.4%) died, and 22 (1.3%) received liver transplant. Compared with ETV, TDF therapy was associated with significantly higher recurrence‐free ( P = 0.02) and overall survival ( P = 0.03) rates by propensity score–matched analysis. By multivariable‐adjusted analysis, the TDF group was associated with significantly lower rates of HCC recurrence (hazard ratio [HR], 0.82; 95% confidence interval, 0.68‐0.98; P = 0.03), and death or transplantation (HR, 0.62; 95% confidence interval, 0.44‐0.88; P = 0.01). TDF therapy was an independent protective factor for both early (&lt;2 years; HR, 0.79; P = 0.03) and late (≥2 years; HR, 0.68; P = 0.03) postoperative HCC recurrence. Conclusions Among patients who underwent curative hepatectomy for HBV‐related HCC, TDF therapy was associated with a significantly lower risk of HCC recurrence and better overall patient survival compared with ETV therapy.
Abstract P109: Factoring Influencing Fruit and Vegetable Intake and Associations with Cardiovascular Disease Risk Factors: The Grenada Heart Project
Authors: Rajesh Vedanthan, Vaani Garg, Samantha Sartori, Rupa L Iyengar, Marcelle Lewis, Marilyn Hunn, Bernadette Boden-Albala, Mark Woodward, Michael Farkouh, Valentin Fuster
Journal: Circulation (2013)

Introduction: Current WHO recommendations to lower cardiovascular disease (CVD) risk include 5 servings of fruits and vegetables (FV) daily. In low- and middle-income countries (LMICs), the amount of FV intake and external factors influencing food choice is not well known. Objective: We examined the factors influencing FV intake and associations with CVD risk in Grenada, a middle-income country. Methods: A modified WHO STEPS survey, including questions on FV intake, was administered to a random sample of the Grenadian adult population. Average daily number of FV servings for each participant was calculated using the typical number of days/week and servings/day of FV consumption. Low FV intake was defined as less than 5 servings per day. External factors affecting FV intake were elicited. CVD risk factors (hypertension, diabetes, hypercholesterolemia and overweight) were assessed per international standards. Multivariable logistic regression was used to evaluate the relationship between 1) external factors...
New Opioid Use after Invasive Mechanical Ventilation and Hospital Discharge
Authors: Hannah Wunsch, Andrea D. Hill, Longdi Fu, Rob A. Fowler, Han Ting Wang, Tara Gomes, Eddy Fan, David N. Juurlink, Ruxandra Pinto, Duminda N. Wijeysundera, Damon C. Scales
Journal: American Journal of Respiratory and Critical Care Medicine (2020)

Patients who receive invasive mechanical ventilation (IMV) are usually exposed to opioids as part of their sedation regimen. The rates of posthospital prescribing of opioids are unknown.
High-dimensional immune profiling by mass cytometry revealed immunosuppression and dysfunction of immunity in COVID-19 patients
Authors: Wenjing Wang, Bin Su, Lijun Pang, Luxin Qiao, Yingmei Feng, Yabo Ouyang, Xianghua Guo, Hongbo Shi, Feili Wei, Xiaogang Su, Jiming Yin, Ronghua Jin, Dexi Chen
Journal: Cellular and Molecular Immunology (2020)
Quality and Safety in Health Care, Part LXIX
Authors: Jay A. Harolds
Journal: Clinical Nuclear Medicine (2020)

Abstract The chief medical officer (CMO) is a key member of the administration of most large health care systems. The CMO helps with communication between the medical staff and the nonphysician administrators. The CMO typically plays an important role in utilization review, ensuring compliance with laws and regulations, peer review, credentialing, and privileging. One of the most important roles of the CMO has been to improve quality and safety while keeping costs under control, although now many institutions also have quality and safety officers. In addition, the CMO plays a major role in advising the administration regarding clinical equipment purchases, including those for emerging technologies, and in long-range clinical planning.
Predictive value of integrated<sup>18</sup>F-FDG PET/MRI in the early response to nivolumab in patients with previously treated non-small cell lung cancer
Authors: Yukihiro Umeda, Miwa Morikawa, Masaki Anzai, Shingo Ameshima, Maiko Kadowaki, Yuko Waseda, Hiroko Shigemi, Tetsuya Tsujikawa, Yasushi Kiyono, Hidehiko Okazawa, Tamotsu Ishizuka
Journal: Journal for ImmunoTherapy of Cancer (2020)

Background The early response to treatment with immune-checkpoint inhibitors is difficult to evaluate. We determined whether changes in integrated [ 18 F]-fluoro-2-deoxy-D-glucose positron emission tomography/MRI ( 18 F-FDG PET/MRI) parameters after the first 2 weeks of antiprogrammed death-1 antibody nivolumab therapy could predict the response of patients with non-small cell lung cancer (NSCLC). Methods Twenty-five patients with previously treated NSCLC were enrolled prospectively and underwent 18 F-FDG PET/MRI before and at 2 weeks after nivolumab therapy. Changes in maximal standardized uptake value, total lesion glycolysis (ΔTLG) and apparent diffusion coefficient (ΔADC) between the two scans were calculated and evaluated for their associations with the clinical response to therapy. Results The disease control rate was 64%. Patients with non-progressive disease (non-PD) had significantly decreased TLG, increased ADC mean (ie, negative ΔADC mean ) and lower ΔTLG+ΔADC mean than patients with PD. Among the parameters tested, receiver operating characteristic curve analysis revealed that a cut-off value of 16.5 for ΔTLG+ΔADC mean had the highest accuracy (92%) for distinguishing between patients with non-PD and PD. A ΔTLG+ΔADC mean value &lt;16.5 was significantly associated with longer median progression-free survival (9.0 vs 1.8 months, p&lt;0.00001) and overall survival (23.6 vs 4.7 months, p=0.0001) compared with ΔTLG+ΔADC mean value ≥16.5. A multivariate Cox model revealed that ≥16.5 ΔTLG+ΔADC mean was an independent predictor of shorter progression-free survival (HR 37.7) and overall survival (HR 9.29). Conclusions A combination of ΔTLG and ΔADC mean measured by integrated 18 F-FDG PET/MRI may have value as a predictor of the response and survival of patients with NSCLC following nivolumab therapy. Trial registration number UMIN 000020707.
SAMD4 family members suppress human hepatitis B virus by directly binding to the Smaug recognition region of viral RNA
Authors: Yuze Wang, Xinrui Fan, Yunlong Song, Yifei Liu, Ruixin Liu, Jianfeng Wu, Xiaoling Li, Quan Yuan, Guo Fu, Ningshao Xia, Jiahuai Han
Journal: Cellular and Molecular Immunology (2020)
Opium use and subsequent incidence of cancer: results from the Golestan Cohort Study
Authors: Mahdi Sheikh, Ramin Shakeri, Hossein Poustchi, Akram Pourshams, Arash Etemadi, Farhad Islami, Masoud Khoshnia, Abdolsamad Gharavi, Gholamreza Roshandel, Hooman Khademi, Sadaf G Sepanlou, Maryam Hashemian, Abdolreza Fazel, Mahdi Zahedi, Behnoush Abedi-Ardekani, Paolo Boffetta, Sanford M Dawsey, Paul D Pharoah, Masoud Sotoudeh, Neal D Freedman, Christian C Abnet, Nicholas E Day, Paul Brennan, Farin Kamangar, Reza Malekzadeh
Journal: The Lancet Global Health (2020)

Evidence is emerging for a role of opiates in various cancers. In this study, we aimed to investigate the association between regular opium use and cancer incidence.
New clinical forms of hereditary apoA-I amyloidosis entail both glomerular and retinal amyloidosis
Authors: Magali Colombat, Jean-Claude Aldigier, Pierre-Raphael Rothschild, Vincent Javaugue, Estelle Desport, Thierry Frouget, Jean-Michel Goujon, Nathalie Rioux-Leclercq, Nathalie Quellard, Jean Philippe Rerolle, François Paraf, Caroline Beugnet, Aurélien Tiple, Antoine Durrbach, Didier Samuel, Antoine Brézin, Frank Bridoux, Sophie Valleix
Journal: Kidney International (2020)
The QT interval in patients with COVID-19 treated with hydroxychloroquine and azithromycin
Authors: Ehud Chorin, Matthew Dai, Eric Shulman, Lalit Wadhwani, Roi Bar-Cohen, Chirag Barbhaiya, Anthony Aizer, Douglas Holmes, Scott Bernstein, Michael Spinelli, David S. Park, Larry A. Chinitz, Lior Jankelson
Journal: Nature Medicine (2020)
John V Dyer
Authors: Peter V Dyer
Journal: BMJ (2020)

John V Dyer, the district medical officer of health for Lancaster and District from 1968 to 1990, died peacefully at his home in Hest Bank. His funeral service was held at the Lancaster and Morecambe Crematorium with just family members because of the coronavirus outbreak restrictions on gatherings. The service was conducted by the Reverend Susan Seed, vicar of St Luke’s Church, Slyne with Hest.

John Dyer did national service in the Royal Air Force and in 1957 gained the diploma in public health at the London School of Hygiene and Tropical Medicine with a distinction. One of his junior hospital …
Locoregional delivery of CAR T cells to the cerebrospinal fluid for treatment of metastatic medulloblastoma and ependymoma
Authors: Laura K. Donovan, Alberto Delaidelli, Sujith K. Joseph, Kevin Bielamowicz, Kristen Fousek, Borja L. Holgado, Alex Manno, Dilakshan Srikanthan, Ahmed Z. Gad, Randy Van Ommeren, David Przelicki, Cory Richman, Vijay Ramaswamy, Craig Daniels, Jonelle G. Pallota, Tajana Douglas, Alyssa C. M. Joynt, Joonas Haapasalo, Carolina Nor, Maria C. Vladoiu, Claudia M. Kuzan-Fischer, Livia Garzia, Stephen C. Mack, Srinidhi Varadharajan, Matthew L. Baker, Liam Hendrikse, Michelle Ly, Kaitlin Kharas, Polina Balin, Xiaochong Wu, Lei Qin, Ning Huang, Ana Guerreiro Stucklin, A. Sorana Morrissy, Florence M. G. Cavalli, Betty Luu, Raul Suarez, Pasqualino De Antonellis, Antony Michealraj, Avesta Rastan, Meenakshi Hegde, Martin Komosa, Olga Sirbu, Sachin A. Kumar, Zied Abdullaev, Claudia C. Faria, Stephen Yip, Juliette Hukin, Uri Tabori, Cynthia Hawkins, Ken Aldape, Mads Daugaard, John M. Maris, Poul H. Sorensen, Nabil Ahmed, Michael D. Taylor
Journal: Nature Medicine (2020)
Real-Time DMSA-SPECT/US Fusion Imaging Revealing Nonscarring Loss of Function After Pyelonephritis
Authors: Martin Freesmeyer, Friederike Weigel, Ulrike John, Hans-Joachim Mentzel, Falk Gühne
Journal: Clinical Nuclear Medicine (2020)

Abstract Using real-time SPECT/US fusion imaging, the localization of an uptake defect in DMSA scan could be identified unambiguously after being uncertain in ultrasound alone. Thereby, a localized functional loss, due to history of pyelonephritis, without scarring, but reduced cortical thickness could be verified. DMSA-SPECT/US primarily demonstrates its utility in depiction of renal pathologies and may be a descriptive tool in equivocal constellation of findings.
The contribution of angiogenesis and inflammation to tumor cell intravasation
Authors: Juneth Ann Partridge, Elena Deryugina, James Quigley
Journal: Cancer Research (2008)

460  Tumor cell intravasation, the process by which cells enter the vasculature, is an understudied but rate-limiting step in metastasis. To analyze molecular mechanisms involved in tumor cell intravasation, we use a spontaneous metastasis model, where tumor cells are grafted on the CAM of the chick embryo. The majority of cells that escape from primary tumors and enter circulation are arrested in the distal CAM, the repository of intravasated cells. Disseminated human tumor cells could be identified among chicken cells by immunohistochemistry and quantified by Alu-specific qPCR. To study intravasation, two cell variants were generated from HT-1080 human fibrosarcoma, HT-lo/diss and HT-hi/diss, which exhibit 50-100-fold differential in their ability to disseminate in the chick embryo. Since intravasating cells have to initially escape from the primary tumor and then invade the stroma, we first focused on the role of matrix metalloproteinases (MMPs). We showed that certain tumor-derived MMPs, i.e. MMP-1, -2, and -9, might have protective functions in intravasation since their downregulation resulted in increased levels of dissemination. However, sensitivity of tumor cell intravasation to broad-range MMP inhibitors indicates involvement of other MMPs, most probably of host origin. Two host MMPs were previously shown to be delivered to the sites of tumor formation and angiogenesis by infiltrating leukocytes, i.e. MMP-9 by neutrophils and MMP-13 by monocytes/macrophages. These inflammatory cells could be attracted by specific growth factors and cytokines produced by tumor cells. Consistent with this notion, immunohistological analysis indicated a substantially enhanced density of neutrophils and monocytes/macrophages in HT-hi/diss tumors compared to HT-lo/diss. Inflammatory leukocytes in turn, can deliver pro-angiogenic factors to facilitate intravasation via increased angiogenesis and provide the means of dissemination through leaky, newly developed blood vessels. In this regard, more lumen-containing blood vessels were found in HT-hi/diss tumors than in HT-lo/diss. In addition, in the chick embryo and mouse angiogenesis models, HT-hi/diss exhibited higher angiogenic potential than its non-intravasating HT-lo/diss counterpart. These findings prompted us to search for inflammatory cytokines and angiogenic growth factors that might contribute to the intravasation of HT-hi/diss cells. To this end, we used two partially overlapping arrays to profile cytokines and proteins that serve as activators or inhibitors of angiogenesis. By comparing conditioned media and tumor lysates from HT-lo/diss and HT-hi/diss, we identified several cytokines and growth factors differentially expressed between the cell variants. Reciprocal modulation of the expression and function of these cytokines in HT-hi/diss versus HT-lo/diss will allow us to determine their individual contribution to the process of intravasation.