tbuckley/cabot-search huggingface dataset:
Efficacy and Safety of Antibiotics for Treatment of Scrub Typhus
Authors: Jiaru Yang, Lisha Luo, Taigui Chen, Lianbao Li, Xin Xu, Yu Zhang, Wenjing Cao, Peng Yue, Fukai Bao, Aihua Liu
Journal: JAMA Network Open (2020)

<h3>Importance</h3> Antibiotics have been used for many years to treat scrub typhus, but their efficacy and safety have not been studied thoroughly. <h3>Objective</h3> To compare and rank different antibiotics to identify which one can safely eliminate<i>Orientia tsutsugamushi</i>and efficiently alleviate fever in patients with scrub typhus. <h3>Data Sources</h3> An electronic search of PubMed and Embase was conducted, from database inception to July 12, 2019. The study was conducted from July 12 to September 2, 2019. <h3>Study Selection</h3> Randomized clinical trials and retrospective studies that evaluated the use of antibiotics for treatment in patients diagnosed with scrub typhus caused by<i>O tsutsugamushi</i>were included. Records of articles in English were considered eligible. Studies were assessed independently by 2 reviewers, with disagreement resolved by consensus. Of 6408 studies initially identified, 10 randomized clinical trials and 4 retrospective study met the criteria for further analysis. <h3>Data Extraction and Synthesis</h3> This study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses extension statement for systematic reviews incorporating network meta-analyses of health care interventions. Data were independently extracted by 2 reviewers and synthesized with frequentist random-effects network meta-analyses. <h3>Main Outcomes and Measures</h3> The primary outcome was efficacy of the antibiotic, considered as the number of patients who achieved complete healing with an antibiotic. Safety, defined as the prevalence of adverse events associated with the antibiotics, was the secondary outcome, and defervescence time was the tertiary outcome. P scores (scale of 0 to 1, with 1 indicating superiority to other treatments) were used to rank the efficacy, safety, and defeverescence time of the antibiotics. <h3>Results</h3> Three searches for articles in Embase and PubMed identified 10 randomized clinical trials (888 participants) and 4 retrospective studies (323 participants) for further analyses. No particular treatment regimen showed a significant advantage or disadvantage with regard to efficacy or safety. However, meta-analysis of retrospective studies indicated that clarithromycin (P score = 0.8730) alleviated fever more efficiently than other antibiotics. <h3>Conclusions and Relevance</h3> No treatment regimen reported in this network meta-analysis showed a significant advantage or disadvantage with regard to efficacy or safety. However, clarithromycin might be a better choice than the other drugs for alleviating fever.
Bladder reconstruction using autologous smooth muscle cell sheets grafted on a pre-vascularized capsule
Authors: Hai-Lin Guo, Xu-Feng Peng, Xing-Qi Bao, Lin Wang, Zhi-Ming Jia, Yi-Chen Huang, Jun-Mei Zhou, Hua Xie, Fang Chen
Journal: Theranostics (2020)

Rationale: Construction of functional vascularized three-dimensional tissues has been a longstanding objective in the field of tissue engineering. The efficacy of using a tissue expander capsule as an induced vascular bed to prefabricate functional vascularized smooth muscle tissue flaps for bladder reconstruction in a rabbit model was tested. Methods: Skin tissue expanders were inserted into the groin to induce vascularized capsule pouch formation. Smooth muscle cells and endothelial progenitor cells were harvested and cocultured to form pre-vascularized smooth muscle cell sheet. Then repeated transplantation of triple-layer cell sheet grafts onto the vascularized capsular tissue was performed at 2-day intervals to prefabricate functional vascularized smooth muscle tissue flaps. Bladder muscular wall defects were created and repaired by six-layer cell sheet graft (sheet only), capsule flap (capsule only) and vascularized capsule prelaminated with smooth muscle cell sheet (sheet plus capsule). The animals were followed for 3 months after implantation and their bladders were explanted serially. Results: Bladder capacity and compliance were maintained in sheet plus capsule group throughout the 3 months. Tissue bath stimulation demonstrated that contractile responses to carbachol and KCl among the three groups revealed a significant difference (p < 0.05). Histologically, inflammation was evident in the capsule only group at 1 month and fibrosis was observed in sheet only group at 3 months. The vessel density in capsule only and sheet plus capsule group were significantly higher than in the sheet only group at each time point (p < 0.05). Comparison of the smooth muscle content among the three groups revealed a significant difference (p < 0.05). Conclusion: These results proved that the capsule may serve as an induced vascular bed for vascularized smooth muscle tissue flap prefabrication. The prefabricated functional vascularized smooth muscle tissue flap has the potential for reliable bladder reconstruction and may create new opportunities for vascularization in 3-D tissue engineering.
Abstract 10370: Circulating Mir-223-3p As A Novel Biomarker And Pathogenesis Of Brugada Syndrome
Authors: Yukiko Nakano, Yuko Onohara, Chikaaki Motoda, Takehito Tokuyama, Naoya Hironobe, Yousaku Okubo, sho okamura, Shunsuke Miyauchi, Yoshihiro Ikeuchi, Orie Nishiyama, Hidenori Ochi, Kazuaki Chayama, Yasuki Kihara
Journal: Circulation (2019)

Introduction: Brugada syndrome (BrS) is able to be diagnosed by type1 BrS ECG. However, ECGs of BrS patients show day to day variations and diagnosis of BrS is sometimes challenging. Many susceptib...
Deep Learning Using Chest Radiographs to Identify High-Risk Smokers for Lung Cancer Screening Computed Tomography: Development and Validation of a Prediction Model
Authors: Michael T. Lu, Vineet K. Raghu, Thomas Mayrhofer, Hugo J.W.L. Aerts, Udo Hoffmann
Journal: Annals of Internal Medicine (2020)

Lung cancer screening with chest computed tomography (CT) reduces lung cancer death. Centers for Medicare & Medicaid Services (CMS) eligibility criteria for lung cancer screening with CT require detailed smoking information and miss many incident lung cancers. An automated deep-learning approach based on chest radiograph images may identify more smokers at high risk for lung cancer who could benefit from screening with CT.To develop and validate a convolutional neural network (CXR-LC) that predicts long-term incident lung cancer using data commonly available in the electronic medical record (EMR) (chest radiograph, age, sex, and whether currently smoking).Risk prediction study.U.S. lung cancer screening trials.The CXR-LC model was developed in the PLCO (Prostate, Lung, Colorectal, and Ovarian) Cancer Screening Trial (n = 41 856). The final CXR-LC model was validated in additional PLCO smokers (n = 5615, 12-year follow-up) and NLST (National Lung Screening Trial) heavy smokers (n = 5493, 6-year follow-up). Results are reported for validation data sets only.Up to 12-year lung cancer incidence predicted by CXR-LC.The CXR-LC model had better discrimination (area under the receiver-operating characteristic curve [AUC]) for incident lung cancer than CMS eligibility (PLCO AUC, 0.755 vs. 0.634; P < 0.001). The CXR-LC model's performance was similar to that of PLCOM2012, a state-of-the-art risk score with 11 inputs, in both the PLCO data set (CXR-LC AUC of 0.755 vs. PLCOM2012 AUC of 0.751) and the NLST data set (0.659 vs. 0.650). When compared in equal-sized screening populations, CXR-LC was more sensitive than CMS eligibility in the PLCO data set (74.9% vs. 63.8%; P = 0.012) and missed 30.7% fewer incident lung cancers. On decision curve analysis, CXR-LC had higher net benefit than CMS eligibility and similar benefit to PLCOM2012.Validation in lung cancer screening trials and not a clinical setting.The CXR-LC model identified smokers at high risk for incident lung cancer, beyond CMS eligibility and using information commonly available in the EMR.None.
Abstract 5352: Acute total body ionizing radiation induces long-term cardiac effects and immediate changes in oxidative carbonylation of cardiac proteins in the rat
Authors: Elliot T. Rosen, Dmitry Kryndushkin, Baikuntha Aryal, Yanira Gonzalez, Leena Chehab, Jennifer Dickey, V. Ashutosh Rao
Journal: Cancer Research (2020)

Abstract Radiation-induced heart disease represents a significant health risk in the event of an accidental radiation exposure as well as to cancer patients who receive acute doses of irradiation as part of radiation therapy. We utilized the Wistar-Kyoto and spontaneously hypertensive rat models, previously shown to demonstrate drug-induced cardiomyopathy, to evaluate the acute and long-term effects of sub-lethal total body irradiation at two, four, and fifty-two weeks. We examined irreversible oxidative protein carbonylation in the heart immediately following irradiation. Both males and females sustained reduced growth and anemic conditions over a one-year period as reflected by reduced body weight and low red blood cell count. Increased inflammation was detected via elevated IL-6 serum levels selectively in males at four weeks. Serum cardiac troponin T and I analyses revealed signs of cardiomyopathy at earlier timepoints, but high variability was observed, especially at one year. Echocardiography at two weeks following 5.0Gy treatment revealed inflammation and a decrease in cardiac output in the short term, but significant differences were not observed at the one-year timepoint. Cardiac output was decreased in both males and females after two weeks, and statistically significant in females. Following 10.0 Gy irradiation, the heart tissue showed an increase in total protein oxidative carbonylation accompanied by DNA damage indicated γ-H2AX. Using proteomic analyses, several novel proteins showed a marked carbonylation profile including those associated with mitochondrial homeostasis and cardiac contractility. Overall, we present findings of acute oxidative protein, DNA damage, and long-term cardiomyopathy in the irradiated animals, along with oxidative proteomic markers of acute damage. Citation Format: Elliot T. Rosen, Dmitry Kryndushkin, Baikuntha Aryal, Yanira Gonzalez, Leena Chehab, Jennifer Dickey, V. Ashutosh Rao. Acute total body ionizing radiation induces long-term cardiac effects and immediate changes in oxidative carbonylation of cardiac proteins in the rat [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5352.
ERCP in patient with Roux-en-Y gastric bypass and high grade duodenal stricture across dual lumen-apposing metal stents
Authors: Kornpong Vantanasiri, Guru Trikudanathan
Journal: Endoscopy (2020)

Endoscopic ultrasound-guided lumen-apposing metal stents (LAMS) placement is a minimally invasive modality that has been increasingly utilized in patients with challenging gastrointestinal anatomy [1].
Suicide rates continue to rise in England and Wales
Authors: Gareth Iacobucci
Journal: BMJ (2020)

The Royal College of Psychiatrists has called for more research to understand why numbers of deaths by suicide in certain groups are increasing in England and Wales, after new figures showed a continuing rise last year.Data published by the Office for National Statistics on 1 September showed that in 2019 the suicide rate among men and boys was 16.9 deaths per 100 000, the highest since 2000 and slightly above the 2018 rate of 16.2 per 100 000.The suicide rate among women and girls was 5.3 deaths per 100 000 in 2019, up from 5.0 per 100 000 in 2018 and the highest since 2004.
Abstract A03: PrOTYPE (Predictor of high-grade-serous Ovarian carcinoma molecular subTYPE): The development and validation of a clinical-grade consensus classifier for the molecular subtypes of high-grade serous tubo-ovarian cancer
Authors: Aline Talhouk, Joshy George, Chen Wang, Ellen Goode, Susan Ramus, Jennifer Doherty, David Bowtell, Michael Anglesio
Journal: Clinical Cancer Research (2020)

Abstract Background: Gene expression-based molecular subtypes of high-grade serous tubo-ovarian cancer (HGSOC) are distinguished by differential immune and stromal infiltration and may provide opportunities for targeted therapies. Integration of molecular subtypes into clinical trials has been hindered by inconsistent subtyping methodology. Methods: Adopting two independent approaches, we derived and internally validated algorithms for molecular subtype prediction from gene-expression array data in 1,650 tumors. We applied resulting models to assign labels to 3829 HGSOCs from the Ovarian Tumor Tissue Analysis (OTTA) consortium evaluated on NanoString. Using the labeled NanoString data, we developed, confirmed, and validated a minimal gene set, clinical-grade test and prediction tool. We also used the OTTA dataset to evaluate associations between molecular subtype, biologic, and clinical features. Findings: The locked-down test included a model with 55 genes that predicted HGSOC molecular subtype with &amp;gt;95% accuracy. Subtype varied between primary and metastatic site taken at the time of primary surgery, and was significantly associated with age, stage, CD8+ lymphocyte infiltration, residual disease, and outcome. In multivariable models, molecular subtypes lose their prognostic significance in the presence of risk factors such as residual disease and BRCA1/2 germline mutations. Interpretation: We validated the Predictor of high-grade-serous Ovarian carcinoma molecular subTYPE, or PrOTYPE, following the Institute of Medicine guidelines for the development of omics-based tests. This simple-to-use, cost-effective, fully defined, and locked-down clinical-grade assay will facilitate molecular subtype stratification into clinical trial design. PrOTYPE will allow for objective assessment of HGSOC molecular subtype predictive value in precision medicine applications. Citation Format: Aline Talhouk, Joshy George, Chen Wang, Ellen Goode, Susan Ramus, Jennifer Doherty, David Bowtell, Michael Anglesio, OTTA Consortium. PrOTYPE (Predictor of high-grade-serous Ovarian carcinoma molecular subTYPE): The development and validation of a clinical-grade consensus classifier for the molecular subtypes of high-grade serous tubo-ovarian cancer [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research; 2019 Sep 13-16, 2019; Atlanta, GA. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(13_Suppl):Abstract nr A03.
Abstract 4512: Mouse model for in vivo evaluation of efficacy and potential cytokine release syndrome of chimeric antigen receptor (CAR) T cell therapy
Authors: Jing Jiao, Chunting Ye, Danying Cai, Mingshan Cheng, James Keck
Journal: Cancer Research (2020)

Abstract Chimeric antigen receptor (CAR) T-cell therapy holds great promise as cancer immunotherapy. While impressive responses have been achieved in patients with hematological malignancies there are challenges for CAR T therapy such as toxicity complications due to cytokine release syndrome (CRS) and limitations due to CAR T cell exhaustion. As increasing number of novel CAR T products are in the discovery and preclinical phase of development, preclinical models to assess efficacy as well as potential toxicity of CAR T in vivo are needed. Here, we describe a new NSG™ mice model to examine CAR T cells for efficacy and potential CRS. Immunodeficient NSG™ mice are commonly used to evaluate CAR T functions. However, human T cells can cause acute xeno-GVHD in NSG™ limiting the use of the model system. A system to study human T cell function in the absence of xeno-GVHD is required. A new NSG™ derivative NSG-MHC Class I/II knockout (KO) strain has MHC class I and MHC class II deficiency in addition to B, T and NK cell deficiency. NSG-MHC Class I/II KO mice are known to have a delayed onset of GVHD and can provide a useful background to study human immunity in the absence of GVHD [M. A. Brehm et al., FASEB J. 33, 3137–3151 (2019)]. Human B-cell lymphoma Raji tumor cells express high levels of CD19 and CD22 which are targets for CAR T therapy. Using NSG-MHC Class I/II KO mice and luciferase-tagged Raji-Luc tumor model we found that compared to controls CD22 CAR T and CD19 CAR T showed significant tumor growth inhibition by Xenogen imaging analysis. No body weight loss was observed with the CAR T treatments. As high tumor burdens are usually associated with the potential of causing CRS we examined CD19 CAR T cells on low and high tumor burdens and the data will be presented in context of efficacy. We have established a new mouse model using NSG-MHCI/II KO mice to enable evaluation of CAR T efficacy and propensity to induce cytokines simultaneously in vivo. Furthermore PBMC-humanized NSG-MHCI/II KO mice can also be established and used to examine CAR T cells prepared from the same PBMC donor to mimic autologous CAR T cell therapy. Citation Format: Jing Jiao, Chunting Ye, Danying Cai, Mingshan Cheng, James Keck. Mouse model for in vivo evaluation of efficacy and potential cytokine release syndrome of chimeric antigen receptor (CAR) T cell therapy [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4512.
Covid-19: US will not join WHO in developing vaccine
Authors: Janice Hopkins Tanne
Journal: BMJ (2020)

The Trump administration said on 1 September that it would not join Covax, the initiative led by the World Health Organization to develop and distribute a covid-19 vaccine.

A White House spokesman told the Washington Post , “The United States will continue to engage our international partners to ensure we defeat this virus, but we will not be constrained by multilateral organizations influenced by the corrupt World Health Organization and China.”1

President Donald Trump withdrew the US from WHO in July because he considered that it favored China, despite protests by health experts.2 Each year the US gives WHO about $450m (£337m; €379m), which provides about 15% of WHO’s budget.

The WHO Covax plan is co-led by the Coalition for Epidemic Preparedness Innovations; Gavi, the Vaccine Alliance; and WHO.3 It involves 172 countries that will work in …
Abstract 162: DNA methylation activates TP73 expression in human breast cancer tumorigenesis
Authors: Zhixing Yao, David R. Yao, William Yu, Zaki A. Sherif
Journal: Cancer Research (2020)

Abstract Epigenetic events that cause changes in gene expression are common in human cancers. However, the connection between TP73 expression and its epigenetic functionality in tumorigenesis has not been widely explored. As a transcription factor, p73 is activated in a similar manner to p53 in response to DNA damage and regulates the expression of downstream genes involved in cell cycle arrest and apoptosis. However, there are other compounding functions of this gene that reflect its non-tumor-related characters, thus making it very difficult to assess its specific role in tumorigenesis, which results from an accumulation of mutational and epigenetic changes that alter normal cell growth and survival pathways. TP73 is the homologue of the master tumor suppressor TP53 involved in cellular responses to stress and development. The TP73 gene encodes two different proteins TAp73 and ΔNp73 and maps to a region on chromosome 1p36 that is frequently deleted in neuroblastoma and other tumors and is thought to contain multiple tumor suppressor genes. However, the analysis of p73-knockout mice yielded conflicting results with respect to tumor suppression. World-wide efforts in sequencing the TP73 gene in patient tumor samples have not provided evidence for genetic alterations as a common cause of TP73 inactivation in human cancers. Therefore, the role of TP73 in tumorigenesis has remained elusive to date. In this study, we determined TP73 expression in normal human mammary epithelial cells (HMEC), non-cancerous Li-Fraumeni Syndrome (LFS) skin fibroblasts, human breast cancer cell lines (MCF7 &amp; MDA321), neuroblastoma cell lines (IMR32 &amp; SK-N-SH) and normal skin fibroblast cell line (HS27). We also conducted an immunohistochemistry analysis of TP73 expression in human normal breast tissues, cancerous breast tissues and non-cancerous (cancer-adjacent) breast tissues. The results show that TP73 expression is evident only in cancer cell lines and breast cancer tissues. Moreover, methylation-specific PCR and bisulfite sequencing studies revealed that TP73 promoter is activated only in cancer cell lines by DNA methylation. Furthermore, ChIP assay results demonstrated that CTCF (a chromosomal networking protein CCCTC binding factor) and tumor protein p53 (TP53) bind to TP73 promoter and regulate TP73 expression. These observations demonstrate the existence of a positive correlation at the promoter site of TP73 between its expression and DNA methylation. However, TP73 expression is not involved in cell proliferation, which may prove significant for the development of future diagnostic and therapeutic applications. Citation Format: Zhixing Yao, David R. Yao, William Yu, Zaki A. Sherif. DNA methylation activates TP73 expression in human breast cancer tumorigenesis [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 162.
Molecular Characteristic of Acute Leukemias with t(16;21)/Fus-Erg
Authors: Elena Zerkalenkova, Agnesa Panfyorova, Anna Kazakova, Pavel Baryshev, Larisa Shelihova, Irina Kalinina, Galina Novichkova, Mikhail Maschan, Alexey A Maschan, Yulia Olshanskaya
Journal: Blood (2017)
Abstract 20999: Cardiac Implantable Electrical Device Related Procedures and Associated Complications in Continuous Flow LVAD Recipients: A Multicenter Experience
Authors: Rakesh Gopinathannair, Rahul Dhawan, Jaimin Trivedi, Henri Roukoz, Adarsh Bhan, Mustafa M Ahmed, Geeta Bhat, Jennifer Cowger, Mark S Slaughter, Ashwin Ravichandran
Journal: Circulation (2017)

Introduction: Patients with continuous flow Left Ventricular Assist Devices (LVAD) and concomitant Cardiac Implantable Electrical Devices (CIED) are prone for device and lead-related complications requiring intervention. Hypothesis: We evaluated the incidence and characteristics of CIED-related procedures and complications and their association with survival in a multicenter LVAD cohort. Methods: We retrospectively reviewed data on 480 LVAD patients with a CIED from 5 centers. Of the 480, 235 patients had accurate long-term CIED follow-up data and were used for this analysis. Kaplan Meier analysis was used to assess survival differences between patients with CIED-related complications versus those who did not. Results: Of 235 patients with an LVAD and a CIED (Age 58±13, 80% male), 130 had a CRT-D and 105 had ICD only. During a median LVAD follow-up of 692 days, 103 patients required a CIED generator replacement with CRT-D patients having a significantly higher rate of generator replacement compared to the ICD only group (68[52%] vs 35[33%], p=0.003). A CIED or lead-related complication occurred in 36 (28%) of CRT-D patients and 16 (15%) of the ICD patients (p=0.06). 20 (15%) patients in the CRT-D group and 14 (13%) in the ICD group underwent lead removal or extraction during follow-up (p=0.5). Both the CRT-D and ICD groups had comparable incidences of pocket hematoma (8% vs 5%), pocket and/or lead infection (9% vs 4%), and lead malfunction (8% vs 9%). Kaplan Meier analysis showed no significant survival difference between those who had a CIED-related complication versus those who did not (log rank p= 0.7). Conclusions: CIED related procedures are common in LVAD patients. Compared to ICD only, continued CRT-D post-LVAD resulted in a significantly higher number of generator changes and showed a trend towards higher device or lead related complications. CIED-related complications were not associated with reduced survival.