tbuckley/cabot-search huggingface dataset:
Origins and consequences of congenital heart defects affecting the right ventricle
Authors: Odilia I. Woudstra, Suchit Ahuja, Jouke P. Bokma, Berto J. Bouma, Barbara J.M. Mulder, Vincent M. Christoffels
Journal: Cardiovascular Research (2017)

Congenital heart disease is a major health issue, accounting for a third of all congenital defects. Improved early surgical management has led to a growing population of adults with congenital heart disease, including patients with defects affecting the right ventricle, which are often classified as severe. Defects affecting the right ventricle often cause right ventricular volume or pressure overload and affected patients are at high risk for complications such as heart failure and sudden death. Recent insights into the developmental mechanisms and distinct developmental origins of the left ventricle, right ventricle, and the outflow tract have shed light on the common features and distinct problems arising in specific defects. Here, we provide a comprehensive overview of the current knowledge on the development into the normal and congenitally malformed right heart and the clinical consequences of several congenital heart defects affecting the right ventricle.
The Imperial County Community Air Monitoring Network: A Model for Community-based Environmental Monitoring for Public Health Action
Authors: Paul B. English, Luis Olmedo, Ester Bejarano, Humberto Lugo, Eduardo Murillo, Edmund Seto, Michelle Wong, Galatea King, Alexa Wilkie, Dan Meltzer, Graeme Carvlin, Michael Jerrett, Amanda Northcross
Journal: Environmental Health Perspectives (2017)

Summary: The Imperial County Community Air Monitoring Network (the Network) is a collaborative group of community, academic, nongovernmental, and government partners designed to fill the need for more detailed data on particulate matter in an area that often exceeds air quality standards. The Network employs a community-based environmental monitoring process in which the community and researchers have specific, well-defined roles as part of an equitable partnership that also includes shared decision-making to determine study direction, plan research protocols, and conduct project activities. The Network is currently producing real-time particulate matter data from 40 low-cost sensors throughout Imperial County, one of the largest community-based air networks in the United States. Establishment of a community-led air network involves engaging community members to be citizen-scientists in the monitoring, siting, and data collection process. Attention to technical issues regarding instrument calibration and validation and electronic transfer and storage of data is also essential. Finally, continued community health improvements will be predicated on facilitating community ownership and sustainability of the network after research funds have been expended. https://doi.org/10.1289/EHP1772
Retention of cryptic genes in microbial populations.
Authors: W H Li
Journal: Molecular Biology and Evolution (1984)

Cryptic genes are silenced genes that can still be reactivated by mutation. Since they can make no positive contribution to the fitness of their carriers, it is not clear why many cryptic genes in microbial populations have not degenerated into useless DNA sequences. Hall et al. (1983) have suggested that cryptic genes have persisted because of occasional strong environmental selection for reactivated genes. The present mathematical study supports their suggestion. It shows that a cryptic gene can be retained without having any selective advantage over a useless DNA sequence, if selection for the reactivated gene occasionally occurs for a substantially long time.
Signal-pathway profiling of cells undergoing photodynamic therapy with reverse phase liquid protein arrays.
Authors: Rene C. Krieg, Kerstin Reher, Kristina Schwamborn, Lance A. Liotta, Emanuel F. Petricoin, Ruth Knuechel-Clarke
Journal: Cancer Research (2004)

3648  Proteomics is a promising direction for clinical and scientific advancement in our understanding and diagnostic treatment of ovarian and other gynecologic cancers. Understanding molecular markers or pathways of drug resistance may allow one to individualize patient treatment strategies increasing probability of patient survival and overall well-being. Cisplatin is the primary treatment for many solid tumors including ovarian cancer. Although, the initial response rate of advanced stage ovarian cancer to platinum-based primary therapy is high, most patients will relapse and die of disease having developed clinical resistance to multiple chemotherapeutic agents. One of the best characterized mechanisms of resistance to platinum drugs is related to an increased cellular capacity to repair DNA through the Transcription-coupled Nucleotide Excision Repair Pathway (TC-NER). Ecteinascidin 743 (Et-743) target cells with an intact TC-NER for cell death (Nature Med. 2001, 7:961), counteracting cisplatin resistance. This has led to our hypothesis that ovarian tumors with intact TC-NER function should be more susceptible to Et-743 treatment. The major components of the TC-NER include RPA, XPA, XPB, XPD, XPF, XPG, ERCC1, CSA and CSB. We have developed and validated reverse phase protein lysate microarrays (containing six ovarian and seven colon cancer cell lines from the NCI 60 cell line screen, XPA-XPG- deficient cell lines, ovarian A2780 and its cisplatin resistant derivative A2780/CP70, Et-743-resistant cells HCT116/ER5, and normal fibroblasts) and Tissue Array Research Program arrays probing for the TC-NER proteins. All antibodies used on the arrays were validated by Microwestern for specificity and optimized for reproducible results. Analysis and quantification of the arrays were performed with the program Peak quantification using Statistical Comparative Analysis (P-SCAN) and a dose-interpolation algorithm in collaboration with NIH/Center for Information Technology. Cluster image map relating the protein expression levels of these TC-NER (XPA to XPG) and other DNA repair interaction proteins (XRCC1, BRCA1, NF-κB, MSH6, MSH2, Keratin 7, Keratin 8, PCNA, XIAP, PARP) on the arrays were produced using the Molecular Pharmacology CIM Maker program package. We plan to add a third dimension to this cluster image map containing the relative drug resistance/sensitivity of the NCI 60 cell screen obtained from the Developmental Therapeutics Program to identify unique protein patterns corresponding to drug toxicity in vitro. Further development and validation of the proteomic microarrays using the forthcoming patient samples from our proposed clinical trial will further characterize the NER pathway in relation to patient sensitivity to Et-743 or cisplatin.
Alternate dosing regimens of brentuximab vedotin for <scp>CD</scp> 30+ cutaneous T‐cell lymphoma
Authors: D.J. Lewis, Y.H. Kim, M. Duvic
Journal: British Journal of Dermatology (2017)

Stranzenbach et al. propose alternate dosing regimens of brentuximab vedotin (BV) for CD30+ cutaneous T-cell lymphomas (CTCLs) such as mycosis fungoides (MF) and primary cutaneous anaplastic large cell lymphoma (pcALCL).1 They emphasize that lower doses or less frequent dosing schedules for CTCL may be equally effective while limiting adverse events.

The authors indicate that CTCLs may require less aggressive therapy than systemic lymphomas such as systemic ALCL (sALCL) or Hodgkin lymphoma (HL).

This article is protected by copyright. All rights reserved.
PSA screening significantly cuts risk of death from prostate cancer, review finds
Authors: Susan Mayor
Journal: BMJ (2017)

Prostate specific antigen (PSA) screening is associated with a reduction in the risk of death from prostate cancer by as much as a third, a review of conflicting randomised trials has found.1

Screening for prostate cancer with PSA has been common since the late 1980s, but two trials published in 2009 found contradictory results regarding its efficacy in reducing prostate cancer deaths. The PLCO (Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial) in the US found low rates of prostate cancer death that did not differ significantly between men who were screened and those who were not, while the ERSPC (European Randomized …
Vaccination of renal cell cancer (RCC) patients with modified vaccinia Ankara (MVA) delivering tumor antigen 5T4 administered alone or with interleukin 2 (IL-2) or interferon-alpha (IFN)
Authors: R. Amato, J. Hernandez-McClain, R. Harrop, P. Cen, G. Doshi
Journal: Journal of Clinical Oncology (2009)

3026 Background: The attenuated vaccinia virus (MVA) has been engineered to deliver the tumor antigen 5T4 (TroVax). More than 90% of RCCs overexpress the 5T4 antigen. A series of clinical trials were conducted to evaluate the effectiveness of MVA 5T4 as a single agent or in combination with either IL-2 or IFN. Methods: Eligibility: Pathologic diagnosis of clear cell or papillary RCC, progressive measurable metastases, any prior therapy, adequate physiological parameters, Karnofsky performance status ≥ 80%, and no active CNS involvement. A regimen of MVA 5T4 alone or in combination with IL-2 or IFN was given. Results: A total of 53 pts received MVA 5T4 alone or in combination with IL-2 or IFN. 13 pts received MVA 5T4 alone, 25 pts received low dose subcutaneous IL-2, and 15 pts received IFN. Clinical responses were assessed by measuring changes in tumor burden via computed tomography or magnetic resonance imaging scan. 5T4-specific cellular and humoral responses were monitored throughout the study. 5T4 was well tolerated with no serious adverse events attributed to vaccination. Of 48 intention-to-treat pts, 43 mounted 5T4-specific antibody responses. 2 pts showed a complete response for &gt; 36 months and 2 other pts had a partial response for &gt; 24 months and 12 months respectively. 20 pts demonstrated disease stabilization for ≥ 3 months. Median progression-free survival and overall survival for all pts was 3.6 months (range 0.8–29.7) and 13.2 months (range 1–38) respectively. A significant relationship was detected between the magnitude of 5T4-specific antibody response and overall survival. Conclusions: 5T4, whether administered alone or in combination, was well tolerated. High frequency of 5T4-specific immune responses and associated enhanced patient survival is encouraging and warrants further investigation. [Table: see text]
Scottish government must act to fill consultant vacancies, says BMA
Authors: Abi Rimmer
Journal: BMJ (2017)

The Scottish government must act now to fill vacancies in the consultant workforce, the BMA has said.

Figures published by Information Services Division Scotland on 5 September showed that 476.4 whole time equivalent (WTE) consultant posts were vacant as of 30 June, representing 8.5% of all posts. Of the …
Oligodendroglia: metabolic supporters of neurons
Authors: Thomas Philips, Jeffrey D. Rothstein
Journal: Journal of Clinical Investigation (2017)

Oligodendrocytes are glial cells that populate the entire CNS after they have differentiated from oligodendrocyte progenitor cells. From birth onward, oligodendrocytes initiate wrapping of neuronal axons with a multilamellar lipid structure called myelin. Apart from their well-established function in action potential propagation, more recent data indicate that oligodendrocytes are essential for providing metabolic support to neurons. Oligodendrocytes transfer energy metabolites to neurons through cytoplasmic "myelinic" channels and monocarboxylate transporters, which allow for the fast delivery of short-carbon-chain energy metabolites like pyruvate and lactate to neurons. These substrates are metabolized and contribute to ATP synthesis in neurons. This Review will discuss our current understanding of this metabolic supportive function of oligodendrocytes and its potential impact in human neurodegenerative disease and related animal models.
Neutrophil FcγRIIA promotes IgG-mediated glomerular neutrophil capture via Abl/Src kinases
Authors: Hiroshi Nishi, Kazuhiro Furuhashi, Xavier Cullere, Gurpanna Saggu, Mark J. Miller, Yunfeng Chen, Florencia Rosetti, Samantha L. Hamilton, Lihua Yang, Spencer P. Pittman, Jiexi Liao, Jan M. Herter, Jeffrey C. Berry, Daniel J. DeAngelo, Cheng Zhu, George C. Tsokos, Tanya N. Mayadas
Journal: Journal of Clinical Investigation (2017)

The kidney glomerular capillaries are frequent sites of immune complex deposition and subsequent neutrophil accumulation in post-infectious and rapidly progressive glomerulonephritis. However, the mechanisms of neutrophil recruitment remain enigmatic, and there is no targeted therapeutic to avert this proximal event in glomerular inflammation. The uniquely human activating Fc receptor FcγRIIA promotes glomerular neutrophil accumulation and damage in anti-glomerular basement membrane-induced (anti-GBM-induced) glomerulonephritis when expressed on murine neutrophils. Here, we found that neutrophils are directly captured by immobilized IgG antibodies under physiological flow conditions in vitro through FcγRIIA-dependent, Abl/Src tyrosine kinase-mediated F-actin polymerization. Biophysical measurements showed that the lifetime of FcγRIIA-IgG bonds increased under mechanical force in an F-actin-dependent manner, which could enable the capture of neutrophils under physiological flow. Kidney intravital microscopy revealed that circulating neutrophils, which were similar in diameter to glomerular capillaries, abruptly arrested following anti-GBM antibody deposition via neutrophil FcγRIIA and Abl/Src kinases. Accordingly, inhibition of Abl/Src with bosutinib reduced FcγRIIA-mediated glomerular neutrophil accumulation and renal injury in experimental, crescentic anti-GBM nephritis. These data identify a pathway of neutrophil recruitment within glomerular capillaries following IgG deposition that may be targeted by bosutinib to avert glomerular injury.
Managing Conflicts of Interest in Practice Guidelines Panels
Authors: Cristina Morciano, Carla Faralli, Vittorio Basevi
Journal: JAMA (2017)

To the Editor Dr Sox examined the issue of COI in practice guidelines panels.1 He reported that, when available, policies for managing COI performed poorly according to 2 studies2,3 published around the time of the 2011 IOM report.4
Testosterone Replacement Therapy and Cardiovascular Risk—A Closer Look to Additional Parameters
Authors: T. Craig Cheetham, Stephen K. VanDenEeden, Steven J. Jacobsen
Journal: JAMA Internal Medicine (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Projections of primary liver cancer to 2030 in 30 countries worldwide
Authors: Patricia C. Valery, Mathieu Laversanne, Paul J. Clark, Jessica L. Petrick, Katherine A. McGlynn, Freddie Bray
Journal: Hepatology (2017)

Primary liver cancer (PLC) is the sixth most common cancer worldwide and the second most common cause of cancer death. Future predictions can inform health planners and raise awareness of the need for cancer control action. We predicted the future burden of PLC in 30 countries around 2030. Incident cases of PLC ( International Classification of Diseases , Tenth Revision, C22) were obtained from 30 countries for 1993‐2007. We projected new PLC cases to 2030 using age‐period‐cohort models (NORDPRED software). Age‐standardized incidence rates per 100,000 person‐years were calculated by country and sex. Increases in new cases and rates of PLC are projected in both sexes. The largest increases in rates are, among men, in Norway (2.9% per annum), US whites (2.6%), and Canada (2.4%) and, among women, in the United States (blacks 4.0%), Switzerland (3.4%), and Germany (3.0%). The projected declines are in China, Japan, Singapore, and parts of Europe (e.g., Estonia, Czech Republic, Slovakia). A 35% increase in the number of new cases annually is expected compared to 2005. This increasing burden reflects both increasing rates (and the underlying prevalence of risk factors) and demographic changes. Japan is the only country with a predicted decline in the net number of cases and annual rates by 2030. Conclusion: Our reporting of a projected increase in PLC incidence to 2030 in 30 countries serves as a baseline for anticipated declines in the longer term through the control of hepatitis B virus and hepatitis C virus infections by vaccination and treatment; however, the prospect that rising levels of obesity and its metabolic complications may lead to an increased risk of PLC that potentially offsets these gains is a concern. (H epatology 2018;67:600‐611).
An aberrant NOTCH2-BCR signaling axis in B cells from patients with chronic GVHD
Authors: Jonathan C. Poe, Wei Jia, Hsuan Su, Sarah Anand, Jeremy J. Rose, Prasanthi V. Tata, Amy N. Suthers, Corbin D. Jones, Pei Fen Kuan, Benjamin G. Vincent, Jonathan S. Serody, Mitchell E. Horwitz, Vincent T. Ho, Steven Z. Pavletic, Frances T. Hakim, Kouros Owzar, Dadong Zhang, Bruce R. Blazar, Christian W. Siebel, Nelson J. Chao, Ivan Maillard, Stefanie Sarantopoulos
Journal: Blood (2017)

Key Points NOTCH2 activation confers a marked increase in BCR responsiveness by cGVHD patient B cells that associates with increased BLNK. ATRA increases the IRF4-to-IRF8 ratio and blocks aberrant NOTCH2-BCR activation without affecting cGVHD patient B-cell viability/function.
Retrospective Study of Intravascular Lymphoma Cases Diagnosed in Quebec
Authors: Vanessa Brunet, Michel Pavic, Sofia Marouan, Jean Pierre Routy, Mohamed Amin Hashem, Vincent Bernier, Raynald Simard, Tony Petrella, Louis Lamarre, Gilles Théorêt, Christian Carrier, Hans Knecht, Isabelle Fleury
Journal: Blood (2016)
A phase 2 study of galunisertib, a novel transforming growth factor-beta (TGF-β) receptor I kinase inhibitor, in patients with advanced hepatocellular carcinoma (HCC) and low serum alpha fetoprotein (AFP).
Authors: Sandrine J. Faivre, Armando Santoro, Edward Gane, Robin Kate Kelley, I Ollivier Hourmand, Eric Assenat, Ivelina Gueorguieva, Ann Cleverly, Durisala Desaiah, Michael M. F. Lahn, Eric Raymond, Karim A. Benhadji, Gianluigi Giannelli
Journal: Journal of Clinical Oncology (2016)

4070 Background: TGFβ signaling is associated with HCC progression. Here we report the results of a cohort of patients with HCC and normal serum AFP treated with galunisertib as part of a larger phase 2 study. Methods: Eligible patients with HCC included: those who had progressed on or were ineligible to receive sorafenib, advanced Child-Pugh A/B7 HCC, AFP < 1.5x ULN, ECOG PS ≤ 1, measurable disease per RECIST 1.1, and ≤ 1 prior systemic regimen. Galunisertib was administered as intermittent dosing of 14 days on/off (300 mg/day, 28 days = 1 cycle). Primary objectives were time-to-progression (TTP) and evaluation of biomarker changes (TGFβ1 and E-cadherin). Secondary objectives included overall survival (OS), toxicity (CTCAE, v 4.0) and pharmacokinetics. Results: 40 patients were enrolled. 90% of patients were male; median age: 68 years; PS = 0/1, 60%/40%; Child-Pugh A/B 75%/23%; etiology: hepatitis C 18%, hepatitis B 15%, alcohol 23%; multiple 10%. Overall, 85% of patients had received prior sorafenib. TTP was 4.16 months 90%CI: (2.76, 5.89). Median OS was 16.8 months (90%CI: 10.4,24.1). Four patients discontinued treatment due to adverse events (AEs). Grade 3/4 possibly treatment related AEs were observed in 6 patients: 1 occurrence of each of the following: hypoalbuminemia, neutropenia, thrombocytopenia, abdominal pain, constipation, drug eruption, pruritus and gall bladder perforation. Median baseline serum TGFβ1 was 3.39 ng/mL (range: 1.16-37.5) and E-cadherin was 6.33 mg/mL (range: 1.45-18.9). TGFβ1 decline of > 20% occurred in 74% of patients. In patients with TGFβ1 reduction > 20%, median OS was 21.8 months vs 7.91 months for patients with reduction of ≤ 20% (Log Rank p = 0.002). E-cadherin reduction of > 20% occurred in 46% of patients. Conclusions: HCC patients with normal AFP and with TGFβ1 reduction showed improvement in OS compared to patients with non-TGFβ1 reduction. Clinical trial information: NCT01246986.
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Authors: Li Yinhui, Xu Di, Ho See-Lok, Li Hung-Wing, Yang Ronghua, Wong Man Shing
Journal: Biomaterials (2016)
Thyroid Surgery Through the Mouth Might Not Be as Crazy as It Sounds
Authors: Michael W. Yeh
Journal: JAMA Surgery (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal