tbuckley/cabot-search huggingface dataset:
Trieste’s mental healthcare model is under threat, claim supporters of the community based approach
Authors: Michael Day
Journal: BMJ (2021)

The mitogenic and anti-apoptotic effects of insulin-like growth factor-I (IGF-I) are regulated by a family of insulin-like growth factor binding proteins (IGFBPs), particularly IGFBP-3. Little is known about the IGF-independent role of IGFBP-3 in breast cancer and the mechanisms regulating its production. The expression of IGFBP-3 in paired malignant and adjacent normal (n=53), and healthy normal (n=17) breast tissue samples was investigated using RT-PCR, immunohistochemistry and ELISA. We compared IGFBP-3 expression with other members of the IGF-I axis, other known tumorigenic genes and clinicopathological parameters. We also developed a novel tissue explant system using fresh normal and malignant breast tissue, with which we examined the in vitro effects of IGFBP-3 alone and in combination with known apoptotic agent, doxorubicin (n=6), on tissue viability and apoptosis. We demonstrated a high level of expression of IGFBP-3 mRNA in all samples. 96% of samples also expressed IGFBP-3 protein. No significant correlation was seen between IGFBP-3 expression and other clinicopathological parameters. The in vitro tissue explant system demonstrated that IGFBP-3 had little effect by itself on apoptosis. However, when used in combination with doxorubicin, increased apoptosis was seen in tumours. In contrast, less apoptosis was seen in normal tissue suggesting a protective effect. These divergent effects suggest a potential novel chemotherapeutic approach in the treatment of breast cancer. These findings suggest that IGFBP-3 may play a role in tumorigenesis, and that IGFBP-3 levels could be used in the future in cancer risk assessment/prevention or as markers of response to cancer treatments.
The Practice of Surgery. A Treatise on Surgery for the Use of Practitioners and Students.
Journal: JAMA (1902)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Valuing teaching in academic public health—time for a culture shift
Authors: Lisa M Sullivan, Sandro Galea
Journal: The Lancet Public Health (2021)

There is a near universality to the mission of all leading schools and programmes of public health, to improve health for all through high-quality education, research, and public health practice. For most leading academic public health schools and programmes, research and teaching share space as the predominant drivers of the financial wellbeing of institutions. And yet, despite the prominence of teaching in the day-to-day realities of many academic institutions, we have paid much less attention to the role of teaching in our academic ecosystem compared with the attention we pay to research.
Abstract 414: Putative Role of MicroRNA-143 in Modulating Natriuretic Peptide Signaling via Down-regulation of the Expression of Natriuretic Peptide Receptor 3
Authors: Juan Wang, Lee L Wong, Arthur M Richards, Yei-Tsung Chen
Journal: Circulation Research (2016)

Cardiac natriuretic peptides (NPs) play important roles in the regulation of intravascular blood volume and vascular tone. Among other clearance mechanisms, bio-active circulating NPs are removed by the clearance receptor, Natriuretic Peptide Receptor 3 (NPR3). We hypothesized that the level of NPR3 could be modulated by microRNAs (miRNAs) resulting in changes in the bioactivity of NPs. We have previously reported a cluster of miRNAs potentially regulating NPR3 expression. To extend these findings, expression of the microRNAs concerned was examined in multiple platforms, including plasma from a clinical heart failure cohort, in the rat myocardial infarction model, and in a human cardiac derived cell line subjected to hypoxic challenge. Results: miR-143 was up-regulated in peripheral blood in heart failure patients compared with controls. The binding of miR-143 to the 3’UTR of NPR3 m RNA was verified by luciferase reporter assay. Antagomir-based silencing of miR-143 enhanced NPR3 expression in human derived cardiac cells. Elevation of miR-143 and down-regulation of NPR3 levels were observed in hypoxia treated cells and in the myocardium from the rat myocardial infarction model. Taken together, these findings suggest miR-143 may be involved in the down-regulation of NPR3 which in turn may provide more cardiac protective bioactivity from NPs in heart failure, myocardial hypoxic stress and in myocardial infarction. In summary, NPR3 is negatively regulated by miR-143, pointing to the therapeutic potential of miR-143 to beneficially enhance NP responses.
Synergistical Starvation and Chemo‐Dynamic Therapy for Combating Multidrug‐Resistant Bacteria and Accelerating Diabetic Wound Healing
Authors: Danxia Li, Tao Chen, Yanfang Zhang, Yuanhong Xu, Haitao Niu
Journal: Advanced Healthcare Materials (2021)

Abstract The application of the antibiotic drug has dramatically decreased the infection and promoted the development of surgery, but drug‐resistant bacteria appeared along with the abuse of antibiotics. Especially, wound in diabetic patients provides more glucose for bacteria resulting in poor wound healing. Therefore, it is imminent to explore advanced agents for combating multidrug‐resistant bacteria and accelerating diabetic wound healing. Herein, metal–organic frameworks based nanoreactors loaded with glucose oxidase (GOx) and peroxidase‐like bovine hemoglobin (BHb) are designed to construct an effective cascaded catalytic antibacterial system. Therein, GOx can cost the glucose, and release H 2 O 2 simultaneously, which can then be transformed into hydroxyl radicals by BHb. As a result, the as‐prepared nanoreactors can play the roles of both starving and killing toward the multidrug‐resistant bacteria. Furthermore, the produced gluconic acid can reduce the pH of working condition, which is beneficial for both the enhancement of peroxidase activity and the inhibition of the bacteria growth. More importantly, the constructed nanoreactors can be degraded and excreted from the body in the form of feces, which render the as‐proposed nanoreactors qualified as effective and safe materials for both combating multidrug‐resistant bacteria in vitro and accelerating the diabetic wound healing in vivo of the mouse model.
CD4+濾胞調節性T細胞はインフルエンザウイルス特異的B細胞応答を最適化する【JST・京大機械翻訳】
Authors: Lu Yisi, Jiang Roy, W Freyn Alec, Wang Jiawei, Strohmeier Shirin, Lederer Katlyn, Locci Michela, Zhao Hongyu, Angeletti Davide, C O’Connor Kevin, H Kleinstein Steven, Nachbagauer Raffael, Craft Joe
Journal: The Journal of Experimental Medicine (2020)
From human to mouse and back offers hope for patients with fibromyalgia
Authors: Kevin J. Tracey
Journal: Journal of Clinical Investigation (2021)

Fibromyalgia syndrome (FMS) is a highly prevalent, debilitating disease with heterogeneous symptoms of widespread pain and tenderness, fatigue, sleep disturbance, and impaired cognition. The cause of FMS is unknown, but the clinical constellation of symptoms and abnormalities in the neuroendocrine system, autonomic nervous system, and sleep implicate the nervous system in its pathogenesis. In this issue of the JCI, Goebel, Krock, et al. identified antibodies from patients with FMS that produce FMS in mice by binding to satellite glial cells (SGCs), which envelope sensory neurons. Because antibodies harvested from patients with FMS, but not controls, stimulated SGCs to an activated state known to mediate chronic pain by augmenting neuronal activity, these findings reveal a pivotal role for autoreactive IgG in the pathophysiology of FMS. These important findings pave a pathway to study mechanism-based experimental therapeutics targeting IgG titers or antibody binding to SGCs underlying the neuroimmune dysfunction of FMS.
Twentieth Century Practice. An International Encyclopedia of Modern Medical Science.
Journal: JAMA (1899)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Confession at Bedside
Authors: David Haosen Xiang
Journal: JAMA Oncology (2021)

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 Oncology 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 Oncology journal
United adversarial learning for liver tumor segmentation and detection of multi-modality non-contrast MRI
Authors: Jianfeng Zhao, Dengwang Li, Xiaojiao Xiao, Fabio Accorsi, Harry Marshall, Tyler Cossetto, Dongkeun Kim, Daniel McCarthy, Cameron Dawson, Stefan Knezevic, Bo Chen, Shuo Li
Journal: Medical Image Analysis (2021)
Omidubicel vs standard myeloablative umbilical cord blood transplantation: results of a phase 3 randomized study
Authors: Mitchell E. Horwitz, Patrick J. Stiff, Corey Cutler, Claudio Brunstein, Rabi Hanna, Richard T. Maziarz, Andrew R. Rezvani, Nicole A. Karris, Joseph McGuirk, David Valcarcel, Gary J. Schiller, Caroline A. Lindemans, William Y. K. Hwang, Liang Piu Koh, Amy Keating, Yasser Khaled, Nelson Hamerschlak, Olga Frankfurt, Tony Peled, Irit Segalovich, Beth Blackwell, Stephen Wease, Laurence S. Freedman, Einat Galamidi-Cohen, Guillermo Sanz
Journal: Blood (2021)
Abstract 246: Acetylation of Vgll4 Regulates Hippo-yap Signaling and Postnatal Cardiac Growth
Authors: Zhiqiang Lin, Haidong Guo, Sylvia Zohrabian, Yuan Cao, William T. Pu
Journal: Circulation Research (2016)

Binding of the transcription co-activator YAP with the transcription factor TEAD stimulates growth of the heart and other organs. Many signaling pathways, including the Hippo kinase cascade, converge to regulate YAP activity. However, less in known about the mechanisms that govern TEAD. YAP overexpression potently stimulates fetal cardiomyocyte (CM) proliferation, but YAP’s mitogenic potency declines postnatally, when mammalian cardiomyocytes largely exit the cell cycle. Here, we show that VGLL4, a CM-enriched TEAD1 binding protein, inhibits CM proliferation by limiting its binding to YAP and by targeting TEAD1 for degradation. VGLL4 antagonism of TEAD1 was governed by its acetylation at K225. Overexpression of VGLL4-K225R, an acetylation-refractory mutant, enhanced TEAD1 degradation, limited neonatal CM proliferation, and caused CM necrosis and heart failure. Our study defines an acetylation-mediated, VGLL4-dependent switch that regulates YAP-TEAD1 activity and restrains CM proliferation. These insights may enable more effective regulation of TEAD-YAP activity in applications ranging from cardiac regeneration to restraining cancer.
Nfix Â Promotes Survival of Immature Hematopoietic Cells Via Regulation of C-Mpl
Authors: Trent Hall, Megan Walker, Miguel Ganuza Fernandez, Per Holmfeldt, Marie Bordas, Guolian Kang, Wenjian Bi, Lance Palmer, David Finkelstein, Shannon McKinney-Freeman
Journal: Blood (2017)
T-cell receptor-based therapy: an innovative therapeutic approach for solid tumors
Authors: Apostolia-Maria Tsimberidou, Karlyle Van Morris, Henry Hiep Vo, Stephen Eck, Yu-Feng Lin, Jorge Mauricio Rivas, Borje S. Andersson
Journal: Journal of Hematology & Oncology (2021)

Abstract T-cell receptor (TCR)-based adoptive therapy employs genetically modified lymphocytes that are directed against specific tumor markers. This therapeutic modality requires a structured and integrated process that involves patient screening (e.g., for HLA-A*02:01 and specific tumor targets), leukapheresis, generation of transduced TCR product, lymphodepletion, and infusion of the TCR-based adoptive therapy. In this review, we summarize the current technology and early clinical development of TCR-based therapy in patients with solid tumors. The challenges of TCR-based therapy include those associated with TCR product manufacturing, patient selection, and preparation with lymphodepletion. Overcoming these challenges, and those posed by the immunosuppressive microenvironment, as well as developing next-generation strategies is essential to improving the efficacy and safety of TCR-based therapies. Optimization of technology to generate TCR product, treatment administration, and patient monitoring for adverse events is needed. The implementation of novel TCR strategies will require expansion of the TCR approach to patients with HLA haplotypes beyond HLA-A*02:01 and the discovery of novel tumor markers that are expressed in more patients and tumor types. Ongoing clinical trials will determine the ultimate role of TCR-based therapy in patients with solid tumors.
Durable Remission of Refractory and Advanced Stage Mycosis Fungoides/Sezary Syndrome (MF/SS) Utilizing an “Outpatient” Alemtuzumab and Fludarabine-Based Reduced Intensity Allogeneic Peripheral Blood Stem Cell Transplantation (PBSCT)
Authors: Phuong Vo, Ramaprasad Srinivasan, Enkhtsetseg Purev, Emily McDuffee, Lisa Cook, Tatyana Worthy, Geri Hawks, Prince Patricia, Reem Shalabi, Brian Wells, Robert Reger, Hanh Khuu, David Stroncek, Xin Tian, Nancy Geller, Georg Aue, Richard Childs
Journal: Blood (2017)
Endoscopic ultrasound-guided renal biopsy: an alternative to transjugular renal biopsy in high-risk patients
Authors: Sridhar Sundaram, Prachi Patil, Aadish Jain, Utkarsh Chhanchure, Suman Kumar Ankathi, Shaila Khubchandani, Shaesta Mehta
Journal: Endoscopy (2021)

A 32-year-old man with hepatocellular cancer who had undergone right hepatectomy 2 years previously presented with facial puffiness and abdominal distension. Ultrasound showed moderate ascites with normal kidneys. Serum albumin was 2.8 g/dL, hemoglobin 8.4 g/dL, platelet count 74 000/μL, and creatinine 1.7 mg/dL. Urine examination showed 3 + proteinuria and 3 + hematuria, while 24-hour urinary protein was 3030 mg/dL. Transjugular renal biopsy (TJRB) was advised after nephrology consultation, due to the ascites with thrombocytopenia, but the patient was not willing to undergo this procedure. Hence, endoscopic ultrasound (EUS)-guided biopsy with a linear echoendoscope (GIF UCT180; Olympus, Tokyo, Japan) was planned.
A review and agenda for integrated disease models including social and behavioural factors
Authors: Jamie Bedson, Laura A. Skrip, Danielle Pedi, Sharon Abramowitz, Simone Carter, Mohamed F. Jalloh, Sebastian Funk, Nina Gobat, Tamara Giles-Vernick, Gerardo Chowell, João Rangel de Almeida, Rania Elessawi, Samuel V. Scarpino, Ross A. Hammond, Sylvie Briand, Joshua M. Epstein, Laurent Hébert-Dufresne, Benjamin M. Althouse
Journal: Nature Human Behaviour (2021)
Abstract 302: Cathepsin D Haploinsufficiency Exacerbates Post Myocardial Infarction Cardiac Remodeling and Malfunction by Impairing Autophagosome Removal
Authors: Penglong Wu, Wei Zhu, Jingbo Li, Xuejun “XJ” Wang
Journal: Circulation Research (2016)

Background: A marked decrease in the protein level and activity of cathepsin D (Ctsd), a major lysosomal protease, has been observed in failing human hearts; however, the pathophysiological significance of Ctsd downregulation in the heart remains undefined. Given the increasingly recognized role of the autophagic-lysosomal pathway in cardiac pathobiology, we sought to determine the impact of Ctsd haploinsufficiency on post myocardial infarction (MI) cardiac remodeling and explore the underlying mechanism. Methods and Results: MI was induced in 2-3 months old mixed-sex wild type (WT) or heterozygous Ctsd knockout (Ctsd +/- ) mice via permanent ligation of the left anterior descending (LAD) coronary artery. Myocardial Ctsd protein levels are reduced by ~50% in Ctsd +/- mice, compared with WT mice. Echocardiography (Echo) did not detect discernible difference between Ctsd +/- and WT mice immediately before and 1 week (wk) after MI; however, compared with the WT MI group, significantly greater left ventricular (LV) internal diameters at end systole and at end diastole and significantly smaller ejection fraction and fractional shortening were detected in the Ctsd +/- MI group at 2, 3, and 4 wks post-MI (p&lt;0.05 ~ 0.001). LV pressure-volume relationship analyses at 4 wks post-MI also revealed that LV maximum and minimum dP/dt values were significantly reduced in the WT MI group, compared with the WT sham control group (p&lt;0.05, 0.01); these post-MI reductions were more pronounced in the Ctsd +/- MI group (P&lt;0.05, 0.01). The infarct size at 4 wks post-MI measured with trichrome staining was significantly enlarged by Ctsd +/- (p&lt;0.002). These results indicate that Ctsd haploinsufficiency exacerbates post-MI cardiac remodeling and malfunction. Post-MI myocardial Ctsd protein levels were increased in WT mice but this increase was not detectable in Ctsd +/- mice. However, the myocardial protein levels of LC3-II, beclin1, and Atg5 were further elevated in Ctsd +/- MI mice, compared with the WT MI mice, indicative of impairment of autophagic flux in Ctsd +/- MI mice. Conclusion: Ctsd haploinsufficiency exacerbates maladaptive post-MI cardiac remodeling and malfunction likely through impairing autophagosome removal.
Three Doses of an mRNA Covid-19 Vaccine in Solid-Organ Transplant Recipients
Authors: Nassim Kamar, Florence Abravanel, Olivier Marion, Chloé Couat, Jacques Izopet, Arnaud del Bello
Journal: New England Journal of Medicine (2021)

Three Covid-19 Vaccine Doses in Transplant Recipients Solid-organ transplant recipients receiving immunosuppressive therapy appear to have a poor response to Covid-19 vaccination. A group of 101 co...
A proteomic strategy for identifying vascular surface proteins as potential targets for cancer treatment
Authors: Lauren A. McCann, Miriam Haywood, Ross A. Davey
Journal: Cancer Research (2006)

953  Actively growing tumors promote the development of their own blood supply in order to expand their growth. There is a wealth of research aimed at developing anti-angiogenic strategies against cancers, most of which involve blocking the growth of the blood vessels. Our approach is to specifically target and kill the endothelial cells, which line the blood vessels, associated with tumors; thereby effectively starving and killing the tumor. We have developed a platform technology to identify the proteins found exclusively on the blood vessel surface of tumors, which we can then use as potential targets for new cancer treatments in the form of therapeutic antibodies or vaccines. Our platform technology involves growing two transplantable syngeneic tumors, the 9L glioma and the MAT13762 breast adenocarcinoma in Fisher 344 rats. We perfuse saline through the whole body of anaesthetized, tumor bearing rats via the left ventricle of heart to remove all serum proteins from the blood vessels. We then perfuse the whole body with a biotinylation reagent, resulting in the covalent attachment of a biotin tag to all of the proteins exposed on the luminal surface of the blood vessels. We can surgically separate tumor tissue from normal tissues, and specifically isolate the proteins from either tumour or normal tissue by streptavidin affinity chromatography. We then comparatively analyse gel profiles from normal and tumor tissue using polyacrylamide gel electrophoresis and silver staining and those bands present in tumors and not in normal tissue are excised from the gel with an equivalent area from the normal gel, trypsin treated and identified using tandem mass spectrometry. We have used this method and identified several bands consistently present in the 9L glioma tissue that were absent in the adjacent normal brain. The tissue distribution of these proteins is currently being investigated. We have also confirmed the effectiveness of our biotinylation labeling of proteins by using streptavidin peroxidase staining of fixed sections of tissues. This showed that the biotinylation was primarily localised in and around the blood vessels of several normal tissues. The staining in normal brain gave a similar appearance to rat blood-brain barrier antigen that is known to be located on brain endothelial cells. We conclude that this strategy of perfusion, in situ labelling and affinity isolation has sufficient sensitivity to identify differences in the protein profiles associated with the blood vessels of tumours and tissues.
Impact of Coronary Artery Calcification on the Development of Future Occurrence of Heart Failure in Patients with Preserved Ejection Fraction
Authors: Yamada Keiji, Sakuragi Satoru, Fujiwara Takashi, Tanimoto Masafumi, Miki Takashi, Otsuka Hiroaki, Yamamoto Kazuhiko, Kawamoto Kenji, Tanakaya Machiko, Katayama Yusuke
Journal: Circulation (2014)
Elevated IgE promotes cardiac fibrosis by suppressing miR-486a-5p
Authors: Hongmei Zhao, Hongqin Yang, Chi Geng, Yang Chen, Yaqin Tang, Zhiwei Li, Junling Pang, Ting Shu, Yu Nie, Yongshuo Liu, Kegang Jia, Jing Wang
Journal: Theranostics (2021)

Cardiac fibrosis is an important feature of cardiac remodeling and is a hallmark of heart failure. Recent studies indicate that elevated IgE plays a causal role in pathological cardiac remodeling. However, the underlying mechanism of how IgE promotes cardiac fibrosis has not been fully elucidated.