tbuckley/cabot-search huggingface dataset:
A Man in His 80s With Hypertension, Left Ventricular Hypertrophy, and Enlarged Biceps
Authors: Raffaele Martone, Federico Perfetto, Francesco Cappelli
Journal: JAMA Cardiology (2019)

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Effect of microRNA-202-3p on cell proliferation and targeting of ADP-ribosylation factor-like 5A in human colorectal carcinoma.
Authors: Qifeng WANG, Xiang Du
Journal: Journal of Clinical Oncology (2013)

e14667 Background: MicroRNAs (miRNAs) are small, non-coding RNAs that are strongly implicated in cancer and reshaped our understanding of the role of non-protein-coding genes in carcinogenesis. Methods: Quantitative RT-PCR was used to evaluate miR-202-3p expression in 94 pairs of human primary CRC and adjacent noncancerous tissues (NCT) to determine the clinicopathologic significance of miR-202-3p. Cell proliferation analysis and Xenograft analysis was used to investigate miR-202-3p function in vitro and in vivo.It’s direct target ARL5A was confirmed by Luciferase assay and Western blot. Immunochemistry was performed to reveal endogenous protein level of ARL5A and analysis clinical significance. Results: In this study, miR-202-3p was verified significantly down regulated in 46.7% (44/94) of the CRC tissues when compared to the corresponding noncancerous tissues(NCT). Subsequently, DNA copy number deletion of Pre-miR-202 in 63.2%(24/38) CRC tissue was proved(compared with NCT), which was considered as a main cause of the low expression of miR-202-3p. Cell proliferation analysis and colony formation assay showed that overexpression of miR-202-3p inhibit CRC cell growth in vitro. Xenograft analysis revealed that ectopic expression of miR-202-3p decreased the tumorigenicity of CRC cells in vivo. Consistent with these results, silencing of miR-202-3p resulted in a increased growth ratio of the colon cancer cells. In addition, ADP-ribosylation factor-like 5A(ARL5A) was predicted as potential target of miR-202-3p which was confirmed by Luciferase assay and Western blot. Overexpression of miR-202-3p could reduced the endogenous protein level of ARL5A, whereas silencing of miR-202-3p obviously up regulated ARL5A expression. In human CRC tissues, miR-202-3p expression levels correlated inversely with ARL5A protein levels which was identified as an prognostic factor in this study. Furthermore, knockdown of ARL5A phenocopied the proliferation-inhibiting effect of miR-202-3p. Conclusions: These results indicated that miR-202-3p, acting as a new tumor suppressor in CRC, could decrease cell proliferation via directly targeting ARL5A, a first reported gene related to CRC prognosis.
Hematopoietic score predicts outcomes in newly diagnosed multiple myeloma patients
Authors: Abdullah S. Al Saleh, M. Hasib Sidiqi, Angela Dispenzieri, Prashant Kapoor, Eli Muchtar, Francis K. Buadi, Rahma Warsame, Martha Q. Lacy, David Dingli, Nelson Leung, Wilson I. Gonsalves, Taxiarchis V. Kourelis, Morie A. Gertz, Ronald S. Go, Robert A. Kyle, S. Vincent Rajkumar, Shaji K. Kumar
Journal: American Journal of Hematology (2019)

Abstract Risk stratification of multiple myeloma (MM) at diagnosis is critical. We examined the ability of hematopoietic indices including mean corpuscular volume (MCV), hemoglobin (Hgb), and platelet (Plt) to predict outcomes. This was a retrospective study of patients treated at Mayo Clinic between January 2004 and April 2018. We incorporated three variables (Hgb &lt; 10 g/dL, Plt &lt; 150 × 10 9 /L, and MCV &gt; 96 fL), assigning a score of 1 to each. We identified 1540 newly diagnosed MM patients, of whom 707 (46%) had a score of 0, 513 (33%) had a score of 1, 260 (17%) had a score of 2, and 60 (4%) had a score of 3. The score risk stratified patients into four groups with differing survivals. The median PFS was 32.3 months for score 0, 24.8 months for score 1, 21.7 months for score 2, and 18.3 months for score 3, for P &lt; .001. The median OS was 80.7 months for score 0, 59.9 months for score 1, 51.7 months for score 2, and 31.3 months for score 3, P &lt; .0001. Predictors of OS on the multivariable analysis were age ≥ 65 (HR, 1.93; P &lt; .0001), R‐ISS stage (1‐2 vs 3) (HR, 0.48; P &lt; .0001), and hematopoietic score (0‐2 vs 3) (HR, 0.51; P = .006). A hematopoietic score can predict survival in newly diagnosed myeloma patients.
Clinical and PET Responses to Long-Term High-Dose Interferon-α Treatment Among Patients with Erdheim-Chester Disease
Authors: Xinxin Cao, Na Niu, Jian Sun, Hao Cai, Feng-dan Wang, Yi-ning Wang, Ding-rong Zhong, Ming-hui Duan, Dao-bin Zhou, Jian Li
Journal: Blood (2018)
Donor T Cells Maintain Myeloma-Immune Equilibrium after Autologous Stem Cell Transplantation and Concurrent Immunotherapy Promotes Cure
Authors: Simone A Minnie, David Smith, Kate H Gartlan, Thomas S Watkins, Kate A Markey, Camille Guillerey, Rachel D Kuns, Kelly R Locke, Antiopi Varelias, Ping Zhang, Nicholas Huntington, Marta Chesi, John J Miles, Mark J Smyth, Slavica Vuckovic, Geoffrey R Hill
Journal: Blood (2018)
Relevance of the antioxidant properties of methotrexate and doxycycline to their treatment of cardiovascular disease
Authors: Dahn L. Clemens, Michael J. Duryee, Johnathan H. Hall, Geoffrey M. Thiele, Ted R. Mikuls, Lynell W. Klassen, Matthew C. Zimmerman, Daniel R. Anderson
Journal: Pharmacology & Therapeutics (2019)
Abstract 230: Disturbed Blood Flow-induced Platelet Transmigration Via C-type Lectin-like Receptor-2 Modulating Vascular Inflammation
Authors: Chaojun Tang, Yulan Sheng, Tao You, Lei Wang, Zhanli Xie, Michael McDaniel, Lijun Xia, Li Zhu
Journal: Circulation Research (2019)

Atherosclerosis preferentially develops at sites under disturbed blood flow (d-flow) that leads to steep multidirectional gradients of wall shear stress at vascular predilection sites, promoting an oxidative, proapoptotic, and proinflammatory gene expression profile in endothelial cells. Sustained d-flow causes endothelial injury characterized by leukocyte infiltration, endothelial barrier dysfunction, and eventually the formation of atherosclerotic plaques. While previous studies suggest a proinflammatory role of platelets via promoting leukocyte activation in atherogenesis, whether and how platelets are regulated by d-flow remains largely unclear. In this study, we showed that d-flow induced by partial carotid ligation (PCL) causes platelet adhesion, endothelial damage and leukocyte recruitment in mice. Unexpectedly, PCL induces platelet transmigration into the subendothelial space. Transmigrated platelets at 2 days of PCL appeared inside the intercellular crevices beneath the damaged endothelium. After sustained d-flow (5-7 days after PCL), more adherent leukocytes and platelets with pseudopodia were observed in the seriously damaged endothelium. In investigating the mechanism of this unexpected observation, we found that mice with platelet-specific deficiency of C-type lectin-like receptor-2 (CLEC-2) showed ~80% reduction in platelet endothelial accumulation and no subendothelial localization of platelets under d-flow, indicating an essential role of CLEC-2 in mediating platelet transmigration. Enhanced platelet transmigration exacerbated monocyte accumulation, while leukocyte depletion or PSGL-1 deletion did not affect platelet transmigration under d-flow. Our results revealed unprecedented platelet transmigration mediated by CLEC-2 in the rheological regulation of vascular homeostasis, controlling vascular inflammation.
Primary care networks: the risk of “mission creep” calls for focused ambition
Authors: Luisa Pettigrew, Nicholas Mays
Journal: BMJ (2019)

Our research12 aligns with Wilson and Lewis’s recent editorial3 and with previous commentaries4 that emphasise the well intentioned, but potentially overambitious, hopes for primary care networks.

Positive impact seems plausible as a result of increasing organisational size, but it is not guaranteed. Unintended consequences frequently occur. Clinical outcomes or patient experience do not necessarily improve and might …
Bortezomib Inhibits mTOR Pathway in Multiple Myeloma Cell Lines Via Induced Expression of REDD1.
Authors: Olivier Decaux, Monique Clement, Florence Magrangeas, Laurence Lode, Catherine Charbonnel, Wilfried Goureau, Herve Avet Loiseau, Stephane Minvielle
Journal: Blood (2007)
Abstract 327: MicroRNA-574-FAM210A Axis Maintains Mitochondrial Translational Homeostasis and Influences Pathological Cardiac Remodeling
Authors: Peng Yao, Jiangbin Wu, Kadiam C. Venkata Subbaiah, Feng Jiang, Omar Hedaya, Wai Hong Wilson Tang, Eric Small, Chen Yan
Journal: Circulation Research (2019)

Rationale: Translational control is a critical regulatory step in altering protein synthesis under disease conditions. Aberrant synthesis of mitochondrial proteins impairs cardiac function and causes heart disease. However, the mechanism of translational control in mitochondria and during cardiac disease remains underexplored. Objective: We have found that multiple pathogenic cardiac stressors induce the expression of miR-574 guide and passenger strands (miR-574-5p/3p) in humans and mice. Here, we aim to define a new miR-574-FAM210A axis that regulates cardiac mitochondrial translational homeostasis and prevents adverse cardiac remodeling. Methods and Results: Echocardiography, histology and biochemical analyses were used to evaluate the cardiac function of miR-574 knockout mice, which exhibit severe cardiac hypertrophy, fibrosis, and cardiac dysfunction under heart failure-triggering stresses. miR-574-5p/3p mimics that were delivered systematically using nanoparticles reduced cardiac pathogenesis with disease insults. Transcriptome analysis of miR-574-null hearts has uncovered FAM210A as a common target mRNA for miR-574-5p/3p. Interactome and translational state analyses identify a FAM210A-bearing trimeric complex that promotes the translation of mitochondrial encoded electron transport chain genes and modulates mitochondrial activities. Moreover, the phenotypic characterization of tamoxifen-inducible CM-specific Fam210a knockout mice suggests that FAM210A plays a critical role in maintaining normal cardiac mitochondrial morphology and function as well as cardiac health and organismal viability. Conclusions: miR-574-5p and miR-574-3p protect against pathological cardiac remodeling through regulation of FAM210A, a key translational control factor of mitochondrial encoded genes. Thus, we discovered a novel miR-574-FAM210A pathway that modulates cardiac mitochondrial translational homeostasis and influences cardiac remodeling in heart failure.
Comprehensive Consideration before the Decision-Making of the Systemic Treatment in Patients with Advanced Hepatocellular Carcinoma
Authors: Mingyu Chen, Jiahao Hu, Jiasheng Cao, Xiujun Cai
Journal: Liver Cancer (2019)

Systemic Treatment Options in Hepatocellular Carcinoma".In this review, the authors summarize the current systemic therapies for hepatocellular carcinoma (HCC) and give some viewpoints that could assist physicians in the treatment decisions for patients with HCC.Although the information outlined is quite complete and can be utilized in the majority of situations in real-life HCC therapy, please allow us to make some further discussions about the problems we may meet.Our humble remarks are as follows.To begin with, we have to acknowledge that as a very heterogeneous malignancy, the inclusion criteria of current clinical trials about HCC are almost based on nonspecific indexes such as liver function and tumor stage, etc.Therefore, though molecular targeted agents such as sorafenib are approved as the first-line treatment for advanced HCC, the application of sorafenib therapy is still lacking biomarkers [2].The exploit of biomarkers for patient selection is necessary.The protooncogene c-MET may participate in the development of HCC, and its overexpression is also relevant for tumor recurrence, microvascular invasion, and poor overall survival (OS), etc. MET-inhibiting agents such as tivantinib, based on their characteristics, are investigated for the targeted treatment of MET-overexpressed HCC.Several clinical trials are being conducted.However, the level of c-MET as a biomarker to predict the benefit is still unclear [2,3].In addition, though that sorafenib was approved as the first-line treatment for advanced HCC is widely accepted, the application of it is still limited due to various causes including primary or acquired resistance, intolerance of its adverse events, and the inability to afford the high expense, etc. [4].Systematic cytotoxic chemotherapy as the conventional treatment is less effective and easily leads to drug resistance.It seems that with the quickly developing small-molecule targeted agents, the continuing exploit of systematic chemotherapy is useless.However, clinical trials comparing the efficacy between sorafenib and cytotoxic chemotherapy are rare.Therefore, systematic chemotherapy for advanced HCC can still be considered.For example, OXA, a highly efficient drug with a relatively low toxicity, has been used clinically.The OXA-containing FOLFOX4 was approved by the Chinese Food and Drug Administration.A multicenter, open-label, randomized phase III study comparing FOLFOX4 and doxorubicin suggests a trend toward improved OS with FOLFOX4, along with increased progression-free survival and response rate (NCT00471965).It discloses the potential benefit patients can gain from systematic chemotherapy.In addition, systematic therapy combined with sorafenib can also be accepted.
Retrovirus-Transduced T Cell Blasts Have Not Only Antigen-Presenting Capabilities but Also Suppressor Regulatory T Cell-Inducing Capability.
Authors: Takayuki Okamura, Ann M. Leen, Uluhan Silli, Stephen M. Gottschalk, Stephane Vigouroux, Helen E. Heslop, Malcolm K. Brenner, Cliona M. Rooney
Journal: Blood (2004)
The Pleiotropic Immunosuppressive Role of Osteoclasts in Multiple Myeloma
Authors: Kenta Mukaihara, Ka Tat Siu, Cristina Panaroni, Keertik Fulzele, Rosemary Soucy, Cherrie Huang, Shrikanta Chattopadhyay, Noopur Raje
Journal: Blood (2018)
Abstract 808: Functional Characterization of a Novel Scn5a Mutation Associated With the Brugada Syndrome
Authors: Anthony Frosio, David Molla, Giorgia Bertoli, Claudia Bazzini, Raffaella Milanesi, Francesca Gennaro, Andrea Barbuti, Annalisa Bucchi, Luciano Moretti, Procolo Marchese, Dario DiFrancesco, Mirko Baruscotti
Journal: Circulation Research (2019)

Background: Brugada syndrome (BrS) is a cardiac disorder characterized by conduction abnormalities that can lead to sudden death; syncope and cardiac arrest are clinical manifestations which are often associated with an enhancement of the vagal activity. Mutations in the SCN5A gene (Na v 1.5 channel) are the most common cause of the inherited forms of BrS. Objective: To characterize the functional behavior of mutant Na v 1.5 channels expressing a novel heterozygous mutation (S805L) recently identified in an Italian family affected by the BrS. Methods: HEK cells were used as experimental model to express both the wild-type (WT) and the mutated S805L channels (alone, Homo or in combination, Hetero) and the accessory β-subunit (SCN1B). Patch-clamp and western blot experiments were carried out to assess the dysfunctional role of the mutation. Results: When compared to the WT current, the S508L mutation significantly (P&amp;It0.05) decreases the peak current density by about 65% for the Homo condition (WT: -120.2±10.2, n=28); Homo: -40.3±4.2, n=16) and by 35% for the Hetero condition (Hetero: -78.2±8.3, n=27). Densitometric analysis carried out on western blot data further support the conclusion that S805L channels are less abundant in the plasma membrane. We also observed that the S805L mutation positively shifts the V½ values of the voltage dependence of the inactivation of both Homo and Hetero currents (V½: WT -85.5±0.2 mV, n=55; Homo -80.9±0.3 mV, n=22; Hetero -81.9±0.2 mV, n=25; P&amp;It0.05); a positive shift of the V½ of the activation was also observed but only in the Homo condition (V½: WT -33.0±0.4 mV, n=28; Homo -30.0±0.5, n=16, P&amp;It0.05). The kinetics of recovery from inactivation and the amplitude of the late sodium current were also evaluated but they were unaffected by the mutation. Conclusion: When expressed in the Hetero condition, the S805L mutation causes a reduction in the channel expression, however, the positive shift of the inactivation curve suggests an increase in Na channel availability. We thus believe that the precise quantitative balance between these two phenomena and their relation with vagal activity may underlie the clinical manifestation of the disease.
Abstract 73: Rapid Whole Body Cooling in Large Swine: Effects on Heart Rate and Arterial Blood Pressure
Authors: William Ohley, Robert B Schock, Cathy Klock, Lorraine Schofield, Marc Cote, Robert Freedman
Journal: Circulation (2007)

There have been recent reports of a variety of cooling methods for reducing the body temperature of victims of post resuscitative syndrome. In the work reported here we cooled a series of large (&gt; 60 kg) domestic swine (n=6) using a whole body approach. The animals were anesthetized using propofol and buprinorphine and instrumented with arterial pressure monitoring and ECG, and thermocouple sensors in the pulmonary artery (PA), carotid artery, tympanic membrane and esophagus. With an initial average PA temperature at 37 (± 0.3) °C, the swine underwent a rapid cooling sequence. This was performed with a flexible surround suit system that provided for a thin 0.5 cm layer of circulating ice water in direct skin contact held between 0.5° and 1.5 °C. A pumping system was used to circulate the water volume of 20 liters at a rate of 15 liters per minute. The average PA temperature at the start was 37 (±0.3) °C. Cooling was targeted at 34 °C with an average value of 34.1 (±0.3) °C. Time to fall 3°C was13.0 (±3.0) min. At the same time, heart rate dropped (although not significantly) from 71 ± 7.9 BPM to 59.5 ± 11.4 BPM while mean carotid pressure dropped from 100.3 ± 16 mmHg to 77.3 ± 14.9 mmHg (p&lt;.05). We interpret these changes as beneficial reductions in cardiac work while the subject is kept cool. It is hypothesized that this is due to a reduction in total body metabolic demands. Thus it is possible, in addition to positive neurological effects, that the process of rapid whole body cooling also may be effective in reducing total workload seen by the heart, and thus may aid in salvaging myocardium in such patients.
Improving interdisciplinary communication in MDT-meetings: Identification of barriers and facilitators in nationwide implementation of standardized structured reporting.
Authors: Julie Elisa Maria Swillens, Rinus Voorham, Iris D. Nagtegaal, Rosella Hermens
Journal: Journal of Clinical Oncology (2019)

321 Background: Standardized structured reporting (SSR) improves quality of diagnostic reporting for cancer patients, resulting in improved interdisciplinary communication in multidisciplinary-team meetings (MTMs) and subsequently better health outcomes and patient safety. In addition, SSR is important to secondary users including (tumor) registry organizations. Nevertheless, SSR-template usage, for example in pathology, varies widely among oncology related medical disciplines. Because of the advantages during MTMs, multidisciplinary-team (MDT) members could play an important role in encouraging and supporting pathologists to use SSR-templates. Therefore, the objective is to identify both barriers and facilitators for SSR-implementation from a MDT-member perspective. Methods: We used a mixed method design. Four focus group interviews with MDT-members, operating in the field of urological, gynecological or gastrointestinal oncology were performed, to identify barriers and facilitators in SSR in relation to the MTMs. Findings were classified into the domains of Flottorp et al. (2013). We used a web-based survey among Dutch MDT-members to quantify the findings. Results: Twenty-three MDT-members of nine medical disciplines participated in the focus group interviews. The survey yielded 211 responses. Main barriers of SSR among MDT-members were lack of information in the standardized structured report, particularly lack of information to retrieve doubts of the pathologist (56%, n = 211); lack of nuances (39%, n = 184); and lack of transparency on development of SSR-templates (50%, n = 211). Pathologists (59%, n = 54) also mentioned the numerous clicking when using SSR-templates as a barrier. Main facilitator was to expand the recommendation of SSR-usage in national guidelines (81%, n = 174). Conclusions: Although the use of SSR by multiple disciplines has benefits, as diagnostic reports are more complete, this study shows important barriers that have to be dealt with in the implementation process of SSR. The next step is to use the barriers for developing and testing implementation tools to encourage SSR-implementation.