tbuckley/cabot-search huggingface dataset:
SiRNA targeting hepatoma-derived growth factor (HDGF) inhibits growth of non-small cell lung cancer in xenograft models.
Authors: Jun Zhang, Li Mao
Journal: Cancer Research (2006)

5135  We recently found that down-regulation of HDGF inhibits anchorage-independent growth and in vitro invasion in non-small cell lung cancer cells A549, H226, H358 and H1944. To determine the role of HDGF in in vivo tumor growth, we performed two types animal experiments using subcutaneous nude mouse models. First, A549 cells either transfected with siRNA-HDGF, scramble siRNA, or lipofectamine alone were inoculated subcutaneously into nude mice (5 mice each group). Tumor sizes were measured every 2 days. After 3 weeks, mice were sacrificed due to the large tumor burden in the control mice. We observed a significantly slower tumor growth in mice inoculated with siRNA-HDGF treated cells compared with mice inoculated with cells treated with scramble siRNA or lipofectamine alone (P = 0.03, P = 0.018, respectively). We then investigated whether siRNA-HDGF has a therapeutic potential for treating lung cancer. We inoculated A549 cells subcutaneously into nude mice and allowed tumors to form at about 100 mm3 in volume. Mice were randomized (5 mice each group) and were treated with either siRNA-HDGF (conjugated with polyethylenimine, PEI), scramble siRNA (with PEI), or PEI alone once every 3 days intra-peritonea (IP) for 5 times. A significant inhibition of tumor growth was observed between the siRNA-HDGF group and the PEI alone group (P = 0.033). No difference was found between the scramble siRNA group and the PEI alone group (P = 0.875). The animals treated with siRNAs did not show any sign of toxicity during the experimentation. Our data suggest that HDGF is important in lung cancer progression and may be a novel therapeutic target. (Supported by Department of Defense grants DAMD17-01-1-01689-1 and W81XWH-04-1-0142)
Abstract 098: Blocking Cardiac Gq-Receptor Coupling Prevents Adverse Remodeling and Preserves Myocardial Function after Ischemic Injury in Mice and Promotes Repair via Cardiac Regeneration
Authors: Erhe Gao, Lin Zuo, Xiying Shang, Matthieu Boucher, Yonghong Lei, Meggie Z. Huang, Kurt J Chuprun, Walter J Koch
Journal: Circulation Research (2013)

Background: Studies have shown that the heterotrimeric G protein, Gq, is a critical molecule in the development of myocardial hypertrophy and heart failure (HF). In the present study, we examined whether Gq signaling is also a critical pathological trigger for adverse remodeling and HF after ischemic injury. Using cardiac-specific transgenic mice with expression of a specific Gq inhibitory peptide (GqI) that blocks Gq-GPCR coupling allowed us to investigate whether Gq inhibition can alter cardiac structure and functional changes after myocardial infarction (MI). Methods and Results: Cardiac-specific GqI transgenic (TG) and non-transgenic littermate control (NLC) mice were subjected to MI. Serial echocardiography performed before ischemia as well as 2, 4, 8 weeks after MI injury show that TG mice develop less progressive LV enlargement and dysfunction. The % LV EF and FS were significantly improved in the TG compared to NLC mice at 8 weeks post-MI. Consistently, cardiac contractility (+dP/dt) and relaxation (-dP/dt) were significantly improved in TG mice also when stimulated with isoproterenol. The LVEDP, the heart weight to body weight (BW) and lung to BW ratios were significantly less in TG mice, indicating that HF was limited with GqI expression. Moreover, TG mice have smaller infarcts, less LV dimensions and lower fibrosis in both the border zone and remote area with clearly more viable tissue in the scar region. Constantly, there are more micro-vessel and more BrdU(+) cardiomyocytes in the scar area and border zone at the 2 week post-MI in TG group. Western blot shows a consistent decrease in phosphorylated PKC substrates and higher levels of activated Akt in TG mice. Over expression of the GqI in cultured H9c2 myoblasts did lead to higher level of Ki67 positive cells (38.06±2.46%) than a control group (21.78±2.64%) and FACS analysis showed that Gq inhibition increased the % of H9c2 cells in S phase and G2/M phase compared to control cells. Conclusion: These data indicate cardiac specific Gq inhibition protects the heart against adverse LV remodeling and HF progression after MI. Mechanisms attributed to GqI expression appear to include improved myocyte survival, less fibrosis, and promotion of angiogenesis and cardiac repair through regeneration.
Two-stage endoscopic mucosal resection is a safe and effective salvage therapy after a failed single-session approach
Authors: David Tate, Lobke Desomer, Luke Hourigan, Alan Moss, Rajvinder Singh, Michael Bourke
Journal: Endoscopy (2017)

Abstract Background and study aims Endoscopic mucosal resection (EMR) of laterally spreading colonic lesions ≥ 20 mm (LSLs) is ideally performed in a single session (ssEMR) and avoids surgery in &gt; 90 % of patients. We investigated whether a second attempt is safe or useful when ssEMR fails at a tertiary center. Patients and methods In a multicenter prospective observational study of patients with LSL treated by EMR at four tertiary centers over 8 years, incompletely resected LSLs were referred for surgery or underwent two-stage EMR (tsEMR). At tsEMR, the scar was located and all visible residual tissue removed by snare, with thermal treatment permitted thereafter. Scheduled surveillance was performed at 5 months (SC1) and 18 months (SC2). The primary outcome was avoidance of surgery. Results A total of 1944 LSLs (median size 35 mm) underwent EMR. ssEMR was unsuccessful in 127 lesions, 43 of which underwent tsEMR, with success in 36 (83.7 %). Compared with ssEMR, tsEMR lesions were larger (median size 50 mm vs. 30 mm; P &lt; 0.001), exhibited more submucosal fibrosis (P &lt; 0.001), and histology was more often tubular adenoma and less often serrated (P = 0.005). Lesions mainly required tsEMR for nonlifting (41.9 %) or poor endoscopic access (37.2 %). Failure of tsEMR was predicted by larger LSL (P = 0.03). Safety was comparable to ssEMR. Of the 33 LSLs that underwent tsEMR for benign disease and completed first surveillance, 27 (81.8 %) avoided surgery to long term follow-up. Conclusions tsEMR shows promise as a salvage therapy for LSLs that cannot be resected in a single session for patients in whom other options such as surgery are not preferred or not possible. Trial registered at ClinicalTrials.gov (NCT01368289).
Acute Platelet Inhibition With Abciximab Does Not Reduce In-Stent Restenosis (ERASER Study)
Journal: Circulation (1999)

Background —Although stents reduce restenosis compared with balloon angioplasty, their long-term efficacy is limited by neointimal hyperplasia. Platelet and α v β 3 integrin receptor inhibition limits neointimal proliferation in animal models of arterial injury. Methods and Results —We tested whether the dual β 3 integrin blocking agent abciximab, administered for 12 or 24 hours at the same intravenous dose as that shown to reduce adverse clinical events (death, infarction, and revascularization) after angioplasty, would reduce restenotic tissue volume, as measured by intravascular ultrasound at 6 months. Two hundred twenty-five patients were randomly allocated to placebo or abciximab before coronary intervention. Of the 215 patients who received stents and study drug, 191 (88.8%) returned for late (≥4 months) coronary evaluation. Tissue volume, expressed as a percentage of stent volume, did not differ: 25±15%, 27±15%, and 29±14% for the patients in the placebo and the 12- and 24-hour abciximab groups, respectively. Lack of abciximab benefit was confirmed by quantitative coronary angiography (dichotomous restenosis: 11.6%, 18.9%, and 19.4%; loss index: 0.33, 0.52, and 0.47, respectively, P =NS). Conclusions —Potent platelet inhibition with abciximab, as administered in this study, does not reduce in-stent restenosis. The interrelationship between stents, platelets, and neointimal proliferation requires further study.
Letter by Naranjo et al Regarding Article, “Hemodynamic Support With a Micro-Axial Percutaneous Left Ventricular Assist Device (Impella) Protects Against Acute Kidney Injury in Patients Undergoing High-Risk Percutaneous Coronary Intervention”
Authors: Mario Naranjo, Janani Rangaswami, Christian Witzke
Journal: Circulation Research (2017)
Cranberry Capsules for Bacteriuria Plus Pyuria in Nursing Home Residents
Authors: Kerry L. LaPlante, Christian M. Gill, David Rowley
Journal: JAMA (2017)

To the Editor Dr Juthani-Mehta and colleagues1 evaluated the effects of cranberry proanthocyanidin (PAC) capsules (72 mg) vs placebo on bacteriuria plus pyuria in women residing in long-term care facilities.
Outcome of neurofibromatosis type 1 patients treated with first line vinblastine for optic pathway gliomas: A Canadian multicenter study.
Authors: Alvaro Lassaletta, Katrin Scheinemann, Shayna M. Zelcer, Juliette Hukin, Beverley Wilson, Nada Jabado, Anne Sophie Carret, Lucie Lafay Cousin, Valerie Larouche, Cynthia Hawkins, Gregory Russell Pond, Ken Poskitt, Ella Barlev, Daniel Keene, Donna Johnston, Ute Katharina Bartels, Uri Tabori, Eric Bouffet
Journal: Journal of Clinical Oncology (2015)

2019 Background: To date, the first line chemotherapy treatment in the majority of countries for children with NF-1 and OPG is vincristine + carboplatin. Toxicity of this regimen consists mostly in neuropathy, allergic reactions, and hearing loss. Vinblastine has shown promising activity in a phase II study in children with recurrent/refractory low grade glioma (LGG). The aim of this study was to assess the activity of vinblastine in chemotherapy naïve children, and to assess the toxicity profile. Methods: Patients < 18 years old with unresectable or progressive LGG were eligible if they had not received any previous treatment with chemotherapy or radiation. Vinblastine was administered weekly at a dose of 6 mg/m2 over a period of 70 weeks. Patients who showed progression on 2 consecutive imaging studies or evidence of clinical progression were removed from treatment. Results: Overall, the study enrolled 54 patients with LGG. A total of 13 patients (24.1%) had NF-1. Patients with NF-1were younger at diagnosis: median age 3.84 y (range, 1.74-16.36 y) vs. 7 years in non-NF-1. Tumor location in all NF-1 patients was the optic pathway. Treatment was very well tolerated, however, 5 patients (38%) needed dose reductions. Most common toxicity was hematological: only 1 patient who experienced grade 3+ neutropenia (vs. 10 patients non-NF1). There were only 2 episodes of febrile neutropenia, no RBC transfusions and no toxic death. Best response to chemotherapy was assessed centrally by an independent radiologist: 2 PR, 1 MR, 8 SD, and 2 PD, for a response rate of 23.1%. At a median follow-up of 5.37 years (3.45 – 6.57 years): Only two NF-1patients had progression. Five year progression free survival (PFS) was 85.1± 9.7% (vs. 42±7,9% for all non-NF1, p = 0.01; and 41.7±14% for non-NF1 with OPG, p = 0.01). None of the NF1 patients received radiation (0 vs. 6 patients non-NF1). No patients died of progression (0 vs. 3 patients non-NF1). Conclusions: Weekly vinblastine is well tolerated and can be used in NF-1 children with OPG as first line chemotherapy with good results. The toxicity profile is lower than with other chemotherapies, offering a better quality of life to these patients. Clinical trial information: NCT00575796.
Association between Tumor Regression Rate and Gene Expression Profile after Iodine 125 Plaque Radiotherapy for Uveal Melanoma
Authors: Prithvi Mruthyunjaya, Michael I. Seider, Sandra Stinnett, Amy Schefler, Prithvi Mruthyunjaya, Michael Seider, Nikolas N. Raufi, Duncan Berry, Sandra Stinnett, J. William Harbour, Jesse Berry, Jonathan Kim, Alison Skalet, Audra Miller, Miguel A. Materin, Tiffany Liu, Hakan Demirci, Zeynep G. Ozkurt, Peter Hovland, Thomas Aaberg, Amy Schefler, Ryan S. Kim, Anne Tann
Journal: Ophthalmology (2017)
Ivan Reginald Clout
Authors: Catherine Clout
Journal: BMJ (2017)

Ivan Reginald Clout initially studied chemistry at Cambridge, but with the outbreak of the second world war he applied for and received a scholarship to study medicine, moving to the Westminster Hospital for his clinical years. After qualifying, he joined the navy and saw active service. After the war, he participated in the physiology experiments into free breathing escape from submarines at HMS Dolphin .

On leaving the navy, Ivan set up a general practice in Crawley New Town. Initially a communist and later a …
Age-related clinical and biological features of PTEN abnormalities in T-cell acute lymphoblastic leukaemia
Authors: M Tesio, A Trinquand, P Ballerini, G Hypolite, L Lhermitte, A Petit, N Ifrah, A Baruchel, H Dombret, E Macintyre, V Asnafi
Journal: Leukemia (2017)
MUC1 inhibition leads to decrease in PD-L1 levels via upregulation of miRNAs
Authors: A R Pyzer, D Stroopinsky, J Rosenblatt, E Anastasiadou, H Rajabi, A Washington, A Tagde, J-H Chu, M Coll, A L Jiao, L T Tsai, D E Tenen, L Cole, K Palmer, A Ephraim, R K Leaf, M Nahas, A Apel, M Bar-Natan, S Jain, M McMasters, L Mendez, J Arnason, B A Raby, F Slack, D Kufe, D Avigan
Journal: Leukemia (2017)
Phosphodiesterase inhibitors such as Viagra do not increase melanoma risk, review finds
Authors: Susan Mayor
Journal: BMJ (2017)

Phosphodiesterase inhibitors such as sildenafil (Viagra) are not associated with increased risk of melanoma in men who take them to treat erectile dysfunction, a meta-analysis has found.1

The US Food and Drug Administration put phosphodiesterase inhibitors on a watch list of drugs with possible safety issues in 2016, after several studies and databases had suggested a link between sildenafil use …
Cardiovascular Outcomes and Antihypertensive Drug Treatment in Older Women
Authors: Michael Bursztyn
Journal: JAMA (2005)

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Understanding gesture in sign and speech: Perspectives from theory of mind, bilingualism, and acting
Authors: Usha Lakshmanan, Zachary Pilot
Journal: Behavioral and Brain Sciences (2017)

Abstract In their article, Goldin-Meadow &amp; Brentari (G-M&amp;B) assert that researchers must differentiate between sign/speech and gesture. We propose that this distinction may be useful if situated within a two-systems approach to theory of mind (ToM) and discuss how drawing upon perspectives from bilingualism and acting can help us understand the role of gesture in spoken/sign language.
What Have We Learned About Movement Disorders from Functional Neurosurgery?
Authors: Andres M. Lozano, William D. Hutchison, Suneil K. Kalia
Journal: Annual Review of Neuroscience (2017)

Modern functional neurosurgery for movement disorders such as Parkinson's disease, tremor, and dystonia involves the placement of focal lesions or the application of deep brain stimulation (DBS) within circuits that modulate motor function. Precise targeting of these motor structures can be further refined by the use of electrophysiological approaches. In particular, microelectrode recordings enable the delineation of neuroanatomic structures. In the course of these operations, there is an opportunity not only to map basal ganglia structures but also to gain insights into how disturbances in neural activity produce movement disorders. In this review, we aim to highlight what the field has uncovered thus far about movement disorders through DBS. The work to date lays the foundation for future studies that will shed further light on dysfunctional circuits mediating diseases of the nervous system and how we might modulate these circuits therapeutically.
Abstract 050: Mutational Spectrum in a Cohort of Chinese Sporadic Dilated Cardiomyopathy by Next-generation Sequencing
Authors: Lei Xu, Aijun Sun, Yunzeng Zou, Kai Hu, Zheng Fan, Junbo Ge
Journal: Circulation Research (2013)

Rationale: Dilated cardiomyopathy (DCM) is a leading cause of heart failure and have a genetic basis in 20-30% of cases. Genetic studies in familial DCM have found mutations identified in more than 30 genes. However, the genetics of sporadic DCM is still unknown. Objective: To provide new insights into the pathophysiology of sporadic DCM, a mutational screening on 30 DCM-causing genes in a cohort was performed. Methods and Results: Patients diagnosed with idiopathic DCM were recruited into the study and underwent clinical evaluation. Genomic DNA was isolated from the peripheral blood and then 30 genes ( ACTC, DES, SGCD, MYH7, TNNT2, TPM1, TTN, VCL, MYBPC3, CSRP3, ACTN2, PLN, LDB3, MYH6, ABCC9, TNNC1, TCAP, TNNI3, EYA4, TMPO, PSEN1/2, CRYAB, PDLIM3, MYPN, LAMA4, ILK, ANKRD1, RBM20, LMNA , and SCN5A ) of every sample were detected by next-generation sequencing. All called variants were compared against National Center for Biotechnology Information SNP Database build 137 and the March 2012 release of the 1000 Genomes project. All variants identified in the cohort were compared in ethnic-matched controls consisting of 197 adult Chinese from the 1000 Genomes. The pathogenicity of the variants absent from controls were evaluated by SIFT software. Sixty-six adult Chinese unrelated DCM patients were tested for up to 30 genes causing familial DCM. The mean age was 49.14±15.97 years. Every patient was detected nonsynonymous variants, and the total 87 variants were composed of 39 novel and 48 known. Among the whole 87 variants, 34 satisfied the criteria (1) absent from ethnic-matched controls and (2) altering evolutionary conservation of amino acid verified by SIFT analysis, which were considered pathogenic mutations, identified in 30 patients accounting for 45.45% of the cohort. The 2 most frequent genes involved in mutation positive patients were SCN5A (12.12%) and MYH7 (10.61%). Conclusions: Mutant genes found in familial DCM were also common in sporadic DCM, and the discovery of novel mutations spanned the spectrum of DCM genetics, implicating that genetic etiologies play an important role in pathogenesis of sporadic DCM.
As others see us: views from abroad: Justice and health care in a caring society
Authors: G. Gillett
Journal: BMJ (1998)

The NHS was founded on the idea that every person, regardless of wealth or position, would have access to excellent health care. The ethical position expressed in this idea is the kind of commitment that one finds in a society that accepts a role in caring for its citizens. This ethical intuition we could call the “caring imperative,” recognising that it is the hallmark of a civilised society. When we look at the underpinning of such a commitment in political philosophy it is found to rest on a judicious balance of liberal concern for individual autonomy and property and a Marxist concern for social justice.

Such a liberal position on welfare accepts the liberal economic principle—respect for personal choice and the right to disposal of income according to individual preference—but also accepts that the individual owes some dues to the community as a whole. One might justify this attitude by appealing to the fact that a society is given its character by the participation of all those who share in creating it, however small their contribution may be. In fact, most of us want to live in a society where the caring imperative operates and the good health of the citizens is thought to contribute to the wellbeing of all. Health care, from this view, is a public good in that its benefits are shared rather than exclusively individual or private (although they also directly benefit the individual). Without a national health service the burden of illness falls on those who suffer the unpredictable vicissitudes of life, and the implicit laissez-faire attitude to the resultant suffering both represents a deterioration in the overall quality of society and exposes individuals to the risk of being caught out by the cruel chances of disease and injury.

#### Summary points

The ideal of access for all …
Recognition and knowledge of on-field management of concussion amongst english professional, semi-professional and amateur rugby union referees
Authors: Tom Gallagher, Ed Mias, Courtney Kipps
Journal: British Journal of Sports Medicine (2017)

Objective to investigate the knowledge and practice of Rugby Union referees regarding the recognition and management of concussion in English professional and semi-professional rugby. Design email survey questionnaire. Setting English Rugby Union Premiership, Championship and National Leagues. Participants All 180 actively practicing referees in England in the Premiership, Championship and National Leagues. Outcome measures Actual and perceived knowledge of concussion, and subjective confidence in diagnosing concussion. Main results 22 referees with an average age 34.77 years (Range 26-49 SD 6.13) and returned surveys. The referees’ level of officiating ranged from Premiership (Level 1) to regional games (Level 8) with the highest proportion of referees officiating at Level 1 (31.80%). A high percentage of referees recognised functional disturbances including loss of balance (90%), slurred speech (73%), dizziness (95%) and blurred vision (100%) as signs of concussion. 59.09% rated their knowledge of concussion as average and 18.18%% good or excellent. Overall, 72% of referees felt they could subjectively diagnose concussion, the professional referees were more confident in diagnosing a concussion versus the amateur referees. Conclusions Referees generally have a good knowledge of concussion and its management although 54.54% have had no previous education. The majority wanted to learn more on the subject (90.90%) but the methods which they are currently using to learn are varied and not standardised. Practical group sessions (59.09%) and online resources (45.45%) were recognised as the most popular method of learning. Further education regarding recognition and on-field management of concussion is recommended for rugby union referees. Future studies should focus on participant information retention after using such resources as HeadCase. Competing interests None.
Comment on “Epigenetic activation of the drug transporter OCT2 sensitizes renal cell carcinoma to oxaliplatin”
Authors: Stefan Winter, Pascale Fisel, Florian Büttner, Anne T. Nies, Arnulf Stenzl, Jens Bedke, Matthias Schwab, Elke Schaeffeler
Journal: Science Translational Medicine (2017)

Although the combination of decitabine and platinum drugs may be promising for therapy of renal cell carcinoma, the role of OCT2 needs further investigations.