tbuckley/cabot-search huggingface dataset:
A retrospective analysis of patients with metastatic germ cell tumor (GCT) treated at Indiana University (IU) from 2000 to 2012.
Authors: Kimberly Ku, Samar Ibrahim, Nabil Adra, Sandra Althouse, Nasser H. Hanna, Lawrence H. Einhorn, Costantine Albany
Journal: Journal of Clinical Oncology (2015)

4539 Background: Metastatic GCT’s have been classified by the International Germ Cell Cancer Collaborative Group (IGCCCG) in 1997 into good, intermediate, and poor risk with 5-year progression free survival (PFS) of 88, 75 and 41%, respectively and 5-year survival rate of 91, 79 and 48%, respectively. Methods: We conducted a retrospective analysis on outcomes of all patients with GCT who were diagnosed and received initial chemotherapy at IU between 2000-2012. We limited our analysis to patients with > 1 year of f/u. 5 years PFS and OS were analyzed using Kaplan Meier methods. Results: 403 patients were evaluable. 240 (58%) good, 46(11%) intermediate and 127 (30%) poor risk. Median time of f/u 5 years. Median age at diagnosis 29. The 5-year PFS of good, intermediate, and poor risk groups were 91, 80 and 52% (P value < 0.01) and 5-year survival rates were 95, 89 and 71%, (P value < 0.01) respectively. Conclusions: There was improvement in OS for men with poor risk metastatic GCT in this contemporary cohort of patients, possibly due to improved salvage chemotherapy compared to patients treated from 1975-1990 reported by the IGCCCG. Good (N = 240) Int (N = 46) Poor (N = 127) Primary Testis Retroperitoneum Mediastinal 235 (97.9%) 4 (1.7%) 0 44 (95.6%) 1 (2.2%) 1 (2.2%) 80 (63.0%) 12 (9.4%) 35 (27.6%) Primary histology Seminoma NSGCT 51 (21.6%) 185 (78.4%) 6 (13%) 37 (86.1%) 0 111 (100%) AFP Pre Chemo Median (range) 7.0 (0.2-871.7) 1912 (1.0-9653) 291.0 (0.9-280000) hCG Pre Chemo Median (range) 6.4 (0.4-4982) 5000 (0.0-41000) 16000 (0.6-1300000) Chemo BEPx3 BEPx4 BEPx3+EPx1 EPx4 VIPx3 VIPx4 Other 183 (79.2%) 3 (1.3%) 12 (5.2%) 14 (6.1%) 0 0 19 (8.2%) 3 (6.5%) 18 (39.1%) 19 (41.3%) 1 (2.2%) 1 (2.2%) 1 (2.2%) 3 (6.5%) 5 (3.9%) 62 (48.8%) 13 (10.2%) 0 3 (2.4%) 35 (27.6%) 9 (7.1%) pcRPLND pathology GCT Teratoma Malignant Transformation of Teratoma Necrosis 4 (1.7%) 44 (18.3%) 4 (1.7%) 27 (11.3%) 2 (4.4%) 9 (19.6%) 0 6 (13.0%) 5 (3.9%) 26 (20.5%) 2 (1.6%) 35 (27.6%) Salvage chemo 23 (10%) 7 (18.0%) 43 (34%)
Inhibitors of kallikrein‐related peptidases: An overview
Authors: Nicolas Masurier, Dominique P. Arama, Chahrazade El Amri, Vincent Lisowski
Journal: Medicinal Research Reviews (2017)

Abstract Kallikrein‐related peptidases (KLKs) are a family of 15 secreted serine proteases that are involved in various physiological processes. Their activities are subtly regulated by various endogenous inhibitors, ranging from metallic ions to macromolecular entities such as proteins. Furthermore, dysregulation of KLK activity has been linked to several pathologies, including cancer and skin and inflammatory diseases, explaining the numerous efforts to develop KLK‐specific pharmacological inhibitors as potential therapeutic agents. In this review, we focus on the huge repertoire of KLKs inhibitors reported to date with a special emphasis on the diversity of their molecular mechanisms of inhibition.
Enticing labelling of vegetables increases consumption, study finds
Authors: Susan Mayor
Journal: BMJ (2017)

Labelling of vegetables using language typically associated with more indulgent foods increases their consumption more than plain labels or those describing health effects, a US study at a large university cafeteria has shown.1

Efforts to reduce obesity have focused on promoting the health benefits of nutritious foods. But this may be counterproductive, previous research has found, because people see foods they perceive to …
The frequency and significance of radiologically detected indeterminate pulmonary nodules in patients with colorectal cancer
Authors: Yelda Varol, Umut Varol, Burçak Karaca, Rüçhan Uslu, Recep Savas
Journal: European Respiratory Journal (2011)

Background:  This study aims to investigate the frequency and significance of indeterminate pulmonary nodules in patients with non-metastatic CRC.   Methods:  We retrospectively evaluated 1344 patients with CRC who underwent thoracic CT scans between the years January 2003-December 2009. Those with evident metastatic disease or already known to have pulmonary malignancies were excluded.   Results:  Among all patients assessed, 55 (0.4%) of them had nodules that met the criteria of indeterminate pulmonary nodule. We analyzed the cases by size and number of nodules. A multivariable analysis demonstrated that indeterminate pulmonary nodules with irregular border (p=0.002), parenchymal localization (p=0.016) and being multiple in number (p=0.006) were predictives of metastatic disease.   Conclusion:  The characteristics of indeterminate pulmonary lesions in CRC cases with no evidence of metastasis elsewhere have to be defined more comprehensively. We believe that for appropriate decision of the frequency for follow -up interval, further studies are required.
Abstract 304: Estrogen Plays a Protective Role in Advanced Heart Failure by Suppressing Cardiac Fibrosis Associated Genes via miR129 Induction
Authors: Salil Sharma, Andrea Iorga, Harnek Singh, Jingyaun Li, Mansoureh Eghbali
Journal: Circulation Research (2013)

We have previously shown that short term treatment of estrogen(E2) can rescue advance heart failure(HF) and decreases associated fibrosis. We hypothesized that E2 can reduce fibrosis by regulating the levels of specific microRNAs including miR129-5p(miR129) through ERβ mediated mechanism. We used transaortic constriction to induce HF in male mice, and once the ejection fraction (EF) reached ~30%, one group of animals was sacrificed (HF), and the other group received 17b-estradiol via a subcutaneous pellet implant (0.012mg/pellet, n=16) (E2) for 10 days. Sham-operated mice served as CTRL. Serial echocardiography was performed to monitor cardiac structure and function. Short-term E2 treatment rescued pressure overload-induced decompensated HF in mice by restoring the EF from 33.17±1.12% to 53.05±1.29 (p &lt;0.001, n=16). E2 decreased both interstitial and perivascular fibrosis in HF. Microarray analysis comparing HF with E2 revealed ~70 microRNAs including miR129 regulated by E2. qPCR validation revealed that E2 treatment upregulates miR129 by 2 folds compared to HF restoring it to CTRL levels. Treatment of HF with ERβ agonist (DPN), but not ERα agonist (PPT) resulted in the upregulation of miR129 indicating the E2 mediated induction of miR129 is mediated through ERβ. In vitro, angiotensin II treatment significantly downregulated miR129 expression in neonatal rat fibroblasts (NRVF) which was restored by E2 and DPN but not by E2+ERβ antagonist (PHPT) further confirming the role of ERβ in regulating miR129. In vitro, OE of miR129 in both neonatal and adult rat cardiac fibroblasts (ARVF) resulted in significant downregulation of transcripts of many in-silico predicted pro-fibrotic target genes including EGFR, RUNX, GREM1, COL2A, PDGFA, PDGFRA and the transcription factor SOX4. OE of miR129 in fibroblasts also resulted in downregulation of EGFR protein. Gain of miR129 prevented the transition of fibroblasts to myofibroblasts in both NRVF and ARVF and inhibited fibroblast proliferation in vitro. In conclusion, E2 treatment during HF induces miR129 likely through ERβ. MiR129 represses fibrosis by targeting key genes associated with cardiac fibrosis, inhibits fibroblast proliferation and fibroblast to myofibroblast transition.
Song for Pollock
Authors: Woods Nash
Journal: JAMA (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 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
Reducing Excessive Use of Antipsychotic Agents in Nursing Homes
Authors: Jerry H. Gurwitz, Alice Bonner, Donald M. Berwick
Journal: JAMA (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 HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Re: Maria Carmen Mir, Ithaar Derweesh, Francesco Porpiglia, Homayoun Zargar, Alexandre Mottrie, Riccardo Autorino. Partial Nephrectomy Versus Radical Nephrectomy for Clinical T1b and T2 Renal Tumors: A Systematic Review and Meta-analysis of Comparative Studies. Eur Urol. 2017;71:606–17
Authors: Lorenzo Marconi, Steven MacLennan, Thomas B.L. Lam, Steven E. Canfield, Yuhong Yuan, Muhammad Imran Omar, James N’Dow, Richard Sylvester
Journal: European Urology (2017)
Abstract 112: An Exercise-induced MicroRNA Pathway That Protects Against Apoptosis and Pathological Cardiac Dysfunction
Authors: Xiaojun Liu, Junjie Xiao, Xin Wei, Colin Platt, Chunyang Xiao, Federico Damilano, Vassilios Bezzerides, Anthony Rosenzweig
Journal: Circulation Research (2015)

Background: Exercise induces physiological cardiac growth and protects against adverse cardiac remodeling. microRNAs (miRNA) are important regulators in cardiovascular pathology and disease. Less is known about miRNA roles in the cardiac effects of exercise, and we investigated their roles in exercise-induced cardiac growth. Methods and Results: Based on cardiac miRNA profiling in two exercise models (swimming, running) and functional screening in neonatal rat cardiomyocytes (NRCMs), miR-222 was selected for further study. miR-222 was upregulated ~2-fold in both exercise models, pathological hypertrophic and failing hearts (p&lt;0.05). We found that ERK, JNK and p38 signal pathways are involved in FBS increasing miR-222 in NRCMs. miR-222 increased NRCM proliferation and size (p&lt;0.01) and reduced NRCM apoptosis induced by serum starvation with or without doxorubicin. Four potential miR-222 targets ( p27 , Hipk1 , Hipk2 , and Hmbox-1 ) were identified and confirmed as direct targets. siRNA knockdown (KD) of p27 or Hipk2 inhibited NRCM apoptosis. To investigate miR-222’s cardiac role in vivo , we made transgenic mice with cardiac-specific, inducible (TgI-miR-222) or constitutive (TgC-miR-222) expression of miR-222. RT-PCR showed that miR-222 is increased ~6-fold in TgI-miR-222 hearts after induction and ~10-fold in TgC-miR-222 hearts. Surprisingly, both transgenic lines have normal heart size and function, and the 4 miR-222 targets are unaffected at baseline. After ischemia-reperfusion injury (IRI), TgI-miR-222 had no difference in initial infarct size or dysfunction but were protected against adverse remodeling over the next six weeks with better function (p&lt;0.01), less cardiac fibrosis (68%, p&lt;0.05), and reduced CM apoptosis (300%, p&lt;0.05). Two weeks after TAC, TgC-miR-222 had less increase in cardiac mass (HW/TL, p&lt;0.05), better cardiac function ([[Unable to Display Character: &amp;#8710;]]32%, p&lt;0.01), reduced expression of markers of fibrosis ( Col1a1 , Col3a1 , Mmp2, p&lt;0.05 ) and apoptosis ( Caspase 1, 3, 8, p&lt;0.05). Four months after TAC, TgC-miR-222 had improved survival (p&lt;0.05) compared to wide type controls. Conclusion: Cardiac miR-222 is upregulated by exercise and protects against adverse remodeling and cardiac dysfunction after IRI or TAC.
A 3D image-based phenotypic screen of bi-specific antibodies targeting stem cells in a panel of patient derived colon carcinoma organoids.
Authors: Leo Price, Bram Herpers, Rob Roovers, Berina Eppink, Marc van de Wetering, Kuan Yan, Lucia Salinaro, Wim de Lau, Robert Vries, Mark Throsby
Journal: Journal of Clinical Oncology (2016)

e23174 Background: Organoid cultures grown in 3D increase the likelihood for accurately predicting drug responses in patients, discriminating different drug responses and flagging toxicity. We used a high content screening platform and a panel of 40 patient derived colorectal cancer (CRC) organoids to characterize the responses to a large panel of (545) bispecific antibodies. These antibodies comprised a HER3 or EGFR targeting arm combined with a LGR4, LGR5, ZNRF3 or RNF43 targeting arm to target CRC stem cells. Methods: Automated 3D imaging and analysis of CRC organoids was performed. Results: The broad mutational spectrum of the organoids was reflected in a broad heterogeneity of organoid phenotypes. Some CRC organoids formed well-differentiated spheroids with a single lumen that resembled wild type organoids, whereas others had multiple lumens or were poorly differentiated without a luminal cavity. A rich set of morphological features was extracted from 3D image data, including organoid size and shape, planar cell polarity, lumen formation as well as cell number and nucleus shape. Some features, such as those that described lumen formation, were more sensitive in detecting drug treatment than features associated with cell proliferation, improving the sensitivity of the assay to detect active molecules. A set of 10 features was selected to create a drug response profile. The bispecific antibody screen was performed in two stages: a primary screen in three different tumoroid models (18,908 wells) and a validation screen in 25 different tumoroid models (23,040 wells). These screens simultaneously measured morphological alterations associated with growth, differentiation and survival (e.g. apoptosis) and identified a panel of bispecific antibodies that potently inhibited the growth of a significant majority of colorectal cancer tumoroid models tested. Conclusions: These results demonstrate that high content screening of CRC organoids is an effective strategy to identify novel inhibitors of CRC tumor outgrowth and enable identification of bispecific antibodies that target colorectal cancer stem cells with different mutational backgrounds.
Short- and long-term outcomes in simultaneous resection of colorectal cancer and liver metastasis with minimally invasive or open surgery.
Authors: Jianmin Xu, Qi Lin, Dexiang Zhu, Qinghai Ye
Journal: Journal of Clinical Oncology (2014)

e14647 Background: Minimally invasive colorectomy and hepatectomy became a realizable option for patients with colorectal and liver cancer, respectively. However, the role of minimally invasive resection for patients undergoing a simultaneous operation for synchronous colorectal liver metastases (SCRLMs) had not been established. This study compared the short- and long-term outcomes between minimally invasive and open resections for patients undergoing simultaneous surgery for SCRLMs by matched-pair analysis. Methods: We reviewed 36 consecutive SCRLM patients who underwent minimally invasive simultaneous resection of colorectal cancer and liver metastases, and another 36 matched with clinicopathologic variables at the same period. Clinicopathologic data and survival outcome were recorded in CRLM database. Results: The two groups had similar clinicopathologic variables. In the minimally invasive group, the estimated blood loss, bowel function return time and postoperative hospital stays was significantly less than in the open group, although the operating time was significantly longer. The two groups did not differ significantly in terms of overall and disease-free survival. Conclusions: Minimally invasive simultaneous resection of SCRLMs is a safe and feasible option for selected patients.
Surveillance after Colorectal Polyps
Authors: RM Mc Loughlin, A Boylan, SS Shaji, P Crotty, HC O'Connor, M Buckley, M O'Morain
Journal: Endoscopy (2004)

Introduction: Both the American Gastroenterology Association and the British Society of Gastroenterology have issued guidelines that increase the interval between surveillance colonoscopies after the discovery of a polyp. If implemented this would greatly reduce the burden in endoscopy units. Our aim was through a retrospective audit of our polyps determine how often scopes were repeated, and could this be reduced safely.
Rifabutin-Based Eradication Therapy after Failure of Standard First- and Second-Line Eradication Therapies in Helicobacter Pylori Infected Patients
Authors: A Qasim, S Sebastian, R McLoughlin, M Umar, M Buckley, H O'Connor, C O'Morain
Journal: Endoscopy (2004)

Background and aims: Various 'rescue' treatments are used in Helicobacter pylori (H pylori) infected patients who fail standard and secondary eradication therapies. We evaluated the efficacy and safety of rifabutin-based eradication therapy in H pylori infected patients with two or more failed eradication attempts.
Abstract 237: Sex-specific Regulation Of Collagen I And III Expression By 17β-estradiol In Rat Cardiac Fibroblasts: Role Of Estrogen Receptors
Authors: Elke Dworatzek, Shokoufeh Mahmoodzadeh, Sandra Kunze, Vera Regitz-Zagrosek
Journal: Circulation Research (2013)

Clinical and animal studies showed in female pressure-overloaded hearts less cardiac fibrosis and collagen I and III gene expression compared to males, suggesting an inhibitory effect of 17β-Estradiol (E2) on collagens. Therefore we investigated the role of E2 and estrogen receptors (ER) on collagen I and III expression in isolated rat cardiac fibroblasts from both sexes. Cardiac fibroblasts were isolated from adult male and female Wistar rats, and treated with E2 (10-8M), vehicle, ERα and ERβ-agonist (10-7M) and/or pre-treated with ICI 182,780 (10-5M) for 24h. Cellular localization of ER in cardiac fibroblasts with/without E2 was detected by immunofluorescence staining, and expression of both ER was determined by western blot. Expression of collagen I and III was determined by qRT-PCR and western blot. E2-treatment led to a nuclear translocation of ERα and ERβ in cardiac fibroblasts, suggesting the functional activity of ER as transcription factors. Furthermore in cardiac fibroblasts from female rats E2 led to a significant down-regulation of collagen I and III gene and protein expression. In contrast there was a significant increase of collagen I and III levels in fibroblasts isolated from male rat hearts by E2. E2-effect could be inhibited by ICI 182, 780 indicating the involvement of ER. In cardiac fibroblasts from female rats, ERα-agonist treatment led to a significant down-regulation of collagen I and III mRNA level, but ERβ-agonist had no effects. In contrast, ERβ-agonist treatment of cardiac fibroblasts from males increased collagen I and III mRNA, but no changes with ERα agonist-treatment were detected. ERα protein levels displayed no sex differences at basal level. After E2-treatment ERα protein was up-regulated in male cells, but decreased in cardiac fibroblasts from females. ERβ protein was higher in female cells compared to males, but the expression was not regulated by E2 in both sexes. Sex-specific regulation of collagen I and III expression by E2 in cardiac fibroblasts might be responsible for sex-differences in cardiac fibrosis. This might be due to sexually dimorphic ER expression and regulation. Understanding how E2 and ER mediate sex-differences in cardiac remodeling may help to design sex-specific pharmacological interventions.
Abstract 244: Regenerative Metabolome and Energetic Signaling Mechanisms Governing Heart Renewal Capacity
Authors: Song Zhang, Emirhan Nemutlu, Andre Terzic, Petras Dzeja
Journal: Circulation Research (2012)

The mammalian heart loses its regenerative potential within a week after birth. Although under certain circumstances adult cardiomyocytes can re-enter the cell cycle, initiate DNA synthesis and progress towards mitosis, however, they do not complete a conventional mitosis cycle and proceed towards endomitosis resulting in polyploidy. This suggests that high-energy dependent steps in cell cycle and myofibrillar disassembly are malfunctioning in adult cardiomyocytes. It is known that nucleotide-based energetic signaling and metabolic environment are critical for initiation of tissue regeneration after injury. The regulatory mechanisms and energetic-metabolic signaling circuits that govern cardiomyocyte cell cycle withdrawal and binucleation are poorly understood. Using mouse neonatal (2 and 10 days) hearts, with high and low regenerative capacity, respectively, we have determined metabolomic profiles and dynamics of phosphotransfer circuits and AMP-signaling using 18O-phosphoryl labeling mass-spectrometric and 18O-assisted 31P NMR techniques. The results demonstrate that loss of heart regenerative capacity 10 days after birth is associated with marked changes in heart metabolome and adenylate kinase (AK)-catalyzed phosphotransfer flux. Among most altered metabolites were putrescine and myo-inositol, involved in tissue regeneration, Krebs cycle and amino acid metabolites, creatinine, glucose-6-phosphate and lactate indicating rearrangements in energy and substrate metabolic systems. AK flux was the only phosphotransfer flux significantly upregulated in hearts at 10 days of age along with increased in mitochondrial and glycolytic capacities and mitochondrial AK2 expression. Increased AK2 expression was associated with augmented AMP phosphorylation, measured by generation of β-ATP[18O], and reduction of AMPK activity. Thus, increased channeling of AMP into mitochondria and reduction of AK-AMP-AMPK signaling axis could contribute to the withdrawal from completion of cell cycle in terminally differentiated adult cardiomyocytes. The uncovered metabolic signaling mechanism opens new avenues for targeted regulation of heart regenerative potential critical for repair of injured hearts.
Bullying in NHS must be “called out,” says head of NHS Improvement
Authors: Tom Moberly
Journal: BMJ (2017)

Bullying and inappropriate behaviour in the NHS need to be “called out” as soon as it happens, Jim Mackey, chief executive of NHS Improvement, has said.

Speaking at the NHS Confederation’s annual conference in Liverpool on 14 June, Mackey said that the problem of bullying and other such inappropriate behaviour needed to be discussed more openly. “If anyone’s in any doubt, these things are unacceptable,” he said. “If we’re doing things in a style that we shouldn’t be, we …