tbuckley/cabot-search huggingface dataset:
The candidate guidance molecule, Semaphorin 5B, is over-expressed in kidney cancers
Authors: William Mallet, Youjun Chen, Gretchen Frantz, Hartmut Koeppen, Leon Parker, Weilan Ye, Paul Polakis
Journal: Cancer Research (2005)

1523  Semaphorins are a family of secreted and transmembrane proteins with roles in axonal guidance, vasculogenesis, and cellular immunity. Recently, members of this family have been implicated in human cancers. Expression of the transmembrane semaphorin, Sema5B, is elevated in various kidney cancers, including clear cell carcinoma and renal adenocarcinoma; expression is low in all normal adult tissues examined. The predicted extracellular domain of Sema5B comprises sema and PSI domains and a series of juxtamembrane thrombospondin type I repeats. We have found that the expression of Sema5B is regulated by oxygen tension and is enhanced by loss of function of pVHL (the von Hippel Lindau protein), a common feature of renal cancers. Additionally, the expression of Sema5B in renal cell carcinomas correlates strongly with the expression of vascular endothelial growth factor (VEGF), a protein known to be up-regulated by hypoxia and a key mediator of angiogenesis in malignancy. The mouse putative ortholog, SemaG, is expressed through embryonic day 12 in a broad mesodermal and ectodermal pattern, consistent with a role in vasculogenesis during development; expression in the brain is also observed, as previously reported. Together, these data suggest an angiogenic and/or migratory function of Sema5B in renal cancer.
A Novel Small Molecule STAT Inhibitor, BP-4-018, Demonstrates Significant Anti-Tumour Activity and Synergism With Bortezomib In Pre-Clinical In Vivo Models Of Multiple Myeloma
Authors: Danielle C Croucher, Zhihua Li, Brent D.G. Page, Ellen Nong Wei, Patrick T. Gunning, Suzanne Trudel
Journal: Blood (2013)
Dietary Factors Reduce Risk of Acute Pancreatitis in a Large Multiethnic Cohort
Authors: Veronica Wendy Setiawan, Stephen J. Pandol, Jacqueline Porcel, Pengxiao C. Wei, Lynne R. Wilkens, Loïc Le Marchand, Malcolm C. Pike, Kristine R. Monroe
Journal: Clinical Gastroenterology and Hepatology (2016)
Phase III trial comparing 3–6 months of adjuvant FOLFOX4/XELOX in stage II–III colon cancer: safety and compliance in the TOSCA trial
Authors: S. Lonardi, A. Sobrero, G. Rosati, M. Di Bartolomeo, M. Ronzoni, G. Aprile, M. Scartozzi, M. Banzi, M.G. Zampino, F. Pasini, P. Marchetti, M. Cantore, A. Zaniboni, L. Rimassa, L. Ciuffreda, D. Ferrari, S. Barni, V. Zagonel, E. Maiello, E. Rulli, R. Labianca, D. Bilancia, G. Rosati, V. Montesarchio, R.V. Iaffaioli, G. Nasti, B. Daniele, V. Zagonel, S. Lonardi, N. Pella, G. Aprile, F. Pasini, P. Marchetti, A. Romiti, L. Ciuffreda, D. Ferrari, P. Foa, A. Zaniboni, R. Labianca, S. Mosconi, A. Sobrero, P. Bidoli, M. Cazzaniga, G.D. Beretta, D.C. Corsi, E. Cortesi, S. Barni, F. Petrelli, M. Cantore, E. Maiello, S. Cinieri, M. Banzi, A. Santoro, F. Artioli, R. Mattioli, D. Amoroso, D. Amadori, L. Frassineti, D. Turci, A. Ravaioli, E. Bajetta, M. Di Bartolomeo, L. Gianni, M. Ronzoni, M.T. Ionta, B. Massidda, M. Scartozzi, M.G. Zampino, A. Bochicchio, A. Ciarlo, A. Di Leo, S. De Placido, C. Carlomagno, V. Adamo, D. Natale, E. Rulli, F. Galli, D. Poli, V. Torri
Journal: Annals of Oncology (2016)
Baseline Metabolic Tumor Volume Predicts Outcome in High–Tumor-Burden Follicular Lymphoma: A Pooled Analysis of Three Multicenter Studies
Authors: Michel Meignan, Anne Ségolène Cottereau, Annibale Versari, Loïc Chartier, Jehan Dupuis, Sami Boussetta, Ilaria Grassi, René-Olivier Casasnovas, Corinne Haioun, Hervé Tilly, Vittoria Tarantino, Julien Dubreuil, Massimo Federico, Gilles Salles, Stefano Luminari, Judith Trotman
Journal: Journal of Clinical Oncology (2016)

Identifying patients at high risk of progression and early death among those with high-tumor-burden follicular lymphoma (FL) is unsatisfactory with current prognostic models. This study aimed to determine the prognostic impact of the total metabolic tumor volume (TMTV) measured at baseline with [18F]fluorodeoxyglucose/positron emission tomography-computed tomography ([18F]FDG/PET-CT) scans and its added value to these models.A pooled analysis was performed by using patient data and centrally reviewed baseline PET-CT scans for 185 patients with FL who were receiving immunochemotherapy within three prospective trials. TMTV was computed by using the 41% maximum standardized uptake value thresholding method, and the optimal cutoff for survival prediction was determined.Median age was 55 years, 92% of patients had stage III to IV disease, 37% had a Follicular Lymphoma International Prognostic Index (FLIPI) score of 3 to 5, and 31% had a FLIPI2 score of 3 to 5. With a median follow-up of 64 months, overall 5-year progression-free survival (PFS) was 55% and overall survival (OS) was 92%. Median TMTV was 297 cm3 (quartile 1 through quartile 3, 135 to 567 cm3). The optimal cutoff identified was 510 cm3, with a markedly inferior survival in the 29% of patients with TMTV > 510 cm3. Five-year PFS was 33% versus 65% (hazard ratio [HR], 2.90; P < .001), and 5-year OS was 85% versus 95% (HR, 3.45; P = .010). On multivariable analysis, TMTV (HR, 2.3; P = .002) and FLIPI2 score (HR, 2.2; P = .002) were independent predictors of PFS. In combination, they identify three risk groups: high TMTV and intermediate-to-high FLIPI2 score with 5-year PFS of 20% (HR, 5.0; P < .001), high TMTV or intermediate-to-high FLIPI2 score with 5-year PFS of 46% (HR, 2.1; P = .007), and low TMTV and low FLIP2 with 5-year PFS of 69%.Baseline TMTV is a strong independent predictor of outcome in FL. In combination with FLIPI2 score, it identifies patients at high risk of early progression. It warrants further validation as a biomarker for development of first-line PET-adapted approaches in FL.
Children’s emergency service is suspended at Stafford hospital on safety grounds
Authors: Adrian O’Dowd
Journal: BMJ (2016)

A high profile NHS hospital trust has decided to close its emergency service for people aged 18 and under because of staff shortages that have made it clinically unsafe to treat people there.

The decision to temporarily close the emergency service for children at University Hospitals of North Midlands NHS Trust County Hospital in Stafford was taken on 25 August, but the emergency department remains operational for adults.

The BMJ was told that the children’s emergency service was unlikely to reopen for children for at least two months while a review is carried out by the trust and the West Midlands Quality Review Service, a collaborative venture by NHS organisations in the region to improve the quality of health services.

The hospital, under its former name Stafford Hospital, was the subject …
Access to Health Care and Preventable Hospitalizations
Authors: Mark Jameson
Journal: JAMA (1995)

To the Editor.  —The article by Dr Bindman and colleagues 1 and the Editorial by Dr Starfield 2 conclude that improving access to care will reduce hospitalization rates for chronic conditions. The authors meticulously evaluated physician behavior by practice style and admitting criteria, but inexplicably ignored a far more important variable: disease-inducing patient behavior. Tobacco use, dietary factors, activity patterns, misuse of alcohol, and illicit drug use account for almost 40% of all deaths in the United States 3 and are directly linked to the five medical conditions evaluated by Bindman et al (asthma, chronic obstructive pulmonary disease, congestive heart failure, diabetes mellitus, and hypertension).  Contrary to the authors' conclusions, I postulate that access to care has reached the point of diminishing returns. The United States dedicates 13% of its gross domestic product to health care, 4 the highest in the world. Additional increments in access to medical care will
Abdominal Pain Following Lower Gastrointestinal Bleeding
Authors: Sunu Philip, Ernesto Drelichman
Journal: JAMA Surgery (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Affinity of Tau antibodies for solubilized pathological Tau species but not their immunogen or insoluble Tau aggregates predicts in vivo and ex vivo efficacy
Authors: Erin E. Congdon, Yan Lin, Hameetha B. Rajamohamedsait, Dov B. Shamir, Senthilkumar Krishnaswamy, Wajitha J. Rajamohamedsait, Suhail Rasool, Veronica Gonzalez, Josien Levenga, Jiaping Gu, Charles Hoeffer, Einar M. Sigurdsson
Journal: Molecular Neurodegeneration (2016)

A few tau immunotherapies are now in clinical trials with several more likely to be initiated in the near future. A priori, it can be anticipated that an antibody which broadly recognizes various pathological tau aggregates with high affinity would have the ideal therapeutic properties. Tau antibodies 4E6 and 6B2, raised against the same epitope region but of varying specificity and affinity, were tested for acutely improving cognition and reducing tau pathology in transgenic tauopathy mice and neuronal cultures.Surprisingly, we here show that one antibody, 4E6, which has low affinity for most forms of tau acutely improved cognition and reduced soluble phospho-tau, whereas another antibody, 6B2, which has high affinity for various tau species was ineffective. Concurrently, we confirmed and clarified these efficacy differences in an ex vivo model of tauopathy. Alzheimer's paired helical filaments (PHF) were toxic to the neurons and increased tau levels in remaining neurons. Both toxicity and tau seeding were prevented by 4E6 but not by 6B2. Furthermore, 4E6 reduced PHF spreading between neurons. Interestingly, 4E6's efficacy relates to its high affinity binding to solubilized PHF, whereas the ineffective 6B2 binds mainly to aggregated PHF. Blocking 4E6's uptake into neurons prevented its protective effects if the antibody was administered after PHF had been internalized. When 4E6 and PHF were administered at the same time, the antibody was protective extracellularly.Overall, these findings indicate that high antibody affinity for solubilized PHF predicts efficacy, and that acute antibody-mediated improvement in cognition relates to clearance of soluble phospho-tau. Importantly, both intra- and extracellular clearance pathways are in play. Together, these results have major implications for understanding the pathogenesis of tauopathies and for development of immunotherapies.
The Association of Vibratory Perception and Muscle Strength With the Incidence and Worsening of Knee Instability: The Multicenter Osteoarthritis Study
Authors: Najia Shakoor, David T. Felson, Jingbo Niu, Uyen‐Sa Nguyen, Neil A. Segal, Jasvinder A. Singh, Michael C. Nevitt
Journal: Arthritis & Rheumatology (2016)

To examine neuromuscular factors that predict the incidence and progression of knee instability symptoms in older adults with or at high risk of knee osteoarthritis (OA).At the 60-month clinic visit, participants in the Multicenter Osteoarthritis Study underwent evaluation of quantitative vibratory sense at the knee and isokinetic quadriceps muscle strength. At this 60-month visit, participants were also asked about knee buckling and sensations of knee shifting or slipping without buckling in the past 3 months and then were asked the same questions at the 72- and 84-month follow-up visits. We performed a person-based analysis using Poisson regression analysis with robust error variance to estimate adjusted relative risks (RRs) for the association of vibratory sense and muscle strength with the incidence and worsening of knee slipping/shifting, buckling, and overall knee instability symptoms (either buckling or knee shifting/slipping), with adjustment for relevant confounders.A total of 1,803 participants (61% women) were included. Approximately one-third of the participants reported incident or worsening of instability symptoms over the study period. After adjustment for relevant confounders, better vibratory acuity (adjusted RR 0.78, 95% confidence interval [95% CI] 0.56-1.09), P = 0.020 for trend) and greater quadriceps strength (adjusted RR 0.53, 95% CI 0.38-0.75, P < 0.001) protected against incident knee instability symptoms. Greater quadriceps strength (adjusted RR 0.73, 95% CI 0.58-0.92, P = 0.008) also protected against worsening of knee instability symptoms.Vibratory acuity and quadriceps muscle strength are important predictors of the incidence and worsening of knee instability over 2 years. These neuromuscular factors are potentially modifiable and should be considered in interventional studies of instability in persons with or at risk of knee OA.
Critical Flaws in the Validation of the Instant Blood Pressure Smartphone App—A Letter from the App Developers—Reply
Authors: Timothy B. Plante, Lawrence J. Appel, Seth S. Martin
Journal: JAMA Internal Medicine (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Ki-67, p53, and p16 expression, and G691S RET polymorphism in desmoplastic melanoma (DM): A clinicopathologic analysis of predictors of outcome
Authors: Nicholas F. Lawrence, Marc R. Hammond, Dennie T. Frederick, Yuhua Su, Dora Dias-Santagata, April Deng, M. Angelica Selim, Meera Mahalingam, Keith T. Flaherty, Mai P. Hoang
Journal: Journal of the American Academy of Dermatology (2016)
Immunomodulatory Drugs Restore Effector Cell Immune Functions In Myeloma Patients With Low Disease Burden After Autologous Stem Cell Transplantation
Authors: Karel Fostier, Jurgen Corthals, Carlo Heirman, Joeri L. Aerts, Kris Thielemans, Rik Schots, Brenda De Keersmaecker
Journal: Blood (2013)
Genetic Predictors of Cardiovascular Mortality During Intensive Glycemic Control in Type 2 Diabetes: Findings From the ACCORD Clinical Trial
Authors: Hetal S. Shah, He Gao, Mario Luca Morieri, Jan Skupien, Skylar Marvel, Guillaume Paré, Gaia C. Mannino, Patinut Buranasupkajorn, Christine Mendonca, Timothy Hastings, Santica M. Marcovina, Ronald J. Sigal, Hertzel C. Gerstein, Michael J. Wagner, Alison A. Motsinger-Reif, John B. Buse, Peter Kraft, Josyf C. Mychaleckyj, Alessandro Doria
Journal: Diabetes Care (2016)

OBJECTIVE To identify genetic determinants of increased cardiovascular mortality among subjects with type 2 diabetes who underwent intensive glycemic therapy in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. RESEARCH DESIGN AND METHODS A total of 6.8 million common variants were analyzed for genome-wide association with cardiovascular mortality among 2,667 self-reported white subjects in the ACCORD intensive treatment arm. Significant loci were examined in the entire ACCORD white genetic dataset (n = 5,360) for their modulation of cardiovascular responses to glycemic treatment assignment and in a Joslin Clinic cohort (n = 422) for their interaction with long-term glycemic control on cardiovascular mortality. RESULTS Two loci, at 10q26 and 5q13, attained genome-wide significance as determinants of cardiovascular mortality in the ACCORD intensive arm (P = 9.8 × 10−9 and P = 2 × 10−8, respectively). A genetic risk score (GRS) defined by the two variants was a significant modulator of cardiovascular mortality response to treatment assignment in the entire ACCORD white genetic dataset. Participants with GRS = 0 experienced a fourfold reduction in cardiovascular mortality in response to intensive treatment (hazard ratio [HR] 0.24 [95% CI 0.07–0.86]), those with GRS = 1 experienced no difference (HR 0.92 [95% CI 0.54–1.56]), and those with GRS ≥2 experienced a threefold increase (HR 3.08 [95% CI 1.82–5.21]). The modulatory effect of the GRS on the association between glycemic control and cardiovascular mortality was confirmed in the Joslin cohort (P = 0.029). CONCLUSIONS Two genetic variants predict the cardiovascular effects of intensive glycemic control in ACCORD. Further studies are warranted to determine whether these findings can be translated into new strategies to prevent cardiovascular complications of diabetes.
Metabolic Plasticity as a Determinant of Tumor Growth and Metastasis
Authors: Camille Lehuédé, Fanny Dupuy, Rebecca Rabinovitch, Russell G. Jones, Peter M. Siegel
Journal: Cancer Research (2016)

Cancer cells must adapt their metabolism to meet the energetic and biosynthetic demands that accompany rapid growth of the primary tumor and colonization of distinct metastatic sites. Different stages of the metastatic cascade can also present distinct metabolic challenges to disseminating cancer cells. However, little is known regarding how changes in cellular metabolism, both within the cancer cell and the metastatic microenvironment, alter the ability of tumor cells to colonize and grow in distinct secondary sites. This review examines the concept of metabolic heterogeneity within the primary tumor, and how cancer cells are metabolically coupled with other cancer cells that comprise the tumor and cells within the tumor stroma. We examine how metabolic strategies, which are engaged by cancer cells in the primary site, change during the metastatic process. Finally, we discuss the metabolic adaptations that occur as cancer cells colonize foreign metastatic microenvironments and how cancer cells influence the metabolism of stromal cells at sites of metastasis. Through a discussion of these topics, it is clear that plasticity in tumor metabolic programs, which allows cancer cells to adapt and grow in hostile microenvironments, is emerging as an important variable that may change clinical approaches to managing metastatic disease. Cancer Res; 76(18); 5201-8. ©2016 AACR.
Antimetastatic Effect by Targeting CTC Cluster—Response
Authors: Jin Woo Choi, Kwon-Ha Yoon, Seok Hyun Yun
Journal: Cancer Research (2016)

We appreciate two commentaries from Dr. Alonso and Dr. Soria's groups regarding our recent publication on "highly metastatic property of clustered circulating tumor cells (CTC)." In our research, we suggested the breakdown of CTC cluster slows metastasis pace with preclinical experiments; urokinase plasminogen activator (uPA) utilized to dissociate the CTC cluster showed no effect on primary tumor growth, but the number of metastasized nodules was reduced, expanding survival rate of the animals (1).Two different animal models, B16F10 melanoma cells in C57BL/6 and 4T1 mammary carcinoma in balb/c, were tested and showed a similarly rapid animal death in 6 to 7 weeks after subcutaneous inoculation of cancer cells. In addition, the subcutaneously transplanted cancer cells have a preexisting metastatic ability, whereas in spontaneous tumor, some cells acquire the invasion ability. Hence, the disease animal models may undergo a physiologically different disease progress and tumor microenvironment from those of human patients who generally suffer from various systemic physical changes due to long disease history. Thus, we agree with the concerns of Dr. Soria and colleagues that the potential of uPA as risk factor may not be ruled out. The other reports consistently support a cancer-promoting role of uPA and chemical intervention on uPA is expected as cancer therapeutic method (2, 3). In our experimental condition, it is likely that CTC cluster–dissociating potential of uPA was dominant over its disease-driving effect due to extremely rapid metastasis. Clinical application of uPA requires additional careful study.Recently, Mego and colleagues reported that uPA-related genes were expressed in epithelial CTC, but not in epithelial–mesenchymal transition CTC, which mainly stands for early metastasis. Interestingly, in primary tumor, the urokinase expression was not associated with the presence of CTC in peripheral blood (4). These data suggest that other pathways than uPA system may regulate the emergence of CTC. The letter from Dr. Alonso and colleagues reminds us of the metastasis-promoting role of the fibrolysis inhibitor and also supports a particular treatment condition, such as perioperative stage that may be helpful for antimetastasis of fibrolytic agents. Thus, a CTC cluster–dissociating and antimetastatic effect of fibrolytic agent can still be considered at a limited condition, compatible with metastasis-stimulating potential of urokinase.We appreciate the comments and interest in our publication as they provide further guidance. We plan to determine factors that influence uPA treatment and how microenvironment controls the interaction between uPA and CTCs in our subsequent studies.See the original Letter to the Editor, p. 4908No potential conflicts of interest were disclosed.
Reply to Mieke Van Hemelrijck, Hans Garmo, Jan Adolfsson, and Pär Stattin's Letter to the Editor re: Adi J. Klil-Drori, Hui Yin, Vicky Tagalakis, Armen Aprikian, Laurent Azoulay. Androgen Deprivation Therapy for Prostate Cancer and Risk of Venous Thromboembolism. Eur Urol 2016;70:56–61
Authors: Adi J. Klil-Drori, Laurent Azoulay
Journal: European Urology (2016)