tbuckley/cabot-search huggingface dataset:
Survival after recurrent osteosarcoma: Data from three European Osteosarcoma Intergroup (EOI) randomized controlled
Authors: H. Gelderblom, M. R. Sydes, R. C. Morgan, P. C. Hogendoorn, I. J. Lewis, M. A. Nooij, A. H. Taminiau, J. Whelan
Journal: Journal of Clinical Oncology (2008)

10505 Background: Between 1983 and 2002, the EOI accrued to three randomized controlled trials of pre- and postoperative chemotherapy for patients (pts) with resectable nonmetastatic high-grade osteosarcoma of the extremity: MRC-BO02, BO03 and BO06 (also known as EORTC-80831, 80861 and 80931) with n=179, 391 and 497 pts randomised, respectively. Control treatment in all trials was doxorubicin 75 mg/m2 + cisplatin 100 mg/m2 (DC). The comparators were additional high-dose methotrexate (BO02), T10-based multi- drug regimen (BO03) and G-CSF intensified-DC (BO06). No statistically significant differences between treatments were reported in the original trial reports. Methods: Survival after recurrence was investigated with standard survival analysis methods, including all 1,067 pts from the 3 trials. Results: Median recurrence-free survival was 31 months (m); only 4 recurrences were reported later than 5 years. In 564 pts with recurrence (median 13m post-randomisation), there was no difference in 5-year survival between first-line treatment arms (13–19%). Pts with good histologic response to preoperative chemotherapy had better overall survival after recurrence than poor responders (p=0.015). Pts whose disease recurred within 2 years after randomization had worse prognosis than those recurring after 2 years (14 vs 35% at 5 years; p<0.001). Local relapse was more often reported after limb saving procedures (5 vs 25%), independent of the primary tumor site. Site of first recurrence (in total: local 20%, lung 62%, other 18%) affected survival as pts recurring with metastases other than lung had significantly worse overall survival (local 27%, lung 18%, other 10% at 5 years, p=0.001). Conclusions: These data describe the largest series of pts with recurrent osteosarcoma. They confirm the relationship between early recurrence and poor survival. New findings include worse survival in pts with a recurrence after poor histologic response to preoperative chemotherapy. No significant financial relationships to disclose.
Weekly Inotuzumab Ozogamicin (InO) In Adult Patients With Relapsed Or Refractory CD22-Positive Acute Lymphoblastic Leukemia (ALL)
Authors: Daniel J. DeAngelo, Wendy Stock, Andrei R. Shustov, Michaela Liedtke, Charles A. Schiffer, Revathi Ananthakrishnan, Joseph P. Boni, Kenneth Luu, Katherine Liau, Erik Vandendries, Anjali S. Advani
Journal: Blood (2013)
The Pedagogy of Pimping
Authors: Douglas R. Reifler
Journal: JAMA (2015)

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
Therapeutic targets in the Wnt signaling pathway: Feasibility of targeting TNIK in colorectal cancer
Authors: Mari Masuda, Masaaki Sawa, Tesshi Yamada
Journal: Pharmacology & Therapeutics (2015)

The genetic and epigenetic alterations occurring during the course of multistage colorectal carcinogenesis have been extensively studied in the last few decades. One of the most notable findings is that the great majority of colorectal cancers (>80%) have mutations in the adenomatous polyposis coli (APC) tumor suppressor gene. Loss of functional APC protein results in activation of canonical Wnt/β-catanin signaling and initiates intestinal carcinogenesis. Mutational inactivation of APC is the first genetic event, but colorectal cancer cells retain their dependency on constitutive Wnt signal activation even after accumulation of other genetic events. Accordingly, pharmacological blocking of Wnt signaling has been considered an attractive therapeutic approach for colorectal cancer. Several therapeutics targeting various molecular components of the Wnt signaling pathway, including porcupine, frizzled receptors and co-receptor, tankyrases, and cAMP response element binding protein (CREB)-binding protein (CBP), have been developed, and some of those are currently being evaluated in early-phase clinical trials. Traf2- and Nck-interacting protein kinase (TNIK) has been identified as a regulatory component of the T-cell factor-4 and β-catenin transcriptional complex independently by two research groups. TNIK regulates Wnt signaling in the most downstream part of the pathway, and its inhibition is expected to block the signal even in colorectal cancer cells with APC gene mutation. Here we discuss some of the TNIK inhibitors under preclinical development.
Multilayered Nanocarrier Systems: Bioinspired Oil Core/Silica Shell Nanocarriers with Tunable and Multimodal Functionalities (Adv. Healthcare Mater. 17/2015)
Authors: Anshuman Jakhmola, Raffaele Vecchione, Daniela Guarnieri, Valentina Belli, Dominic Calabria, Paolo A. Netti
Journal: Advanced Healthcare Materials (2015)

Bioinspired silica nanocapsules displaying two different contrasting agents are described by R. Vecchione and co-workers on page 2688. The nanocapsules have drug molecules loaded into different regions. The image illustrates how these nanocapsules can release the drug (red dots) to a magnified cancerous region, tumor detection (represented by yellow fluorescence) and MRI activity (waves).
Research Domain Criteria (RDoC) and the<i>DSM</i>—Two Methodological Approaches to Mental Health Diagnosis
Authors: Helena Chmura Kraemer
Journal: JAMA Psychiatry (2015)

This Viewpoint argues that a valid diagnosis of mental health disorders is a developing process based on accumulating evidence rather than a fixed goal, and a physician should use all resources available: both dimensional and categorical, both DSM and Research Domain Criteria.
Progression to Overt or Silent CAD in Asymptomatic Patients With Diabetes Mellitus at High Coronary Risk
Authors: Michael J. Zellweger, Michael Maraun, Hans H. Osterhues, Ulrich Keller, Jan Müller-Brand, Raban Jeger, Otmar Pfister, Thilo Burkard, Friedrich Eckstein, Stefanie von Felten, Stefan Osswald, Matthias Pfisterer
Journal: JACC. Cardiovascular imaging (2014)

The purpose of this study was to evaluate prevalence, progression, treatment, and outcome of silent coronary artery disease (CAD) in asymptomatic patients with diabetes (DM) at high coronary risk. Despite the close association of diabetes and CAD, general CAD screening in asymptomatic patients with DM is discouraged even though outcome data in patients at high coronary risk are lacking. Prospective multicenter outcome study—with a pilot randomized treatment substudy. The study comprised 400 asymptomatic patients with DM (type 2) without history or symptoms of CAD at high CAD risk. They underwent clinical evaluation and myocardial perfusion single-photon emission computed tomography (MPS) at baseline and after 2 years. Patients with normal MPS received usual care; those with abnormal MPS received medical or combined invasive and medical management. An abnormal MPS was found in 87 of 400 patients (22%). In patients with normal MPS, MACE occurred in 2.9% and ischemia or new scar in 3.2%. Patients with abnormal MPS had more MACE (9.8%; hazard ratio: 3.44; 95% confidence interval [CI]: 1.32 to 8.95; p = 0.011) and ischemia or new scar (34.2%; odds ratio: 15.91; 95% CI: 7.24 to 38.03; p < 0.001) despite therapy, resulting in “overt or silent CAD progression” of 35.6% versus 4.6% (odds ratio: 11.53; 95% CI: 5.63 to 24.70; p < 0.001). Patients with abnormal MPS randomized to medical versus invasive-medical strategies had similar event rates (p = 0.215), but more ischemic or new scar findings (54.3% vs. 15.8%; p < 0.001). High-risk asymptomatic patients with DM and normal MPS (78%) have a low rate of first manifestations of CAD. Patients with abnormal MPS at baseline (22%) have a 7-fold higher rate of progression to “overt or silent CAD,” despite therapy. Randomized patients’ outcomes suggest that a combined invasive and medical strategy for silent CAD may reduce scintigraphic but not symptomatic CAD progression versus medical therapy alone. (Trial of Invasive versus Medical therapy of Early coronary artery disease in Diabetes Mellitus ISRCTN87953632).
Bridging small interfering RNA with giant therapeutic outcomes using nanometric liposomes
Authors: Yuvraj Singh, Sandeep Tomar, Shariq Khan, Jaya Gopal Meher, Vivek K. Pawar, Kavit Raval, Komal Sharma, Pankaj K. Singh, Mohini Chaurasia, B. Surendar Reddy, Manish K. Chourasia
Journal: Journal of Controlled Release (2015)
A functional connectome: regulation of Wnt/TCF-dependent transcription by pairs of pathway activators
Authors: Jamie Freeman, David Smith, Branko Latinkic, Ken Ewan, Lee Samuel, Massimo Zollo, Natascia Marino, Lorraine Tyas, Nick Jones, Trevor C. Dale
Journal: Molecular Cancer (2015)

Wnt/β-catenin signaling is often portrayed as a simple pathway that is initiated by Wnt ligand at the cell surface leading, via linear series of interactions between 'core pathway' members, to the induction of nuclear transcription from genes flanked by β-catenin/TCF transcription factor binding sites. Wnt/β-catenin signaling is also regulated by a much larger set of 'non-core regulators'. However the relationship between 'non-core regulators' is currently not well understood. Aberrant activation of the pathway has been shown to drive tumorgenesis in a number of different tissues. Mammalian cells engineered to have a partially-active level of Wnt/β-catenin signaling were screened by transfection for proteins that up or down-regulated a mid-level of TCF-dependent transcription induced by transient expression of an activated LRP6 Wnt co-receptor (∆NLRP). 141 novel regulators of TCF-dependent transcription were identified. Surprisingly, when tested without ∆NLRP activation, most up-regulators failed to alter TCF-dependent transcription. However, when expressed in pairs, 27 % (466/1170) functionally interacted to alter levels of TCF-dependent transcription. When proteins were displayed as nodes connected by their ability to co-operate in the regulation of TCF-dependent transcription, a network of functional interactions was revealed. In this network, 'core pathway' components (Eg. β-catenin, GSK-3, Dsh) were found to be the most highly connected nodes. Activation of different nodes in this network impacted on the sensitivity to Wnt pathway small molecule antagonists. The 'functional connectome' identified here strongly supports an alternative model of the Wnt pathway as a complex context-dependent network. The network further suggests that mutational activation of highly connected Wnt signaling nodes predisposed cells to further context-dependent alterations in levels of TCF-dependent transcription that may be important during tumor progression and treatment.
The Histone Methyltransferase Enzyme Enhancer of Zeste Homolog 2 Protects against Podocyte Oxidative Stress and Renal Injury in Diabetes
Authors: Ferhan S. Siddiqi, Syamantak Majumder, Kerri Thai, Moustafa Abdalla, Pingzhao Hu, Suzanne L. Advani, Kathryn E. White, Bridgit B. Bowskill, Giuliana Guarna, Claudia C. dos Santos, Kim A. Connelly, Andrew Advani
Journal: Journal of the American Society of Nephrology (2015)

Epigenetic regulation of oxidative stress is emerging as a critical mediator of diabetic nephropathy. In diabetes, oxidative damage occurs when there is an imbalance between reactive oxygen species generation and enzymatic antioxidant repair. Here, we investigated the function of the histone methyltransferase enzyme enhancer of zeste homolog 2 (EZH2) in attenuating oxidative injury in podocytes, focusing on its regulation of the endogenous antioxidant inhibitor thioredoxin interacting protein (TxnIP). Pharmacologic or genetic depletion of EZH2 augmented TxnIP expression and oxidative stress in podocytes cultured under high-glucose conditions. Conversely, EZH2 upregulation through inhibition of its regulatory microRNA, microRNA-101, downregulated TxnIP and attenuated oxidative stress. In diabetic rats, depletion of EZH2 decreased histone 3 lysine 27 trimethylation (H3K27me3), increased glomerular TxnIP expression, induced podocyte injury, and augmented oxidative stress and proteinuria. Chromatin immunoprecipitation sequencing revealed H3K27me3 enrichment at the promoter of the transcription factor Pax6, which was upregulated on EZH2 depletion and bound to the TxnIP promoter, controlling expression of its gene product. In high glucose–exposed podocytes and the kidneys of diabetic rats, the lower EZH2 expression detected coincided with upregulation of Pax6 and TxnIP. Finally, in a gene expression array, TxnIP was among seven of 30,854 genes upregulated by high glucose, EZH2 depletion, and the combination thereof. Thus, EZH2 represses the transcription factor Pax6, which controls expression of the antioxidant inhibitor TxnIP, and in diabetes, downregulation of EZH2 promotes oxidative stress. These findings expand the extent to which epigenetic processes affect the diabetic kidney to include antioxidant repair.
Season of birth shapes neonatal immune function
Authors: Anna Hammerich Thysen, Morten Arendt Rasmussen, Eskil Kreiner-Møller, Jeppe Madura Larsen, Nilofar Vahman Følsgaard, Klaus Bønnelykke, Jakob Stokholm, Hans Bisgaard, Susanne Brix
Journal: Journal of Allergy and Clinical Immunology (2015)
A Smart Antibacterial Surface for the On‐Demand Killing and Releasing of Bacteria
Authors: Ting Wei, Qian Yu, Wenjun Zhan, Hong Chen
Journal: Advanced Healthcare Materials (2015)

For various human healthcare and industrial applications, endowing surfaces with the capability to not only efficiently kill bacteria but also release dead bacteria in a rapid and repeatable fashion is a promising but challenging effort. In this work, the synergistic effects of combining stimuli‐responsive polymers and nanomaterials with unique topographies to achieve smart antibacterial surfaces with on‐demand switchable functionalities are explored. Silicon nanowire arrays are modified with a pH‐responsive polymer, poly(methacrylic acid), which serves as both a dynamic reservoir for the controllable loading and release of a natural antimicrobial lysozyme and a self‐cleaning platform for the release of dead bacteria and the reloading of new lysozyme for repeatable applications. The functionality of the surface can be simply switched via step‐wise modification of the environmental pH and can be effectively maintained after several kill–release cycles. These results offer a new methodology for the engineering of surfaces with switchable functionalities for a variety of practical applications in the biomedical and biotechnology fields.
Hepatitis B virus, hepatitis C virus and human immunodeficiency virus infection in undocumented migrants and refugees in southern Italy, January 2012 to June 2013
Authors: Nicola Coppola, Loredana Alessio, Luciano Gualdieri, Mariantonietta Pisaturo, Caterina Sagnelli, Nunzio Caprio, Rita Maffei, Mario Starace, Italo Francesco Angelillo, Giuseppe Pasquale, Evangelista Sagnelli
Journal: Eurosurveillance (2015)

Screening of undocumented migrants or refugees for hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV) infections has been offered free of charge and free from bureaucratic procedures since 2012 at four primary-level clinical centres in Naples and Caserta, Italy. Of 926 undocumented migrants and refugees visiting one of the primary-level clinical centres from January 2012 to June 2013, 882 (95%) were screened for hepatitis B surface antigen (HBsAg), total hepatitis B core antibody (anti-HBc) and antibodies against HCV and HIV. Of the 882 individuals enrolled, 78 (9%) were HBsAg positive, 35 (4%) anti-HCV positive and 11 (1%) anti-HIV positive (single infections); seven (1%) had more than one infection (three were HBsAg positive). Of the 801 HBsAg-negative patients, 373 (47%) were anti-HBc positive. The HBsAg-positivity rate was high (14%; 62/444) in individuals from sub-Saharan Africa and intermediate in those from eastern Europe (6%; 12/198), northern Africa (2%; 2/80) and Bangladesh, India, Pakistan and Sri Lanka (the ‘India-Pakistan area’) (3%; 4/126). Anti-HCV was detected in 9/126 (7%) individuals originating from the India-Pakistan area, in 12/198 (6%) from eastern Europe, in 17/444 (4%) from sub-Saharan and in 2/80 (2%) from northern Africa. The HBV, HCV and HIV infections in the undocumented migrants and refugees screened serve as a reminder to the Italian healthcare authorities to carry out extensive screening and educational programmes for these populations.
‘Real-life’ effectiveness studies of omalizumab in adult patients with severe allergic asthma: systematic review
Authors: I. Abraham, A. Alhossan, C. S. Lee, H. Kutbi, K. MacDonald
Journal: Allergy (2015)

We reviewed 24 'real-life' effectiveness studies of omalizumab in the treatment of severe allergic asthma that included 4117 unique patients from 32 countries with significant heterogeneity in patients, clinicians and settings. The evidence underscores the short- and long-term benefit of anti-IgE therapy in terms of the following: improving lung function; achieving asthma control and reducing symptomatology, severe exacerbations and associated work/school days lost; reducing healthcare resource utilizations, in particular hospitalizations, hospital lengths of stay and accident specialist or emergency department visits; reducing or discontinuing other asthma medications; and improving quality of life – thus confirming, complementing and extending evidence from randomized trials. Thus, omalizumab therapy is associated with signal improvements across the full objective and subjective burden of illness chain of severe allergic asthma. Benefits of omalizumab may extend up to 2–4 years, and the majority of omalizumab-treated patients may benefit for many years. Omalizumab has positive short- and long-term safety profiles similar to what is known from randomized clinical trials. Initiated patients should be monitored for treatment response at 16 weeks. Those showing positive response at that time are highly likely to show sustained treatment response and benefit in terms of clinical, quality of life and health resource utilization outcomes.
Using GIS to contemplate geographical distribution of non-tuberculous mycobacteria and its relationship with socio- economic and climate factors
Authors: Hanieh Baghaei, Alireza Vafaei Nezhad, Majid Marjani, Parvaneh Baghaei, Payam Tabarsi
Journal: European Respiratory Journal (2014)

Introduction: Nowadays, Geographic Information System (GIS) is considered as a main part of many public health and epidemiological projects. The purpose of this study was to use GIS in presenting geographic distribution of pulmonary non-tuberculous  Mycobacteria  (PNTM) disease and identify environmental and socio-economic factors predictive of disease.  Methods: PNTM cases from National Research Institute of Tuberculosis and Lung Disease (NRITLD) in three states (Khuzestan, Eastern Azarbayjan, Ghom), which have the highest prevalence of PNTM in country, were manually geocoded with permission of patients. Patients9 addresses were considered as locations, in which NTM exists. By Maxent model, other NTM presence locations in area of study were predicted and the relationship identified.Socio-economic factors and their relationship with patients were reflected in maps.  Results: Response curves yield from Maxent approach for each environmental factor, showed that increasing in elevation and annual precipitation cause to decrease in NTM presence probability. Areas with greater temperature seasonality and also greater organic carbon seem to have greater probability of NTM presence. NTM can be found in soils with pH more than 5 and the chance of presence can increase in such environment. Contemplate of socio-economic factors showed that most of PNTM patients were residents of towns, had lower education and income level, and were older than 50 years old.  Conclusion: GIS is a valuable tool in studying and analyzing incidence and prevalence of diseases because of its immense capabilities in gathering and preparing, and also analyzing data.
Financial Hardship Associated With Cancer in the United States: Findings From a Population-Based Sample of Adult Cancer Survivors
Authors: K. Robin Yabroff, Emily C. Dowling, Gery P. Guy, Matthew P. Banegas, Amy Davidoff, Xuesong Han, Katherine S. Virgo, Timothy S. McNeel, Neetu Chawla, Danielle Blanch-Hartigan, Erin E. Kent, Chunyu Li, Juan L. Rodriguez, Janet S. de Moor, Zhiyuan Zheng, Ahmedin Jemal, Donatus U. Ekwueme
Journal: Journal of Clinical Oncology (2015)

To estimate the prevalence of financial hardship associated with cancer in the United States and identify characteristics of cancer survivors associated with financial hardship.We identified 1,202 adult cancer survivors diagnosed or treated at ≥ 18 years of age from the 2011 Medical Expenditure Panel Survey Experiences With Cancer questionnaire. Material financial hardship was measured by ever (1) borrowing money or going into debt, (2) filing for bankruptcy, (3) being unable to cover one's share of medical care costs, or (4) making other financial sacrifices because of cancer, its treatment, and lasting effects of treatment. Psychological financial hardship was measured as ever worrying about paying large medical bills. We examined factors associated with any material or psychological financial hardship using separate multivariable logistic regression models stratified by age group (18 to 64 and ≥ 65 years).Material financial hardship was more common in cancer survivors age 18 to 64 years than in those ≥ 65 years of age (28.4% v 13.8%; P < .001), as was psychological financial hardship (31.9% v 14.7%, P < .001). In adjusted analyses, cancer survivors age 18 to 64 years who were younger, female, nonwhite, and treated more recently and who had changed employment because of cancer were significantly more likely to report any material financial hardship. Cancer survivors who were uninsured, had lower family income, and were treated more recently were more likely to report psychological financial hardship. Among cancer survivors ≥ 65 years of age, those who were younger were more likely to report any financial hardship.Cancer survivors, especially the working-age population, commonly experience material and psychological financial hardship.
Aberrant Expression Pattern and Location of Cullin 1 are Associated With the Development of Papillary Carcinoma in Thyroid and Cyclin D1 Expression
Authors: Sung-Im Do, Kyungeun Kim, Hyunjoo Lee, Hyun-Soo Kim, Tae Gu Do, Jisup Yun, Dong-Hoon Kim, Seoung Wan Chae, Yong Lai Park, Chan Heun Park, Jin Hee Sohn, Kyueng-Whan Min, Jung-Soo Pyo
Journal: Endocrine Pathology (2014)