tbuckley/cabot-search huggingface dataset:
Independent Prognostic Value of Serum Markers in Diffuse Large B-Cell Lymphoma in the Era of the NCCN-IPI
Authors: Thomas Melchardt, Katharina Troppan, Lukas Weiss, Clemens Hufnagl, Daniel Neureiter, Wolfgang Tränkenschuh, Konstantin Schlick, Florian Huemer, Alexander Deutsch, Peter Neumeister, Richard Greil, Martin Pichler, Alexander Egle
Journal: Journal of the National Comprehensive Cancer Network (2015)

Background: Several serum parameters have been evaluated for adding prognostic value to clinical scoring systems in diffuse large B-cell lymphoma (DLBCL), but none of the reports used multivariate testing of more than one parameter at a time. The goal of this study was to validate widely available serum parameters for their independent prognostic impact in the era of the National Comprehensive Cancer Network–International Prognostic Index (NCCN-IPI) score to determine which were the most useful. Patients and Methods: This retrospective bicenter analysis includes 515 unselected patients with DLBCL who were treated with rituximab and anthracycline-based chemoimmunotherapy between 2004 and January 2014. Results: Anemia, high C-reactive protein, and high bilirubin levels had an independent prognostic value for survival in multivariate analyses in addition to the NCCN-IPI, whereas neutrophil-to-lymphocyte ratio, high gamma-glutamyl transferase levels, and platelets-to-lymphocyte ratio did not. Conclusions: In our cohort, we describe the most promising markers to improve the NCCN-IPI. Anemia and high C-reactive protein levels retain their power in multivariate testing even in the era of the NCCN-IPI. The negative role of high bilirubin levels may be associated as a marker of liver function. Further studies are warranted to incorporate these markers into prognostic models and define their role opposite novel molecular markers.
Quantitative Echocardiographic Determinants of Clinical Outcome in Asymptomatic Patients With Aortic Regurgitation
Authors: Delphine Detaint, David Messika-Zeitoun, Joseph Maalouf, Christophe Tribouilloy, Douglas W. Mahoney, A. Jamil Tajik, Maurice Enriquez-Sarano
Journal: JACC. Cardiovascular imaging (2008)
Research trends in British gastroenterology: publication rates in newly appointed NHS consultants over a nine year period
Authors: A D Hopper, R Atkinson, L Prtak, D S Sanders
Journal: Gut (2004)

It has been suggested that medical research within the UK may be in decline.1,2 Possible explanations for this could be the shortened training scheme created by the Calman Specialist Registrar (SpR) post, reduced availability of research funding, or the progressive expansion of the consultant body (as a government imperative to provide a consultant delivered service).1–4 Although this may be the perception, there has previously been no published evidence to demonstrate a reduction in research output. In this study, we wished to observe any overall trend in the number of publications and higher degrees that trainees (in gastroenterology) have at the time of their National Health Service (NHS) consultant appointments over a nine year period.

All consultant appointments and place of training were noted over a fixed period from February 1993 …
DNA methylation pattern of brain stem pilocytic astrocytomas in children
Authors: H. Witt, A. Korshunov, M. Remke, W. G. Janzarik, A. Gnekow, W. Scheurlen, A. E. Kulozik, P. Lichter, S. Pfister
Journal: Journal of Clinical Oncology (2009)

10021 Background: Pilocytic astrocytoma (WHO grade I) comprises the most frequent brain tumor in childhood. We were recently able to identify BRAF as a centrally important oncogene in these tumors showing duplication or activation in a majority of cases. Although histologically indistinguishable, tumors with brain stem location have a particularly poor prognosis. It is not well established, whether this is due to their close proximity to pivotal anatomic sites or due to distinct biological characteristics. Methods: To identify novel genes involved in astrocytoma pathogenesis, we performed a genome-wide DNA methylation analysis of 78 pilocytic astrocytoma samples from different tumor locations (diencephalic, cerebral, cerebellar, brain stem). BeadChip methylation technology was used to identify genes showing differential promoter methylation among tumors. Two CpG sites were analyzed for each of a total of 14.000 promoters per sample. Clinical and molecular subgroups were compared using Significance Analysis of Microarrays (SAM). Results: In this genome-wide approach, we identified an 11-gene signature that was able to correctly separate all brain stem tumors (n = 8) from the majority of tumors from other locations (56/70). Moreover, from 14 tumors clustering together with the brain stem tumors, 5 patients experienced disease recurrence (38%) as opposed to 20% in the remaining group. Genes contained in the signature most interestingly included three homeobox family genes (HOXB1, HOXD3, and HOXD4), and NES, a tumor stem cell marker. Conclusions: These data suggest that brain stem pilocytic astrocytomas display biologic features different from most tumors of other locations and share a methylation signature with tumors prone to disease recurrence from other locations. We provide first evidence for a role of differentially methylated homeobox family genes in the pathogenesis of pilocytic astrocytoma. No significant financial relationships to disclose.
An exploratory analysis of bone scan lesion area (BSLA), circulating tumor cell (CTC) change, pain reduction, and overall survival (OS) in patients (pts) with castration-resistant prostate cancer (CRPC) treated with cabozantinib (cabo): Updated results of a phase II nonrandomized expansion (NRE) cohort.
Authors: Howard I. Scher, Matthew R. Smith, Christopher Sweeney, Paul Gettys Corn, Christopher Logothetis, Nicholas J. Vogelzang, David C. Smith, Maha Hussain, Daniel J. George, Johann Sebastian De Bono, Celestia S. Higano, Eric Jay Small, Jonathan Goldin, Matthew S. Brown, Dana T. Aftab, Mojtaba Noursalehi, Aaron Weitzman, Ethan M. Basch
Journal: Journal of Clinical Oncology (2013)

5026 Background: The results of 144 pts with metastatic CRPC treated in a phase II NRE cohort with daily cabo 100 mg and 40 mg starting doses have been previously reported. Substantial rates of bone scan improvement, reductions in CTC counts and pain relief were observed. To better understand the implication of these effects, the association with OS was explored. Methods: Relevant baseline variables (LDH, BSLA, visceral disease, pain, hemoglobin, CTCs) and post-treatment changes at week 6: ≥30% reduction in BSLA using computer-aided assessment, CTC conversion (&gt;5 vs. 4 or less/7.5 ml of blood), and pain intensity (7 day averaged worst pain score; BPI scale; using an IVR system) were associated with OS in 144 CRPC pts with bone metastasis who progressed within 6 months of docetaxel (D) treatment (≥225 mg/m 2 ) in either bone or soft tissue. Median OS was compared between responders and non-responders for each of the above outcomes categories using a Cox proportional hazard model. The findings were examined further after adjusting for significant baseline covariates selected from a stepwise Cox regression model. Results: See Table. Conclusions: Recognizing the limitations of associating response with survival, this retrospective analysis of decreases in BSLA, CTC conversions and reductions in pain intensity support further study in ongoing phase III trials. Clinical trial information: NCT00940225. [Table: see text]
Phase II study of AEZS-108 (AN-152), a targeted cytotoxic LHRH analog, in patients with LHRH receptor-positive platinum resistant ovarian cancer.
Authors: G. Emons, S. Tomov, P. Harter, J. Sehouli, P. Wimberger, A. Staehle, L. C. Hanker, F. Hilpert, P. Dall, C. Gruendker
Journal: Journal of Clinical Oncology (2010)

5035 Background: Gynecologic cancers commonly express receptors for luteinizing hormone-releasing hormone (LHRH-R). AEZS-108 (AN-152) is a targeted cytotoxic drug in which doxorubicin is linked to [D-Lys(6)]-LHRH. A Phase I study in patients (pts) with LHRH-R positive tumors recommended a dose of 267 mg/m2 by 2-hour intravenous infusion in 3-week cycles. Methods: Pts with histologically confirmed taxane-pretreated platinum-resistant/refractory LHRH-R positive advanced (FIGO III or IV) or recurrent ovarian cancer received up to 6 cycles of AEZS-108. At least 1 measurable lesion or CA-125 ≥ 200% of the upper normal range limit were required at baseline. An independent radiologic review was performed. Response rate (RECIST and/or GCIG criteria) was defined as primary endpoint. Secondary endpoints were safety, time-to-progression (TTP) and overall survival (OS). Results: 43 pts entered the study and received a total of 175 treatment courses. Efficacy included PR in 5 pts (11.6%) and SD for > 12 weeks in 14 pts (32.6%). Hematologic toxicities of G3/4 (% pts) were: leukopenia 44% (G4: 9.2%), anemia 4.6%, thrombocytopenia 2.3%. Febrile neutropenia occurred in 3 pts (7%). Hematotoxicity was usually rapidly reversible; 6 pts (14%) received G-CSF, 2 pts (4.6%) RBC transfusion, 1 pt (2.3%) dose reduction (160 mg/m2). Non hematologic toxicities of G2/3 (% pts; no G4) were: alopecia 32.6%, nausea 20.9% (G3:2.3%), vomiting 14%, diarrhea 4.6%, mucositis 4.6%, allergic reaction 4.6%. No cardiac toxicity was reported. Conclusions: AEZS-108 was active and well tolerated in pts with heavily pretreated platinum-/taxane resistant ovarian cancer. The safety profile confirmed the dose of 267 mg/m2. The trial was supported by AEterna Zentaris, Frankfurt, Germany. No significant financial relationships to disclose.
Critical Illness Brain Injury
Authors: Timothy D. Girard, Robert S. Dittus, E. Wesley Ely
Journal: Annual Review of Medicine (2016)

A growing body of literature has shown that survivors of critical illness often struggle with cognitive impairment that persists months to years after hospital discharge. We describe the epidemiology of this form of cognitive impairment—which we refer to as critical illness brain injury—and review the history and maturation of the investigation of this previously unrecognized, yet common problem. We then review the characteristics of critical illness brain injury, which can vary in severity and typically affects multiple domains of cognition. Finally, we examine known risk factors for critical illness brain injury and, based on these data, suggest approaches to patient management.
New Life for Immunotoxin Cancer Therapy
Authors: Raffit Hassan, Christine Alewine, Ira Pastan
Journal: Clinical Cancer Research (2015)

Immunotoxins are targeted anticancer therapeutics that kill cancer cells using a cytotoxic bacterial toxin payload. Their development for use in solid tumor malignancies was delayed due to issues with their immunogenicity and limited therapeutic window. However, new research has rejuvenated the field. Coadministration with a lymphocyte-depleting regimen of pentostatin and cyclophosphamide can delay antidrug antibody formation, increasing the number of treatment cycles that patients can receive and resulting in durable responses in heavily pretreated patients. In addition, a new generation of immunotoxin molecules with reduced immunogenicity and nonspecific toxicity has been developed through protein engineering techniques, and one has recently entered the clinic. In preclinical studies in mouse models, these new agents are effective against many tumor types as single agents, and also produce synergistic antitumor responses in combination with chemotherapy. These new immunotoxins have renewed excitement in the field and may prove a promising addition to the targeted therapy repertoire.
Cor a 14 is the superior serological marker for hazelnut allergy in children, independent of concomitant peanut allergy
Authors: E. Eller, C. G. Mortz, C. Bindslev-Jensen
Journal: Allergy (2015)

Background Hazelnut is the most frequent cause of tree nut allergy, but up to half of all children with hazelnut allergy additionally suffer from peanut allergy. Our aim was to identify diagnostic values of the most promising serological markers (Cor a 9 and Cor a 14) and to address the influence of concomitant peanut allergy and PR10 sensitization. Method We included 155 children suspected of hazelnut allergy and challenged according to the guidelines. Concomitant allergy to peanuts was verified or ruled out by challenge. Skin prick test, s-IgE and CRD to hazelnut, peanut, PR10 and LPT protein families were measured using ImmunoCAP. Results Sixty-five children had a positive hazelnut challenge, and 60% of these also had a concomitant peanut allergy. Children allergic to hazelnut were sensitized to Cor a 9 and Cor a 14; peanut-allergic children were sensitized to Ara h 2. Sensitization to PR10 protein components was seen in 45% of all included children, irrelevant to allergy to peanut or hazelnut. A cut-off >0.72 kU/L of IgE towards Cor a 14 diagnosed 87% correctly, making Cor a 14 the superior serology marker. However, nine hazelnut-allergic children were primarily sensitized to Cor a 9. Conclusion Concomitant peanut allergy is common in hazelnut-allergic children, but decision points as well as diagnostic values for Cor a 14 are not affected. We found three independent and well-characterized serotypes; hazelnut-allergic children were sensitized to Cor a 14, peanut-allergic children were sensitized to Ara h 2, and independently of this were children sensitized to birch pollen (Bet v 1).
Surveillance and Screening for Social Determinants of Health
Authors: Arvin Garg, Paul H. Dworkin
Journal: JAMA Pediatrics (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 Pediatrics 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 Pediatrics journal
Estimating the Reduction in the Radiation Burden From Nuclear Cardiology Through Use of Stress-Only Imaging in the United States and Worldwide
Authors: Mathew Mercuri, Thomas N. B. Pascual, John J. Mahmarian, Leslee J. Shaw, Maurizio Dondi, Diana Paez, Andrew J. Einstein
Journal: JAMA Internal Medicine (2015)

This study estimates current rates of stress-only imaging in cardiology patients in the United States and worldwide, as well as the potential effect of changes in this rate on the radiation burden to the US population.
Interdependence between Interleukin-1 and Tumor Necrosis Factor Regulates TNF-Dependent Control of Mycobacterium tuberculosis Infection
Authors: Nelson C. Di Paolo, Shahin Shafiani, Tracey Day, Thalia Papayannopoulou, David W. Russell, Yoichiro Iwakura, David Sherman, Kevin Urdahl, Dmitry M. Shayakhmetov
Journal: Immunity (2015)
Na+/H+ exchange hyperactivity and myocardial hypertrophy Are they linked phenomena?
Authors: H Cingolani
Journal: Cardiovascular Research (1999)

Time for primary review 22 days. 

Intracellular pH (pHi) in the majority of living cells is about 6.8–7.2, considerably more alkaline than that predicted for passive distribution of H+ across the cell membrane. For the average membrane potential and for an extracellular pH of 7.4, a pHi value of 6.4 should be expected if H+ were in electrochemical equilibrium. At such a pHi, metabolism and a variety of other cellular functions would be impaired. The existence of mechanisms extruding H+ (or acid equivalents) can explain the maintenance of pHi well above the equilibrium. The Na+/H+ exchanger (NHE) is one of these mechanisms and plays a central role in the regulation of pHi as well as in the control of cell volume and of intracellular Na+ concentration ([Na+]i). In addition, the exchanger appears to facilitate the induction of cellular growth and proliferation in response to numerous growth factors. The NHE has been found in virtually all living cells and may be phylogenetically one of the most primitive transport systems. The system catalyses the electroneutral exchange of Na+ for H+, with a coupled 1:1 stoichiometry. Under physiological conditions, the inwardly directed Na+ gradient, which is maintained by the activity of the Na+–K+-ATPase and the Na+/Ca2+ exchanger, provides a constant driving force for H+ extrusion. According to the electrochemical transmembrane gradients, the NHE should extrude intracellular H+ in exchange for extracellular Na+ until a pHi far beyond physiological values (8.2–8.5) is obtained. However, at a pHi of around 7.1–7.2 the antiporter extrudes only the protons generated by the intermediate metabolism and those leaking into the cell, so that pHi reaches … 

* Corresponding author. Tel.: +54-221-483-4833; fax: +54-221-425-5861
Metagenome-wide Association Studies Potentiate Precision Medicine for Rheumatoid Arthritis
Authors: Yigang Tong
Journal: Genomics Proteomics & Bioinformatics (2015)

An article recently published in Nature Medicine by the group led by Drs. Jun Wang and Yingrui Li from BGI-Shenzhen and Xuan Zhang from Beijing Union Medical College Hospital, Chinese Academy of Medical Sciences revealed the relationship between the human microbiome and rheumatoid arthritis (RA) [1]. Zhang et al. performed metagenomic shotgun sequencing and a metagenome-wide association study (MGWAS) on fecal, dental, and salivary samples from a large cohort of treatment-naive RA individuals and healthy controls. As a result, they found that the gut microbiome and the oral microbiome exhibited significant differences between RA patients and normal subjects. More importantly, the altered gut microbiome and oral microbiome of RA patients were partially corrected by disease-modifying antirheumatic drugs (DMARDs). Therefore, their findings suggest that the gut and oral microbiome composition of RA patients could be potentially used to stratify RA patients and facilitate disease diagnosis and prognosis.
Ex vivo conditioning with IL-12 decreases T cell sensitivity to intratumoral INF-γ-induced apoptosis following adoptive transfer
Authors: C Marcela Diaz-Montero, Charles Tannenbaum, Patricia Rayman, Paul Pavicic, Jin Sub Kim, Marc Ernstoff, James Finke
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts In order to induce significant tumor regression T cells must effectively recognize and kill target cells. Secretion of IFN-γ is considered a key effector function of activated CD8+ T cells via induction of apoptosis. Thus programming T cells to secrete high levels of IFN-γ after
Lithium in the Kidney: Friend and Foe?
Authors: Mohammad Alsady, Ruben Baumgarten, Peter M.T. Deen, Theun de Groot
Journal: Journal of the American Society of Nephrology (2015)

Trace amounts of lithium are essential for our physical and mental health, and administration of lithium has improved the quality of life of millions of patients with bipolar disorder for &gt;60 years. However, in a substantial number of patients with bipolar disorder, long–term lithium therapy comes at the cost of severe renal side effects, including nephrogenic diabetes insipidus and rarely, ESRD. Although the mechanisms underlying the lithium–induced renal pathologies are becoming clearer, several recent animal studies revealed that short-term administration of lower amounts of lithium prevents different forms of experimental AKI. In this review, we discuss the knowledge of the pathologic and therapeutic effects of lithium in the kidney. Furthermore, we discuss the underlying mechanisms of these seemingly paradoxical effects of lithium, in which fine-tuned regulation of glycogen synthase kinase type 3, a prime target for lithium, seems to be key. The new discoveries regarding the protective effect of lithium against AKI in rodents call for follow-up studies in humans and suggest that long-term therapy with low lithium concentrations could be beneficial in CKD.
'Nodophagy'
Authors: Mahendrasingh Ramjeet, Séamus Hussey, Dana J. Philpott, Leonardo H. Travassos
Journal: Gut Microbes (2010)

Autophagy is a homeostatic pathway that processes and recycles damaged organelles and other cytoplasmic contents. While studies have implicated autophagy in the immune response to infection, the understanding of how the autophagic machinery specifically targets intracellular pathogens has remained elusive. Two recent studies have uncovered an autophagy-mediated immune response to bacteria through their detection by Nod receptors. In particular, Nod1 and Nod2 recruit the autophagic protein ATG16L1 to the plasma membrane at the bacterial entry site to promote an autophagy-dependent elimination of bacteria. In addition, Nod2 and ATG16L1 synergize to initiate an adaptive immune response to bacterial invasion by enhancing major histocompatibility complex (MHC) class II antigen presentation. These findings link two Crohn disease-associated susceptibility genes and reveal that cells expressing the risk-associated variants of ATG16L1 are defective in autophagy-mediated bacterial handling and antigen presentation. This could lead to bacterial persistence and contribute to the pathogenesis of the disease.
Enhanced therapeutic effect using sequential administration of antigenically distinct oncolytic viruses expressing oncostatin M in a Syrian hamster orthotopic pancreatic cancer model
Authors: Estanislao Nistal-Villan, Maria Bunuales, Joanna Poutou, Manuela Gonzalez-Aparicio, Carlos Bravo-Perez, Jose I. Quetglas, Beatriz Carte, Gloria Gonzalez-Aseguinolaza, Jesus Prieto, Esther Larrea, Ruben Hernandez-Alcoceba
Journal: Molecular Cancer (2015)

The limited efficacy of current treatments against pancreatic cancer has prompted the search of new alternatives such as virotherapy. Activation of the immune response against cancer cells is emerging as one of the main mechanisms of action of oncolytic viruses (OV). Direct oncolysis releases tumor antigens, and viral replication within the tumor microenvironment is a potent danger signal. Arming OV with immunostimulatory transgenes further enhances their therapeutic effect. However, standard virotherapy protocols do not take full advantage of OV as cancer vaccines because repeated viral administrations may polarize immune responses against strong viral antigens, and the rapid onset of neutralizing antibodies limits the efficacy of redosing. An alternative paradigm based on sequential combination of antigenically distinct OV has been recently proposed. We have developed a protocol consisting of sequential intratumor administrations of new Adenovirus (Ad) and Newcastle Disease Virus (NDV)-based OV encoding the immunostimulatory cytokine oncostatin M (OSM). Transgene expression, toxicity and antitumor effect were evaluated using an aggressive orthotopic pancreatic cancer model in Syrian hamsters, which are sensitive to OSM and permissive for replication of both OVs. NDV-OSM was more cytolytic, whereas Ad-OSM caused higher OSM expression in vivo. Both viruses achieved only a marginal antitumor effect in monotherapy. In addition, strong secretion of OSM in serum limited the maximal tolerated dose of Ad-OSM. In contrast, moderate doses of Ad-OSM followed one week later by NDV-OSM were safe, showed a significant antitumor effect and stimulated immune responses against cancer cells. Similar efficacy was observed when the order of virus administrations was reversed. Sequential administration of oncolytic Ad and NDV encoding OSM is a promising approach against pancreatic cancer.