tbuckley/cabot-search huggingface dataset:
Correlation of Segmented Metabolic Tumor Volume with Outcome - Letter
Authors: Esther G.C. Troost, Dominic A.X. Schinagl, Johan Bussink, Johannes H.A.M. Kaanders, Wim J.G. Oyen, Otto C. Boerman
Journal: Clinical Cancer Research (2010)

Comment on Chung et al. “Metabolic tumor volume of [18F]-fluorodeoxyglucose positron emission tomography/computed tomography predicts short-term outcome to radiotherapy with or without chemotherapy in pharyngeal cancer” published in Clinical Cancer Research 2009;15(18):5861-5866.

With great interest, we read the publication by Chung et al. (1). In 82 pharyngeal cancer patients undergoing (chemo)radiation, the authors studied the prognostic value of a “metabolic tumor volume” (MTV), defined as increased 18FDG-PET uptake in primary tumors and lymph node metastases. Although this concept seems appealing, we feel that comments about the methods are justified.

First, the authors chose a threshold of 2.5 for the standardized uptake value (SUV) for segmentation of the 18FDG-PET images, which is commonly applied in NSCLC. Not only is this threshold arbitrary and protocol dependent (2), but the most appropriate threshold for 18FDG-PET segmentation in head and neck tumors remains to be determined. As opposed to NSCLC, head and neck tumors are surrounded by closely packed tissue consisting of squamous cells, the cell type the tumor originated from, and peritumoral inflammation hampering PET segmentation. In two recent publications, we showed the effect of applying different thresholds, including SUV 2.5, on the segmentation of primary head and neck tumors and cervical lymph nodes and advocated the validation of iterative methods (3, 4). Furthermore, as shown by Nagakawa et al. (5), a threshold of SUV 2.5 is ineffective for the segmentation of metastatic lymph nodes, as 30% of patients had reactive cervical lymph nodes with a maximum SUV of 2.5 or higher.

Second, the authors did not incorporate necrotic areas within the tumor or lymph nodes in the MTVs because they do not consume 18FDG. However, necrotic volumes are often the result of severe hypoxia, a tumor characteristic adversely affecting treatment outcome and prognosis. Thus, although this approach may be legitimate in terms of defining the MTV, these patients should be either excluded from the analysis or analyzed as separate cohort because this confounding characteristic may also influence the correlation of MTVs with short-term outcome.

Third and most importantly, Chung et al. omitted to correlate the gross tumor volumes (GTV) on CT with the MTVs and short-term treatment outcomes in both univariate and multivariate analyses. There is solid evidence that the GTV of the primary tumor and metastatic cervical lymph nodes is one of the most powerful prognostic factors for treatment outcome among patients with advanced-stage disease (6). That is why the anatomic tumor size still forms the basis of the TNM staging system. Consequently, establishing any added value of MTV over anatomic GTV information should have been one of the main goals of the study.

Disclosure of Potential Conflicts of Interest No potential conflicts of interest were disclosed.
The surface-anchored NanA protein promotes pneumococcal brain endothelial cell invasion
Authors: Satoshi Uchiyama, Aaron F. Carlin, Arya Khosravi, Shannon Weiman, Anirban Banerjee, Darin Quach, George Hightower, Tim J. Mitchell, Kelly S. Doran, Victor Nizet
Journal: The Journal of Experimental Medicine (2009)

In humans, Streptococcus pneumoniae (SPN) is the leading cause of bacterial meningitis, a disease with high attributable mortality and frequent permanent neurological sequelae. The molecular mechanisms underlying the central nervous system tropism of SPN are incompletely understood, but include a primary interaction of the pathogen with the blood–brain barrier (BBB) endothelium. All SPN strains possess a gene encoding the surface-anchored sialidase (neuraminidase) NanA, which cleaves sialic acid on host cells and proteins. Here, we use an isogenic SPN NanA-deficient mutant and heterologous expression of the protein to show that NanA is both necessary and sufficient to promote SPN adherence to and invasion of human brain microvascular endothelial cells (hBMECs). NanA-mediated hBMEC invasion depends only partially on sialidase activity, whereas the N-terminal lectinlike domain of the protein plays a critical role. NanA promotes SPN–BBB interaction in a murine infection model, identifying the protein as proximal mediator of CNS entry by the pathogen.
Evaluation of pulmonary function and functional capacity in patients with liver cirrhosis
Authors: Olga Corlateanu, Eugen Tcaciuc, Alexandru Corlateanu
Journal: European Respiratory Journal (2012)

Background:  Various changes can be detected by pulmonary function tests in patients diagnosed with chronic hepatic diseases. These changes characterize the hepatopulmonary syndrome result in hypoxemia and affect one-third of all patients diagnosed with cirrhosis.  The aim of this study was to evaluate and compare the pulmonary function and functional capacity in patients with liver cirrhosis according to the Child-Pugh score and to correlate these variables within each group.  Methods:  40 patients with liver cirrhosis were enrolled into the study. Spirometry (FEV1, FVC, FEV1/FVC), hemoglobin levels, dyspnoea by BORG scale, exercise capacity by 6-min walking test (6MWT), blood gas analysis were evaluated. Blood gases were measured in supine and sitting positions.  Results:  The patients were classified into three groups, according to cirrhotic severity, using Childs-Pugh classification (A - 7 patients; B - 24 patients; C - 9 patients). There were significant differences (p  Conclusion:  The progress of liver disease contributes to the onset of several complications which together appear to contribute to the reduction of pulmonary function and functional capacity of patients.
Analysis of Mortality in Mental Disorders—Reply
Authors: Elizabeth Reisinger Walker, Robin E. McGee, Benjamin G. Druss
Journal: JAMA Psychiatry (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 Psychiatry 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 Psychiatry journal
Reversal of Glomerulosclerosis after High-Dose Enalapril Treatment in Subtotally Nephrectomized Rats
Authors: Marcin Adamczak, Marie-Luise Gross, Jan Krtil, Andreas Koch, Karin Tyralla, Kerstin Amann, Eberhard Ritz
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. Interventions to block the renin-angiotensin system (RAS) halt the progression of renal lesions in renal damage models. It has recently also been reported that established glomerulosclerosis can be reversed by pharmacologic blockade of the RAS. It was the aim of this study to confirm that high doses of angiotensin-converting enzyme (ACE) inhibitors reverse established glomerulosclerosis and to extend the findings by providing quantitative information on glomerular geometry, podocytes and other glomerular cells, renal vessels and tubulointerstitial tissue. Male Sprague Dawley rats were subjected to subtotal surgical renal ablation (SNX) ( n = 27) or sham operation ( n = 31) and fed using a pair-feeding protocol. Eight weeks after surgery, rats were either sacrificed or allocated to two arms: enalapril treatment (48 mg/kg body wt per day administered in the drinking fluid for 4 wk) or no treatment. Renal morphology was evaluated after 8 or 12 wk, respectively, by stereology in tissue fixed by pressure-controlled perfusion. Both systolic BP and albumin excretion rate were significantly higher in SNX compared with sham-operated controls. They were significantly reduced in SNX after delayed enalapril treatment. The glomerulosclerosis (GSI), tubulointerstitial (TII), and vascular (VI) damage indices were significantly higher in all SNX groups than in sham-operated controls. At the end of the experiment (12 wk after SNX) GSI, TII, and VI were significantly lower in SNX with delayed enalapril treatment (0.77 ± 0.18, 0.63 ± 0.19 and 0.43 ± 0.16, respectively) compared with untreated SNX (1.64 ± 0.14, 1.16 ± 0.34 and 0.67 ± 0.29, respectively). GSI, TII, and VI were also significantly lower in SNX with delayed enalapril treatment compared with SNX sacrificed without treatment 8 wk after SNX. The same was true for glomerular volume. The number of podocytes was not affected by SNX, but podocyte volume was increased. Both indices remained unaffected by treatment. The numbers of cells within the mesangium and endothelial cells per glomerulus were significantly lower in SNX after delayed enalapril treatment compared with untreated SNX. These results strongly suggest regression of preexisting lesions, i.e. , glomerular, tubular, and vascular remodeling as well as reversal of glomerular hypertrophy by ACE inhibitor treatment. The study confirms that high-dose ACE inhibitor treatment causes partial reversal of glomerular as well as interstitial lesions in subtotally nephrectomized rats. E-mail: kerstin.amann@patho.imed.uni-erlangen.de
Tumor Biologic Factors and Breast Cancer Prognosis Among White, Hispanic, and Black Women in the United States
Authors: R. M. Elledge, G. M. Clark, G. C. Chamness, C. K. Osborne
Journal: JNCI Journal of the National Cancer Institute (1994)

In the United States, prognosis and survival after the diagnosis of breast cancer is poorer among black patients and, to a lesser extent, among Hispanic patients, compared with white patients. Patients who are black or Hispanic have been reported to present with higher stage or more advanced disease. Even after adjusting for stage, however, survival rates are lower for blacks but not for Hispanics. Purpose : Our purpose was to compare survival, age, tumor size, nodal status, estrogen-receptor (ER) and progesterone-receptor (PgR) status, histologic type, S-phase fraction, DNA ploidy status, HER-2/neu protein expression, and p 53 protein status, along with systemic treatment, in a large group of white, black, and Hispanic U.S. women. Methods: From 1970 to 1991, breast tumor specimens were submitted to The University of Texas Health Science Center from 31 contributing hospitals throughout the United States for ER and PgR assay. A total of 4885 white, 1016 black, and 777 Hispanic women were eligible for this study. Median follow-up was 57 months. Results : Overall, white women were significantly more likely to be older and to have smaller tumors, have less lymph node involvement, have tumors with positive ER and PgR status, and have a lower S-phase fraction compared with Hispanic or black women. There were no clinically important differences in DNA ploidy, histologic type, HER-2/neu, and p 53 expression among the three groups. Considering all stages, white women had the best overall survival (date of diagnosis to date of death) at 5 years–75% ±1% (means ± SE), with a median survival of 166 months, but Hispanic women had an intermediate survival—70% ± 2% (median survival, 156 months), and black women had the worst survival—65% ± 2% (median survival, 117 months) ( P <.0001). For node-negative patients, there was no significant difference in disease-free survival (date of diagnosis to date of first recurrence) or overall survival, although blacks tended to have a worse prognosis. For node-positive or locally advanced disease and for metastatic disease, blacks had significantly ( P <.0001) worse disease-free and overall survival than did white or Hispanic women. Differences in the use of systemic therapy did not explain these outcomes. Conclusion : A number of biologic factors associated with poor prognosis are found with a significantly increased frequency in breast tumors from Hispanic and, particularly, from black women. Tumors with a more aggressive biology could lead to a higher stage at diagnosis and a poorer survival for the group as a whole. [J Natl Cancer Inst 86: 705–712, 1994]
Cutaneous Anthrax Associated With Microangiopathic Hemolytic Anemia and Coagulopathy in a 7-Month-Old Infant
Authors: Abigail Freedman, Olubunmi Afonja, Mary Wu Chang, Farzad Mostashari, Martin Blaser, Guillermo Perez-Perez, Herb Lazarus, Robert Schacht, Jane Guttenberg, Michael Traister, William Borkowsky
Journal: JAMA (2002)

A 7-month-old infant with cutaneous anthrax developed severe systemic illness despite early treatment with antibiotics. The infant displayed severe microangiopathic hemolytic anemia with renal involvement, coagulopathy, and hyponatremia. These findings are unusual with cutaneous anthrax, but have been described in illness resulting from spider toxin and may delay correct diagnosis. The systemic manifestations of the disease persisted for nearly a month despite corticosteroid therapy, but resolved.
Quantum Dots: An Insight and Perspective of Their Biological Interaction and How This Relates to Their Relevance for Clinical Use
Authors: Martin J. D. Clift, Vicki Stone
Journal: Theranostics (2012)

Due to their novel physico-chemical characteristics, semi-conductor nanocrystal quantum dots (QDs) provide an advantageous perspective towards numerous different consumer and medical applications.The most notable potential application of QDs is their use as therapeutic and diagnostic tools in nanomedicine.Despite the many benefits posed by QDs, the proposed, intentional exposure to humans has raised concerns towards their potential impact upon human health.These concerns are predominantly based upon the heterogeneous composition of QDs, which most commonly comprises of a cadmium-based core and zinc sulphide shell.Whilst other nanoparticle (NP) types possess a similar structure to QDs (i.e.core-shell technology (e.g.Fe 2 O 3 , Au and superparamagnetic iron oxide NPs)), the importance of the concerns surrounding human exposure to QDs is amplified further since, due to the sophisticated chemical and light-emitting properties of QDs, the use of these NPs within any (nano)medical setting/application could be suggested as realistic, rather than simply an advantageous possibility.It is therefore imperative that a thorough understanding of how QDs interact with various biological systems, predominantly those relative to humans and what the consequences of such interactions are is gained with extreme alacrity.It is the aim of this review to highlight the current knowledge base of QD-biological system interactions, where the knowledge gaps (still) remain and how the understanding of this interaction relates to the most notable of applications for QDs; their clinical relevance.
Predisposition to essential hypertension and the development of diabetic nephropathy.
Authors: G C Viberti, K Earle
Journal: Journal of the American Society of Nephrology (1992)

Only a subset of insulin-dependent diabetic patients are at risk of developing nephropathy. Prospective studies of uncomplicated insulin-dependent diabetic cohorts have shown that a rise in systemic arterial pressure is a concomitant feature of the progression to early nephropathy. The development of hypertension is an integral feature of established nephropathy in diabetes, and its amelioration retards the progression of disease and may improve overall mortality. Family studies have suggested that nondiabetic parents of insulin-dependent diabetic patients with nephropathy have a greater prevalence of hypertension, and in certain groups of non-insulin dependent patients, it has been found that the blood pressure before the onset of diabetes correlates with the development of nephropathy after the onset of diabetes. These results indicate that a propensity to hypertension may be part of the genetic predisposition to nephropathy. This contention is further supported by the finding that a raised erythrocyte sodium-lithium countertransport, a biochemical marker of hypertension and cardiovascular disease whose activity is largely genetically determined, occurs with greater frequency in proteinuric diabetic patients and their nondiabetic parents than in those diabetic patients without nephropathy and their parents. Recent family studies have also shown that a family history of cardiovascular disease significantly increases the risk of nephropathy by up to three-fold in insulin-dependent diabetes. It is suggested that the cardiorenal complications of diabetes mellitus may be linked to reduced insulin sensitivity, which itself is associated with hypertension, raised sodium-lithium countertransport rates, and cardiovascular disease.
Estrogen Paradox in Pulmonary Hypertension
Authors: Soban Umar, Marlene Rabinovitch, Mansoureh Eghbali
Journal: American Journal of Respiratory and Critical Care Medicine (2012)

Although the incidence of pulmonary hypertension is higher in female patients, numerous experimental studies have demonstrated better outcome in female animals, exacerbation of the disease after ovariectomy, and a strong protective effect of estrogen: a phenomenon known as the "estrogen paradox" of pulmonary hypertension. On the other hand, some clinical studies have indirectly linked estrogen to increased risk of portopulmonary hypertension, whereas others implicate increased estrogen metabolism and high levels of certain estrogen metabolites in promoting pulmonary vascular remodeling in familial pulmonary arterial hypertension. In this review we investigate the estrogen paradox through highlighting the differential receptor-mediated effects of estrogen. Although estrogen and estrogen receptor-based therapies have shown promise in rescuing preexisting pulmonary hypertension in animals, their role is yet to be defined in humans.
Cardiac involvement and superior vena caval obstruction in Behcet's disease.
Authors: N Roguin, S Haim, R Reshef, E Peleg, E Riss
Journal: Thorax (1978)

A patient with Behçet9s disease developed the rare complications of pericarditis and, two months later, superior vena caval obstruction. The latter complication was investigated by angiography to exclude other causes. As a result of this investigation the caval obstruction was managed conservatively, the symptoms and signs improving spontaneously.
EZH2-Regulated DAB2IP Is a Medulloblastoma Tumor Suppressor and a Positive Marker for Survival
Authors: Michiel Smits, Sjoerd van Rijn, Esther Hulleman, Dennis Biesmans, Dannis G. van Vuurden, Marcel Kool, Christine Haberler, Eleonora Aronica, W. Peter Vandertop, David P. Noske, Thomas Würdinger
Journal: Clinical Cancer Research (2012)

Medulloblastoma is the most common malignant brain tumor in children. Despite recent improvements, the molecular mechanisms driving medulloblastoma are not fully understood and further elucidation could provide cues to improve outcome prediction and therapeutic approaches.Here, we conducted a meta-analysis of mouse and human medulloblastoma gene expression data sets, to identify potential medulloblastoma tumor suppressor genes.We identified DAB2IP, a member of the RAS-GTPase-activating protein family (RAS GAP), and showed that DAB2IP expression is repressed in medulloblastoma by EZH2-induced trimethylation. Moreover, we observed that reduced DAB2IP expression correlates significantly with a poor overall survival of patients with medulloblastoma, independent of metastatic stage. Finally, we showed that ectopic DAB2IP expression enhances stress-induced apoptosis in medulloblastoma cells and that reduced expression of DAB2IP in medulloblastoma cells conveys resistance to irradiation-induced cell death.These results suggest that repression of DAB2IP may at least partly protect medulloblastoma cells from apoptotic cell death. Moreover, DAB2IP may represent a molecular marker to distinguish patients with medulloblastoma at high risk from those with a longer survival prognosis.
Quantifying the Role of Angiogenesis in Malignant Progression of Gliomas: <i>In Silico</i> Modeling Integrates Imaging and Histology
Authors: Kristin R. Swanson, Russell C. Rockne, Jonathan Claridge, Mark A. Chaplain, Ellsworth C. Alvord, Alexander R.A. Anderson
Journal: Cancer Research (2011)

Abstract Gliomas are uniformly fatal forms of primary brain neoplasms that vary from low- to high-grade (glioblastoma). Whereas low-grade gliomas are weakly angiogenic, glioblastomas are among the most angiogenic tumors. Thus, interactions between glioma cells and their tissue microenvironment may play an important role in aggressive tumor formation and progression. To quantitatively explore how tumor cells interact with their tissue microenvironment, we incorporated the interactions of normoxic glioma cells, hypoxic glioma cells, vascular endothelial cells, diffusible angiogenic factors, and necrosis formation into a first-generation, biologically based mathematical model for glioma growth and invasion. Model simulations quantitatively described the spectrum of in vivo dynamics of gliomas visualized with medical imaging. Furthermore, we investigated how proliferation and dispersal of glioma cells combine to induce increasing degrees of cellularity, mitoses, hypoxia-induced neoangiogenesis and necrosis, features that characterize increasing degrees of “malignancy,” and we found that changes in the net rates of proliferation (ρ) and invasion (D) are not always necessary for malignant progression. Thus, although other factors, including the accumulation of genetic mutations, can change cellular phenotype (e.g., proliferation and invasion rates), this study suggests that these are not required for malignant progression. Simulated results are placed in the context of the current clinical World Health Organization grading scheme for studying specific patient examples. This study suggests that through the application of the proposed model for tumor–microenvironment interactions, predictable patterns of dynamic changes in glioma histology distinct from changes in cellular phenotype (e.g., proliferation and invasion rates) may be identified, thus providing a powerful clinical tool. Cancer Res; 71(24); 7366–75. ©2011 AACR.