tbuckley/cabot-search huggingface dataset:
Real-Time Cancer Cell Tracking by Bioluminescence in a Preclinical Model of Human Bladder Cancer Growth and Metastasis
Authors: Geertje van der Horst, Joost J. van Asten, Anne Figdor, Christel van den Hoogen, Henry Cheung, Rob F.M. Bevers, Rob C.M. Pelger, Gabri van der Pluijm
Journal: European Urology (2011)
Nonablative Allogeneic Stem-Cell Transplantation for Advanced/Recurrent Mantle-Cell Lymphoma
Authors: Issa F. Khouri, Ming-S. Lee, Rima M. Saliba, Gu Jun, Luis Fayad, Anas Younes, Barbara Pro, Sandra Acholonu, Peter McLaughlin, Ruth L. Katz, Richard E. Champlin
Journal: Journal of Clinical Oncology (2003)

Purpose: Patients with relapsed mantle-cell lymphoma have poor prognosis and short survival. Our aim was to determine the efficacy of nonablative allogeneic stem-cell transplantation in patients with relapsed mantle-cell lymphoma. Patients and Methods: Eighteen patients were treated in one of two consecutive trials. Thirteen patients underwent a conditioning regimen of fludarabine (30 mg/m 2 daily for 3 days), cyclophosphamide (750 mg/m 2 daily for 3 days), and high-dose rituximab. For the remaining five patients, the conditioning regimen consisted of cisplatin (25 mg/m 2 daily for 4 days), fludarabine (30 mg/m 2 daily for 2 days), and cytarabine (1,000 mg/m 2 daily for 2 days). Tacrolimus and methotrexate were used for graft-versus-host disease prophylaxis. Results: The median age was 56.5 years. Patients underwent a median of three prior chemotherapy regimens. Prior autologous transplantation failed in five (28%) patients and 16 (89%) had chemosensitive disease. Donor cell engraftment occurred in all patients. Eight patients (44%) required no platelet or RBC transfusion, and acute graft-versus-host disease of greater than grade 2 did not develop in any patient. The day-100 mortality was 0%. Complete remission (CR) occurred in 17 patients. Three patients progressed, and one was reinduced into continuous CR with donor lymphocyte infusion. With a median follow-up period of 26 months, the actuarial probability of current-event-free-survival at 3 years was 82% (95% CI, 65% to 99%). Conclusion:Our data suggest that nonablative allogeneic transplantation is a safe and potentially effective strategy for patients with relapsed and chemosensitive mantle-cell lymphoma.
Junior doctors lobby MPs in MTAS protest
Authors: Lynn Eaton
Journal: BMJ (2007)

Junior doctors lobbied MPs on Tuesday because they are so aggrieved at the computerised application process for jobs that start this August in the United Kingdom.

This was the latest protest against the medical training application service (MTAS) organised by Remedy UK, which was behind similar marches in London and Glasgow in March ( BMJ 2007;334:602-3, doi: 10.1136/bmj.39160.616470.DB, 24 Mar).

The protesters started with a rally outside the Houses of Parliament then some of the doctors went on to lobby their MPs inside the House of Commons. Although only three doctors or their supporters were …
Myoglobinuria Precipitated by Viral Infection
Authors: Byron S. Berlin
Journal: JAMA (1974)

A 30-year-old man had an episode of acute myoglobinuria in association with infection due to type A2 (Hong Kong) influenza virus in December 1968. He was well until he again experienced myoglobinuria in July 1972. This episode was in association with a coxsackievirus B5 infection. The occurrence of two separate instances of myoglobinuria with demonstrated virus infections is interpreted as clear evidence that virus infections can precipitate rhabdomyolysis.
Augmentation of Antigen Receptor–mediated Responses by Histamine H1 Receptor Signaling
Authors: Yasmin Banu, Takeshi Watanabe
Journal: The Journal of Experimental Medicine (1999)

Histamine is considered one of the important mediators of immediate hypersensitivity and inflammation, and acts via G protein-coupled receptors. Here, we report that histamine may affect antigen receptor-mediated immune responses of T and B cells via a signal(s) from histamine H1 receptors (H1Rs). Histamine exhibited enhancing effects on the in vitro proliferative responses of anti-CD3epsilon- or anti-IgM-stimulated spleen T and B cells, respectively, at the culture condition that the fetal calf serum was dialyzed before culture and c-kit-positive cells were depleted from the spleen cells. In studies of histamine H1R knockout mice, H1R-deficient T cells had low proliferative responses to anti-CD3epsilon cross-linking or antigen stimulation in vitro. B cells from H1R-deficient mice were also affected, demonstrating low proliferative responses to B cell receptor cross-linking. Antibody production against trinitrophenyl-Ficoll was reduced in H1R-deficient mice. Other aspects of T and B cell function were normal in the H1R knockout mice. H1R-deficient T and B cells showed normal responses upon stimulation with interleukin (IL)-2, IL-4, CD40 ligand, CD40 ligand plus IL-4, and lipopolysaccharide. Collectively, these results imply that the signal generated by histamine through H1R augments antigen receptor-mediated immune responses, suggesting cross-talk between G protein-coupled receptors and antigen receptor-mediated signaling.
Abstract 225: Overexpression of truncated Ron augments benzyl isothiocyanate-induced apoptosis in human breast cancer cells
Authors: Anuradha Sehrawat, Shivendra V. Singh
Journal: Cancer Research (2014)

Abstract Phytochemicals from edible plants remain attractive for prevention of breast cancer, which is a leading cause of cancer-related mortality in women worldwide. We have shown previously that benzyl isothiocyanate (BITC), a small-molecule found in edible cruciferous vegetables such as garden cress, confers significant protection against mammary cancer development in MMTV-neu transgenic mice. BITC-mediated prevention of mammary carcinogenesis in MMTV-neu mice in vivo is associated with tumor cell apoptosis induction and elimination of breast cancer stem cells (bCSC). In cultured human breast cancer cells, BITC-induced apoptosis is accompanied by activation of multidomain proapoptotic protein Bax whereas inhibition of bCSC self-renewal is significantly attenuated by overexpression of truncated Ron (recepteur d’origine nantais) tyrosine kinase. Ron expression is very low in normal human breast epithelium but its overexpression has been reported in about 50% of primary breast cancers. In addition, mammary-specific overexpression of wild-type Ron as well as its constitutively active form induces highly metastatic breast tumors in mice. The present study was undertaken to study the role of truncated Ron (sfRon) in BITC-induced apoptosis using MCF-7 and MDA-MB-361 human breast cancer cells. Overexpression of sfRon resulted in statistically significant augmentation of BITC-induced apoptotic cell death in both cell lines as judged by flow cytometry after staining with Annexin V and propidium iodide, analysis of histone associated DNA fragment release into the cytosol, and/or cell proliferation assay. On the other hand, sfRon overexpressing MCF-7 cells were resistant to BITC-mediated G2/M phase cell cycle arrest when compared with parental cells. Increased apoptosis following BITC treatment in sfRon overexpressing cells was due to enhanced activation of Bax and/or Bak. Taken together, these findings indicate that overexpression of sfRon sensitizes human breast cancer cells to BITC-induced apoptosis. This investigation was supported by the NCI grant CA129347-06. Citation Format: Anuradha Sehrawat, Shivendra V. Singh. Overexpression of truncated Ron augments benzyl isothiocyanate-induced apoptosis in human breast cancer cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 225. doi:10.1158/1538-7445.AM2014-225
Influence of Low HDL on Progression of Coronary Artery Disease and Response to Fluvastatin Therapy
Authors: Christie M. Ballantyne, J. Alan Herd, Laura L. Ferlic, J. Kay Dunn, John A. Farmer, Peter H. Jones, Jeffrey R. Schein, Antonio M. Gotto
Journal: Circulation (1999)

Background —Patients with coronary artery disease (CAD) commonly have low HDL cholesterol (HDL-C) and mildly elevated LDL cholesterol (LDL-C), leading to uncertainty as to whether the appropriate goal of therapy should be lowering LDL-C or raising HDL-C. Methods and Results —Patients in the Lipoprotein and Coronary Atherosclerosis Study (LCAS) had mildly to moderately elevated LDL-C; many also had low HDL-C, providing an opportunity to compare angiographic progression and the benefits of the HMG-CoA reductase inhibitor fluvastatin in patients with low versus patients with higher HDL-C. Of the 339 patients with biochemical and angiographic data, 68 had baseline HDL-C &lt;0.91 mmol/L (35 mg/dL), mean 0.82±0.06 mmol/L (31.7±2.2 mg/dL), versus 1.23±0.29 mmol/L (47.4±11.2 mg/dL) in patients with baseline HDL-C ≥0.91 mmol/L. Among patients on placebo, those with low HDL-C had significantly more angiographic progression than those with higher HDL-C. Fluvastatin significantly reduced progression among low–HDL-C patients: 0.065±0.036 mm versus 0.274±0.045 mm in placebo patients ( P =0.0004); respective minimum lumen diameter decreases among higher–HDL-C patients were 0.036±0.021 mm and 0.083±0.019 mm ( P =0.09). The treatment effect of fluvastatin on minimum lumen diameter change was significantly greater among low–HDL-C patients than among higher–HDL-C patients ( P =0.01); among low–HDL-C patients, fluvastatin patients had improved event-free survival compared with placebo patients. Conclusions —Although the predominant lipid-modifying effect of fluvastatin is to decrease LDL-C, patients with low HDL-C received the greatest angiographic and clinical benefit.
Psychological Assessment in Cardiac Rehabilitation
Authors: Chiara Rafanelli, Renzo Roncuzzi, Livio Finos, Eliana Tossani, Elena Tomba, Lara Mangelli, Stefano Urbinati, Giuseppe Pinelli, Giovanni A. Fava
Journal: Psychotherapy and Psychosomatics (2003)

While there has been an upsurge of interest in the psychiatric correlates of myocardial infarction, little is known about the presence of psychological distress in the setting of cardiac rehabilitation.A consecutive series of 61 patients with recent myocardial infarction who participated in a cardiac rehabilitation program was evaluated by means of both observer-rated (DSM and DCPR) and self-rated (Psychosocial Index) methods. A follow-up of this patient population was undertaken (median = 2 years). Survival analysis was used to characterize the clinical course of patients.Twenty percent of patients had a DSM-IV diagnosis (in half of the cases minor depression). An additional 30% of patients presented with a DCPR cluster, such as type A behavior and irritable mood. Only high levels of self-perceived stressful life circumstances and psychological distress approached statistical significance as a psychological risk factor for cardiovascular events after myocardial infarction.Psychological evaluation of patients undergoing cardiac rehabilitation needs to incorporate both clinical (DSM) and subclinical (DCPR) methods of classification. Type A behavior was present in about a quarter of patients and can be studied in specific subgroups of cardiovascular patients defined by DCPR.
Preservation of insulin mRNA levels and insulin secretion in HIT cells by avoidance of chronic exposure to high glucose concentrations.
Authors: R P Robertson, H J Zhang, K L Pyzdrowski, T F Walseth
Journal: Journal of Clinical Investigation (1992)

Glucose toxicity of the pancreatic beta cell is considered to play a secondary role in the pathogenesis of type II diabetes mellitus. To gain insights into possible mechanisms of action of glucose toxicity, we designed studies to assess whether the loss of insulin secretion associated with serial passages of HIT-T15 cells might be caused by chronic exposure to high glucose levels since these cells are routinely cultured in media containing supramaximal stimulatory concentrations of glucose. We found that late passages of HIT cells serially cultured in media containing 11.1 mM glucose lost insulin responsivity and had greatly diminished levels of insulin content and insulin mRNA. In marked contrast, late passages of HIT cells cultured serially in media containing 0.8 mM glucose retained insulin mRNA, insulin content, and insulin responsivity to glucose in static incubations and during perifusion with glucose. No insulin gene mutation or alteration of levels of GLUT-2 were found in late passages of HIT cells cultured with media containing 11.1 mM glucose. These data uniquely indicate that loss of beta cell function in HIT cells passed serially under high glucose conditions is caused by loss of insulin mRNA, insulin content, and insulin secretion and is preventable by culturing HIT cells under low glucose conditions. This strongly suggests potential genetic mechanisms of action for glucose toxicity of beta cells.
The four pillars of global academic medicine
Authors: Kamran Abbasi
Journal: BMJ (2004)

Have you ever slept during a lecture? A quarter of university students have, although the figure might be higher for medical students—who learn a great deal from role models, such as professors snoozing in grand rounds. Academia must be in crisis when, according to a survey in the Independent newspaper, more students have sent a text message during a lecture (63%) than asked a question (49%).

If you manage to stay awake more than you sleep you may be aware that medical education has a hidden curriculum, which, say Heidi …
Treatment Rationale in Thyroid Carcinoma Effect of Scan Dose
Authors: LALITHA RAMANNA, ALAN D. WAXMAN, MICHAEL B. BRACHMAN, DOINA E. TANASESCU, NANCY CHAPMAN, GLENN D. BRAUNSTEIN
Journal: Clinical Nuclear Medicine (1985)

The authors have previously shown that the definition of ablation of thyroid tissue in patients treated with thyroidectomy and radioiodine (l-131) for thyroid carcinoma depends upon the dose of l-131 used to scan the patient. The therapeutic response to l-131 therapy was evaluated in a group of ten differentiated thyroid cancer patients who had a negative 2-mCi (-2 mCi) diagnostic study, but had a positive 10-mCi (+10 mCi) diagnostic study (group 1) during their follow-up evaluation. These results were compared to another group of ten differentiated thyroid cancer patients who received l-131 ablation therapy based on a positive 2-mCi (+2 mCi) l-131 scan (group 2). Six patients in group 1 and eight in group 2 had improvement or ablation of residual tissue based on the 10-mCi scan following therapy. The difference in response between the two groups was not statistically significant (P=0.63) by two-tailed Fisher's exact test, indicating that even patients with -2-mCi, but +10-mCi scans may respond to l-131 therapy. Whether the large dose therapy makes any impact on the clinical outcome has not been answered by this study.
A Genomic Fossil Reveals Key Steps in Hemoglobin Loss by the Antarctic Icefishes
Authors: T. J. Near
Journal: Molecular Biology and Evolution (2006)

Antarctic icefishes are the only vertebrates that do not have hemoglobin and erythrocytes in their blood. These startling phenotypes are associated in several icefish species with deletions of juvenile and adult globin loci, which in red-blooded teleosts are typically composed of tightly linked pairs of alpha- and beta-globin genes. It is unknown if the loss of hemoglobin expression in icefishes was the direct result of such deletions or if other mutational events compromised globin chain synthesis prior to globin gene loss. In this study, we show that 15 of the 16 icefish species have lost the adult beta-globin gene but retain a truncated alpha-globin pseudogene. Surprisingly, a phylogenetically derived icefish species, Neopagetopsis ionah, possesses a complete, but nonfunctional, adult alphabeta-globin complex. This cluster contains 2 distinct beta-globin pseudogenes whose phylogenetic origins span the entire Antarctic notothenioid radiation, consistent with an origin via introgression. Maximum likelihood ancestral state reconstruction supports a scenario of icefish globin gene evolution that involves a single loss of the transcriptionally active adult alphabeta-globin cluster prior to the diversification of the extant species in the clade. Through lineage sorting of ancestral polymorphism, 2 types of alleles became fixed in the clade: 1) the alpha-globin pseudogene of the majority of species and 2) the inactive alphabeta-globin complex of N. ionah. We conclude that the globin pseudogene complex of N. ionah is a "genomic fossil" that reveals key intermediate steps on the pathway to loss of hemoglobin expression by all icefish species.
Abstract 2103: Reduced Tip60 expression as a predictive biomarker for advanced melanoma and patient outcome
Authors: Guangdi Chen, Yabin Chen, Zhizhong Zhang, Magdalena Martinka, Gang Li
Journal: Cancer Research (2011)

Abstract The tumor suppressor Tip60 plays a major role in transcription, DNA damage response, apoptosis and cancer development. We investigated the role of Tip60 in melanoma pathogenesis and assessed the prognostic value of Tip60 expression on melanoma patient survival. Two sets of tissue microarrays were constructed consisting of 448 cases of melanomas (201 for the training set and 247 for the validation set) and 105 cases of nevi. The TMA was assessed for Tip60 expression by immunohistochemistry. The Kaplan-Meier method was used to evaluate the patient survival, and univariate and multivariate Cox regression models were performed to estimate the harzard ratios (HR) at five-year follow-up. We found that Tip60 expression was significantly reduced in metastatic melanoma compared to normal nevi (P = 0.045), dysplastic nevi (P = 0.047) and primary melanoma (P = 0.001). Tip60 expression correlated with AJCC stages (I-II vs III-IV, P = 0.001) and tumor thickness (≤4.00 vs. &amp;gt;4.00 mm, P = 0.037). Reduced Tip60 expression was associated with a poor five-year disease-specific survival in primary melanoma (P = 0.016) and metastatic melanoma patients (P = 0.027). Furthermore, Cox regression analyses indicated that Tip60 expression was an independent prognostic marker for primary (P = 0.002) and metastatic melanomas (P = 0.035). In conclusion, reduced Tip60 expression is significantly associated with thick primary melanoma and metastatic melanoma, as well as poor patient prognosis, suggesting that Tip60 may serve as a potential biomarker for advanced melanoma and patient outcome. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2103. doi:10.1158/1538-7445.AM2011-2103
The ecological rationality of strategic cognition
Authors: Christophe Heintz
Journal: Behavioral and Brain Sciences (2005)

I argue that altruistic behavior and its variation across cultures may be caused by mental cognitive mechanisms that induce cooperative behavior in contract-like situations and adapt that behavior to the kinds of contracts that exist in one's socio-cultural environment. I thus present a cognitive alternative to Henrich et al.'s motivation-based account. Rather than behaving in ways that reveal preferences, subjects interpret the experiment in ways that cue their social heuristics. In order to distinguish the respective roles of preferences and cognitive processes that determine economic behavior, we need more ethnography of strategies “in the wild.”
Cortico – (thalamo) – cortical interactions, gamma resonance, and auditory hallucinations in schizophrenia
Authors: Ralph E. Hoffman, Daniel H. Mathalon, Judith M. Ford, John H. Krystal
Journal: Behavioral and Brain Sciences (2004)

Transcranial magnetic stimulation, EEG, and behavioral studies by our group implicate spurious activation of speech perception neurocircuitry in the genesis of auditory hallucinations in schizophrenia. The neurobiological basis of these abnormalities remains uncertain, however. We review our ongoing studies, which suggest that altered cortical coupling underlies speech processing in schizophrenia and is expressed via disrupted gamma resonances and impaired corollary discharge function of self-generated verbal thought.
Flawed Meta-Analyses Comparing Psychotherapy With Pharmacotherapy
Authors: Donald F. Klein
Journal: American Journal of Psychiatry (2000)

OBJECTIVE: The author sought to illustrate the invalidity of meta-analyses that claim to quantitatively compare the benefits of psychotherapy to pharmacotherapy in patients with psychiatric disorders. METHOD: Studies included in four meta-analyses were retrieved and their study designs evaluated. RESULTS: The meta-analyses compared effect sizes from disparate studies that were not uniformly blind, random, controlled, or of high quality. The studies did not directly address the comparative efficacy question or lacked assay sensitivity. CONCLUSIONS: Numerous types of studies exemplify the need for caution in evaluating meta-analytic conclusions without first critically examining the included studies. Estimates of the relative efficacy of different treatments are not well founded when based almost exclusively on indirect, multiply confounded comparisons. Meta-analyses based on flawed studies or studies that lack demonstrated assay sensitivity are also inadequate for the criticism of treatment guidelines. Some bodies of data are inadequate to support a proper meta-analysis.
Engineering Adolescence
Authors: Xiulan Yang, Lil Pabon, Charles E. Murry
Journal: Circulation Research (2014)

The discovery of human pluripotent stem cells (hPSCs), including both human embryonic stem cells and human-induced pluripotent stem cells, has opened up novel paths for a wide range of scientific studies. The capability to direct the differentiation of hPSCs into functional cardiomyocytes has provided a platform for regenerative medicine, development, tissue engineering, disease modeling, and drug toxicity testing. Despite exciting progress, achieving the optimal benefits has been hampered by the immature nature of these cardiomyocytes. Cardiac maturation has long been studied in vivo using animal models; however, finding ways to mature hPSC cardiomyocytes is only in its initial stages. In this review, we discuss progress in promoting the maturation of the hPSC cardiomyocytes, in the context of our current knowledge of developmental cardiac maturation and in relation to in vitro model systems such as rodent ventricular myocytes. Promising approaches that have begun to be examined in hPSC cardiomyocytes include long-term culturing, 3-dimensional tissue engineering, mechanical loading, electric stimulation, modulation of substrate stiffness, and treatment with neurohormonal factors. Future studies will benefit from the combinatorial use of different approaches that more closely mimic nature's diverse cues, which may result in broader changes in structure, function, and therapeutic applicability.
Segmental bone regeneration using an rhBMP-2-loaded gelatin/nanohydroxyapatite/fibrin scaffold in a rabbit model
Authors: Yue Liu, Yun Lu, Xuezhong Tian, Geng Cui, Yanmei Zhao, Qiang Yang, Shunlu Yu, Guosheng Xing, Boxun Zhang
Journal: Biomaterials (2009)
TREATMENT OF CHRONIC PURULENT OTITIS MEDIA.
Authors: D. A. KUYK
Journal: JAMA (1903)

When we take into consideration the vast number of people, both children and adults, who suffer from chronic suppurative ear disease, the greater majority of whom will allow their disease to continue and progress, thereby courting disaster and perhaps death, rather than submit to operative intervention, it behooves us to endeavor to study out some plan of treatment other than the surgical for the relief and cure of these sufferers, and any time given to the study of this subject is time well spent, for we then fulfill the task to which we have dedicated our lives—namely, the relief of suffering humanity. The relief and cure by conservative essentially non-surgical methods of a large per cent. of these cases is not only probable, but highly possible, and if we can give these patients a fairly hopeful prognosis very many more of them will submit to treatment and be