tbuckley/cabot-search huggingface dataset:
Dietary cholesterol, rather than liver steatosis, leads to hepatic inflammation in hyperlipidemic mouse models of nonalcoholic steatohepatitis
Authors: Kristiaan Wouters, Patrick J. van Gorp, Veerle Bieghs, Marion J. Gijbels, Hans Duimel, Dieter Lütjohann, Anja Kerksiek, Roger van Kruchten, Nobuyo Maeda, Bart Staels, Marc van Bilsen, Ronit Shiri‐Sverdlov, Marten H. Hofker
Journal: Hepatology (2008)

Nonalcoholic steatohepatitis (NASH) involves liver lipid accumulation (steatosis) combined with hepatic inflammation. The transition towards hepatic inflammation represents a key step in pathogenesis, because it will set the stage for further liver damage, culminating in hepatic fibrosis, cirrhosis, and liver cancer. The actual risk factors that drive hepatic inflammation during the progression to NASH remain largely unknown. The role of steatosis and dietary cholesterol in the etiology of diet-induced NASH was investigated using hyperlipidemic mouse models fed a Western diet. Livers of male and female hyperlipidemic (low-density lipoprotein receptor–deficient [ldlr−/−] and apolipoprotein E2 knock-in [APOE2ki]) mouse models were compared with livers of normolipidemic wild-type (WT) C57BL/6J mice after short-term feeding with a high-fat diet with cholesterol (HFC) and without cholesterol. Whereas WT mice displayed only steatosis after a short-term HFC diet, female ldlr−/− and APOE2ki mice showed steatosis with severe inflammation characterized by infiltration of macrophages and increased nuclear factor κB (NF-κB) signaling. Remarkably, male ldlr−/− and APOE2ki mice developed severe hepatic inflammation in the absence of steatosis after 7 days on an HFC diet compared with WT animals. An HFC diet induced bloated, "foamy" Kupffer cells in male and female ldlr−/− and APOE2ki mice. Hepatic inflammation was found to be linked to increased plasma very low-density lipoprotein (VLDL) cholesterol levels. Omitting cholesterol from the HFC diet lowered plasma VLDL cholesterol and prevented the development of inflammation and hepatic foam cells. Conclusion: These findings indicate that dietary cholesterol, possibly in the form of modified plasma lipoproteins, is an important risk factor for the progression to hepatic inflammation in diet-induced NASH. (HEPATOLOGY 2008;48:474–486.)
Fidelity of Runx2 Activity in Breast Cancer Cells Is Required for the Generation of Metastases-Associated Osteolytic Disease
Authors: George L. Barnes, Kerri E. Hebert, Mohammad Kamal, Amjad Javed, Thomas A. Einhorn, Jane B. Lian, Gary S. Stein, Louis C. Gerstenfeld
Journal: Cancer Research (2004)

Abstract The osteolytic bone destruction associated with breast cancer skeletal metastases represents a serious and incurable clinical condition. However, the molecular mechanisms regulating tumor cell expression of factors involved in the generation of osteolytic disease remain elusive. We demonstrated recently that breast cancer cells express the Runx2 transcription factor, essential for bone formation and a regulator of skeletal homeostasis. Our experimental results demonstrate that perturbation of Runx2 regulatory function in tumor cells abolishes their ability to form osteolytic lesions in vivo. In vitro, we show that breast cancer cells inhibit osteoblast differentiation while concurrently enhancing osteoclast differentiation in marrow stromal cell cultures. Disruption of Runx2 activity abrogates both of these cancer cell-mediated effects on bone cells. These results demonstrate that Runx2 expression in breast cancer cells provides a molecular phenotype that enables the interactions between tumor cells and the bone microenvironment that lead to osteolytic disease.
Biochemical Recurrence After Robot-assisted Radical Prostatectomy in a European Single-centre Cohort with a Minimum Follow-up Time of 5 Years
Authors: Prasanna Sooriakumaran, Leif Haendler, Tommy Nyberg, Henrik Gronberg, Andreas Nilsson, Stefan Carlsson, Abolfazl Hosseini, Christofer Adding, Martin Jonsson, Achilles Ploumidis, Lars Egevad, Gunnar Steineck, Peter Wiklund
Journal: European Urology (2012)
Late luteal rescue in the baboon (Papio cynocephalus)
Authors: V. Castracane
Journal: Human Reproduction Update (1998)

Numerous studies have used human chorionic gonadotrophin (HCG) administration to study the response of the primate ovary to gonadotrophin stimulation. These studies are generally performed in the luteal phase with very few studies of the follicular phase. We have studied the effect of both HCG and gonadotrophin releasing hormone (GnRH) agonist administered at the early follicular phase in normally cycling baboons (Papio cynocephalus). Five baboons were treated with increasing doses of HCG for 5 consecutive days starting on day 1 of the cycle and three untreated baboons served as controls. Follicular and luteal phase lengths were determined and serum samples were assayed for progesterone, oestradiol and 17α-OH progesterone. In a separate study, six baboons were treated with GnRH agonist (WY-40972) on days 2-6 of the cycle and saline-treated baboons served as controls (n = 5). Mean peak progesterone concentrations (± SE) during the treatment interval were 3.88 ± 0.56 ng/ml in HCG-treated baboons compared to 0.19 ± 0.07 ng/ml in controls (P <0.001). A similar significant increase (P <0.001) in serum 17α-OH progesterone concentrations was also observed (6.13 ± 1.12 ng/ml versus 1.13 ± 0.49 ng/ml). In association with the increase in luteal steroids there was also a significant prolongation of menstrual cycle length from 32.7 ± 1.2 days in controls to 46.8 ± 4.9 days in HCG-treated baboons (P <0.05), which involved prolongation of the follicular phase (16.7 ± 1.2 days to 29.0 ± 4.6 days, P <0.05) with no difference in luteal phase length or progesterone concentrations. In GnRH agonist-treated baboons, mean (± SE) cycle length was prolonged to 46.3 ± 1.6 days and in saline-treated controls was 32.8 ± 0.8 days (P <0.001), again this was completely represented by the change in follicular phase length, from 13.4 ± 0.7 days in controls to 27.2 ± 2.1 days in agonist-treated baboons (P <0.001). In contrast, there was no significant difference in luteal phase length between these two groups (19.4 ± 0.7 versus 19.2 ± 1.0 days). The prolongation of the follicular phase was accompanied by significant increases in both progesterone (P <0.01) and oestradiol (P <0.01) during GnRH agonist treatment above control concentrations. Luteal phase concentrations of these hormones were not different from controls. These results demonstrate the previously unreported finding that gonadotropin stimulation will rescue the corpus luteum in the next follicular phase. Key words: baboon/corpus luteum/gonadotropin/menstrual cycle/progesterone
Evidence-Based Diagnostic Algorithm for Glioma: Analysis of the Results of Pathology Panel Review and Molecular Parameters of EORTC 26951 and 26882 Trials
Authors: Johan M. Kros, Karin Huizer, Aurelio Hernández-Laín, Gianluca Marucci, Alex Michotte, Bianca Pollo, Elisabeth J. Rushing, Teresa Ribalta, Pim French, David Jaminé, Nawal Bekka, Denis Lacombe, Martin J. van den Bent, Thierry Gorlia
Journal: Journal of Clinical Oncology (2015)

With the rapid discovery of prognostic and predictive molecular parameters for glioma, the status of histopathology in the diagnostic process should be scrutinized. Our project aimed to construct a diagnostic algorithm for gliomas based on molecular and histologic parameters with independent prognostic values.The pathology slides of 636 patients with gliomas who had been included in EORTC 26951 and 26882 trials were reviewed using virtual microscopy by a panel of six neuropathologists who independently scored 18 histologic features and provided an overall diagnosis. The molecular data for IDH1, 1p/19q loss, EGFR amplification, loss of chromosome 10 and chromosome arm 10q, gain of chromosome 7, and hypermethylation of the promoter of MGMT were available for some of the cases. The slides were divided in discovery (n = 426) and validation sets (n = 210). The diagnostic algorithm resulting from analysis of the discovery set was validated in the latter.In 66% of cases, consensus of overall diagnosis was present. A diagnostic algorithm consisting of two molecular markers and one consensus histologic feature was created by conditional inference tree analysis. The order of prognostic significance was: 1p/19q loss, EGFR amplification, and astrocytic morphology, which resulted in the identification of four diagnostic nodes. Validation of the nodes in the validation set confirmed the prognostic value (P < .001).We succeeded in the creation of a timely diagnostic algorithm for anaplastic glioma based on multivariable analysis of consensus histopathology and molecular parameters.
Serum Surfactant Proteins A and D as Prognostic Factors in Idiopathic Pulmonary Fibrosis and Their Relationship to Disease Extent
Authors: HIROKI TAKAHASHI, TAKUYA FUJISHIMA, HIROYUKI KOBA, SEIJI MURAKAMI, KEIZO KUROKAWA, YOSHIE SHIBUYA, MASANORI SHIRATORI, YOSHIO KUROKI, SHOSAKU ABE
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Idiopathic pulmonary fibrosis (IPF) is a progressive, life-threatening, interstitial lung disease of unknown etiology. For optimal therapeutic management of IPF an accurate tool is required for discrimination between reversible and irreversible types of the disease. However, such noninvasive tools are few, and even with high-resolution computed tomography (HRCT), which is the most trusted method for doing so, the nature of the disease activity in IPF cannot always be accurately predicted. The aims of the present study were to assess the values of surfactant protein (SP)-A and SP-D in semiquantifying the extent of disease in IPF and in predicting deterioration in restrictive pulmonary function and survival over a follow-up period of 3-yr. SP-A and SP-D in sera were measured with enzyme-linked immunosorbent assays as previously described. Fifty-two IPF patients were studied to evaluate the association between serum SP-A and SP-D and disease extent on HRCT, deterioration in pulmonary function, and survival during 3 yr of follow-up. Both SP-A and SP-D concentrations were significantly correlated with the extent of alveolitis (a reversible change), whereas they did not correlate with the progression of fibrosis (an irreversible change). The SP-D concentration, unlike that of SP-A, was also related to the extent of parenchymal collapse and the rate of deterioration per year in pulmonary function. The concentrations of SP-A and SP-D in patients who died within 3 yr were significantly higher than in patients who were still alive after 3 yr. We propose that assays of SP-A and SP-D in sera from IPF patients are useful tools for understanding some pathologic characteristics of the disease, that SP-D may be a good predictive indicator of the rate of decline in pulmonary function, and that a combination of the assays for SP-A and SP-D may be helpful in predicting the outcome of patients with IPF.
The prognostic significance of aldehyde dehydrogenase 1A1 (ALDH1A1) and CD133 expression in early stage non-small cell lung cancer
Authors: Muhammad Alamgeer, Vinod Ganju, Anette Szczepny, Prudence A Russell, Zdenka Prodanovic, Beena Kumar, Zoe Wainer, Tracey Brown, Michal Schneider-Kolsky, Matthew Conron, Gavin Wright, D Neil Watkins
Journal: Thorax (2013)

<h3>Background</h3> Expression of aldehyde dehydrogenase 1A1 (ALDH1A1) and CD133 has been functionally associated with a stem cell phenotype in normal and malignant cells. The prevalence of such cells in solid tumours should therefore correlate with recurrence and/or metastasis following definitive surgical resection. The aim of this study was to evaluate the prognostic significance of ALDH1A1 and CD133 in surgically resected, early stage non-small cell lung cancer (NSCLC). <h3>Methods</h3> A retrospective analysis of ALDH1A1 and CD133 expression in 205 patients with pathologic stage I NSCLC was performed using immunohistochemistry. The association between the expression of both markers and survival was determined. <h3>Results</h3> We identified 62 relapses and 58 cancer-related deaths in 144 stage 1A and 61 stage 1B patients, analysed at a median of 5-years follow-up. Overexpression of ALDH1A1 and CD133, detected in 68.7% and 50.7% of primary tumours, respectively, was an independent prognostic indicator for overall survival by multivariable Cox proportional hazard model (p=0.017 and 0.039, respectively). Overexpression of ALDH1A1, but not of CD133, predicted poor recurrence-free survival (p=0.025). When categorised into three groups according to expression of ALDH1A1/CD133, patients with overexpression of both ALDH1A1 and CD133 belonged to the group with the shortest recurrence-free and overall survival (p=0.015 and 0.017, respectively). <h3>Conclusions</h3> Expression of ALDH1A1 and CD133, and coexpression of ALDH1A1 and CD133, is strongly associated with poor survival in early-stage NSCLC following surgical resection. These data are consistent with the hypothesis that expression of stem cell markers correlates with recurrence as an indirect measure of self-renewal capacity.
Prognostic Significance of <i>NPM1</i> Mutations in the Absence of <i>FLT3</i>–Internal Tandem Duplication in Older Patients With Acute Myeloid Leukemia: A SWOG and UK National Cancer Research Institute/Medical Research Council Report
Authors: Fabiana Ostronoff, Megan Othus, Michelle Lazenby, Elihu Estey, Frederick R. Appelbaum, Anna Evans, John Godwin, Amanda Gilkes, Kenneth J. Kopecky, Alan Burnett, Alan F. List, Min Fang, Vivian G. Oehler, Stephen H. Petersdorf, Era L. Pogosova-Agadjanyan, Jerald P. Radich, Cheryl L. Willman, Soheil Meshinchi, Derek L. Stirewalt
Journal: Journal of Clinical Oncology (2015)

Younger patients with acute myeloid leukemia (AML) harboring NPM1 mutations without FLT3-internal tandem duplications (ITDs; NPM1-positive/FLT3-ITD-negative genotype) are classified as better risk; however, it remains uncertain whether this favorable classification can be applied to older patients with AML with this genotype. Therefore, we examined the impact of age on the prognostic significance of NPM1-positive/FLT3-ITD-negative status in older patients with AML.
Epidemiology and prognosis of subungual melanoma in 34 Japanese patients
Authors: T. KATO, T. SUETAKE, Y. SUGIYAMA, N. TABATA, H. TAGAMI
Journal: British Journal of Dermatology (1996)

The incidence of malignant melanoma is much lower in the Japanese than in caucasians. However, amongst the various types of malignant melanoma, the subungual and periungual sites are commonly found in the Japanese. One hundred and fifty-one cases of cutaneous malignant melanoma were seen over a 25-year period at our hospital. We found that, in 34 patients (23%), the subungual region was involved, a high frequency for one institution. We have analysed these patients and looked at their treatment. The finger nails were affected in 21 cases (62%) and the toe nails in 13 cases (38%). The thumb nails or great toe nails were affected in 25 of the 34 patients (73%). In 25 patients, histopathological features of acral lentiginous melanoma were found, with four cases of superficial spreading melanoma and five of nodular amelanotic melanoma. Of the latter group, four mimicked fibrous histiocytic tumour, and one was a desmoplastic malignant melanoma. The proportion of patients presenting with stage III disease decreased after 1982, with a corresponding increase in patients whose tumour thickness was less than 4 mm (stage II). Concurrently, the prognosis for subungual malignant melanoma improved. The 5-year survival rate in each of the periods 1969-82 and 1983-93 was 53 and 87%, respectively. This is similar to that found in plantar malignant melanoma and is felt to be due to a greater public awareness of the condition and to the introduction of effective chemotherapy (the DTIC-AC nitrosurea-vincristine (DAV) regimen). Although the frequency of malignant melanoma is rather low in the Japanese, our data indicate that there is a high incidence of subungual malignant melanoma. Public awareness of the early stage of malignant melanoma seems to have improved prognosis.
Effects of atrial natriuretic peptide on proximal epicardial coronary arteries and coronary blood flow in conscious dogs.
Authors: A Chu, F R Cobb
Journal: Circulation Research (1987)

The effects of atrial natriuretic peptide (ANP) on proximal epicardial coronary artery dimensions and coronary blood flow were examined in 7 awake dogs chronically instrumented with miniature coronary dimension crystals and Doppler flow probes on the circumflex coronary artery. ANP (10, 50, and 150 micrograms) was infused as a bolus via the left atrial catheter. Aortic pressure, left ventricular end-diastolic pressure, heart rate, and dP/dt did not change significantly with any dose of ANP. ANP caused transient (1-5 minutes) dose-related increases in coronary blood flow; maximum increases were 28.1 +/- 6.9%, 40.2 +/- 6.2%, and 73.9 +/- 12.5% with the 10-, 50-, and 150-micrograms doses, respectively. ANP also induced prolonged (average 70.2 +/- 28.6 minutes with 150-micrograms dose) dose-related increases in coronary diameter; maximum increases were 3.1 +/- 1.0%, 3.9 +/- 1.5%, and 5.7 +/- 1.3% with the 10-, 50-, and 150-micrograms doses, respectively. The increase in diameter was not attenuated when the transient increase in blood flow was prevented by partial occlusion with a pneumatic snare. Combined autonomic blockade with propranolol (1 mg/kg), phentolamine (1 mg/kg), and atropine (0.06 mg/kg) attenuated the relative increase in coronary flow but did not alter the increases in epicardial coronary diameter produced by ANP. These data demonstrate that bolus injection of ANP effects preferential, sustained, dose-dependent, flow-independent increases in epicardial coronary dimensions and relatively brief dose-dependent increases in coronary blood flow. The vasodilator effects of ANP on epicardial vessels are direct and are not mediated via the autonomic nervous system.(ABSTRACT TRUNCATED AT 250 WORDS)
Idiopathic Extreme Osteoporosis, Especially of the Spinal Column and Thoracic Cage, with Collapse of Front of Chest
Authors: H. C. Lauber, F. P. Weber, J. G. Greenfield
Journal: Annals of the Rheumatic Diseases (1948)

<h3>Abstract</h3> <h3>Background</h3> Previous online mindfulness-based interventions (MBI) for burnout and stress reduction in medical personnel suffered from limited effect size and high dropout rate. The results were equivocal across studies with several limitations in their study designs. Therefore, we developed an online MBI entitled “Mindful Senses (MS)”, a minimally therapist-guided online audio-based mindfulness program, with aims to increase the effect size and lower dropout rate and tested its efficacy and feasibility with randomized active-controlled study design. <h3>Methods</h3> We recruited online 90 medical personnel who had moderate or high levels of burnout and stress from across Thailand. Participants were randomly allocated into Group A and B equally. Group A read four weekly Psychological Self-Help Articles (PSA) and attended the MS program during weeks 1-4. Group B read PSA during weeks 1-4 and attended MS program during week 9-12. Outcomes including burnout, stress, depression, anxiety, mindfulness, and quality of life (QOL) were measured at baseline (T<sub>0</sub>), week 4 (T<sub>1</sub>), and week 8 (T<sub>2</sub>) for both groups. Group X time interaction was analyzed by repeated-measures ANOVA. <h3>Results</h3> MS + PSA had significantly better improvement than PSA only in burnout, stress, anxiety, depression, mindfulness, and QOL, with medium-to-very large effect sizes (<i>d</i> = 1.33, 1.42, 1.04, 1.14, 0.70, and 1.03, respectively) at T<sub>1</sub>. The outcome differences remained at T<sub>2</sub> with medium-to-large effect sizes (<i>d</i> = 0.84, 0.98, 0.73, 0.73, 0.66, and 0.94, respectively). The dropout rate was 4.4%. <h3>Conclusions</h3> MS program is an online MBI that reduced burnout and stress in medical personnel with a large effect size and low dropout rate. Its effects remained at one-month follow-up. The MS program is feasible and has a potential to be an alternative intervention for medical personnel suffering from burnout and stress. <h3>Trial registration</h3> thaiclinicaltrials.org TCTR20210416001
Analgesia After Open Abdominal Surgery in the Setting of Enhanced Recovery Surgery
Authors: Michael J. Hughes, Nicholas T. Ventham, Stephen McNally, Ewen Harrison, Stephen Wigmore
Journal: JAMA Surgery (2014)

The optimal analgesic technique following open abdominal surgery within an enhanced recovery protocol remains controversial. Thoracic epidural is often recommended; however, its role is increasingly being challenged and alternative techniques are being suggested as suitable replacements.To determine by meta-analysis whether epidurals are superior to alternative analgesic techniques following open abdominal surgery within an enhanced recovery setting in terms of postoperative morbidity and other markers of recovery.A literature search was performed of EMBASE, Medline, PubMed, and the Cochrane databases from 1966 through May 2013.All randomized clinical trials comparing epidurals with an alternative analgesic technique following open abdominal surgery within an enhanced recovery protocol were included.All studies were assessed by 2 independent reviewers. Study quality was assessed using the Cochrane bias assessment tool and the Jadad and Chalmers modified bias risk assessment tools. Dichotomous data were analyzed by random or fixed-effects odds ratios. Qualitative analysis was performed where appropriate.Seven trials with a total of 378 patients were identified. No significant difference in complication rate was detected between epidurals and alternative analgesic methods (odds ratio, 1.14; 95% CI, 0.49-2.64; P = .76). Subgroup analysis showed fewer complications in the patient-controlled analgesia group compared with epidural analgesia (odds ratio, 1.97; 95% CI, 1.10-3.53; P = .02). Following qualitative assessment, epidural analgesia was associated with faster return of gut function and reduced pain scores; however, no difference was observed in length of stay.Epidurals may be associated with superior pain control but this does not translate into improved recovery or reduced morbidity when compared with alternative analgesic techniques when used within an enhanced recovery protocol.