tbuckley/cabot-search huggingface dataset:
Residual strain in the ventricle of the stage 16-24 chick embryo.
Authors: L A Taber, N Hu, T Pexieder, E B Clark, B B Keller
Journal: Circulation Research (1993)

Residual stress and strain, i.e., the stress and strain remaining in a solid when all external loads are removed, may be produced in biological tissues by differential growth. During cardiac development, residual stress and strain may play a role in cardiac morphogenesis by affecting ventricular wall stress. After a transmural radial cut, a passive ventricular cross section opens into a sector, and the size of the opening angle provides a measure of the circumferential residual strain. Residual strains were characterized in this manner for the apical region of the diastolic embryonic chick heart for Hamburger-Hamilton stages 16, 18, 21, and 24 (approximately 2.5, 3.5, 4.0, and 4.5 days, respectively, of a 21-day incubation period). The average opening angle at these stages was 107 +/- 10 degrees, 79 +/- 10 degrees, 73 +/- 11 degrees, and 74 +/- 7 degrees, respectively (n &gt; or = 5 for each stage). These measured angles were correlated with changes in ventricular morphology. Scanning electron micrographs of the apex revealed that the wall of the ventricle is smooth at stage 16. Then at stage 18, myocardial trabeculae develop, forming ridges with primarily a circumferential orientation. By stage 21, the trabeculae develop into a mesh, giving the ventricular wall a spongelike appearance, and the preferred orientation is lost by stage 24. The large decrease in opening angle between stages 16 and 18 corresponded to the onset of trabeculation, which is the greatest change in form during the studied stages. We speculate that residual strain is an important biomechanical factor during cardiac morphogenesis.
Why promote the findings of single research studies?
Authors: Paul Wilson, Mark Petticrew
Journal: BMJ (2008)

> “Since when has a single scientific study constituted ‘the truth’ about anything?”1

Scientists have known about biases in single observations for centuries.2 A wealth of empirical evidence amassed across many disciplines tells us that single studies can be biased, are often seriously methodologically flawed and highly time and context dependent, and have findings that are likely to be misinterpreted and misrepresented (sometimes by the authors themselves). Increasingly it is accepted that decisions should not be based on the findings from single primary studies but rather informed by actionable messages derived from synthesised evidence based on systematic reviews.3 4 5 Over the past decade there has been substantial public funding of synthesised evidence and guidance to support healthcare decision making. In the United Kingdom this investment has been described as NHS research and development’s most important contribution to the global science base.6

Despite this investment the evidence indicates that although the transfer of research knowledge is possible its success can be variable.7 8 There is now renewed interest and emphasis on the gaps between research and policy and practice, nationally9 10 and internationally.11 …
Cumulative Lead Exposure and Age at Menopause in the Nurses’ Health Study Cohort
Authors: Ki-Do Eum, Marc G. Weisskopf, Linda H. Nie, Howard Hu, Susan A. Korrick
Journal: Environmental Health Perspectives (2014)

Background: Early menopause has been associated with many adverse health outcomes, including increased risk of cardiovascular disease morbidity and mortality. Lead has been found to be adversely associated with female reproductive function, but whether exposures experienced by the general population are associated with altered age at menopause has not been explored.Objective: Our goal was to assess the association between cumulative lead exposure and age at natural menopause.Methods: Self-reported menopausal status and bone lead concentration measured with K-shell X-ray fluorescence—a biomarker of cumulative lead exposure—were obtained from 434 women participants in the Nurses' Health Study.Results: The mean (± SD) age at natural menopause was 50.8 ± 3.6 years. Higher tibia lead level was associated with younger age at menopause. In adjusted analyses, the average age of menopause for women in the highest tertile of tibia lead was 1.21 years younger (95% CI: –2.08, –0.35) than for women in the lowest tertile (p-trend = 0.006). Although the number of cases was small (n = 23), the odds ratio for early menopause (< 45 years of age) was 5.30 (95% CI: 1.42, 19.78) for women in the highest tertile of tibia lead compared with those in the lowest tertile (p-trend = 0.006). There was no association between patella or blood lead and age at menopause.Conclusions: Our results support an association between low-level cumulative lead exposure and an earlier age at menopause. These data suggest that low-level lead exposure may contribute to menopause-related health outcomes in older women through effects on age at menopause.Citation: Eum KD, Weisskopf MG, Nie LH, Hu H, Korrick SA. 2014. Cumulative lead exposure and age at menopause in the Nurses' Health Study Cohort. Environ Health Perspect 122:229–234; http://dx.doi.org/10.1289/ehp.1206399
Hepatopulmonary Syndrome — A Liver-Induced Lung Vascular Disorder
Authors: Roberto Rodríguez-Roisin, Michael J Krowka
Journal: New England Journal of Medicine (2008)

The hepatopulmonary syndrome is characterized by defects in oxygenation due to pulmonary abnormalities associated with chronic liver disease. Dyspnea and hypoxemia can be severe and often worsen in the upright position. Gross dilatation of the precapillary and capillary vessels occurs with ventilation–perfusion mismatch. The syndrome usually improves after liver transplantation.
Changes in ventilatory mechanics and diaphragmatic function after lung volume reduction surgery in patients with COPD
Authors: E. M. Tschernko, W. Wisser, T. Wanke, M. A. Rajek, M. Kritzinger, H. Lahrmann, M. Kontrus, H. Benditte, W. Klepetko
Journal: Thorax (1997)

Lung volume reduction (LVR) has recently been used to treat severe emphysema. About 25% of the volume of each lung is removed with this method. Little is known about the mechanism of functional improvement so a study was undertaken to investigate the changes in ventilatory mechanics and diaphragmatic function in eight patients after LVR.Measurements of work of breathing (WOB), intrinsic positive end expiratory pressure (PEEPi), dynamic compliance (Cdyn), and arterial carbon dioxide tension (PaCO2) were performed on the day before surgery and daily for seven days after surgery, as well as one, three, and six months after surgery. All measurements were performed on spontaneously breathing patients, simultaneously assessing oesophageal pressure via an oesophageal balloon catheter and air flow via a tightly adjusted mask. Diaphragmatic function was evaluated by measuring oesophageal and transdiaphragmatic pressure (Pdi) preoperatively and at one, three, and six months postoperatively.Mean forced expiratory volume in one second (FEV1) was 23 (3.6)% predicted, and all patients were oxygen dependent before the-operation. One day after LVR the mean decrease in WOB was 0.93 (95% confidence interval (CI) 0.46 to 1.40) joule/l, the mean decrease in PEEPi was 0.61 (95% CI 0.35 to 0.87) kPa, and the mean increase in Cdyn was 182.5 (95% CI 80.0 to 284.2) ml/kPa. Similar changes were found seven days and six months after surgery. PaCO2 was higher on the day after the operation but was significantly reduced six months later. Pdi was increased three and six months after surgery.Ventilatory mechanics improved immediately after LVR, probably by decompression of lung tissue and relief of thoracic distension. An improvement in diaphragmatic function three and six months postoperatively also contributes to improved respiratory function after LVR.
Effects of exercise on C-reactive protein, inflammatory cytokine and adipokine in patients with type 2 diabetes: A meta-analysis of randomized controlled trials
Authors: Yasuaki Hayashino, Jeffrey L. Jackson, Takumi Hirata, Norio Fukumori, Fumiaki Nakamura, Shunichi Fukuhara, Satoru Tsujii, Hitoshi Ishii
Journal: Metabolism (2013)
NFATc1 in mice represses osteoprotegerin during osteoclastogenesis and dissociates systemic osteopenia from inflammation in cherubism
Authors: Antonios O. Aliprantis, Yasuyoshi Ueki, Rosalyn Sulyanto, Arnold Park, Kirsten S. Sigrist, Sudarshana M. Sharma, Michael C. Ostrowski, Bjorn R. Olsen, Laurie H. Glimcher
Journal: Journal of Clinical Investigation (2008)

Osteoporosis results from an imbalance in skeletal remodeling that favors bone resorption over bone formation. Bone matrix is degraded by osteoclasts, which differentiate from myeloid precursors in response to the cytokine RANKL. To gain insight into the transcriptional regulation of bone resorption during growth and disease, we generated a conditional knockout of the transcription factor nuclear factor of activated T cells c1 (Nfatc1). Deletion of Nfatc1 in young mice resulted in osteopetrosis and inhibition of osteoclastogenesis in vivo and in vitro. Transcriptional profiling revealed NFATc1 as a master regulator of the osteoclast transcriptome, promoting the expression of numerous genes needed for bone resorption. In addition, NFATc1 directly repressed osteoclast progenitor expression of osteoprotegerin, a decoy receptor for RANKL previously thought to be an osteoblast-derived inhibitor of bone resorption. “Cherubism mice”, which carry a gain-of-function mutation in SH3-domain binding protein 2 (Sh3bp2), develop osteoporosis and widespread inflammation dependent on the proinflammatory cytokine, TNF-α. Interestingly, deletion of Nfatc1 protected cherubism mice from systemic bone loss but did not inhibit inflammation. Taken together, our study demonstrates that NFATc1 is required for remodeling of the growing and adult skeleton and suggests that NFATc1 may be an effective therapeutic target for osteoporosis associated with inflammatory states.
Bile salt malabsorption in regional ileitis, ileal resection, and mannitol-induced diarrhea
Authors: Walter E. Meihoff, Fred Kern
Journal: Journal of Clinical Investigation (1968)

Fecal bile salt excretion was studied in healthy volunteers, patients with regional ileitis, and patients with ileal resection. 10 μc of carboxyl-14C-cholic acid was given orally. Stools and urine were collected daily for 5-10 days, the bile salts extracted, and the radioactivity assayed. Urinary excretion was negligible. All patients with ileal resection excreted bile salts in the feces significantly faster than controls, and five of the six excreted 50% of the radioactivity within 24 hr. Their mean intestinal transit time was 5.6 hr compared to 26 hr for the controls. Two of the three patients with regional ileitis excreted bile salts almost as rapidly as patients with ileal resection. Vitamin B12 absorption was also defective in those patients, but the intestinal transit time was not decreased.
A Secreted Form of ADAM9 Promotes Carcinoma Invasion through Tumor-Stromal Interactions
Authors: Antonio Mazzocca, Roberto Coppari, Raffaella De Franco, Je-Yoel Cho, Towia A. Libermann, Massimo Pinzani, Alex Toker
Journal: Cancer Research (2005)

Tumor cell invasion is a process regulated by integrins, matrix-degrading enzymes, and interactions with host tissue stromal cells. The ADAM family of proteins plays an important role in modulating various cellular responses. Here, we show that an alternatively spliced variant of ADAM9 is secreted by hepatic stellate cells and promotes carcinoma invasion. ADAM9-S induced a highly invasive phenotype in several human tumor cell lines in Matrigel assays, and the protease activity of ADAM9-S was required for invasion. ADAM9-S binds directly to alpha6beta4 and alpha2beta1 integrins on the surface of colon carcinoma cells through the disintegrin domain. ADAM9-S was also able to cleave laminin and promote invasion. Analysis of human liver metastases revealed that ADAM9 is expressed by stromal liver myofibroblasts, particularly those that are localized within the tumor stroma at the invasive front. These results emphasize the importance of tumor-stromal interactions in invasion and suggest that ADAM9-S can be an important determinant in the ability of cancer cells to invade and colonize the liver.
Application of Phi29 Motor pRNA for Targeted Therapeutic Delivery of siRNA Silencing Metallothionein-IIA and Survivin in Ovarian Cancers
Authors: Pheruza Tarapore, Yi Shu, Peixuan Guo, Shuk-Mei Ho
Journal: Molecular Therapy (2010)

Ovarian cancer is a highly metastatic and lethal disease, making it imperative to find treatments that target late-stage malignant tumors. The packaging RNA (pRNA) of bacteriophage phi29 DNA-packaging motor has been reported to function as a highly versatile vehicle to carry small interference RNA (siRNA) for silencing of survivin. In this article, we explore the potential of pRNA as a vehicle to carry siRNA specifically targeted to metallothionein-IIa (MT-IIA) messenger RNA (mRNA), and compare it to survivin targeting pRNA. These two anti-apoptotic cell survival factors promote tumor cell viability, and are overexpressed in recurrent tumors. We find that pRNA chimeras targeting MT-IIA are processed into double-stranded siRNA by dicer, are localized within the GW/P-bodies, and are more potent than siRNA alone in silencing MT-IIA expression. Moreover, knockdown of both survivin and MT-IIA expression simultaneously results in more potent effects on cell proliferation in the aggressive ovarian tumor cell lines than either alone, suggesting that therapeutic approaches that target multiple genes are essential for molecular therapy. The folate receptor-targeted delivery of siRNA by the folate-pRNA dimer emphasizes the cancer cell-specific aspect of this system. The pRNA system, which has the capability to assemble into multivalent nanoparticles, has immense promise as a highly potent therapeutic agent.
Survival and Prognostic Stratification of 670 Patients With Advanced Renal Cell Carcinoma
Authors: Robert J. Motzer, Madhu Mazumdar, Jennifer Bacik, William Berg, Alison Amsterdam, Joseph Ferrara
Journal: Journal of Clinical Oncology (1999)

PURPOSE: To identify prognostic factors and a model predictive for survival in patients with metastatic renal-cell carcinoma (RCC). PATIENTS AND METHODS: The relationship between pretreatment clinical features and survival was studied in 670 patients with advanced RCC treated in 24 Memorial Sloan-Kettering Cancer Center clinical trials between 1975 and 1996. Clinical features were first examined univariately. A stepwise modeling approach based on Cox proportional hazards regression was then used to form a multivariate model. The predictive performance of the model was internally validated through a two-step nonparametric bootstrapping process. RESULTS: The median survival time was 10 months (95% confidence interval [CI], 9 to 11 months). Fifty-seven of 670 patients remain alive, and the median follow-up time for survivors was 33 months. Pretreatment features associated with a shorter survival in the multivariate analysis were low Karnofsky performance status (&lt;80%), high serum lactate dehydrogenase (&gt; 1.5 times upper limit of normal), low hemoglobin (&lt; lower limit of normal), high “corrected” serum calcium (&gt; 10 mg/dL), and absence of prior nephrectomy. These were used as risk factors to categorize patients into three different groups. The median time to death in the 25% of patients with zero risk factors (favorable-risk) was 20 months. Fifty-three percent of the patients had one or two risk factors (intermediate-risk), and the median survival time in this group was 10 months. Patients with three or more risk factors (poor-risk), who comprised 22% of the patients, had a median survival time of 4 months. CONCLUSIONS: Five prognostic factors for predicting survival were identified and used to categorize patients with metastatic RCC into three risk groups, for which the median survival times were separated by 6 months or more. These risk categories can be used in clinical trial design and interpretation and in patient management. The low long-term survival rate emphasizes the priority of clinical investigation to identify more effective therapy.
Immunology of the gut and liver: a love/hate relationship
Authors: D H Adams, B Eksteen, S M Curbishley
Journal: Gut (2008)

The gut digests, absorbs and metabolises nutrients whilst also acting as a barrier to pathogens entering from the intestinal lumen.  Not all intestinal microbes are harmful and the full development of the gut immune system is shaped by interactions with commensal bacteria in a complex interplay which allows responses to harmless bacteria and nutrients to be suppressed whilst developing protective immune response against pathogens(1;2).  Most of these responses occur in the intestinal mucosa and underlying lamina propria however transport of nutrients or translocation of pathogens into the portal circulation means that a second level of protection is required in the liver to respond to antigens that evade the gut immune system(3).  In addition pathogens can enter the liver directly via the systemic circulation or from the gut lumen via the biliary epithelium.  Immune responses in the gut and to a lesser extent liver are well-described but the mechanisms that control immunological cross-talk between these two linked sites are only beginning to be elucidated(4).  They provide insights into the pathogenesis of diseases that affect both sites including infections and inflammatory bowel disease (IBD).
Effect of Intracoronary Delivery of Autologous Bone Marrow Mononuclear Cells 2 to 3 Weeks Following Acute Myocardial Infarction on Left Ventricular Function
Authors: Jay H. Traverse
Journal: JAMA (2011)

Clinical trial results suggest that intracoronary delivery of autologous bone marrow mononuclear cells (BMCs) may improve left ventricular (LV) function when administered within the first week following myocardial infarction (MI). However, because a substantial number of patients may not present for early cell delivery, the efficacy of autologous BMC delivery 2 to 3 weeks post-MI warrants investigation.
Identification of Genes Differentially Expressed in Benign versus Malignant Thyroid Tumors
Authors: Nijaguna B. Prasad, Helina Somervell, Ralph P. Tufano, Alan P.B. Dackiw, Michael R. Marohn, Joseph A. Califano, Yongchun Wang, William H. Westra, Douglas P. Clark, Christopher B. Umbricht, Steven K. Libutti, Martha A. Zeiger
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Although fine-needle aspiration biopsy is the most useful diagnostic tool in evaluating a thyroid nodule, preoperative diagnosis of thyroid nodules is frequently imprecise, with up to 30% of fine-needle aspiration biopsy cytology samples reported as “suspicious” or “indeterminate.” Therefore, other adjuncts, such as molecular-based diagnostic approaches are needed in the preoperative distinction of these lesions. Experimental Design: In an attempt to identify diagnostic markers for the preoperative distinction of these lesions, we chose to study by microarray analysis the eight different thyroid tumor subtypes that can present a diagnostic challenge to the clinician. Results: Our microarray-based analysis of 94 thyroid tumors identified 75 genes that are differentially expressed between benign and malignant tumor subtypes. Of these, 33 were overexpressed and 42 were underexpressed in malignant compared with benign thyroid tumors. Statistical analysis of these genes, using nearest-neighbor classification, showed a 73% sensitivity and 82% specificity in predicting malignancy. Real-time reverse transcription–PCR validation for 12 of these genes was confirmatory. Western blot and immunohistochemical analyses of one of the genes, high mobility group AT-hook 2, further validated the microarray and real-time reverse transcription–PCR data. Conclusions: Our results suggest that these 12 genes could be useful in the development of a panel of markers to differentiate benign from malignant tumors and thus serve as an important first step in solving the clinical problem associated with suspicious thyroid lesions.
Activation of the aryl hydrocarbon receptor by doxorubicin mediates cytoprotective effects in the heart
Authors: Maria Volkova, Monica Palmeri, Kerry S. Russell, Raymond R. Russell
Journal: Cardiovascular Research (2011)

Doxorubicin (DOX) is a highly effective chemotherapeutic agent; however, cumulative dose-dependent cardiotoxicity is a significant side effect of this therapy. Because DOX is a polyaromatic hydrocarbon, we hypothesized that it will be metabolized by the activation of the aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor that is involved in the metabolism of numerous xenobiotic agents. These studies were performed to determine whether DOX activates AhR and whether this activation modulates the toxicity of DOX in cardiomyocytes. Treatment with DOX induced AhR migration to the nucleus, increased AhR binding with its co-factor, aryl hydrocarbon receptor nuclear translocator-1 (ARNT1), and increased the expression of AhR-regulated phase I (CYP1A1) and phase II (GSTA1) drug-metabolizing enzymes in both cardiomyocytes and in the intact heart. Knockdown of AhR in H9C2 cells abolished DOX-induced increases in CYP1A1 and GSTA1 expression. Similar results were obtained by treating adult rat ventricular myocytes with the AhR antagonist, CH-223191. Taken together, these findings indicate that DOX-induced upregulation of CYP1A1 and GSTA1 expression is AhR dependent. AhR null mice treated with 10 mg/kg DOX did not show any activation of CYP1A1 or GSTA1 expression. Moreover, lack of AhR in vivo resulted in a significant decrease in left ventricular function compared with wild-type animals, and increased p53 activation and apoptosis in the heart after treatment with DOX. These findings indicate that AhR plays an important role in DOX metabolism by the heart and further demonstrate that AhR is cardioprotective against DOX-induced cardiotoxicity.
neuroConstruct: A Tool for Modeling Networks of Neurons in 3D Space
Authors: Padraig Gleeson, Volker Steuber, R. Angus Silver
Journal: Neuron (2007)

Conductance-based neuronal network models can help us understand how synaptic and cellular mechanisms underlie brain function. However, these complex models are difficult to develop and are inaccessible to most neuroscientists. Moreover, even the most biologically realistic network models disregard many 3D anatomical features of the brain. Here, we describe a new software application, neuroConstruct, that facilitates the creation, visualization, and analysis of networks of multicompartmental neurons in 3D space. A graphical user interface allows model generation and modification without programming. Models within neuroConstruct are based on new simulator-independent NeuroML standards, allowing automatic generation of code for NEURON or GENESIS simulators. neuroConstruct was tested by reproducing published models and its simulator independence verified by comparing the same model on two simulators. We show how more anatomically realistic network models can be created and their properties compared with experimental measurements by extending a published 1D cerebellar granule cell layer model to 3D.