tbuckley/cabot-search huggingface dataset:
Association Between Urinary Albumin Excretion and Coronary Heart Disease in Black vs White Adults
Authors: Orlando M. Gutiérrez, Yulia A. Khodneva, Paul Muntner, Dana V. Rizk, William M. McClellan, Mary Cushman, David G. Warnock, Monika M. Safford
Journal: JAMA (2013)

Excess urinary albumin excretion is more common in black than white individuals and is more strongly associated with incident stroke risk in black vs white individuals. Whether similar associations extend to coronary heart disease (CHD) is unclear.
The impact of medical technologies on the future of hospitals
Authors: C. B Wilson
Journal: BMJ (1999)

During the next decade diseases requiring medical intervention will be much the same as those being treated today. The site of care may, however, be moved away from the community general hospital to a non-hospital site or to a higher order or specialty hospital at a distance. 

With the applications of technological advances, procedures that once were performed in hospitals are now done in free standing facilities, accelerating a trend that began in the United States in the 1980s with the introduction of magnetic resonance imaging, fibreoptic endoscopes and arthroscopes, and ambulatory surgicentres. Just as the discovery and successful treatment of Helicobacter pylori for peptic ulcer replaced a commonly performed operation so new advances will eliminate the need for care once provided by hospitals, and hospitals will become places that treat conditions that cannot be treated in other settings.

#### Summary points

Pharmaceuticals will replace some procedures and will decrease the need for admission to hospital, and newer vaccines will treat as well as prevent disease

Minimally invasive surgery will reduce hospital stay and promote outpatient operations

Sensors will change central laboratories and intensive care units of today

Digitised images will be accessible to all clinicians

Xenotransplantation from transgenic pigs is ever more likely

Economics and superior outcomes will favour specialty hospitals

An abundance of new pharmaceuticals will alleviate a wide range of common diseases that account for a large proportion of patients currently admitted to hospital for inpatient care. New pharmaceuticals will reduce the incidence of atherosclerosis, coronary artery disease, and in particular stroke. Other pharmaceutical advances will promote the opening of stenotic arteries and the dissolution of acute thrombi Biotechnology companies are developing products that will prevent, modify, or treat a variety of cancers—breast cancer being one of the first treated.1 2 How significantly pharmaceuticals will affect infectious diseases, and …
Abstract 462: Targeting hepatocellular carcinoma by suppressing HIF-1 alpha alone and in combination with therapeutic drugs
Authors: Zhi Xie, Xin Wu, Kai Wang, David Pocalyko, Young-II Yeom, Hyang-Sook Yoo
Journal: Cancer Research (2010)

Abstract Hepatocellular carcinoma (HCC) is the sixth most common cancer worldwide and the third most common cause of cancer related death. HIF-1 alpha (HIF1α) is overexpressed in many human cancers as a result of intratumoral hypoxia as well as genetic alterations, such as gain-of-function mutations in oncogenes and loss-of-function mutations in tumour-suppressor genes. It has many important functions including angiogenesis, survival, chemo-resistance metastasis, and glucose metabolism. The overexpression of HIF1α is associated with poor prognosis in many types of cancer. To understand the role of HIF1α in HCC, we analyzed the HIF1α gene expression in the clinical tumor tissues and found that HIF1α mRNA was upregulated compared with the non-tumor adjacent tissue. This upregulation was positively correlated with the poor overall survival and disease free survival of the HCC patients. In addition, we knocked down the HIF1α expression by siRNA and examined its impact on the growth of a panel of HCC cell lines under both hypoxia and normaxia conditions. HIF1α siRNA suppressed 90% of HIF1α mRNA and 50% of its protein expression without affecting the expression of HIF1β and HIF2α. Hep1 and Snu182 cell lines were sensitive to HIF1α suppression (&amp;gt;70%) while Huh 7.5 and SNU398 showed little response. The effect of HIF1α on cell growth inhibition is similar under both hypoxia and normoxia conditions. PDGFR and mTOR were reported to regulate HIF1α synthesis. We examined the efficacy of rapamycin and PDGFR inhibitors in combination with HIF1α siRNA. We found differential response in different HCC cell lines. Rapamycin had limited suppression on both Hep1 and SNU182 cell growth. When combined with HIF1α siRNA, we observed significantly enhanced suppression. PDGFR inhibitor suppressed Hep1 and SNU182 in a dose-dependant manner and the efficacy was further enhanced when combined with HIF1α. To understand the molecular mechanism of HIF1α function, we carried out the gene expression analysis on these “sensitive” and “resistant” cell lines under different treatment conditions. The differential expression signature will provide important insight to the function of HIF1α and the other targeted therapeutic drugs in these HCC cell lines. It will also provide understanding of possible resistance mechanisms and combinational drug strategy to overcome these resistances. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 462.
Preperitoneal prosthetic herniorrhaphy.
Authors: L. F. Tinckler
Journal: BMJ (1968)

limiting screening to women over 35 years, but as there has not been an overwhelming demand for the interpretation of smears these days are past.Incidentally in our area, where the incidence of cervical cancer is falling,' there have been no fewer than five women with overt clinical cervical cancer in the past two years who were multiparous and under 30 years of age.-I am, etc.,
Crusted scabies in pregnancy
Authors: M.R JUDGE, A. KOBZA-BLACK
Journal: British Journal of Dermatology (1995)

An otherwise healthy 19‐year‐old pregnant woman developed crusted scabies. She and her husband had previously been treated for scabies. In spite of appropriate treatment both suffered several relapses, and later their infant was also affected. Ultimately, the infection was eradicated. As far as we are aware, this is the first recorded case of crusted scabies occurring in a healthy pregnant woman.
Production of CFTR-null and CFTR-ΔF508 heterozygous pigs by adeno-associated virus–mediated gene targeting and somatic cell nuclear transfer
Authors: Christopher S. Rogers, Yanhong Hao, Tatiana Rokhlina, Melissa Samuel, David A. Stoltz, Yuhong Li, Elena Petroff, Daniel W. Vermeer, Amanda C. Kabel, Ziying Yan, Lee Spate, David Wax, Clifton N. Murphy, August Rieke, Kristin Whitworth, Michael L. Linville, Scott W. Korte, John F. Engelhardt, Michael J. Welsh, Randall S. Prather
Journal: Journal of Clinical Investigation (2008)

Progress toward understanding the pathogenesis of cystic fibrosis (CF) and developing effective therapies has been hampered by lack of a relevant animal model. CF mice fail to develop the lung and pancreatic disease that cause most of the morbidity and mortality in patients with CF. Pigs may be better animals than mice in which to model human genetic diseases because their anatomy, biochemistry, physiology, size, and genetics are more similar to those of humans. However, to date, gene-targeted mammalian models of human genetic disease have not been reported for any species other than mice. Here we describe the first steps toward the generation of a pig model of CF. We used recombinant adeno-associated virus (rAAV) vectors to deliver genetic constructs targeting the CF transmembrane conductance receptor (CFTR) gene to pig fetal fibroblasts. We generated cells with the CFTR gene either disrupted or containing the most common CF-associated mutation (DeltaF508). These cells were used as nuclear donors for somatic cell nuclear transfer to porcine oocytes. We thereby generated heterozygote male piglets with each mutation. These pigs should be of value in producing new models of CF. In addition, because gene-modified mice often fail to replicate human diseases, this approach could be used to generate models of other human genetic diseases in species other than mice.
PWE-016 Evolution of endotherapy for high grade dysplasia and early cancer in Barrett's oesophagus: completing the audit cycle in a single centre
Authors: M Usman-Saeed, K Gowland, C Carr, J Buchanan, S Mahmood, H L Smart
Journal: Gut (2012)

<h3>Introduction</h3> We have previously reported our outcomes for endotherapy in Barrett9s oesophagus (BO) patients with high grade dysplasia (HGD) and intra-mucosal adenocarcinoma (IMAC) to this Society. Using Endoscopic Mucosal Resection (EMR) and Argon Plasma Coagulation (APC) in patients unfit for surgery, no procedure related mortality, minimal morbidity but a recurrence rate of 27% was seen.<sup>1</sup> We were interested to complete the audit cycle, particularly with the advent of Radiofrequency Ablation (RFA), which has become available since our initial report. <h3>Methods</h3> The aim was to re-audit the outcomes of endotherapy for HGD and IMAC in patients with BO attending our gastroenterology unit and to compare the results to our previous audit in terms of outcome and complications. A retrospective review of patient records using specialised endoscopy and patahology databases was performed. Demographic information, diagnosis, procedural details and subsequent progress was entered into a Microsoft Access database and analysed using Microsoft Excel. <h3>Results</h3> A total of 54 patients who underwent endotherapy from January 2005 to December 2011 were identified. The mean age of the group was 71 (range 45–89) years. There were 42 males and 12 females. The underlying diagnosis was HGD in 49 and IMAC in 5. Patients with focal raised lesions were treated by EMR, while diffuse dysplasia was treated by mucosal ablation (APC or RFA). Eight patients had EMR alone. EMR was followed by APC in six patients and RFA in 20. Five patients had EMR, APC and RFA. Ten patients had RFA and five APC alone. Six patients (11%) developed an oesophageal stricture requiring dilatation. No bleeding, perforation or procedure related mortality occurred. Over a median follow-up of 18.9 months (range 0–71), two patients (4%) developed a recurrence of their condition, defined as the reappearance of HGD or IMAC after one or more negative biopsies. Two patients (4%) had persistent disease. These four patients (7%) were referred for surgery and underwent oesophagectomy. Seven patients are still under treatment with RFA, 38 have no dysplasia, four low grade dysplasia with one lost to follow-up. During the follow-up period three patients have died, one in the post-operative period. <h3>Conclusion</h3> In our department, endotherapy has evolved with APC being replaced by RFA, often in combination with EMR. This has resulted in a considerable improvement in patient outcomes (7 vs 27% recurrence/persistent disease), no procedure related mortality and minimal morbidity. Endotherapy is now used as the primary treatment for HGD and IMAC with surgery being reserved as a salvage procedure if no response or disease recurs. <h3>Competing interests</h3> None declared. <h3>Reference</h3> 1. <b>Duffy U</b>, <i>et al.</i><i>Gut</i> 2009;<b>58</b>(Suppl 1):A146.
Prognostic Factors and Long-Term Survivors in Inflammatory Breast Cancer.
Authors: R. Woods, J. Huang, R. Livingston, L. Grasso-LeBeau, K. Hendershott, A. Gruessner, J. Mayo, J. Lang
Journal: Cancer Research (2009)

Abstract Background: Inflammatory Breast Cancer (IBC) carries a worse overall survival and demonstrates distinct clinicopathologic qualities which require refinement of prognostic indicators specific to IBC. We hypothesized that given IBC's typically rapid course, nodal status would not be a significant prognostic factor. We also investigated the impact of treatment with radiation and surgery on IBC survival.Material and Methods: Retrospective data from the Surveillance, Epidemiology, and End Results of the National Cancer Institute (SEER 13 and 17 registries) were used to evaluate the prognostic effects of nodal status, surgical resection, and radiation on mortality of patients with IBC. We compared survival between patients with or without positive lymph node status and treatment with radiation, surgery, and those patients treated with both. Data were subjected to multivariate statistical analysis.Results: A total of 3755 IBC patients were diagnosed and reported to SEER between 1995 and 2005. IBC survival appears independent of lymph node status with mean survival times of 34 months for node negative patients and 32 months for node positive patients (figure 1, p= 0.11). We identified 735 cases with adequate local treatment records and follow-up information. In this subset we compared survival between groups that received both surgery and radiation (SR), groups that received one of these therapies independently (S or R respectively), to those without either therapy (NT, no therapy) given positive lymph node status at diagnosis (fig. 2, p&amp;lt;0.001).Discussion: Our data suggests that the prognosis of IBC is not related to lymph node status at the time of diagnosis. Because patients with IBC amenable to surgical intervention or radiation are likely to have more favorable biology then those who progress on chemotherapy, it remains difficult to quantify the impact of local therapies. NCCN guidelines currently recommend first-line chemotherapy before moving to local treatments; therefore one limitation of our study is the assumption that centers reporting data to SEER follow NCCN guidelines. Of special interest is the substantial number of patients that show prolonged survival with local therapies. This supports previous reports that about 30% of patients who complete chemotherapy, surgery and radiation therapy may survive five years or more after IBC diagnosis. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4039.
Abstract 1708: LINE-1 methylation level is a molecular marker with little intra-patient heterogeneity in primary and synchronous metastatic colorectal cancer
Authors: Aika Matsunoki, Kazuyuki Kawakami, Masanori Kotake, Mami Kaneko, Go Watanabe, Toshinari Minamoto
Journal: Cancer Research (2012)

Abstract Introduction: Epigenetic alterations including hypermethylation of gene promoter regions and global hypomethylation of DNA are common in colorectal cancer (CRC). We recently reported that long interspersed nuclear element 1 (LINE-1) methylation level in tumor, a surrogate of global methylaiton, predicts prognosis and response to oral fluoropyrimidines of CRC patients. This suggests that the LINE-1 methylation level is a useful marker for tailored therapy in CRC. However, the LINE-1 methylation level in tumor may be heterogeneous because the DNA methylaion is reversible, which is a problem when the LINE-1 methylation level in tumor is used for decision making in clinic. In this study we investigated LINE-1 methylation level in cancer cells isolated from multiple tumor sites to evaluate intra-patient heterogeneity of the LINE-1 methylation level in tumor tissues. Methods: Primary tumor, metastatic lymph nodes, and distant metastases in 41 CRC patients were used for measurement of LINE-1 methylation level. Cancer cells in primary tumors were collected from tumor center and invasion front by laser capture microdissection (LCMD). Cancer cells in metastatic lymph nodes and distant metastases were also collected by LCMD. The LINE-1 methylation level was measured by multicolor MethyLight assay following bisulfite modification of DNA and was correlated with clinicopathological parameters. Results: There was no significant difference in the LINE-1 methylation level between cancer cells from the center and those from invasion front of the primary tumor tissue. In the same patient, there was no significant difference in the LINE-1 methylation level between the samples from primary tumor, metastatic lymph nodes, and distant metastases. The LINE-1 methylation level was decreased as the tumor stage advances. Discussion: The results suggest that the LINE-1 methylation level is a molecular marker with little intra-patient heterogeneity in primary and synchronous metastatic colorectal cancer. Prediction of patients’ prognosis using LINE-1 methylation level may be possible by multiple tumor specimen such as biopsy specimen by colonoscopy and surgically resected tumor. Measuring LINE-1 methylation level in primary tumor may be useful for prediction of response to fluoropyrimidines in metastatic tumor. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1708. doi:1538-7445.AM2012-1708
A PECULIAR CASE OF RECURRENT BULLOUS ERUPTION.
Authors: WILLIAM S. GOTTHEIL
Journal: JAMA (1902)

It may well be that the case which I shall briefly describe is of a type not unusual in some localities, or that it is not infrequently seen by those who practice in pediatrics. But I have never come across one precisely similar, and its characteristics, both positive and negative, are such that I am unable to classify it under the heading of any of the ordinary dermatoses. These considerations embolden me to place on record the following case:  Mamie K., 5½ years old, was brought to my clinic at Lebanon Hospital, with the following history: Since her second year there has appeared each autumn a skin eruption similar to the one that is now present; during the spring and summer there is absolutely nothing the matter with her integument. Each attack began with the appearance of a few watery blisters, which increased up to a certain size, and then
M1 macrophages, key contributors to lymphoid neogenesis in atherosclerotic aorta
Authors: A. Bobik, T. S. Kyaw, P. Tipping, B.-H. Toh
Journal: Cardiovascular Research (2014)

This editorial refers to ‘M1 macrophages act as LTβR-independent lymphoid tissue inducer cells during atherosclerosis-related lymphoid neogenesis’ by K. Guedj et al. , pp. 434–443, this issue. 

The immune system has evolved to optimize the chances of encounter between rare antigen-specific T and B cells of the adaptive immune system with antigen presenting cells of the innate immune system through development of organized secondary lymphoid organs (SLOs) such as the spleen and lymph nodes. This system efficiently eradicates pathogens, including foreign antigens. However, when antigens are constantly replenished, as in atherosclerosis, this can lead to local or systemic chronic inflammation. Under such conditions, tissues that persistently harbour target antigens are infiltrated by cellular effectors of the immune system, including T cells, B cells, and macrophages as well as dendritic cells and plasma cells. These cellular elements frequently organize themselves anatomically and functionally similar to SLOs, leading to de novo formation of B-cell follicles and T-cell areas by a process called lymphoid neogenesis or tertiary lymphoid organ (TLO) formation. TLOs have been observed in autoimmune diseases such as autoimmune thyroiditis, rheumatoid arthritis, and myasthenia gravis as well as in chronic allograft rejection,1,2 diabetes,3 and in atherosclerosis.4 Whilst the role of TLOs is still yet to be fully elucidated in diseases such as atherosclerosis, there is evidence that like SLOs, they can contribute to immune disease progression.5 For example, B cells in TLOs within lungs of patients with rheumatoid arthritis …
Nongenomic Effects of Cisplatin: Acute Inhibition of Mechanosensitive Transporters and Channels without Actin Remodeling
Authors: Nina Milosavljevic, Christophe Duranton, Nadir Djerbi, Pierre Henri Puech, Pierre Gounon, Dominique Lagadic-Gossmann, Marie Thérèse Dimanche-Boitrel, Cyril Rauch, Michel Tauc, Laurent Counillon, Mallorie Poët
Journal: Cancer Research (2010)

Cisplatin is an antineoplastic drug, mostly documented to cause cell death through the formation of DNA adducts. In patients, it exhibits a range of short-term side effects that are unlikely to be related to its genomic action. As cisplatin has been shown to modify membrane properties in different cell systems, we investigated its effects on mechanosensitive ion transporters and channels. We show here that cisplatin is a noncompetitive inhibitor of the mechanosensitive Na(+)/H(+) exchanger NHE-1, with a half-inhibition concentration of 30 μg/mL associated with a decrease in V(max) and Hill coefficient. We also showed that it blocks the Cl(-) and K(+) mechanosensitive channels VSORC and TREK-1 at similar concentrations. In contrast, the nonmechanosensitive Cl(-) and K(+) channels CFTR and TASK-1 and the Na(+)-coupled glucose transport, which share functional features with VSORC, TREK-1, and NHE-1, respectively, were insensitive to cisplatin. We next investigated whether cisplatin action was due to a direct effect on membrane or to cortical actin remodeling that would affect mechanosensors. Using scanning electron microscopy, in vivo actin labeling, and atomic force microscopy, we did not observe any modification of the Young's modulus and actin cytoskeleton for up to 60 and 120 μg/mL cisplatin, whereas these concentrations modified membrane morphology. Our results reveal a novel mechanism for cisplatin, which affects mechanosensitive channels and transporters involved in cell fate programs and/or expressed in mechanosensitive organs in which cisplatin elicits strong secondary effects, such as the inner ear or the peripheral nervous system. These results might constitute a common denominator to previously unrelated effects of this drug.
The self-organizing consciousness as an alternative model of the mind
Authors: Pierre Perruchet, Annie Vinter
Journal: Behavioral and Brain Sciences (2002)

Through the concept of self-organizing consciousness (SOC), we posit that the dynamic of the mind stems from the recurrent interplay between the properties of conscious experiences and the properties of the world, hence making it unnecessary to postulate the existence of an unconscious mental level. In contrast, arguments are provided by commentators for the need for a functional level of organization located between the neural and the conscious. Other commentaries challenge us concerning the ability of our model to account for specific phenomena in the domains of language, reasoning, incubation, and creativity. The possibility of unconscious semantic access and other alleged instances of adapted performance in the absence of any conscious counterpart are also put forth as evidence against our view. Our response emphasizes the fact that opponents to our model often present as factual, theory-free evidence which is in fact nothing more than the postulates underlying the classical computational framework.