tbuckley/cabot-search huggingface dataset:
Abstract 57: Integrating transcriptome profiling and <i>in silico</i> pathway analysis toward reduction of therapeutic dimensionality in nasopharyngeal carcinoma
Authors: Ying-Na Bao, Yilin Dai, Yongpan Yan, Wen-Hua Lu, Li-Xia Peng, Fang-Jing Zheng, Xin-Jian Li, Tie-Bang Kang, Yi-Xin Zeng, Jeffrey M. Trent, Chao-Nan Qian
Journal: Cancer Research (2011)

Abstract Nasopharyngeal carcinoma (NPC) has its highest incidence in southern China and Southeast Asia. In order to obtain deeper insights into the molecular mechanism of NPC tumorigenesis, we performed genome expression profiling combined with computerized pathway analyses on 18 NPC tissues and 18 age-matched tissues of non-cancerous nasopharyngeal mucosa from individuals in the endemic area, Guangdong province, China, between Dec 2007 and Oct 2010. Gene expression profiling was performed using an Agilent gene expression kit and Agilent 4×44K microarray gene chips. One-way analysis of variance was used to identify the genes differentially expressed between cancer and non-cancerous tissues. Genes with a false discovery rate of less than 0.001 and a fold-change larger than 2 or less than 0.5 were selected for in silico network mapping combined with pathway analysis using GeneGo software. Pathways were prioritized based on the gene enrichment analysis. The genes’ connectivity was also integrated to identify the regulatory hotspots in the key pathways. Genes within or surrounding these hotspots constitute potential therapeutic targets. Genes previously known to be up-regulated in NPC that were detected in our study included CCND1, CDKN1A, STAT1, BCL2A1, SGK1, RAI14, FOXM1, EPHB2, PMAIP1, COL1A1, GADD45A, ICAM1, FANC1, ZWINT, LAMB3, CKAP4, ISG15, and MMP3; known down-regulated genes included ATM and INPP5D. However, what was of interest was the identification of a series of previously unrecognized genes: those up-regulated more than 10-fold included MMP1, HOXC8, KREMEN2, and HOXA1, and those down-regulated more than 10-fold included LTF, C7, SHISA3, SKLC26A7, and C16orf89. Although the deregulated pathways in NPC encompass many cytological functions, pathway analysis has been helpful in ranking a series of the most significant deregulated pathways, which include ECM remodeling pathways; alternative complement pathway; plasmin signaling pathway; the TGF, WNT, and cytoskeletal remodeling pathways; leukocyte chemotaxis pathway; and the BAFF and PLAU signaling pathways. Results will be presented on key genetic changes within these pathways that have been verified by biologically. In conclusion, we are beginning to recognize key genes and pathways, prioritized by pathway analysis, that appear likely to identify possible novel mechanisms of NPC tumorigenesis. 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 57. doi:10.1158/1538-7445.AM2011-57
GENETICS AND THE PHYSICIAN
Authors: James A. Peters
Journal: JAMA (1960)

Unless the physician has attempted to familiarize himself with genetics and to keep pace with its rapidly changing concepts and theories, he is likely to prove a source of misinformation to his patients, quite unwittingly. It is typical of people in general, in our conforming world, that they accept unquestionably the word of authority, regardless of the validity of that word. For the layman, the physician is the authority on human genetics, whether he is familiar with it or not. One of the things anyone exposed to a little genetics is likely to know is that, since brown eyes are dominant and blue eyes recessive, obviously two blue-eyed parents cannot have brown-eyed children. This has been taught for many years, in high school science courses and in some college genetics courses. Fortunately, for the peace of mind of such brown-eyed offspring, a modern understanding of the biochemical relationships of the
Review of uptake of interventions to reduce mother to child transmission of HIV by women aware of their HIV status
Authors: E G H. Lyall, C. Stainsby, G. P Taylor, M. Ait-Khaled, S. Bingham, J. A Evans, A. Wright, J. N Weber, M. O McClure, S. Walters, G. Tudor-Williams
Journal: BMJ (1998)

To examine the change in uptake of interventions to reduce transmission of HIV from mothers to infants from January 1994 to July 1997.Review of mother-infant pairs who presented for infant diagnosis of HIV infection.Central London hospital with facilities for diagnosis of infant HIV infection.57 consecutive mother-infant pairs, mainly from central London but also referred from surrounding hospitals.Data were collected on mother's country of origin; CD4 count at delivery; plasma HIV RNA copies/ml; mode of delivery; antiretroviral therapy; infant feeding; and HIV infection in infants.HIV infection of infants.The vertical transmission rate was 12% (7 pairs; 95% confidence interval 3% to 22%). All mothers chose not to breast feed. The caesarean section rate was 53% (30/57). Antiretroviral therapy was taken by 68.5% (39/57) of mother-infant pairs. With antiretroviral therapy or caesarean section, or both, transmission occurred in 6% (0% to 13%) of pairs (3/50). During the 24 months of 1994 and 1995, 21% (4/19) of infants were infected with HIV; 7.9% (3/38) were infected over the 19 months January 1996 to July 1997. The caesarean section rate did not change over these periods. Use of antiretroviral therapy increased from 31.5% (6/19) to 86.8% (33/38) (P < 0.0001).Women with a diagnosis of HIV infection acted to reduce the risk of transmission to their infants. Uptake of antiretroviral therapy increased significantly over time, and the caesarean section rate was persistently high.
Src homology 2 domain–containing inositol-5-phosphatase and CCAAT enhancer-binding protein β are targeted by miR-155 in B cells of Eμ-MiR-155 transgenic mice
Authors: Stefan Costinean, Sukhinder K. Sandhu, Irene M. Pedersen, Esmerina Tili, Rossana Trotta, Danilo Perrotti, David Ciarlariello, Paolo Neviani, Jason Harb, Lauren Rachel Kauffman, Aaditya Shidham, Carlo Maria Croce
Journal: Blood (2009)
Ultrasound-Targeted Microbubble Destruction to Deliver siRNA Cancer Therapy
Authors: Andrew R. Carson, Charles F. McTiernan, Linda Lavery, Michelle Grata, Xiaoping Leng, Jianjun Wang, Xucai Chen, Flordeliza S. Villanueva
Journal: Cancer Research (2012)

Microbubble contrast agents can specifically deliver nucleic acids to target tissues when exposed to ultrasound treatment parameters that mediate microbubble destruction. In this study, we evaluated whether microbubbles and ultrasound-targeted microbubble destruction (UTMD) could be used to enhance delivery of EGF receptor (EGFR)-directed siRNA to murine squamous cell carcinomas. Custom-designed microbubbles efficiently bound siRNA and mediated RNAse protection. UTMD-mediated delivery of microbubbles loaded with EGFR-directed siRNA to murine squamous carcinoma cells in vitro reduced EGFR expression and EGF-dependent growth, relative to delivery of control siRNA. Similarly, serial UTMD-mediated delivery of EGFR siRNA to squamous cell carcinoma in vivo decreased EGFR expression and increased tumor doubling time, relative to controls receiving EGFR siRNA-loaded microbubbles but not ultrasound or control siRNA-loaded microbubbles and UTMD. Taken together, our results offer a preclinical proof-of-concept for customized microbubbles and UTMD to deliver gene-targeted siRNA for cancer therapy.
Beta-blockers in the treatment of myocardial infarction.
Authors: N S Baber, J A Lewis
Journal: BMJ (1980)

non-crying babies.Hutt7 describes parallels.High pulse rates have been found in withdrawn psychotic patients.8While preparing a paper on adolescent suicide attempts in this health district over 12 months I noted that, with a few exceptions, both the mothers' memory and medical records indicated that the 40 teenagers were non-crying babies.I had hoped to entitle the presentation "The unheard cry growing up."Although, as Dunn surmises,2 parents and babies are allowed time to adjust and early reactions are certainly not exclusively all- important for future emotional development, awareness of "silent" infant protest is im- portant.We can then deal with causative factors and learn to contain also the anxiety or aggression arising therefrom.
Is the SF-36 a valid measure of change in population health? Results from the Whitehall II study
Authors: H. Hemingway, M. Stafford, S. Stansfeld, M. Shipley, M. Marmot
Journal: BMJ (1997)

<h3>Abstract</h3> <b>Objective:</b> To measure within-person change in scores on the short form general health survey (SF-36) by age, sex, employment grade, and disease status. <b>Design:</b> Longitudinal study with a mean of 36 months (range 23–59 months) follow up, with screening examination and questionnaire to detect physical and psychiatric morbidity. <b>Setting:</b> 20 civil service departments originally located in London. <b>Participants:</b> 5070 male and 2197 female office based civil servants aged 39–63 years. <b>Main outcome measures:</b> Change in the eight scales of the SF-36 (adjusted for baseline score and length of follow up) and effect sizes (adjusted change/standard deviation of differences). <b>Results:</b> Within-person declines (worsening health) with age were greater than estimated by cross sectional data alone. General mental health showed greater declines among younger participants (P for linear trend &lt;0.001). Employment grade was inversely related to change; lower grades had greater deteriorations than higher grades (P&lt;0.001 for each scale in men; P&lt;0.05 for each scale in women except general health perceptions and role limitations due to physical problems). The greatest declines were seen among participants with disease at baseline, with the effects of physical and psychiatric morbidity being additive. Effect sizes ranged from 0.20 to 0.65 in participants with both physical and psychiatric morbidity. <b>Conclusions:</b> Health functioning, as measured by the SF-36, changed in hypothesised directions with age, employment grade, and disease status. These changes occurred within a short follow up period, in an occupational, high functioning cohort which has not been the subject of intervention, suggesting that the SF-36 is sensitive to changes in health in general populations. <h3>Key messages</h3> The SF-36, an inexpensive measure of health outcomes, is capable of detecting change in health in a general population Health and functioning do not decline uniformly with age; general mental health shows greater declines among younger participants Socioeconomic status is associated inversely with baseline functioning and, independently, with decline in health The greatest declines were seen among subjects with physical and psychiatric morbidity at baseline Performance of 28 doctors and medical laboratory scientific officers in distinguishing pairs of slides
Improving the management of environmental health.
Authors: L B Lave
Journal: Environmental Health Perspectives (1985)

Environmental health regulation has been developed on the premise that both problems and solutions are obvious, requiring only attention and commitment. The result has been impossible legislative goals and frenetic, unfocused agency efforts to deal with too many issues. Preventing all environmental health problems is impossible and not the best approach; instead, attention ought to be shifted toward reacting quickly to problems before irreversible, severe health damage has occurred. Rather than having regulatory agencies attempt to manage all problems, they should be focused on exemplifying goals and productive approaches, and on handling a few major issues. Regulatory agencies should be managing the nonregulatory institutions to ensure that they are effective in dealing with the myriad issues that the agencies will never be able to handle. The inherent limitations of federal regulatory agencies must be recognized to restructure environmental health management to be more effective in lowering risks while being efficient, administratively simple, and more equitable.
Moderate use of painkillers presents no harm to kidneys
Authors: D. Josefson
Journal: BMJ (2001)

A new study counters the belief that moderate, chronic use of common analgesics results in kidney damage ( JAMA 2001;286:315-21).

The study investigated moderate, chronic intake of analgesics—equivalent to three or four tablets a week. It was conducted by researchers from Brigham and Women's Hospital in Boston and was funded by the National Institutes of Health and by MacNeil Consumer Products, the maker of Tylenol, a popular brand of paracetamol.

Kathryn Rexrode, Julie Buring, and colleagues compared analgesic intake and renal function in a cohort of 11 032 initially healthy men, ranging in age from 40 to 84, who were enrolled in the physicians' health study. This study lasted 14 years, from September …
Surgery for Diverticulitis in the 21st Century
Authors: Scott E. Regenbogen, Karin M. Hardiman, Samantha Hendren, Arden M. Morris
Journal: JAMA Surgery (2014)

Diverticulitis of the sigmoid colon is an increasingly common disease. Patterns of care and management guidelines have significantly evolved in recent years.To review and classify the primary data published since 2000 that are guiding decision making, technical considerations, and the outcomes of surgery for sigmoid diverticulitis.We searched the National Guideline Clearinghouse, PubMed, and Cochrane databases for studies pertaining to the diagnosis and management of chronic and recurrent diverticulitis from January 1, 2000, to March 31, 2013. We supplemented this automated search with references drawn from included studies and PubMed. We rated the level of evidence according to American College of Cardiology/American Heart Association guidelines.We identified 68 studies meeting inclusion criteria for final review. The studies were almost exclusively observational and had limited certainty of treatment effect. We found that complicated recurrence after recovery from an uncomplicated episode of diverticulitis is rare (<5%) and that age at onset younger than 50 years and 2 or more recurrences do not increase the risk of complications. Chronic symptoms may persist even after resection in 5% to 22% of patients. Prophylactic surgery is generally not recommended for average-risk patients with diverticulitis, irrespective of the number of episodes of acute, noncomplicated disease. Decisions to proceed with colon resection should be based instead on the patient-reported frequency and severity of diverticulitis symptoms.The prior standard for proceeding with elective colectomy following 2 episodes of diverticulitis is no longer accepted. Decisions to proceed with colectomy should be made based on consideration of the risks of recurrent diverticulitis, the morbidity of surgery, ongoing symptoms, the complexity of disease, and operative risk. Laparoscopic surgery is preferred to open approaches. Recent evidence suggests that existing guidelines should be updated.
Hematopoietic overexpression of Cyp27a1 reduces hepatic inflammation independently of 27-hydroxycholesterol levels in Ldlr−/− mice
Authors: Tim Hendrikx, Mike L.J. Jeurissen, Veerle Bieghs, Sofie M.A. Walenbergh, Patrick J. van Gorp, Fons Verheyen, Tom Houben, Yasmin Dias Guichot, Marion J.J. Gijbels, Eran Leitersdorf, Marten H. Hofker, Dieter Lütjohann, Ronit Shiri-Sverdlov
Journal: Journal of Hepatology (2014)
MicroRNA-320 Is Involved in the Regulation of Cardiac Ischemia/Reperfusion Injury by Targeting Heat-Shock Protein 20
Authors: Xiao-Ping Ren, Jinghai Wu, Xiaohong Wang, Maureen A. Sartor, Jiang Qian, Keith Jones, Persoulla Nicolaou, Tracy J. Pritchard, Guo-Chang Fan
Journal: Circulation (2009)

Background— Recent studies have identified critical roles for microRNAs (miRNAs) in a variety of cellular processes, including regulation of cardiomyocyte death. However, the signature of miRNA expression and possible roles of miRNA in the ischemic heart have been less well studied. Methods and Results— We performed miRNA arrays to detect the expression pattern of miRNAs in murine hearts subjected to ischemia/reperfusion (I/R) in vivo and ex vivo. Surprisingly, we found that only miR-320 expression was significantly decreased in the hearts on I/R in vivo and ex vivo. This was further confirmed by TaqMan real-time polymerase chain reaction. Gain-of-function and loss-of-function approaches were employed in cultured adult rat cardiomyocytes to investigate the functional roles of miR-320. Overexpression of miR-320 enhanced cardiomyocyte death and apoptosis, whereas knockdown was cytoprotective, on simulated I/R. Furthermore, transgenic mice with cardiac-specific overexpression of miR-320 revealed an increased extent of apoptosis and infarction size in the hearts on I/R in vivo and ex vivo relative to the wild-type controls. Conversely, in vivo treatment with antagomir-320 reduced infarction size relative to the administration of mutant antagomir-320 and saline controls. Using TargetScan software and proteomic analysis, we identified heat-shock protein 20 (Hsp20), a known cardioprotective protein, as an important candidate target for miR-320. This was validated experimentally by utilizing a luciferase/GFP reporter activity assay and examining the expression of Hsp20 on miR-320 overexpression and knockdown in cardiomyocytes. Conclusions— Our data demonstrate that miR-320 is involved in the regulation of I/R-induced cardiac injury and dysfunction via antithetical regulation of Hsp20. Thus, miR-320 may constitute a new therapeutic target for ischemic heart diseases.
TOXEMIA OF PREGNANCY.
Authors: W. M. JORDAN
Journal: JAMA (1907)

The pernicious vomiting of pregnancy, acute yellow atrophy of the liver, and eclampsia, are generally grouped together as manifestations of the toxemia of pregnancy. While eclampsia is admittedly a toxemia, it seems unwise to class it with the other two conditions, from which it differs widely in symptoms, pathology, and prognosis, if not in other respects. For this reason it seems to me that eclampsia should be studied entirely apart from the other two types. I wish it to be understood, therefore, that wherever the term toxemia is used in the present article it refers only to the toxemia responsible for pernicious vomiting and acute yellow atrophy and not to eclampsia unless so stated. The most pronounced lesion to be found postmortem in a case of toxemia of pregnancy is a degeneration and necrosis of the parenchyma of the liver. While this lesion is characteristic of the toxemia of pregnancy,
Peritoneoscopy: A Valuable Staging Tool in Ovarian Carcinoma
Authors: STEPHEN H. ROSENOFF
Journal: Annals of Internal Medicine (1975)

Peritoneoscopy was done within 1 month of exploratory laparotomy in 30 consecutive patients, with ovarian carcinoma as part of their pretreatment evaluation. Six of the 7 patients who were thought to have ovarian carcinoma localized to the pelvis (stages I and II) were found to have advanced disease (stage III) at peritoneoscopy and thus required a change in therapy. Metastatic diaphragmatic involvement in ovarian carcinoma is common and was found in 77 percent of all patients studied. The routine shielding if the liver area ordinarily used with total abdominal radiotherapy would select these patients for therapeutic failure. Peritoneoscopy supplied reevaluable finding in 2 of 7 patients having normal physical, roentgenologic, and laboratory examinations, as well as in 93 percent of all patients stuided. "Second look" peritoneoscopy precluded the need the laparotomy in 5 to 13 patients achieving as apparent clinical remission.
Reply to N. Rompoti et al
Authors: Imke Satzger, Annette Degen, Hiba Asper, Alexander Kapp, Axel Hauschild, Ralf Gutzmer
Journal: Journal of Clinical Oncology (2013)

perilesional edema) when combining brain radiation and BRAF inhibitor therapy.Results of brain magnetic resonance imaging performed 12 weeks after radiotherapy showed a mixed response in two patients, stable disease in one patient, and progressive disease in one patient.Brain metastases are common in patients with metastatic melanoma and are associated with a poor prognosis.Radiation is still the first treatment option for melanoma metastases of the brain.However, recently, both dabrafenib 2 and ipilimumab 3 showed clinical activity in patients with melanoma suffering from brain metastasis in larger phase II clinical trials.So far, little is known about the combination of these new therapeutic agents with brain radiotherapy.In contrast to the report by Satzger et al, 1 we observed no severe (grade 3) skin toxicity during and after radiation.None of the observed skin reactions needed specific therapy.No interruption of the radiation course was indicated at any time, and all patients were able to continue BRAF inhibitor treatment during and after brain radiation treatment.Our observations suggest that although BRAF inhibitors may generally increase cutaneous radiation-induced reactions, 4 BRAF inhibitors and brain radiotherapy combined do not lead to obviously increased intracranial toxicity in comparison with brain radiotherapy alone.This is in line with the results of a recent study by Narayana et al. 5 In addition, phosphorylated histone H2AX repair foci were measured in peripheral blood lymphocytes, taken from our patients 2 and 4, who received BRAF inhibitor treatment before radiotherapy.Induction after in vitro lymphocyte irradiation and retention of these foci at 24 hours were in the range of values obtained from patients with cancer who did not receive concurrent drug therapy. 6Therefore, no indication for impaired nonhomologous end joining of DNA double-strand breaks was observed in these patients.Because of the limited number of patients treated, more clinical experience will be required to evaluate the safety of BRAF inhibitor treatment combined with radiotherapy.In conclusion, the simultaneous combination of BRAF inhibitors and brain radiotherapy emerges as a therapeutic option for patients who have progressive intracranial disease while showing an extracranial response to BRAF inhibitor therapy.Nevertheless, thorough dermatologic surveillance in patients receiving BRAF inhibitors and radiotherapy seems warranted, especially when high-dose radiation therapy is applied.