tbuckley/cabot-search huggingface dataset:
Abstract 2431: Downregulation of PHLPP promotes glycolysis in colon cancer cells
Authors: Yang-an Wen, Xiaopeng Xiong, Tianyan Gao
Journal: Cancer Research (2014)

Abstract PHLPP belongs to a novel family of Ser/Thr protein phosphatases. Our previous studies have shown that PHLPP can antagonize multiple signaling pathways by negatively regulating signaling molecules such as Akt, S6K, and PKC. Functionally, PHLPP serves as a tumor suppressor to inhibit cell proliferation, promote apoptosis and increase therapeutic sensitivity in colon cancer cells. Here, we further examined the role of PHLPP in regulating metabolic pathways in colon cancer. Control and PHLPP knockdown cells colon cancer cells, as well as wild-type and Phlpp knockout MEF cells, were subjected to bioenergetic phenotype analysis using Seahorse XF96 analyzer. The mitochondrial respiration measurements revealed that decreased PHLPP expression resulted in an increase in oxygen consumption rate (OCR) suggesting enhanced cellular respiration. In addition, PHLPP depletion significantly stimulated glycolysis as indicated by increased extracellular acidification rate (ECAR). Consistently, the rates of glucose consumption and lactate production were significantly increased in PHLPP knockdown cells. Furthermore, the numbers of apoptotic cells were increased in PHLPP knockdown cells compared to control cells when cultured in glucose-free medium, suggesting that loss of PHLPP expression render cells more sensitive to glucose deprivation as they became relied on glycolysis. To begin determining the underlying molecular mechanism, we found that the activity of both Akt and S6K was largely induced in PHLPP-knockdown cancer cells and PHLPP-knockout MEF cells. Since both kinases are known to play important roles in re-programming metabolic networks to favor tumor growth, it is likely that PHLPP inhibits glycolysis by negatively regulating Akt- and S6K-mediated metabolic effects. Taken together, our studies identified PHLPP as a novel regulator of glucose metabolism in colon cancer cells. Downregulation of PHLPP may promote tumorigenesis by providing metabolic advantages in colon cancer Citation Format: Yang-an Wen, Xiaopeng Xiong, Tianyan Gao. Downregulation of PHLPP promotes glycolysis in colon 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 2431. doi:10.1158/1538-7445.AM2014-2431
Gene expression profiling of CD8+ T cells predicts prognosis in patients with Crohn disease and ulcerative colitis
Authors: James C. Lee, Paul A. Lyons, Eoin F. McKinney, John M. Sowerby, Edward J. Carr, Francesca Bredin, Hannah M. Rickman, Huzefa Ratlamwala, Alexander Hatton, Tim F. Rayner, Miles Parkes, Kenneth G.C. Smith
Journal: Journal of Clinical Investigation (2011)

Crohn disease (CD) and ulcerative colitis (UC) are increasingly common, chronic forms of inflammatory bowel disease. The behavior of these diseases varies unpredictably among patients. Identification of reliable prognostic biomarkers would enable treatment to be personalized so that patients destined to experience aggressive disease could receive appropriately potent therapies from diagnosis, while those who will experience more indolent disease are not exposed to the risks and side effects of unnecessary immunosuppression. Using transcriptional profiling of circulating T cells isolated from patients with CD and UC, we identified analogous CD8+ T cell transcriptional signatures that divided patients into 2 otherwise indistinguishable subgroups. In both UC and CD, patients in these subgroups subsequently experienced very different disease courses. A substantially higher incidence of frequently relapsing disease was experienced by those patients in the subgroup defined by elevated expression of genes involved in antigen-dependent T cell responses, including signaling initiated by both IL-7 and TCR ligation - pathways previously associated with prognosis in unrelated autoimmune diseases. No equivalent correlation was observed with CD4+ T cell gene expression. This suggests that the course of otherwise distinct autoimmune and inflammatory conditions may be influenced by common pathways and identifies what we believe to be the first biomarker that can predict prognosis in both UC and CD from diagnosis, a major step toward personalized therapy.
A SUMMARY DESCRIPTION OF FIFTY "NORMAL" WHITE MALES
Authors: JULES GOLDEN, NATHAN MANDEL, BERNARD C. GLUECK, ZETTA FEDER
Journal: American Journal of Psychiatry (1962)

All of the above raises in our minds a question which has been stated in a number of different ways in the past concerning the balance between the needs and the wants of individuals on the one hand— in this group apparently very much in balance—and the various factors that have been considered to be part of the richer, more creative, spontaneous type of personality. Does "normality," as evidenced by lack of intrapsychic tension, adequate social, economic and familial adaptation, and harmonious integration with other individuals at all levels, necessarily imply a lack of creativity, imagination, and spontaneity? Our data are suggestive of this conclusion. Confirmation would be dependent upon a study of those individuals in the original sample of 1,953 male ninth-graders who have subsequently been more creative, although they showed evidence of some disturbance at that time as measured by their MMPI profiles; at the very least. It is our opinion that the 23 subjects described in this study as being free of symptomatology and as having made a stable, successful adaptation, represent a very normal, healthy, socially acceptable and desirable group of individuals. We would feel that an additional 12 subjects represent the broader "range of normal," which allows for some degree of intrapsychic tension and some minimal adaptational difficulties, none serious enough to interfere with a basically adequate and successful social and economic adjustment. The remainder of the group, with 2 exceptions, while having somewhat greater difficulty in making an adaptation, are still quite successful in most areas and will probably continue to make a successful adaptation without psychiatric help, although perhaps at the cost of greater tension and psychic stress and strain than might otherwise be the case. The authors believe that the characteristics of this group of subjects are consistent with a general conception of the well adjusted average American male. Further, that these multi-dimensional data provide a meaningful baseline of personal adaptation within contemporary American society to which other groups may be compared.
Plasma Phospholipid Long-Chain ω-3 Fatty Acids and Total and Cause-Specific Mortality in Older Adults
Authors: Dariush Mozaffarian, Rozenn N. Lemaitre, Irena B. King, Xiaoling Song, Hongyan Huang, Frank M. Sacks, Eric B. Rimm, Molin Wang, David S. Siscovick
Journal: Annals of Internal Medicine (2013)

Chinese translation Background: Long-chain ω-3 polyunsaturated fatty acids (ω3-PUFAs), including eicosapentaenoic acid (EPA) (20:5ω-3), docosapentaenoic acid (DPA) (22:5ω-3), and docosahexaenoic acid (DHA) (22:6ω-3), have been shown to reduce cardiovascular risk, but effects on cause-specific and total mortality and potential dose-responses remain controversial. Most observational studies have assessed self-reported dietary intake and most randomized trials have tested effects of adding supplements to dietary intake and evaluated secondary prevention, thus limiting inference for dietary ω3-PUFAs or primary prevention. Objective: To investigate associations of plasma phospholipid EPA, DPA, DHA, and total ω3-PUFA levels with total and cause-specific mortality among healthy older adults not receiving supplements. Design: Prospective cohort study. Setting: 4 U.S. communities. Participants: 2692 U.S. adults aged 74 years (±5 years) without prevalent coronary heart disease (CHD), stroke, or heart failure at baseline. Measurements: Phospholipid fatty acid levels and cardiovascular risk factors were measured in 1992. Relationships with total and cause-specific mortality and incident fatal or nonfatal CHD and stroke through 2008 were assessed. Results: During 30 829 person-years, 1625 deaths (including 570 cardiovascular deaths), 359 fatal and 371 nonfatal CHD events, and 130 fatal and 276 nonfatal strokes occurred. After adjustment, higher plasma levels of ω3-PUFA biomarkers were associated with lower total mortality, with extreme-quintile hazard ratios of 0.83 for EPA (95% CI, 0.71 to 0.98; P for trend = 0.005), 0.77 for DPA (CI, 0.66 to 0.90; P for trend = 0.008), 0.80 for DHA (CI, 0.67 to 0.94; P for trend = 0.006), and 0.73 for total ω3-PUFAs (CI, 0.61 to 0.86; P for trend < 0.001). Lower risk was largely attributable to fewer cardiovascular than noncardiovascular deaths. Individuals in the highest quintile of phospholipid ω3-PUFA level lived an average of 2.22 more years (CI, 0.75 to 3.13 years) after age 65 years than did those in the lowest quintile. Limitation: Temporal changes in fatty acid levels and misclassification of causes of death may have resulted in underestimated associations, and unmeasured or imperfectly measured covariates may have caused residual confounding. Conclusion: Higher circulating individual and total ω3-PUFA levels are associated with lower total mortality, especially CHD death, in older adults. Primary Funding Source: National Institutes of Health.
Amnesty team claims to have found human rights abuses in Jenin
Authors: K. Inman
Journal: BMJ (2002)

A British professor of forensic medicine is part of a team that claims to have found evidence of human rights abuses carried out by the Israeli army during conflict in the West Bank.

A delegation from the human rights organisation Amnesty International returned from a preliminary fact finding mission this week having visited the devastated Jenin refugee camp, gathered witness statements of civilian deaths, and conducted postmortem examinations at Jenin Government Hospital. The organisation has called for an independent international inquiry into events in the camp. …
Anaemia in the older surgical patient: a review of prevalence, causes, implications and management
Authors: Judith Partridge, Danielle Harari, Jessica Gossage, Jugdeep Dhesi
Journal: Journal of the Royal Society of Medicine (2013)

This review provides the clinician with a summary of the causes, implications and potential treatments for the management of anaemia in the older surgical patient. The prevalence of anaemia increases with age and is frequently identified in older surgical patients. Anaemia is associated with increased postoperative morbidity and mortality. Allogenic blood transfusion is commonly used to treat anaemia but involves inherent risks and may worsen outcomes. Various strategies for the correction of pre- and postoperative anaemia have evolved. These include correction of nutritional deficiencies and the use of intravenous iron and erythropoesis stimulating therapy. Clear differences exist between the elective and emergency surgical populations and the translation of research findings into these individual clinical settings requires more work. This should lead to a standardized approach to the management of this frequently encountered clinical scenario.
Abstract 254: Genome-wide shRNA screening identifies candidate proteins modulating the extrinsic apoptotic pathway
Authors: Zhigang Kang, Liang Cao
Journal: Cancer Research (2012)

Abstract Apoptosis is a highly regulated process critical for embryonic development, and tissue and organ homeostasis. Deregulation of apoptosis is a common occurrence in cancer. Emerging oncology therapeutic agents designed to engage apoptosis are currently undergoing clinical investigations. To identify unknown proteins that modulate the sensitivity to death receptor DR5 targeted agent drozitumab and to uncover predictive biomarkers, we perform a genome-wide screening of 18,000 genes by using pooled short hairpin RNA libraries, followed by the next generation sequencing for candidate identification. We have identified and confirmed candidate shRNA constructs and target genes that resulted in selective desensitizing of the cells to drozitumab. The roles and mechanisms of action of the newly identified proteins in modulating the extrinsic apoptotic pathway will be presented. 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 254. doi:1538-7445.AM2012-254
NF-κB Gene Signature Predicts Prostate Cancer Progression
Authors: Renjie Jin, Yajun Yi, Fiona E. Yull, Timothy S. Blackwell, Peter E. Clark, Tatsuki Koyama, Joseph A. Smith, Robert J. Matusik
Journal: Cancer Research (2014)

In many patients with prostate cancer, the cancer will be recurrent and eventually progress to lethal metastatic disease after primary treatment, such as surgery or radiation therapy. Therefore, it would be beneficial to better predict which patients with early-stage prostate cancer would progress or recur after primary definitive treatment. In addition, many studies indicate that activation of NF-κB signaling correlates with prostate cancer progression; however, the precise underlying mechanism is not fully understood. Our studies show that activation of NF-κB signaling via deletion of one allele of its inhibitor, IκBα, did not induce prostatic tumorigenesis in our mouse model. However, activation of NF-κB signaling did increase the rate of tumor progression in the Hi-Myc mouse prostate cancer model when compared with Hi-Myc alone. Using the nonmalignant NF-κB-activated androgen-depleted mouse prostate, a NF-κB-activated recurrence predictor 21 (NARP21) gene signature was generated. The NARP21 signature successfully predicted disease-specific survival and distant metastases-free survival in patients with prostate cancer. This transgenic mouse model-derived gene signature provides a useful and unique molecular profile for human prostate cancer prognosis, which could be used on a prostatic biopsy to predict indolent versus aggressive behavior of the cancer after surgery.
CD30+ large cell transformation of mycosis fungoides after psoralen plus ultraviolet A photochemotherapy
Authors: J. Ogino, K. Saga, M. Kagaya, A. Kamada, K. Hirosaki, R. Kaneko, K. Jimbow
Journal: British Journal of Dermatology (2006)

Psoralen plus ultraviolet A (PUVA) photochemotherapy is widely used for the therapy of mycosis fungoides (MF). Clinical progression of MF is often associated with an increase in the size of tumour cells known as transformation. We report two patients with CD30+ large cell transformation that appeared after low-dose PUVA therapy for MF. Clinical data, histopathology, immunohistopathology and T-cell receptor gene rearrangement were studied. Nodules consisted of atypical large cells that expressed CD30. Monoclonal rearrangement of T-cell receptors was observed in one case. Low-dose PUVA therapy may be associated with CD30+ large cell transformation in patients with MF.
OC-051 Patients Undergoing Radiofrequency Ablation (Rfa) for Barrett’S Related Neoplasia have Improved outcomes with Decreasing Lenghths of Baseline Barrett’S Oesophagus (Be) & Increasing Number of RFA Sessions
Authors: R Haidry, M Banks, M Butt, A Gupta, J Dunn, H L Smart, P Bhandari, L-A Smith, R Willert, G Fullarton, M di Pietro, I Penman, R Narayanasamy, D O’Toole, C Gordon, P Patel, H Barr, P Boger, N Kapoor, B Mahon, J Hoare, J Morris, E Cheong, Y Ang, N Direkze, M Novelli, L B Lovat
Journal: Gut (2013)

<h3>Introduction</h3> BE is the pre-cursor to oesophageal adenocarcinoma (OAC). High grade dysplasia (HGD) &amp; early mucosal neoplasia in BE have a 40–60% risk of progressing to OAC. Endoscopic mucosal resection (EMR) &amp; RFA are alternatives to surgery for curative treatment of these patients. We present prospective data from 19 centres in the UK HALO RFA registry. <h3>Methods</h3> Before RFA, superficial lesions were removed by EMR. Patients then underwent RFA 3 monthly until all BE was ablated or cancer developed (endpoints). Biopsies were taken at 12 months for Primary outcomes (clearance for HGD (CR-HGD), all dysplasia (CR-D) &amp; BE (CR-BE)). <h3>Results</h3> 630 patients have outcomes recorded. We report on 370 who have completed treatment. 81% male, mean age 68 years (40–91). Patient’s underwent mean 2.5 ablations (1–6) during protocol. 70% baseline histology HGD, 27% IMC &amp; 3% LGD. Mean length baseline BE 5.6cm (1–20). At 12 months CR-HGD was 87% patients, CR-D 82%, &amp; CR-BE 64%. 97% with no dysplasia at 12 months remain disease free at most recent follow up (median 18 months,range 2–68). Kaplan Meier statistics predict CR-D is durable at 5 years with 88% remaining disease free. Logistic regression demonstrate each extra 1 cm of BE reduces chances of attaining CR-D by 15.7% (OR 1.156, SE 0.048, CI 1.07–1.26, p = 0.0003) &amp; for each extra RFA treatment likelihood of CR-D increases by 31.7% (OR = 0.683, SE 0.95, CI 0.52–0.89, p = 0.0006). Progression to invasive cancer at 12 months is 2.7%. Symptomatic strictures requiring dilatation occurred in 9% after treatment. <h3>Conclusion</h3> End of protocol CR-D is encouraging at 83% &amp; successful eradication appears durable. Patients with shorter segment BE respond better &amp; multiple treatments are more likely to achieve CR-D. Our data represent real life outcomes of integrating novel endotherapy into demanding endoscopy service commitments <h3>Disclosure of Interest</h3> None Declared
EFFECTIVE REMEDIES IN TYPHOID FEVER.
Authors: THOMAS B. HEIMSTREET
Journal: JAMA (1897)

age.If not relieved the patient's condition will be made better by getting rid of the pus, and later on an abdominal-operation can be done and the patient cured by the removal of the appendages-and perhaps of one side only.The French surgeons, in some cases, when unable to remove the diseased tubes and ovaries after hysterectomy, have been contented to open the masses
The Lyme Disease Vaccine: Conception, Development, and Implementation
Authors: Wendy Todaro Thanassi, Robert T. Schoen
Journal: Annals of Internal Medicine (2000)

In the past 20 years, remarkable strides have been made toward understanding and preventing Lyme disease in humans. In December 1998, the U.S. Food and Drug Administration approved a recombinant outer surface protein A vaccine against Lyme disease (LYMErix, SmithKline Beecham, Philadelphia, Pennsylvania). The vaccine, which is derived from a lipidated outer surface protein of the causative spirochete Borrelia burgdorferi, is important because it may decrease the morbidity and financial costs associated with Lyme disease. Its mechanism is unique because it works inside the tick vector itself, preventing the human from becoming infected.
High doses of purified stem cells cause early hematopoietic recovery in syngeneic and allogeneic hosts.
Authors: N Uchida, A Tsukamoto, D He, A M Friera, R Scollay, I L Weissman
Journal: Journal of Clinical Investigation (1998)

In humans, autologous transplants derived from bone marrow (BM) usually engraft more slowly than transplants derived from mobilized peripheral blood. Allogeneic BM transplants show a further delay in engraftment and have an apparent requirement for donor T cells to facilitate engraftment. In mice, Thy-1.1(lo)Lin-/loSca-1+ hematopoietic stem cells (HSCs) are the principal population in BM which is responsible for engraftment in syngeneic hosts at radioprotective doses, and higher doses of HSCs can radioprotect an allogeneic host in the absence of donor T cells. Using the mouse as a preclinical model, we wished to test to what extent engraftment kinetics was a function of HSC content, and whether at high doses of c-Kit+Thy-1.1(lo)Lin-/loSca-1+ (KTLS) cells rapid allogeneic engraftment could also be achieved. Here we demonstrate that engraftment kinetics varied greatly over the range of KTLS doses tested (100-10,000 cells), with the most rapid engraftment being obtained with a dose of 5,000 or more syngeneic cells. Mobilized splenic KTLS cells and the rhodamine 123(lo) subset of KTLS cells were also able to engraft rapidly. Higher doses of allogeneic cells were needed to produce equivalent engraftment kinetics. This suggests that in mice even fully allogeneic barriers can be traversed with high doses of HSCs, and that in humans it may be possible to obtain rapid engraftment in an allogeneic context with clinically achievable doses of purified HSCs.
Diabetes in pregnancy and cesarean delivery.
Authors: K E Remsberg, R E McKeown, K F McFarland, L S Irwin
Journal: Diabetes Care (1999)

To evaluate the effect of diabetes during pregnancy on cesarean delivery and to determine whether the association between diabetes during pregnancy and cesarean delivery is mediated by birth weight.South Carolina 1993 birth certificates were matched through a unique identifier with infant and maternal hospital discharge records for the same year, yielding a total study population of 42,071 singleton births. Adjusted odds ratios (ORs) and 95% CIs were determined for the association between diabetes in pregnancy and cesarean delivery through multiple logistic regression, controlling for maternal age, race, education, number of prenatal care visits, length of gestation, birth weight, and a number of medical indications.Of the study population, 0.7% were pregnancies complicated by preexisting diabetes, 2.9% were pregnancies complicated by gestational diabetes, and 23.4% were cesarean deliveries. After controlling for confounders, including birth weight, cesarean delivery was strongly associated with both preexisting diabetes (OR [95% CI] 6.20 [4.47-8.61]) and gestational diabetes (1.71 [1.41-2.07]). The estimates remained essentially unchanged without birth weight in the model, and were substantially higher in analyses restricted to deliveries without common medical indications for cesarean delivery.Both preexisting and gestational diabetes increase the risk for cesarean delivery, independent of the effect of birth weight. The association is markedly greater among women without other medical indications for cesarean delivery. The increased risk of cesarean delivery for women with diabetes is mediated through other factors, which may include practice patterns and physician referrals to high-risk care.
Company bans sale of its drug propofol for the purpose of lethal injections
Authors: C. Dyer
Journal: BMJ (2012)

One of the world’s biggest makers of the anaesthetic propofol has barred its sale for the purpose of lethal injections, as US states that still have the death penalty face growing problems obtaining drugs for executions.

Fresenius Kabi USA has written to healthcare providers to tell them that its propofol would be supplied only to an approved list of selected wholesalers and distributors who agreed not to sell it on to any correctional facilities or even to retail pharmacies or other distributors.

The ban followed a decision …