tbuckley/cabot-search huggingface dataset:
Identification of Potentially Avoidable Hospitalizations in Patients With GI Cancer
Authors: Gabriel A. Brooks, Thomas A. Abrams, Jeffrey A. Meyerhardt, Peter C. Enzinger, Karen Sommer, Carole K. Dalby, Hajime Uno, Joseph O. Jacobson, Charles S. Fuchs, Deborah Schrag
Journal: Journal of Clinical Oncology (2014)

Purpose To identify and characterize potentially avoidable hospitalizations in patients with GI malignancies. Patients and Methods We compiled a retrospective series of sequential hospital admissions in patients with GI cancer. Patients were admitted to an inpatient medical oncology or palliative care service between December 2011 and July 2012. Practicing oncology clinicians used a consensus-driven medical record review process to categorize each hospitalization as “potentially avoidable” or “not avoidable.” Patient demographic and clinical data were abstracted, and quantitative and qualitative analyses were performed to identify patient characteristics and outcomes associated with potentially avoidable hospitalizations. Results We evaluated 201 hospitalizations in 154 unique patients. The median age was 62 years, and colorectal cancer was the most common diagnosis (32%). The majority of hospitalized patients had metastatic cancer (81%). In all, 53% of hospitalizations were attributable to cancer symptoms, and 28% were attributable to complications of cancer treatment. Medical oncologists identified 39 hospitalizations (19%) as potentially avoidable. Hospitalizations were more likely to be categorized as potentially avoidable for patients with the following characteristics: age ≥ 70 years (odds ratio [OR], 2.63; 95% CI, 1.15 to 6.02), receipt of an oncologist's advice to consider hospice (OR, 6.09; 95% CI, 2.54 to 14.58), or receipt of three or more lines of chemotherapy (OR, 2.68; 95% CI, 1.01 to 7.08). Ninety-day mortality was higher after avoidable hospitalizations compared with hospitalizations that were not avoidable (OR, 6.4; 95% CI, 1.8 to 22.3). Conclusion Potentially avoidable hospitalizations are common in patients with advanced GI cancer. The majority of potentially avoidable hospitalizations occurred in patients with advanced treatment-refractory cancers near the end of life.
Different mechanisms define the antiadhesive function of high molecular weight kininogen in integrin- and urokinase receptor–dependent interactions
Authors: Triantafyllos Chavakis, Sandip M. Kanse, Florea Lupu, Hans-Peter Hammes, Werner Müller-Esterl, Robin A. Pixley, Robert W. Colman, Klaus T. Preissner
Journal: Blood (2000)
Infections in IVF: review and guidelines
Authors: S. R. Steyaert
Journal: Human Reproduction Update (2000)

Since the inception of in-vitro fertilization (IVF), questions about contamination and the transmission of infection have been raised.In this review, screening for Chlamydia trachomatis, as well as medical and ethical considerations on IVF in couples infected with hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunode®ciency virus (HIV), are discussed.IVF is not contraindicated in case of HBV or HCV infection, but the decision is far more delicate in case of HIV infection.If donor gametes or embryos are used, prevention of infectious disease transmission resides in accurate donor selection, including screening for C. trachomatis, HIV, HBV, cytomegalovirus and Treponema pallidum.In the embryology laboratory, microbial contamination of the IVF system deserves attention, and can be prevented by using sterile technique and supplementing culture media with screened sera or serum substitutes and antibiotics.Persons whose biological material is to be cryopreserved should be screened for HBV, HCV and HIV, and separate containers should be used for infected and non-infected material.Finally, transmission of infectious diseases to laboratory personnel can be prevented by adherence to strict safety guidelines, wearing of protective clothing, HBV vaccination, prohibition of mouth pipetting, and developing a plan for the disposal of bio-hazardous material.
Emerging Role of MicroRNAs in Cardiovascular Biology
Authors: Michael V.G. Latronico, Daniele Catalucci, Gianluigi Condorelli
Journal: Circulation Research (2007)

The heart is among the most conserved organs of the body and is susceptible to defects more than any other organ. Heart malformations, in fact, occur in roughly 1% of newborns. Moreover, cardiovascular disease arising during adult life is among the main causes of morbidity and mortality in developed countries. It is not surprising, therefore, that much effort is being channeled into understanding the development, physiology, and pathology of the cardiovascular system. MicroRNAs, a newly discovered class of small ribonucleotide-based regulators of gene expression, are being implicated in an increasing number of biological processes, and the study of their role in cardiovascular biology is just beginning. Here, we briefly overview microRNAs in general and report on the recent findings regarding their importance for the heart and vasculature, in particular. The new insights that are being gained will permit not only a greater understanding of cardiovascular pathologies but also, hopefully, the development of novel therapeutic strategies.
Oxaliplatin, Fluorouracil, and Leucovorin as Adjuvant Treatment for Colon Cancer
Authors: Thierry André, Corrado Boni, Lamia Mounedji-Boudiaf, Matilde Navarro, Josep Tabernero, Tamas Hickish, Clare Topham, Marta Zaninelli, Philip Clingan, John Bridgewater, Isabelle Tabah-Fisch, Aimery de Gramont
Journal: New England Journal of Medicine (2004)

The standard adjuvant treatment of colon cancer is fluorouracil plus leucovorin (FL). Oxaliplatin improves the efficacy of this combination in patients with metastatic colorectal cancer. We evaluated the efficacy of treatment with FL plus oxaliplatin in the postoperative adjuvant setting.We randomly assigned 2246 patients who had undergone curative resection for stage II or III colon cancer to receive FL alone or with oxaliplatin for six months. The primary end point was disease-free survival.A total of 1123 patients were randomly assigned to each group. After a median follow-up of 37.9 months, 237 patients in the group given FL plus oxaliplatin had had a cancer-related event, as compared with 293 patients in the FL group (21.1 percent vs. 26.1 percent; hazard ratio for recurrence, 0.77; P=0.002). The rate of disease-free survival at three years was 78.2 percent (95 percent confidence interval, 75.6 to 80.7) in the group given FL plus oxaliplatin and 72.9 percent (95 percent confidence interval, 70.2 to 75.7) in the FL group (P=0.002 by the stratified log-rank test). In the group given FL plus oxaliplatin, the incidence of febrile neutropenia was 1.8 percent, the incidence of gastrointestinal adverse effects was low, and the incidence of grade 3 sensory neuropathy was 12.4 percent during treatment, decreasing to 1.1 percent at one year of follow-up. Six patients in each group died during treatment (death rate, 0.5 percent).Adding oxaliplatin to a regimen of fluorouracil and leucovorin improves the adjuvant treatment of colon cancer.
Perturbation of the T Lymphocyte Lineage In Transgenic Mice Expressing a Constitutive Repressor of Nuclear Factor (NF)-κB
Authors: Mark R. Boothby, Ana L. Mora, David C. Scherer, Jeffrey A. Brockman, Dean W. Ballard
Journal: The Journal of Experimental Medicine (1997)

Members of the nuclear factor (NF)-κB/Rel family transcription factors are induced during thymic selection and in mature T lymphocytes after ligation of the T cell antigen receptor (TCR). Despite these findings, disruption of individual NF-κB/Rel genes has revealed no intrinsic defect in the development of mature T cells, perhaps reflecting functional redundancy. To circumvent this possibility, the T cell lineage was targeted to express a trans-dominant form of IκBα that constitutively represses the activity of multiple NF-κB/Rel proteins. Transgenic cells expressing this inhibitor exhibit a significant proliferative defect, which is not reversed by the addition of exogenous interleukin-2. Moreover, mitogenic stimulation of splenocytes leads to increased apoptosis of transgenic T cells as compared with controls. In addition to deregulated T cell growth and survival, transgene expression impairs the development of normal T cell populations as evidenced by diminished numbers of TCRhi CD8 single-positive thymocytes. This defect was significantly amplified in the periphery and was accompanied by a decrease in CD4+ T cells. Taken together, these in vivo findings indicate that the NF-κB/Rel signaling pathway contains compensatory components that are essential for the establishment of normal T cell subsets.
Underglycosylation of IgA1 Hinge Plays a Certain Role for Its Glomerular Deposition in IgA Nephropathy
Authors: YOSHIYUKI HIKI, TOHRU KOKUBO, HITOO IWASE, YOSHIHIKO MASAKI, TAKASHI SANO, ATSUSHI TANAKA, KAZUNORI TOMA, KYOKO HOTTA, YUTAKA KOBAYASHI
Journal: Journal of the American Society of Nephrology (1999)

Abstract. This study was performed to isolate and investigate the IgA1 that could accumulate in glomeruli (glomerulophilic IgA1). IgA1 was fractionated by the electric charge and the reactivity to Jacalin. Serum IgA1 of IgA nephropathy patients was separated and fractionated using a Jacalin column and subsequent ion-exchange chromatography. The fractions were divided into three groups of relatively cationic (C), neutral (N), and anionic (A). IgA1 was also divided into Jacalin low (L), intermediate (I), and high (H) affinity fractions by serial elution using 25, 100, and 800 mM galactose. The left kidneys of Wistar rats were perfused with 2, 5, or 10 mg of each group of IgA1. The rats were sacrificed 15 min, 30 min, 3 h, or 24 h after the perfusion. The accumulation of each IgA1 in the glomeruli was then observed by immunofluorescence. The IgA1 of the fractions N and H separated by the two methods was definitely accumulated in the rat glomeruli with a similar pattern. The electrophoresis revealed that the macromolecular IgA1 was increased in fraction H compared with other fractions. Therefore, Jacalin high-affinity IgA1 (fraction H) was applied on a diethylaminoethyl column and divided into electrically cationic (HC), neutral (HN), and anionic (HA). Only the asialo-Galβ1,3GalNAc chain was identified in the fraction HN IgA1 by gas-phase hydrazinolysis. Furthermore, the IgA1 fraction was strongly recognized by peanut agglutinin, Vicia Villosa lectins, and antisynthetic hinge peptide antibody. These results indicated that the IgA1 molecules having the underglycosylated hinge glycopeptide played a certain role in the glomerular accumulation of IgA1 in IgA nephropathy.
A meta-analysis of the effectiveness of psychological interventions for adults with skin conditions
Authors: A.C. Lavda, T.L. Webb, A.R. Thompson
Journal: British Journal of Dermatology (2012)

Skin conditions can be associated with heightened levels of psychological morbidity, suggesting the need for psychological interventions. A number of specific interventions (such as habit reversal) have been developed. However, to date, there has not been a systematic review of the effectiveness of psychological interventions. We sought to systematically evaluate the effectiveness of psychological interventions designed to improve the severity of and adjustment to skin conditions in adults. Database, archival and citation searches were conducted. Studies were included if participants were allocated to either a psychological intervention (excluding educational interventions and complementary therapies) or a comparison condition, and if they measured outcomes relevant to the skin condition. Twenty-two studies met these inclusion criteria. Effect sizes for each intervention were computed and we also coded a number of potential moderators of intervention efficacy. Psychological interventions were found to have a medium-sized effect on skin conditions (g = 0·54). The type of skin condition, age of sample, nature of the intervention, time interval between the end of the intervention and follow-up, and type of outcome measure all moderated the effect of interventions on outcomes. For example, interventions had a medium effect on the severity of the condition (g = 0·40) and psychosocial outcomes (g = 0·53), and a medium-to-large effect on itch/scratch reactions (g = 0·67). Psychological interventions are beneficial for people with skin conditions. However, more research is needed to extend the variety and focus of the psychological interventions that are available. Studies are also needed to explore the longer-term benefits of such interventions.
Obesity and Diabetes in the Developing World — A Growing Challenge
Authors: Parvez Hossain, Bisher Kawar, Meguid El Nahas
Journal: New England Journal of Medicine (2007)

Propelling an upsurge in cases of diabetes and hypertension is the growing prevalence of overweight and obesity. Drs. Parvez Hossain, Bisher Kawar, and Meguid El Nahas write that preventing obesity, diabetes, and hypertension will require fundamental social and political changes.
A unified framework for addiction: Vulnerabilities in the decision process
Authors: A. David Redish, Steve Jensen, Adam Johnson
Journal: Behavioral and Brain Sciences (2008)

Abstract The understanding of decision-making systems has come together in recent years to form a unified theory of decision-making in the mammalian brain as arising from multiple, interacting systems (a planning system, a habit system, and a situation-recognition system). This unified decision-making system has multiple potential access points through which it can be driven to make maladaptive choices, particularly choices that entail seeking of certain drugs or behaviors. We identify 10 key vulnerabilities in the system: (1) moving away from homeostasis, (2) changing allostatic set points, (3) euphorigenic “reward-like” signals, (4) overvaluation in the planning system, (5) incorrect search of situation-action-outcome relationships, (6) misclassification of situations, (7) overvaluation in the habit system, (8) a mismatch in the balance of the two decision systems, (9) over-fast discounting processes, and (10) changed learning rates. These vulnerabilities provide a taxonomy of potential problems with decision-making systems. Although each vulnerability can drive an agent to return to the addictive choice, each vulnerability also implies a characteristic symptomology. Different drugs, different behaviors, and different individuals are likely to access different vulnerabilities. This has implications for an individual's susceptibility to addiction and the transition to addiction, for the potential for relapse, and for the potential for treatment.
Time course of arteriogenesis following femoral artery occlusion in the rabbit
Authors: Imo E. Hoefer, Niels van Royen, Ivo R. Buschmann, Jan J. Piek, Wolfgang Schaper
Journal: Cardiovascular Research (2001)

Objective: We examined the time course of arteriogenesis (collateral artery growth) after femoral artery ligation and the effect of monocyte chemoattractant protein-1 (MCP-1). Methods: New Zealand White rabbits received MCP-1 or phosphate buffered saline (PBS) for a 1-week period, either directly or 3 weeks after femoral artery ligation (non-ischemic model). A control group was studied with intact femoral arteries and another 1 min after acute femoral artery ligation. Results: Collateral conductance index significantly increased when MCP-1 treatment started directly after femoral artery ligation (acute occlusion: 0.94±0.19; without occlusion: 168.56±15.99; PBS: 4.10±0.48; MCP-1: 33.96±1.76 ml/min/100 mmHg). However, delayed onset of treatment 3 weeks after ligation and final study of conductance at 4 weeks showed no significant difference against a 4-week control (PBS: 79.08±7.24; MCP-1: 90.03±8.73 ml/min/100 mmHg). In these groups increased conductance indices were accompanied by a decrease in the number of visible collateral vessels (from 18 to 36 identifiable vessels at day 7 to about four at 21 days). Conclusion: We conclude that the chemokine MCP-1 markedly accelerated collateral artery growth but did not alter its final extent above that reached spontaneously as a function of time. We show thus for the first time that a narrow time window exists for the responsiveness to the arteriogenic actions of MCP-1, a feature that MCP-1 may share with other growth factors. We show furthermore that the spontaneous adaptation by arteriogenesis stops when only about 50% of the vasodilatory reserve of the arterial bed before occlusion are reached. The superiority of few large arterial collaterals in their ability to conduct large amounts of blood flow per unit of pressure as compared to the angiogenic response where large numbers of small vessels are produced with minimal ability to allow mass transport of bulk flow is stressed.
Tumor Survivin Is Downregulated by the Antisense Oligonucleotide LY2181308: A Proof-of-Concept, First-in-Human Dose Study
Authors: Denis C Talbot, Malcolm Ranson, Joanna Davies, Michael Lahn, Sophie Callies, Valérie André, Sunil Kadam, Michael Burgess, Christopher Slapak, Anna L Olsen, Peter J McHugh, Johann S de Bono, Julian Matthews, Azeem Saleem, Patricia Price
Journal: Clinical Cancer Research (2010)

Enhanced tumor cell survival through expression of inhibitors of apoptosis (IAP) is a hallmark of cancer. Survivin, an IAP absent from most normal tissues, is overexpressed in many malignancies and associated with a poorer prognosis. We report the first-in-human dose study of LY2181308, a second-generation antisense oligonucleotide (ASO) directed against survivin mRNA.A dose-escalation study evaluating the safety, pharmacokinetics, and pharmacodynamics of LY2181308 administered intravenously for 3 hours as a loading dose on 3 consecutive days and followed by weekly maintenance doses. Patients were eligible after signing informed consent, had exhausted approved anticancer therapies and agreed to undergo pre- and posttreatment tumor biopsies to evaluate reduction of survivin protein and gene expression.A total of 40 patients were treated with LY2181308 at doses of 100 to 1,000 mg. Twenty-six patients were evaluated at the recommended phase 2 dose of 750 mg, at which level serial tumor sampling and [(11)C]LY2183108 PET (positron emission tomography) imaging demonstrated that ASO accumulated within tumor tissue, reduced survivin gene and protein expression by 20% and restored apoptotic signaling in tumor cells in vivo. Pharmacokinetics were consistent with preclinical modeling, exhibiting rapid tissue distribution, and terminal half-life of 31 days.The tumor-specific, molecularly targeted effects demonstrated by this ASO in man underpin confirmatory studies evaluating its therapeutic efficacy in cancer.
V<scp>ITAMIN</scp>D<scp>AND ITS</scp>A<scp>NALOGS AS</scp>R<scp>EGULATORS OF</scp>I<scp>MMUNE</scp>A<scp>CTIVATION AND</scp>A<scp>NTIGEN</scp>P<scp>RESENTATION</scp>
Authors: Matthew D. Griffin, Nianzeng Xing, Rajiv Kumar
Journal: Annual Review of Nutrition (2003)

▪ Abstract It has been a little more than 20 years since the first appreciation that the biologically active hormonal form of the secosteroid vitamin D—classically categorized as a regulator of calcium/phosphorous metabolism and bone mineralization—can exert effects on cells of the immune system. Since then a substantial literature has accumulated to suggest that these effects are exerted on multiple immune cell types, are predominantly suppressive at pharmacologic levels, and are potent enough to have true therapeutic potential in the management or prevention of immune-mediated diseases. Less clear at present, however, are the physiological roles played by the vitamin D endocrine system in the regulation of normal and abnormal immune responses. In this review, an appraisal of the current understanding of vitamin D–mediated immune regulation is presented that emphasizes progress towards its clinical application as well as the manner in which emerging models of normal immune function may facilitate a more complete understanding of its physiologic significance.
Big Costs for Little Gain in Ovarian Cancer
Authors: Martee L. Hensley
Journal: Journal of Clinical Oncology (2011)

BRAF mutations, as has been well-documented for amplified human epidermal growth factor receptor 2 (HER2)/neu in breast cancer treated with HER2-targeted therapies. 11 Others have previously reported that BRAF-mutant thyroid cancers are more likely to invade regional lymph nodes then their wildtype counterparts. 12 And there appears to be a strong association between BRAF mutation and the highly favorable micro-satellite unstable phenotype in colorectal cancer. 13 Thus, the role of any given oncogenic alteration must be considered in the context of the other concomitant changes required to promote carcinogenesis.Only in this way can one explain how the same mutated oncogene can be present in a poor prognosis group in one tumor type and in a good prognosis group in another.In fact, in melanoma it may be that the associated genetic or epigenetic changes that coexist with BRAF mutation that are the true drivers of a difference in tumor biology among these patients.As the technology to interrogate numerous oncogenes and tumor suppressor genes in parallel becomes more widely available, the next generation of investigations into genetic changes that relate to prognosis will likely describe more complex signatures or networked contributors to aggressive biology.For now, we know that BRAF mutation is a powerful predictive marker, and is in the running to become the first molecular prognostic marker in melanoma.
Phase Ib trial of radiotherapy in combination with combretastatin-A4-phosphate in patients with non-small-cell lung cancer, prostate adenocarcinoma, and squamous cell carcinoma of the head and neck
Authors: Q.-S. Ng, H. Mandeville, V. Goh, R. Alonzi, J. Milner, D. Carnell, K. Meer, A.R. Padhani, M.I. Saunders, P.J. Hoskin
Journal: Annals of Oncology (2011)
Value of Mismatch Repair, <i>KRAS</i>, and <i>BRAF</i> Mutations in Predicting Recurrence and Benefits From Chemotherapy in Colorectal Cancer
Authors: Gordon Hutchins, Katie Southward, Kelly Handley, Laura Magill, Claire Beaumont, Jens Stahlschmidt, Susan Richman, Philip Chambers, Matthew Seymour, David Kerr, Richard Gray, Philip Quirke
Journal: Journal of Clinical Oncology (2011)

Purpose It is uncertain whether modest benefits from adjuvant chemotherapy in stage II colorectal cancer justify the toxicity, cost, and inconvenience. We investigated the usefulness of defective mismatch repair (dMMR), BRAF, and KRAS mutations in predicting tumor recurrence and sensitivity to chemotherapy. Patients and Methods Immunohistochemistry for dMMR and pyrosequencing for KRAS/BRAF were performed for 1,913 patients randomly assigned between fluorouracil and folinic acid chemotherapy and no chemotherapy in the Quick and Simple and Reliable (QUASAR) trial. Results Twenty-six percent of 695 right-sided colon, 3% of 685 left-sided colon, and 1% of 407 rectal tumors were dMMR. Similarly, 17% of right colon, 2% of left colon, and 2% of rectal tumors were BRAF mutant. KRAS mutant tumors were more evenly distributed: 40% right colon, 28% left colon, and 36% rectal tumors. Recurrence rate for dMMR tumors was half that for MMR-proficient tumors (11% [25 of 218] v 26% [438 of 1,695] recurred; risk ratio [RR], 0.53; 95% CI, 0.40 to 0.70; P &lt; .001). Risk of recurrence was also significantly higher for KRAS mutant than KRAS wild-type tumors (28% [150 of 542] v 21% [219 of 1,041]; RR, 1.40; 95% CI, 1.12 to 1.74; P = .002) but did not differ significantly between BRAF mutant and wild-type tumors (P = .36). No marker predicted benefit from chemotherapy with efficacy not differing significantly by MMR, KRAS, or BRAF status. The prognostic value of MMR and KRAS was similar in the presence and absence of chemotherapy. Conclusion MMR assays identify patients with a low risk of recurrence. KRAS mutational analysis provides useful additional risk stratification to guide use of chemotherapy.