bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enrichment with anti-cytokeratin alone or combined with anti-EpCAM antibodies significantly increases the sensitivity for circulating tumor cell detection in metastatic breast cancer patients
Authors: Deng Glenn , Herrler Michael , Burgess David , Manna Edward , Krag David , Burke Julian F 
Published: August 2008

Abstract
Introduction
Circulating tumor cells (CTCs) are detectable in most cancer patients and they can meet an existing medical need to monitor cancer patients during a course of treatment and to help determine recurrent disease. CTCs are rarely found in the blood of cancer patients and enrichment is necessary for sensitive CTC detection. Most CTC enrichment technologies are anti-EpCAM antibody based even though CTC identification criteria are cytokeratin positive (CK+), CD45 negative (CD45-) and 4'6-diamidino-2-phenylindole (nuclear stain) positive (DAPI+). However, some tumor cells express low or no EpCAM. Here we present a highly sensitive and reproducible enrichment method that is based on binding to anti-CK alone or a combination of anti-CK and anti-EpCAM antibodies.

Methods
Blood samples from 49 patients with metastatic breast cancer were processed using the CellSearch™ system (Veridex, LLC, Raritan, NJ, USA), in parallel with our CTC assay method. We used anti-CK alone or in combination with anti-EpCAM antibodies for CTC enrichment. Brightfield and fluorescence labeled anti-CK, anti-CD45 and DAPI (nuclear stain) images were used for CTC identification. The Ariol® system (Genetix USA Inc, San Jose, CA, USA) was used for automated cell image capture and analysis of CTCs on glass slides.

Results
Our method has the capability to enrich three types of CTCs including CK+&EpCAM+, CK+&EpCAM-/low, and CK-/low&EpCAM+ cells. In the blind method comparison, our anti-CK antibody enrichment method showed a significantly higher CTC positive rate (49% vs. 29%) and a larger dynamic CTC detected range (1 to 571 vs. 1 to 270) than that of the CellSearch™ system in the total of 49 breast cancer patients. Our method detected 15 to 111% more CTCs than the CellSearch™ method in patients with higher CTC counts (>20 CTCs per 7.5 ml of blood). The three fluorescent and brightfield images from the Ariol® system reduced the number of false-positive CTC events according to the established CTC criteria.

Conclusion
Our data indicate that the tumor-specific intracellular CK marker could be used for efficient CTC enrichment. Enrichment with anti-CK alone or combined with anti-EpCAM antibodies significantly enhances assay sensitivity. The three fluorescent and brightfield superior images with the Ariol® system reduced false-positive CTC events.
Chorionic gonadotropin up-regulates long pentraxin 3 expression in myeloid cells
Authors: Wan Hui , van Helden-Meeuwsen Cornelia G , Garlanda Cecilia , Leijten Lonneke M E , Maina Virginia , Khan Nisar A , Drexhage Hemmo A , Mantovani Alberto , Benner Robbert , Versnel Marjan A 
Published: August 2008

AbstractPentraxin 3 (PTX3) is an acute-phase response protein that initiates innate immunity against diverse microorganisms. It is produced in response to proinflammatory stimuli by many cell types including myeloid cells. Increased serum levels of PTX3 are found in pregnancy, a condition characterized by increased serum levels of the pregnancy hormone human chorionic gonadotropin (hCG). As myeloid cells bear the receptor for hCG, we hypothesized that hCG can promote innate immunity by affecting the PTX3 production by myeloid cells. In this paper, we demonstrate that hCG increases PTX3 expression by human monocytes, mouse dendritic cells, and mouse macrophages in vitro. This increased PTX3 expression by hCG is mediated via the protein kinase A signaling pathway. hCG injection in mice also increases the PTX3 serum levels. This serum PTX3 is produced mainly by blood monocytes, which from pregnant women, express more PTX3 compared with nonpregnant controls. The hCG-induced hormones progesterone and estrogen also increase the PTX3 production by human monocytes. In conclusion, hCG increases innate immunity via induction of PTX3 in myeloid cells.
Evidence-Based Recommendations for Cancer Fatigue, Anorexia, Depression, and Dyspnea
Authors: Dy Sydney M. , Lorenz Karl A. , Naeim Arash , Sanati Homayoon , Walling Anne , Asch Steven M. 
Published: August 2008

Purpose The experience of patients with cancer often involves symptoms of fatigue, anorexia, depression, and dyspnea. Methods We developed a set of standards through an iterative process of structured literature review and development and refinement of topic areas and standards and subjected recommendations to rating by a multidisciplinary expert panel. Results For fatigue, providers should screen patients at the initial visit, for newly identified advanced cancer, and at chemotherapy visits; assess for depression and insomnia in newly identified fatigue; and follow up after treatment for fatigue or a secondary cause. For anorexia, providers should screen at the initial visit for cancer affecting the oropharynx or gastrointestinal tract or advanced cancer, evaluate for associated symptoms, treat underlying causes, provide nutritional counseling for patients undergoing treatment that may affect nutritional intake, and follow up patients given appetite stimulants. For depression, providers should screen newly diagnosed patients, those started on chemotherapy or radiotherapy, those with newly identified advanced disease, and those expressing a desire for hastened death; document a treatment plan in diagnosed patients; and follow up response after treatment. For general dyspnea, providers should evaluate for causes of new or worsening dyspnea, treat or symptomatically manage underlying causes, follow up to evaluate treatment effectiveness, and offer opioids in advanced cancer when other treatments are unsuccessful. For dyspnea and malignant pleural effusions, providers should offer thoracentesis, follow up after thoracentesis, and offer pleurodesis or a drainage procedure for patients with reaccumulation and dyspnea. Conclusion These standards provide a framework for evidence-based screening, assessment, treatment, and follow-up for cancer-associated symptoms.
Role of Hormones, Genes, and Environment in Human Cryptorchidism
Authors: Foresta Carlo , Zuccarello Daniela , Garolla Andrea , Ferlin Alberto 
Published: August 2008

AbstractCryptorchidism is the most frequent congenital birth defect in male children (2–4% in full-term male births), and it has the potential to impact the health of the human male. In fact, although it is often considered a mild malformation, it represents the best-characterized risk factor for reduced fertility and testicular cancer. Furthermore, some reports have highlighted a significant increase in the prevalence of cryptorchidism over the last few decades. Etiology of cryptorchidism remains for the most part unknown, and cryptorchidism itself might be considered a complex disease. Major regulators of testicular descent from intraabdominal location into the bottom of the scrotum are the Leydig-cell-derived hormones testosterone and insulin-like factor 3. Research on possible genetic causes of cryptorchidism has increased recently. Abundant animal evidence supports a genetic cause, whereas the genetic contribution to human cryptorchidism is being elucidated only recently. Mutations in the gene for insulin-like factor 3 and its receptor and in the androgen receptor gene have been recognized as causes of cryptorchidism in some cases, but some chromosomal alterations, above all the Klinefelter syndrome, are also frequently involved. Environmental factors acting as endocrine disruptors of testicular descent might also contribute to the etiology of cryptorchidism and its increased incidence in recent years. Furthermore, polymorphisms in different genes have recently been investigated as contributing risk factors for cryptorchidism, alone or by influencing susceptibility to endocrine disruptors. Obviously, the interaction of environmental and genetic factors is fundamental, and many aspects have been clarified only recently.
Resolving the Conundrum of Islet Transplantation by Linking Metabolic Dysregulation, Inflammation, and Immune Regulation
Authors: Huang Xiaolun , Moore Daniel J. , Ketchum Robert J. , Nunemaker Craig S. , Kovatchev Boris , McCall Anthony L. , Brayman Kenneth L. 
Published: August 2008

AbstractAlthough type 1 diabetes cannot be prevented or reversed, replacement of insulin production by transplantation of the pancreas or pancreatic islets represents a definitive solution. At present, transplantation can restore euglycemia, but this restoration is short-lived, requires islets from multiple donors, and necessitates lifelong immunosuppression. An emerging paradigm in transplantation and autoimmunity indicates that systemic inflammation contributes to tissue injury while disrupting immune tolerance. We identify multiple barriers to successful islet transplantation, each of which either contributes to the inflammatory state or is augmented by it. To optimize islet transplantation for diabetes reversal, we suggest that targeting these interacting barriers and the accompanying inflammation may represent an improved approach to achieve successful clinical islet transplantation by enhancing islet survival, regeneration or neogenesis potential, and tolerance induction. Overall, we consider the proinflammatory effects of important technical, immunological, and metabolic barriers including: 1) islet isolation and transplantation, including selection of implantation site; 2) recurrent autoimmunity, alloimmune rejection, and unique features of the autoimmune-prone immune system; and 3) the deranged metabolism of the islet transplant recipient. Consideration of these themes reveals that each is interrelated to and exacerbated by the other and that this connection is mediated by a systemic inflammatory state. This inflammatory state may form the central barrier to successful islet transplantation. Overall, there remains substantial promise in islet transplantation with several avenues of ongoing promising research. This review focuses on interactions between the technical, immunological, and metabolic barriers that must be overcome to optimize the success of this important therapeutic approach.
A study of roll gap adjustment due to roll wear in groove rolling: Experiment and modelling
Authors: Byon S M , Lee Y 
Published: August 2008

In the tandem groove rolling process, when a certain amount of wear on the work roll exists and the roll speed is not changed, the roll gap, i.e. the section height, should be adjusted to keep a mass balance between stands, i.e. multiply the exit cross-sectional area by the roll speed between stands. To investigate the actual relationship between the amount of wear on the work roll and the subsequent exit cross-sectional area variation, the authors designed wear contours and machined them on the original roll groove, i.e. on the roll groove with no wear. They then performed a pilot hot rolling test using a work roll with a worn-down groove and one with a groove with no wear, and measured the exit cross-sectional area of the workpiece while the roll gap changed. To predict the amount of roll gap adjustment that compensates wear, a model for roll gap adjustment is proposed. In the proposed model, the authors introduced the concept of equivalent roll gap adjustment, which reduces the increased exit cross-sectional area owing to wear up to a base exit cross-sectional area of the workpiece. Results reveal that the exit cross-sectional area calculated by the roll gap adjustment model is in good agreement with the exit cross-sectional area measured. It has been found from the pilot hot rolling test that variation in exit cross-sectional area is almost linearly proportional to roll gap change while the roll gap decreases from a datum roll gap to about half of the datum one.
The patient's experience of being a human subject
Authors: Kerrison Susan , Laws Sophie , Cane Mary , Thompson Alan 
Published: August 2008

Summary Objective To explore the patient's experience of clinical research with a view to improving its conduct. Design Qualitative analysis of focus groups, semi-structured telephone interviews and questionnaires undertaken with subjects of clinical research. Subjects 265 patients enrolled in two therapeutic and four non-therapeutic clinical studies were invited to take part. 95 agreed; 32 took part in focus groups, 34 in telephone interviews and 29 returned a questionnaire. Response rate (36%). Results Most patients are channeled into research by the health care professionals treating them. Benefits of taking part were seen as: extra care; increased surveillance; obtaining expert information; and being able to help others. Participants also had criticisms which included lack of information about research findings, problems in making sense of adverse events, insufficient attention to their comfort and ‘unscientific’ aspects of particular studies. Conclusion Participation in clinical research is not entirely altruistic. Patients expected reciprocity in their on-going relationship with the researcher. Therefore to help ensure that patients continue to support clinical research, we suggest that: time should be allowed for providing information; greater attention should be paid to physical comfort; opportunities should be provided for involvement in research design, in the excitement of research and for giving feedback on the findings; and contact between patients taking part in the same study should be facilitated. By investing in the idea of scientific progress through research, some subjects are able to transform their suffering into hope for the future.
Geriatric surgery is about disease, not age
Authors: Preston Stephen D , Southall Ashley RD , Nel Mark , Das Saroj K 
Published: August 2008

Summary Maintaining life span and quality of life remains a valid aim of surgery in elderly people. Surgery can be an effective way of restoring both length and quality of life to older people. Minimally invasive techniques and surgery under local anaesthesia make fewer demands on geriatric physiology; given that co-morbidity is a stronger predictor of outcome from surgery than age, this is a significant consideration.
Isopropanol Protein Precipitation for the Analysis of Plasma Free Metanephrines by Liquid Chromatography–Tandem Mass Spectrometry
Authors: Marney Luke C , Laha Thomas J , Baird Geoffrey S , Rainey Petrie M , Hoofnagle Andrew N 
Published: August 2008

Abstract
Background: High-performance liquid chromatography–tandem mass spectrometric (LC-MS/MS)1 analysis of plasma free metanephrines is the most diagnostically sensitive and specific screening test for the diagnosis of pheochromocytoma. We sought to develop an in-house method for this expensive test
Methods: We used off-line isopropanol protein precipitation of plasma to remove interfering substances before LC-MS/MS analysis. We compared the extraction efficiency and limits of quantification of protein precipitation to those of previously reported solid-phase techniques.
Results: The new method had limits of quantification of 0.09 nmol/L and 0.17 nmol/L for metanephrine and normetanephrine, respectively. Method comparison with a previously described solid-phase extraction method revealed Deming regression slopes of 0.904 and 0.994, intercepts of 0.007 and 0.023, and SEs of the residuals (Sy|x) of 0.071 and 0.284 for metanephrine and normetanephrine, respectively. Extraction efficiency of isopropanol protein precipitation was 66% for metanephrine and 35% for normetanephrine, results that were superior to the efficiencies of 4% and 1% for our adapted solid-phase extraction method. No ion suppression was observed at the retention times for metanephrine and normetanephrine.
Conclusions: Isopropanol protein precipitation is a novel and effective off-line sample preparation method for metanephrines that offers a less expensive alternative to on-line solid-phase extraction for low-volume testing and requires a sample volume of only 200 μL. The mass spectrometric analysis time is equivalent to that of solid-phase techniques.
““Breaking Bread with a Spread”” in a San Francisco County Jail
Authors: cate sandra 
Published: August 2008

In many jails and prisons, inmates devise a cuisine that supplements –– or replaces –– the official meals provided them. Nearly every evening in the San Francisco County jails, inmates make ““spread,”” the generic term for this cuisine, out of dried ramen noodles and ingredients saved from their meal trays or purchased on weekly commissary orders. Based on a series of over thirty interviews, inmate's recipes indicate wide ethnic variations in spread, as well as skills in inventing pies and other desserts. Obtaining ingredients and sharing spread establishes bonds between individuals and groups within the jail setting.
As both product and practice, spread's significance emerges out of its oppositions –– in appearance, taste, and origins –– to jail food. According to the inmates, despite its adherence to nutritional standards, the jailhouse diet represents monotony, insufficiency, and a lack of autonomy; spreading thus provides a creative and social outlet that counters the constraints of incarceration.
The effect of weight loss after gastric banding on the molecular distribution of serum adiponectin
Authors: Leth Henrik , Kroustrup Jens Peter , Larsen Jens Fromholt , Andersen Kristian Kjær , Flyvbjerg Allan , Frystyke Jan 
Published: August 2008

The above article has been retracted by the authors, as they have withdrawn the data upon which it was based.The retraction was made before the article reached its final form in the publication process. However, the authors' manuscript, prior to copy editing, page layout and proofing, was initially made available online upon acceptance as an Accepted Preprint.
Potential for Dissemination of the Nonnative Salmonid Parasite Myxobolus cerebralis in Alaska
Authors: Arsan E. Leyla , Bartholomew Jerri L. 
Published: August 2008

Abstract
Myxobolus cerebralis, the myxozoan parasite responsible for whirling disease in salmonids, was first introduced into the United States in 1958 and has since spread across the country, causing severe declines in wild trout populations in the intermountain western United States. The recent detection of the parasite in Alaska is further evidence of the species' capability to invade and colonize new habitat. This study qualitatively assesses the risk of further spread and establishment of M. cerebralis in Alaska. We examine four potential routes of dissemination: human movement of fish, natural dispersal by salmonid predators and straying salmon, recreational activities, and commercial seafood processing. Potential for establishment was evaluated by examining water temperatures, spatial and temporal overlap of hosts, and the distribution and genetic composition of the oligochaete host, Tubifex tubifex. The most likely pathway of M. cerebralis transport in Alaska is human movement of fish by stocking. The extent of M. cerebralis infection in Alaskan salmonid populations is unknown, but if the parasite becomes dispersed, conditions are appropriate for establishment and propagation of the parasite life cycle in areas of south-central Alaska. The probability of further establishment is greatest in Ship Creek, where the abundance of susceptible T. tubifex, the presence of susceptible rainbow trout Oncorhynchus mykiss, and the proximity of this system to the known area of infection make conditions particularly suitable for spread of the parasite.
Antinociceptive effects of tumor necrosis factor α neutralization in a rat model of antigen‐induced arthritis: Evidence of a neuronal target
Authors: Boettger Michael K. , Hensellek Susanne , Richter Frank , Gajda Mieczyslaw , Stöckigt Renate , von Banchet Gisela Segond , Bräuer Rolf , Schaible Hans‐Georg 
Published: August 2008

AbstractObjectiveThe reduction of pain in the course of antiinflammatory therapy can result from an attenuation of the inflammatory process and/or from the neutralization of endogenous mediators of inflammation that act directly on nociceptive neurons. The purpose of this study was to investigate whether analgesic effects of the neutralization of tumor necrosis factor α (TNFα) are due to an attenuation of inflammation or whether direct neuronal effects significantly contribute to pain relief in the course of therapy.MethodsLocomotor and pain‐related behavior and histology were assessed in rats with chronic antigen‐induced arthritis (AIA) in the knee joint, and the rats were treated with systemic saline, etanercept, or infliximab. The expression of TNF receptors (TNFRs) in dorsal root ganglia was measured using immunohistochemical analysis and polymerase chain reaction. Action potentials were recorded from afferent Aδ fibers and C fibers of the medial knee joint nerve, and etanercept and infliximab were injected intraarticularly into normal or inflamed knee joints (AIA or kaolin/carrageenan‐induced inflammation).ResultsIn rats with AIA, both etanercept and infliximab significantly decreased inflammation‐induced locomotor and pain‐related behavior, while joint swelling was only weakly attenuated and histomorphology still revealed pronounced inflammation. A large proportion of dorsal root ganglion neurons showed TNFRI‐ and TNFRII‐like immunoreactivity. Intraarticular injection of etanercept reduced the responses of joint afferents to mechanical stimulation of the inflamed joint starting 30 minutes after injection, but had no effect on responses to mechanical stimulation of the uninflamed joint.ConclusionOverall, these data show the pronounced antinociceptive effects of TNFα neutralization, thus suggesting that reduction of the effects of TNFα on pain fibers themselves significantly contributes to pain relief.
Anti‐DNA Ig peptides promote Treg cell activity in systemic lupus erythematosus patients
Authors: Hahn Bevra H. , Anderson Marissa , Le Elizabeth , Cava Antonio La 
Published: August 2008

AbstractObjectiveTreg cells oppose autoreactive responses in several autoimmune diseases, and their frequency is reduced in systemic lupus erythematosus (SLE). In murine lupus models, treatment with anti‐DNA Ig–based peptides can expand the number of Treg cells in vivo. This study was undertaken to test the possibility that functional human Treg cells can be induced by exposure to anti‐DNA Ig–based peptides.MethodsPeripheral blood mononuclear cells were isolated from 36 lupus patients and 32 healthy individuals matched for ethnicity, sex, and age. Short‐term culture experiments in the presence of several independent stimuli including anti‐DNA Ig peptides were followed by flow cytometric analysis for identification of CD4+,CD25high T cells, cell sorting for in vitro suppression assays, and analysis of correlations between the expression of forkhead box P3 (FoxP3) and serologic and clinical characteristics of the SLE patients.ResultsThe number of in vitro CD4+,CD25high T cells increased after culture with anti‐DNA Ig peptides in the SLE patients, but not in the controls. The expanded CD4+,CD25high T cells required FoxP3 for cell contact–mediated suppression of proliferation and interferon‐γ production in target CD4+,CD25− T cells. The induction of FoxP3 in SLE Treg cells occurred only in seropositive patients, and was correlated with anti‐DNA and IgG serum titers.ConclusionThese results suggest a new modality to reverse the functional deficit of Treg cells in SLE patients with positive autoimmune serology, and identify a new strategy to enhance immunoregulatory T cell activity in human SLE.