Miracle-dz/UniFAR-FTUs huggingface dataset:
Implementing guidelines for cancer pain management: results of a randomized controlled clinical trial.

PURPOSE Pain and symptom management is an integral part of the clinical practice of oncology. A number of guidelines have been developed to assist the clinician in optimizing comfort care. We implemented clinical guidelines for cancer pain management in the community setting and evaluated whether these guidelines improved care. PATIENTS AND METHODS Eighty-one cancer patients, aged 37 to 76 years, were enrolled onto a prospective, longitudinal, randomized controlled study from the outpatient clinic settings of 26 western Washington-area medical oncologists. A multilevel treatment algorithm based on the Agency for Health Care Policy and Research Guidelines for Cancer Pain Management was compared with standard-practice (control) pain and symptom management therapies used by community oncologists. The primary outcome of interest was pain (Brief Pain Inventory); secondary outcomes of interest were all other symptoms (Memorial Symptom Assessment Scale) and quality of life (Functional Assessment of Cancer Therapy Scale). RESULTS Patients randomized to the pain algorithm group achieved a statistically significant reduction in usual pain intensity, measured as slope scores, when compared with standard community practice (P < .02). Concurrent chemotherapy and patient adherence to treatment were significant mediators of worst pain. There were no significant differences in other symptoms or quality of life between the two treatment groups. CONCLUSION This guideline implementation study supports the use of algorithmic decision making in the management of cancer pain. These findings suggest that comprehensive pain assessment and evidence-based analgesic decision-making processes do enhance usual pain outcomes.
Dental pulp stem cells: function, isolation and applications in regenerative medicine

Dental pulp stem cells (DPSCs) are a promising source of cells for numerous and varied regenerative medicine applications. Their natural function in the production of odontoblasts to create reparative dentin support applications in dentistry in the regeneration of tooth structures. However, they are also being investigated for the repair of tissues outside of the tooth. The ease of isolation of DPSCs from discarded or removed teeth offers a promising source of autologous cells, and their similarities with bone marrow stromal cells (BMSCs) suggest applications in musculoskeletal regenerative medicine. DPSCs are derived from the neural crest and, therefore, have a different developmental origin to BMSCs. These differences from BMSCs in origin and phenotype are being exploited in neurological and other applications. This review briefly highlights the source and functions of DPSCs and then focuses on in vivo applications across the breadth of regenerative medicine. © 2014 The Authors. Journal of Tissue Engineering and Regenerative Medicine published by John Wiley & Sons, Ltd.
Hantavirus Infection Induces the Expression of RANTES and IP-10 without Causing Increased Permeability in Human Lung Microvascular Endothelial Cells

ABSTRACT Sin Nombre virus (SNV) and Hantaan virus (HTN) infect endothelial cells and are associated with different patterns of increased vascular permeability during human disease. It is thought that such patterns of increased vascular permeability are a consequence of endothelial activation and subsequent dysfunction mediated by differential immune responses to hantavirus infection. In this study, the ability of hantavirus to directly induce activation of human lung microvascular endothelial cells (HMVEC-Ls) was examined. No virus-specific modulation in the constitutive or cytokine-induced expression of cellular adhesion molecules (CD40, CD54, CD61, CD62E, CD62P, CD106, and major histocompatibility complex classes I and II) or in cytokines and chemokines (eotaxin, tumor necrosis factor alpha, interleukin 1β [IL-1β], IL-6, IL-8, MCP-1, MIP-1α, and MIP-1β) was detected at either the protein or message level in hantavirus-infected HMVEC-Ls. Furthermore, no virus-specific enhancement of paracellular or transcellular permeability or changes in the organization and distribution of endothelial intercellular junctional proteins was observed. However, infection with either HTN or SNV resulted in detectable levels of the chemokines RANTES and IP-10 (the 10-kDa interferon-inducible protein) in HMVEC-Ls within 72 h and was associated with nuclear translocation of interferon regulatory factor 3 (IRF-3) and IRF-7. Gamma interferon (IFN-γ)-induced expression of RANTES and IP-10 could also be detected in uninfected HMVEC-Ls and was associated with nuclear translocation of IRF-1 and IRF-3. Treatment of hantavirus-infected HMVEC-Ls with IFN-γ for 24 h resulted in a synergistic enhancement in the expression of both RANTES and IP-10 and was associated with nuclear translocation of IRF-1, IRF-3, IRF-7, and NF-κB p65. These results reveal a possible mechanism by which hantavirus infection and a TH1 immune response can cooperate to synergistically enhance chemokine expression by HMVEC-Ls and trigger immune-mediated increases in vascular permeability.
Attachment style measurement: A clinical and epidemiological perspective

Shaver and Mikulincer's article is to be applauded for its integrative approach to investigating attachment-related phenomena. The authors attempt to break the polarisation and the 'in-out group' mentality associated with the two strands of research into attachment style, broadly grouped into narrative style interviews aimed at tapping states of mind (particularly unconscious processes), and the social psychological approaches using self-reports to assess individual differences in adult perceptions of relationships (particularly romantic ones). Effectively these follow the different disciplinary missions of developmentalists and personality theorists, although each has also been directed towards clinical ends. Shaver & Mikulincer comment that researchers from either tradition have tended to ignore each other's work and rarely combine the approaches in the same studies. Typically the problem is greater for investigators based in the self-report tradition to utilise interview measures than vice-versa, provoking the statement reported elsewhere that 'researchers in the personality/social subculture have not taken the time to master the interview techniques' (Bartholomew & Shaver, 1998). The aim of Shaver and Mikulincer's review is first to highlight the wide potential usage of self-report scales in testing causal attachment hypotheses and second to advocate a multi-measure approach to attachment research in order to encapsulate the several different levels at which attachment works. Ultimately they strive to encompass a personality theory which incorporates attachment concepts as central.
Bombesin Improves Survival from Methotrexate‐Induced Enterocolitis

ObjectiveThe authors determined whether bombesin could improve survival from methotrexate (MTX). induced enterocolitis. Summary Background DataBombesin prevents gut mucosal atrophy, which is produced by feeding rats an elemental diet. Administration of MTX produces a lethal enterocolitis in rats fed an elemental diet. MethodsOn treatment day 0,60 rats were divided randomly into three groups and fed an elemental diet (Vivonex TEN, Sandoz, Minneapolis, MN) as the only source of nutrition. Groups were subdivided further to receive either saline or bombesin (10 μg/kg, subcutaneously, three times a day) beginning either on day 0 or day 14. Methotrexate (20 mg/kg, intraperitoneally) was given to all rats 14 days after the start of an elemental diet. ResultsBombesin prevented the mucosal atrophy in the ileum produced by the elemental diet and significantly decreased mortality in rats given MTX (whether given as a pretreatment or at the time of MTX administration). ConclusionBombesin significantly improved survival in a lethal model of MTX-induced enterocolitis, possibly by maintaining gut mucosal structure. Administration of bombesin to patients receiving chemotherapy may be clinically useful in preventing the severe enterocolitis induced by various chemotherapeutic agents.
The Prophylactic Effect of Timolol Versus Propranolol and Placebo in Common Migraine: Beta-Blockers in Migraine

A multicentre double-blind, cross-over trial was planned to evaluate the prophylactic effect of timolol in migraine. The effectiveness of the drug was compared to propranolol and placebo. In the Norwegian part of the trial described in this paper, 18 patients completed the study. The data suggest that timolol is equivalent in effectiveness to propranolol in migraine prophylaxis. Firm conclusions should not be drawn until the results from the multicentre trial are available.
Incidence and risk factors for non-alcoholic steatohepatitis: prospective study of 5408 women enrolled in Italian tamoxifen chemoprevention trial

Abstract Objective To assess the incidence, cofactors, and excess risk of development of non-alcoholic fatty liver disease, including non-alcoholic steatohepatitis, attributable to tamoxifen in women. Design Prospective, randomised, double blind, placebo controlled trial. Setting and participants 5408 healthy women who had had hysterectomies, recruited into the Italian tamoxifen chemoprevention trial from 58 centres in Italy. Intervention Women were randomly assigned to receive tamoxifen (20 mg daily) or placebo for five years. Main outcome measure Development of non-alcoholic fatty liver disease in all women with normal baseline liver function who showed at least two elevations of alanine aminotransferase (≥ 1.5 times upper limit of normal) over a six month period. Results During follow up, 64 women met the predefined criteria: 12 tested positive for hepatitis C virus, and the remaining 52 were suspected of having developed non-alcoholic fatty liver disease (34 tamoxifen, 18 placebo)—hazard ratio = 2.0 (95% confidence interval 1.1 to 3.5; P = 0.04). In all 52 women ultrasonography confirmed the presence of fatty liver. Other factors associated with the development of non-alcoholic fatty liver disease included overweight (2.4, 1.2 to 4.8), obesity (3.6, 1.7 to 7.6), hypercholesterolaemia (3.4, 1.4 to 7.8), and arterial hypertension (2.0, 1.0 to 3.8). Twenty women had liver biopsies: 15 were diagnosed as having mild to moderate steatohepatitis (12 tamoxifen, 3 placebo), and five had fatty liver alone (1 tamoxifen, 4 placebo). No clinical, biochemical, ultrasonic, or histological signs suggestive of progression to cirrhosis were observed after a median follow up of 8.7 years. Conclusions Tamoxifen was associated with higher risk of development of non-alcoholic steatohepatitis only in overweight and obese women with features of metabolic syndrome, but the disease, in both the tamoxifen and the placebo group, after 10 years of follow up seems to be indolent.
The trace of -functions on an irregular subset

Certain basic results on the boundary trace discussed in Maz′ya’s monograph on Sobolev spaces are generalized to a wider class of regions. The paper is an extended and supplemented version of a preliminary publication, where some results were presented without proofs or in a weaker form. In Maz′ya’s monograph, the boundary trace was defined for regions Ω with finite perimeter, and the main results were obtained under the assumption that normals in the sense of Federer exist almost everywhere on the boundary. Instead, now it is assumed that the region boundary is a countably (n− 1)-rectifiable set, which is a more general condition. §
Tissue plasminogen activator increases canine endothelial cell proliferation rate through a plasmin-independent, receptor-mediated mechanism.

BACKGROUND Tissue plasminogen activator (tPA) is elevated in cancer patients and is thought to promote tumor angiogenesis by facilitating endothelial cell migration through plasmin-mediated degradation of extracellular matrix. Due to the presence of an epidermal growth factor (EGF)-finger domain in the tPA A-chain and the existence of an endothelial cell (EC) receptor that binds this domain, it was hypothesized that tPA has a direct receptor-mediated effect on EC proliferation, independent of plasmin. METHODS AND RESULTS Using cultured canine ECs, tPA (7.25 microg/ml, approximately 107 nM) increased proliferation as much as 50 and 170% in the absence and presence of growth factors, respectively. tPA-induced increases in EC proliferation occurred independent of plasmin generation, as the plasmin inhibitor, aprotinin (10 microg/ml) did not inhibit tPA-induced proliferation. However, tPA-induced proliferation was inhibited dose-dependently to a maximum of 78% using a monoclonal antibody against the tPA EGF-finger domain. This antibody, known to inhibit tPA binding to its receptor, did not inhibit tPA-induced plasmin generation. To investigate the role of potential signal transduction pathways, ECs were exposed to lavendustin A, a tyrosine kinase inhibitor, at 33.5 microM (IC50 for basic fibroblast growth factor). Lavendustin A did not inhibit tPA-induced EC proliferation. However, Rp-cAMP, an inhibitor of cAMP-dependent kinases, specifically inhibited tPA-induced EC proliferation in a dose-dependent manner (IC50 = 50.5 microM). Pertussis toxin at maximal concentrations for this system (0.5 ng/ml) did not inhibit tPA-induced EC proliferation. CONCLUSION These results lend support to the hypothesis that tPA may have a direct receptor-mediated effect on EC proliferation and that this effect occurs independent of plasmin and may be dependent upon protein kinase A activity.
Population pharmacokinetics of vancomycin in patients receiving extracorporeal membrane oxygenation.

AIMS Extracorporeal membrane oxygenation (ECMO) is a life support system used during severe respiratory or cardiorespiratory failure. The objective of this study was to characterize the population pharmacokinetics of vancomycin during ECMO. METHODS A population model was developed using WinNonMix (Version 2.0.1) from a total of 366 plasma observations in 45 patients, including term neonates, older children and adults. The study utilized both rich prospective and sparse retrospective data. Prospective samples were drawn at baseline and then 30, 60,90, 120, 180, 240, 300, 360 and 420 min postinfusion. Steady state concentrations were obtained retrospectively from an assay database, cross-referencing with the patients' medical records. RESULTS Data were examined using a two-compartment model with an additive and proportional residual error. Model fit improved substantially when clearance, CL (l kg(-1) h(-1)) was modelled as a nonlinear function of serum creatinine (Cr) micromol l(-1). There was a linear relationship between CL and age up to 1000 days: CL (Age < 1000 days) = [2.4 + 0.0018 x Age (days)]/Cr; CL (Age > 1000 days) = 4.3/Cr. Age also influenced central volume (V1) when included in the model as a dichotomous variable: V1 (Age < 4000 days) = 0.45 l kg(-1); V1 (Age > 4000 days) = 0.36 l kg(-1). Intercompartmental clearance and tissue volume were estimated to be 0.09 l kg(-1) h(-1) and 0.25 l kg(-1), respectively. Model validation in a separate group of 20 patients revealed a bias of -7.7% and a precision of 26.7%. CONCLUSIONS The clearance of vancomycin was decreased and its volume of distribution increased in patients receiving ECMO, suggesting altered drug disposition during this treatment.
Extrinsic attributes that influence parents' purchase of chocolate milk for their children.

UNLABELLED The consumption of milk is essential for children's heath; and flavored milk, especially chocolate milk, is often purchased to increase children's milk consumption. However, the sugar content of chocolate milk has raised health concerns. As such, it is important to understand chocolate milk extrinsic attributes that influence parents' purchase decisions when they are purchasing chocolate milk for their children. The objective of this study was to determine the key extrinsic attributes for parents when they purchase chocolate milk for their children. An online survey with a conjoint analysis design, emotions questions, and Kano questionnaire that focused on chocolate milk was conducted targeting parents. Three hundred and twelve parents participated in the survey. Parents reported positive emotions including good, good natured, happy, loving, and satisfied when purchasing chocolate milk for their kids. Three segments of parents were identified with subtle but distinct differences in their key preferences for chocolate milk attributes for their children. Type of sweetener was the primary driver of choice for purchasing chocolate milk for children followed by fat content. Among sweetener types, natural noncaloric/nonnutritive sweeteners or sucrose were preferred over artificial sweeteners, and reduced fat was preferred over full fat or skim milk. Kano results revealed that reduced fat and sugar with an all natural label and added vitamins, minerals, and protein were attractive to the majority of parents when purchasing chocolate milk for their kids. PRACTICAL APPLICATION Understanding the driving extrinsic attributes for parents when they purchase chocolate milk for their children will assist manufacturers to target extrinsic attributes that are attractive to parents for chocolate milk. This study established that sweetener type and fat content are the primary extrinsic attributes affecting parents purchase decisions when choosing chocolate milk for their children. Different segments of parents have distinct preferences for sweetener type and fat content, and they were also segmented by sugar content, natural/organic/conventional claim, and brand of chocolate milk. Manufactures can target different segments of parents based on their specific preferences.
Hz Mid-wave Infrared LED Scene Projector

Infrared imaging systems are widely used in law enforcement, military and industrial applications. They operate in a range of wavelengths from 0.8 to 10 microns, with one common range being 3 to 5 microns (commonly known as mid-wave IR or MWIR). Due to their complexity, IR imaging systems are expensive, sensitive, and highly complex devices. To test and assess proper operation of these systems requires frequent testing and calibration. Infrared scene projectors (IRSPs) are a critical tool for simulation and real-time testing of infrared imaging systems. These projectors create an accurate two-dimensional infrared scene. Established device technologies for building emitter arrays are MEMS thermal resistors. LED based IRSP technology potentially gives faster frame rates, higher spatial resolution, and the ability to display higher temperature scenes. This paper describes the world’s first infrared LED scene projector. It displays 512x512 MWIR images from a DVI computer interface. The projector has been successfully evaluated at multiple user facilities and has logged several hundred hours of operation.
Negative regulation in correct tissue-specific expression of mouse mammary tumor virus in transgenic mice

Mouse mammary tumor virus (MMTV) is an endogenous murine retrovirus that is expressed in the epithelial cells of the mammary and salivary glands, lungs, kidneys, and seminal vesicles and in the lymphoid cells of the spleen and thymus. Several studies have shown that the long terminal repeat (LTR) of this virus can direct the expression of reporter genes to the same tissues in transgenic mice. To determine whether multiple regulatory elements within the LTR are involved in this tissue-specific expression, we have established lines of transgenic mice containing transgenes that have deletions in the MMTV LTR. Deletions of all LTR sequences upstream of -364 or of LTR sequences from -165 to -665 both result in the expression of linked reporter genes such as the simian virus 40 early region or the bacterial enzyme chloramphenicol acetyltransferase in novel sites, such as the heart, brain, and skeletal muscle; expression of endogenous MMTV and transgenes containing the full-length LTR is not detected in these organs. Negative regulation appears to involve more than one region, since deletion of sequences between either -201 and -471 or -201 and -344, as well as sequences upstream of -364, results in inappropriate expression in heart, brain, and skeletal muscle. Therefore, a negative regulatory element(s) in the MMTV LTR can suppress transcription from the viral promoter in several different organs. This represents the first example of generalized negative regulatory elements that act in many different tissues in transgenic mice to prevent inappropriate expression of a gene.
Anti‐Candida albicans Antibody Levels and in vitro Lymphoproliferative Response to Candida albicans in Neonates and their Mothers/Anti‐Candida‐albicans‐Spiegel und Candida‐albicans‐bedingte Lymphozyten‐Stimulation in vitro bei Neugeborenen und ihren Müttern

Summary: Candida antibodies in 35 full‐term healthy neonates and their mothers were determined by the indirect hemagglutination test (HAT) and by the indirect immunofluorescence. In addition, lymphocyte stimulation by Candida albicans was studied in 22 neonates and their mothers.
Heterogeneous distribution of neurotensin-like immunoreactive neurons and fibers in the midbrain periaqueductal gray of the rat

The midbrain periaqueductal gray (PAG) has been shown to be a site where various manipulations induce pain suppression. Recent physiological evidence (Behbehani and Pert, 1984; Behbehani et al., 1987) suggests that neurotensin has pronounced physiological actions in PAG and effects pain suppression. We have performed immunohistochemical studies in order to determine the magnitude and distribution of neurotensin-like immunoreactive (NT-IR) cell bodies and fibers in PAG. NT-IR cell bodies were common throughout PAG, although there were more in the caudal than the rostral half. NT-IR neurons were much more numerous in the ventral than the dorsal half of PAG, and some appeared to be located within the dorsal raphe nucleus. The pattern of NT-IR fibers was analyzed with the aid of image enhancement/analysis and densitometry. The fibers were found to be heterogeneously distributed, being most heavily concentrated in the region adjacent to the cerebral aqueduct in the caudal two-thirds of PAG. The distribution of NT fibers closely matches sites where exogenously applied NT elicits long-lasting excitation of PAG neurons (Behbehani et al., 1987). Based on the known physiological and behavioral actions of NT in PAG, the present anatomical results suggest that NT acts on elements located predominantly in the medial and ventrolateral parts of PAG. Neurons activated by NT may project directly to the nucleus raphe magnus and adjacent ventral medulla (Behbehani and Pert, 1984) to activate neurons that project to the spinal cord and modulate nociceptive circuits.