Miracle-dz/UniFAR-FTUs huggingface dataset:
Cytotoxic antimelanoma drugs suppress the activation of M2 macrophages

Together with regulatory T cells (Tregs), tumor‐associated macrophages (TAMs) play roles in maintaining the tumor microenvironment. Although cytotoxic antimelanoma drugs such as dacarbazine (DTIC), nimustine hydrochloride (ACNU) and vincristine (VCR) have been used for the treatment of malignant melanoma as adjuvant therapy in Japan, the detailed mechanisms of their immunomodulatory effects are not fully understood. As the majority of TAMs are alternatively activated M2 macrophages that favour tumor development, the aim of this study was to elucidate the immunomodulatory effects of these reagents on human monocyte‐derived M2 macrophages. First, mRNA expressions and protein production of immune checkpoint molecules, PD‐L1 and chemokines by CD163+ CD206+ M2 macrophages derived from peripheral blood mononuclear cells were investigated to determine the immunomodulatory effects of DTIC, ACNU, and VCR. DTIC and VCR significantly decreased PD‐L1 mRNA expression, which was confirmed by flow cytometry. Moreover, the mRNA expression and production of CCL22 were significantly decreased by DTIC, which suggested that DTIC might suppress the recruitment of Tregs in the tumor site. Furthermore, the decreased expression of PD‐L1 and production of CCL22 were validated in vivo, using the B16F10 mouse melanoma model, leading to abrogation of the suppressive function of T‐cell proliferation. The present report suggests one of the possible antimelanoma mechanisms of DAV combination chemotherapy for melanoma patients.
Relationships of Age and Gender to Hope and Spiritual Well-Being Among Adolescents With Cancer

The purpose of this study was to examine hope and spiritual well-being, with its 2 dimensions of religious well-being and existential well-being, as they relate to age and gender among adolescents with cancer. A cross-sectional design was guided by the conceptual framework, Adolescent Psychosocial Adaptation to the Cancer Experience. A total of 78 adolescents with a diagnosis of cancer were enrolled from 2 pediatric oncology clinics. Middle adolescents (15-17 years of age) reported higher religious well-being than late adolescents (18-20 years of age). Middle-adolescent boys were more hopeful than were early adolescent boys (13- 14 years of age). Also, girls were more hopeful and reported higher spiritual well-being than age the boys. Developmental phase and/or gender may influence adolescents’ levels of hope, spiritual well-being, religious well-being, and existential well-being as they cope during the cancer experience. The nurse should consider developmental phase and gender when planning interventions to foster hope and spiritual well-being in adolescents’ adaptations to the cancer experience.
Bayesian Dyadic Trees and Histograms for Regression

Many machine learning tools for regression are based on recursive partitioning of the covariate space into smaller regions, where the regression function can be estimated locally. Among these, regression trees and their ensembles have demonstrated impressive empirical performance. In this work, we shed light on the machinery behind Bayesian variants of these methods. In particular, we study Bayesian regression histograms, such as Bayesian dyadic trees, in the simple regression case with just one predictor. We focus on the reconstruction of regression surfaces that are piecewise constant, where the number of jumps is unknown. We show that with suitably designed priors, posterior distributions concentrate around the true step regression function at a near-minimax rate. These results do not require the knowledge of the true number of steps, nor the width of the true partitioning cells. Thus, Bayesian dyadic regression trees are fully adaptive and can recover the true piecewise regression function nearly as well as if we knew the exact number and location of jumps. Our results constitute the first step towards understanding why Bayesian trees and their ensembles have worked so well in practice. As an aside, we discuss prior distributions on balanced interval partitions and how they relate to an old problem in geometric probability. Namely, we relate the probability of covering the circumference of a circle with random arcs whose endpoints are confined to a grid, a new variant of the original problem.
CysLTR1 promoter polymorphism and requirement for leukotriene receptor antagonist in aspirin-intolerant asthma patients.

OBJECTIVES Leukotriene receptor antagonists (LTRA), such as montelukast, have been used as a first-line treatment for patients with aspirin-intolerant asthma (AIA). This study evaluated associations between the clinical requirement for LTRA and genetic polymorphisms of the ALOX5, LTC4S, COX-2, CysLTR1 and TBXA2R genes in the arachidonic acid cascade in the long-term management of 89 AIA patients from a Korean population. METHODS Asthma control status was monitored for 1 year with maintenance medications of inhaled corticosteroid and oral LTRA, and AIA patients were classified into three groups according to the mean montelukast dose required per month to maintain asthma control for 1 year: group I (> or = 200 mg montelukast/month; n = 37), group II (5-150 mg/month; n = 25) and group III (< 5 mg/month; n = 27). Genetic polymorphisms in the arachidonic acid cascade were determined using a single-base extension method. RESULTS We found that there was a significant difference in the genotype frequency of the CysLTR1 promoter polymorphism -634C > T among the three groups (p = 0.007 for group I vs group II, p = 0.017 for group I vs group III), while there were no significant associations between LTRA requirements and polymorphisms of the other genes. The patients with the variant genotype (CT or TT) of the -634C = T CysLTR1 promoter polymorphism showed a higher expression level than those with the common genotype (CC). CONCLUSION These findings indicate that the CysLTR1 promoter polymorphism is a useful genetic marker for predicting LTRA requirements in the long-term management of AIA patients.
GaInNAs-GaAs long-wavelength vertical-cavity surface-emitting laser diodes

Vertical-cavity surface-emitting laser diodes with GaInNAs-GaAs quantum-well (QW) active layers are demonstrated for the first time. GaInNAs permits the realization of a long-wavelength vertical-cavity laser grown directly on a GaAs substrate. Room-temperature (RT) pulsed operation is achieved, with an active wavelength near 1.18 /spl mu/m, threshold current density of 3.1 kA/cm/sup 2/, slope efficiency of /spl sim/0.04 W/A, and output power above 5 mW for 45-/spl mu/m-diameter devices. Laser oscillation is observed for temperatures at high as 95/spl deg/C.
Repair of deletions and double-strand gaps by homologous recombination in a mammalian in vitro system

We have designed an in vitro system using mammalian nuclear extracts, or fractions derived from them, that can restore the sequences missing at double-strand breaks (gaps) or in deletions. The recombination substrates consist of (i) recipient DNA, pSV2neo with gaps or deletions ranging from 70 to 390 bp in the neo sequence, and (ii) donor DNAs with either complete homology to the recipient (pSV2neo) or plasmids whose homology with pSV2neo is limited to a 1.0- to 1.3-kbp neo segment spanning the gaps or deletions. Incubation of these substrates with various enzyme fractions results in repair of the recipient DNA's disrupted neo gene. The recombinational repair was monitored by transforming recA Escherichia coli to kanamycin resistance and by a new assay which measures the extent of DNA strand transfer from the donor substrate to the recipient DNA. Thus, either streptavidin- or antidigoxigenin-tagged beads are used to separate the biotinylated or digoxigeninylated recipient DNA, respectively, after incubation with the isotopically labeled donor DNA. In contrast to the transfection assay, the DNA strand transfer measurements are direct, quantitative, rapid, and easy, and they provide starting material for the characterization of the recombination products and intermediates. Accordingly, DNA bound to beads serves as a suitable template for the polymerase chain reaction. With appropriate pairs of oligonucleotide primers, we have confirmed that both gaps and deletions are fully repaired, that deletions can be transferred from the recipient DNA to the donor's intact neo sequence, and that cointegrant molecules containing donor and recipient DNA sequences are formed.
Subclavian artery pseudoaneurysm complicating central venous catheterization

Central venous catheterization is a routine vascular access procedure; however, it may be associated with life‐threatening complications such as arterial puncture, leading to pseudoaneurysm formation. We report a case of a 41‐year‐old female that developed an iatrogenic left subclavian pseudoaneurysm complicating the attempt of left internal jugular vein cannulation for temporary hemodialysis therapy. The patient underwent urgent endovascular treatment with deployment of covered stent into the left subclavian artery (SCA) after embolization of the origin of the left internal mammary artery with Amplatzer Vascular Plug 4. The patient's recovery was unremarkable. Follow‐up till 24 months reveals total exclusion of the pseudoaneurysm of the left SCA with patency of the distal branches. © 2013 Wiley Periodicals, Inc.
Morphologic and Molecular Features of Hepatocellular Adenoma with Gadoxetic Acid-enhanced MR Imaging.

PURPOSE To evaluate the diagnostic performance of imaging features of gadoxetic acid-enhanced magnetic resonance (MR) imaging to differentiate among hepatocellular adenoma (HCA) subtypes by using the histopathologic results of the new immunophenotype and genotype classification and to correlate the enhancement pattern on the hepatobiliary phase (HBP) with the degrees of expression of organic anion transporting polypeptide (OATP1B1/3), multidrug resistance-associated protein 2 (MRP) (MRP2), and MRP 3 (MRP3) transporters. MATERIALS AND METHODS This retrospective study was approved by the institutional review board, and the requirement for informed consent waived. MR imaging findings of 29 patients with 43 HCAs were assessed by two radiologists independently then compared with the histopathologic analysis as the standard of reference. Receiver operating characteristic curves and Spearman rank correlation coefficient were used to test the diagnostic performance of gadoxetic acid-enhanced MR imaging features, which included the retention or washout at HBP and degree of transporter expression. Interreader agreement was assessed by using the κ statistic with 95% confidence interval. RESULTS The area under the curve for the diagnosis of inflammatory HCA was 0.79 (95% confidence interval: 0.64, 0.90); for the steatotic type, it was 0.90 (95% confidence interval: 0.77, 0.97); and for the β-catenin type, it was 0.87 (95% confidence interval: 0.74, 0.95). There were no imaging features that showed a significant statistical correlation for the diagnosis of unclassified HCAs. On immunohistochemical staining, OATP1B1/3 expression was the main determinant for the retention, whereas MRP3 was the key determinant for washout of gadoxetic acid at HBP (P < .001). MRP2 appeared to have no role. CONCLUSION Gadoxetic acid-enhanced MR imaging features may suggest the subtype of HCA. The degree of OATP1B1/3 and MRP3 expression correlated statistically with gadoxetic acid retention and washout, respectively, in the HBP.
Differences in T‐helper polarizing capability between human monocyte‐derived dendritic cells and monocyte‐derived Langerhans’‐like cells

Langerhans’ cells (LCs) represent a specific subset of dendritic cells (DCs) which are important for detecting and processing pathogens that penetrate the skin and epithelial barriers. The aim of our study was to explain what makes their in vitro counterparts – monocyte‐derived Langerhans’‐like cells (MoLCs) – unique compared with monocyte‐derived dendritic cells (MoDCs). Immature MoDCs were generated by incubating peripheral blood monocytes with granulocyte–macrophage colony‐stimulating factor (GM‐CSF) and interleukin (IL)‐4. The addition of transforming growth factor‐β (TGF‐β) to this cytokine cocktail resulted in the generation of MoLCs. MoLCs showed a lower expression of CD83, CD86, HLA‐DR and CCR7 compared with MoDCs, regardless of their maturational status. Both immature and mature MoLCs secreted higher quantities of IL‐23 compared with MoDCs and this finding correlated with a higher secretion of IL‐17 in co‐culture of MoLCs with allogeneic CD4+ T cells. Mature MoLCs, which produced higher levels of IL‐12 and lower levels of IL‐10 compared with mature MoDCs, were more potent at inducing interferon‐γ (IFN‐γ) production by CD4+ T cells in the co‐culture system. In conclusion, the finding that mature MoLCs stimulate stronger T‐helper 1 and T‐helper 17 immune responses than mature MoDCs, makes them better candidates for use in the preparation of anti‐tumour DC vaccines.
CB1 receptors: emerging evidence for central and peripheral mechanisms that regulate energy balance, metabolism, and cardiovascular health

Insulin resistance, dyslipidaemia and obesity are the major cardiometabolic risk factors contributing to the development of type 2 diabetes and cardiovascular disease (CVD). Owing to the increasing prevalence of obesity, type 2 diabetes, and CVD, new and effective pharmacologic therapies are urgently needed. In this regard, the endogenous cannabinoid system (ECS), a neuromodulatory system involved in the regulation of various aspects of energy balance and eating behaviour through central and peripheral mechanisms, may present the potential to meet this need. In the central nervous system (CNS), cannabinoid type 1 (CB1) receptors and their respective ligands, the endocannabinoids, have a significant role in the modulation of food intake and motivation to consume palatable food. CB1 receptors have also been found in organs involved in the regulation of metabolic homeostasis, such as liver, white adipose tissue, muscle and pancreas. Dysregulation of the ECS has been associated with the development of dyslipidaemia, glucose intolerance, and obesity, and CB1 receptor blockade may have a role in ameliorating these metabolic abnormalities. Thus, pharmacologic options targeting the ECS may provide a novel, effective approach to the prevention and management of CVD, type 2 diabetes and obesity. Copyright © 2007 John Wiley & Sons, Ltd.
Social Recognition, Participation, and the Dynamic Between the Environment and Personal Factors of Students With Deafblindness

The study describes environmental and personal factors that, from the student perspective, impede participation in education in secondary upper schools by students with postlingual deafblindness. The discussion is framed by the International Classification of Functioning, Disability, and Health. The researchers use the theory of social recognition as a theoretical tool in understanding the dynamics between personal factors and environment in the context of secondary upper-school education. Thirty-four students with deafblindness responded to a questionnaire; the survey's findings indicate experiences of barriers in the natural and social environments that restrict participation. Experience of considerateness—such as concern for the special requirements of students with deafblindness—and experience of the lack of considerateness are the most important factors. Negative roles adapted by some students for themselves may be interpreted as resulting from a lack of recognition, in the form of denigration or insults.
Effect of Quinalphos on Testicular Steroidogenesis in Rats

Summary: The effect of quinalphos (250 μg/kg i.p.) an organophosphorus insecticide treatment for 13 and 26‐days on the testicular steroidogenic enzymes viz. 3/β‐Hydroxysteroid Dehydrogenase and 17β‐Hydroxysteroid Dehydrogenase, as well as cholesterol content and histology of the testes of the Wistar strain rats was studied. The time duration of 13 days is approximately equivalent to one cycle of the seminiferous epithelium in Wistar strain rats. Treatment of quinalphos for 13 days failed to produce any effect on the relative weights of the testes and accessory sex glands. However, significant inhibition of 3β‐HSD activity and increased cholesterol level in testis were observed. The rats treated for 26 days similarly showed a highly significant inhibition of the activity of both 3β‐HSD and 17β‐HSD. The relative weights of the testes and accessory sex glands were also significantly reduced. Histological examination of the testis revealed that quinalphos treatment produced detrimental changes in the seminiferous epithelium. Treatment with quinalphos for 13‐days produced no toxic effect with the exception of a significant increase in serum alkaline phosphatase. However, after 26‐days of treatment toxicity was significantly increased as reflected on serum transaminases, phosphatases and blood urea levels of rat. Present study indicated that quinalphos impairs testicular functions in rats.
Nurse Practitioners' Knowledge of Occupational Therapy

Objective. The purpose of this study was to determine what nurse practitioners (NPs) in western New York know about occupational therapy's (OT) roles and functions. Method. A self-designed survey of 27 questions was mailed to 150 randomly selected NPs in western New York who are members of New York State Coalition of Nurse Practitioners. A modified Dillman procedure was used for mailing the materials to the NPs. One hundred of the NPs responded. Results. The NPs have a broad general knowledge about OT although there are areas of uncertainty about the profession. Uncertainties about who formulates the patients' goals, who pays for OT, and aspects of OT, such as working with prosthetic devices, working with cardiovascular patients, working with young adults in prevocational and vocational skills, and making appropriate goals for elderly patients were identified. They also had limited awareness regarding the importance of OTs' contributions to patient care in certain work environments and regarding certain specialty areas. The results also suggested direct OT contact was their primary source of acquiring information about OT and also was the most beneficial method for their learning. Conclusion. This study may help to shape OTs' efforts in educating NPs since it identifies the areas of uncertain knowledge and the ways in which their information is best obtained. Some strategies for increasing NPs' understanding of OT include presenting information about OT at an NP conference, role playing or lecturing during the NPs' final clinical course, and direct discussions about cases regarding patient progress.
Crowdfunding, business angels, and venture capital: an exploratory study of the concept of the funding trajectory

ABSTRACT The market for entrepreneurial finance has witnessed the arrival of new players – specifically, different types of crowdfunding platforms – which have joined the more traditional forms of entrepreneurial finance such as BAs and VCs over the last decade. Taking stock of this increasingly diverse landscape, the present study explores the concept of a complex funding trajectory and its impact on the dynamics of nascent venture governance. Using a processual case-study design, we explore the particular funding trajectory of a young technology venture, successively combining different actors: reward based crowdfunding (RBC) first, then equity based crowdfunding (ECF) combined with business angels (BAs), followed by ECF combined with BAs and VCs. Our contribution to the literature is two-fold. The case makes an empirical contribution by deepening insights from prior quantitative studies on the determinants of follow-on funding after initial crowdfunding campaigns. The present study also makes a theoretical contribution by demonstrating that, beyond particular determinants of fundraising from various sources linked to initial venture characteristics and individual campaign attributes, the specific shape and sequencing of the overall funding trajectory plays a central role for the success of follow-on funding and the nascent governance of the young venture.
New Fibrin Conduit for Peripheral Nerve Repair

An ideal substitute to treat a nerve gap has not been found. Initially, silicone conduits were employed. Later, conduits were fabricated from collagen or polyesters carbonates. More recently, it has been shown that a bioresorbable material, poly-3-hydroxybutyrate (PHB), can enhance nerve repair. The present investigation shows the use of fibrin as a conduit to guide nerve regeneration and bridge nerve defects. In this study we prepared and investigated a novel nerve conduit made from fibrin glue. Using a rodent sciatic nerve injury model (10-mm gap), we compared the extent of nerve regeneration through the new fibrin conduits versus established PHB conduits. After 2 and 4 weeks, conduits containing proximal and distal stumps were harvested. We evaluated the initial axon and Schwann cell stimulation using immunohistochemistry. The conduits presented full tissue integration and were completely intact. Axons crossed the gap after 1 month. Immunohistochemistry using the axonal marker PGP 9.5 showed a superior nerve regeneration distance in the fibrin conduit compared with PHB (4.1 mm versus 1.9 mm). Schwann cell intrusion (S100 staining) was similarly enhanced in the fibrin conduits, both from the proximal (4.2 mm versus 2.1 mm) and distal ends (3.2 mm versus 1.7 mm). These findings suggest an advantage of the new fibrin conduit for the important initial phase of peripheral nerve regeneration. The use of fibrin glue as a conduit is a step toward a usable graft to bridge peripheral nerve lesions. This might be clinically interesting, given the widespread acceptance of fibrin glue among the surgical community.
Palliative Care Edema: Patient Population, Causal Factors, and Types of Edema Referred to a Specialist Palliative Care Edema Service.

BACKGROUND Edema in palliative care patients is a common symptom, however, the research base for all aspects of its care is extremely poor. OBJECTIVE To evaluate a specialist palliative care edema service in order to report on the patient population referred, the types of edema encountered, and the causes of edema. DESIGN Prior to study, three different edema types were described for evaluation: lymphedema, nonlymphatic edema, and a combination of the two. Retrospective chart evaluation was completed from August 2013 through January 2014. SUBJECTS Patients with edema assessed by the specialist palliative care physiotherapy edema service. RESULTS Sixty-three cases were included, comprising 10.5% of all new palliative care referrals during the study period. Ninety-two percent (n = 58) had a diagnosis of cancer and 57% (n = 36) were female. Age ranged from 45-97 years. The most common edema type was a mixed edema (46%, n = 29), followed by lymphedema (27%, n = 18) and nonlymphatic edema (16%, n = 10). Lymphorrhea occurred in 9.5% of cases. The most common reasons for edema, based on clinical opinion, were blocked lymphatics (33%) and dependency from immobility (27%). The most common site for edema was in the lower limbs (89%, n = 56). The time lapse from the last treatment to death ranged from 1-225 days. Having a mixed edema type or lymphorrhea was a relatively poor prognostic sign. CONCLUSIONS This is the first study to describe in detail the occurrence of edema in palliative care patients. Edema may be present for many months prior to death making the search for effective treatments imperative.