Miracle-dz/UniFAR-FTUs huggingface dataset:
A Comparison of Plasma Versus Histologic Indices of Angiogenic Markers in Breast Cancer

BackgroundOver-expression of angiogenic growth factors and their receptors, and high levels of these molecules in the blood, are a common feature of cancer although the relationships between cell expression and plasma levels are unknown. We hypothesized a significant correlation between the expression and cellular distribution of vascular endothelial growth factor (VEGF), its receptor Flt-1, and the angiopoietin receptor Tie-2 with levels of these molecules in the plasma. MethodsThe tissue expression of VEGF, Flt-1, and Tie-2 were investigated by immunohistochemistry, and plasma levels assessed by enzyme-linked immunosorbent assay in 36 patients with breast cancer and 15 with benign breast disease. ResultsDespite expected significant differences in plasma levels of the molecules (P<0.03 to <0.001), no significant differences were found in Tie-2, VEGF, and Flt-1 tissue expression between breast cancer and benign disease controls. No significant correlations were observed between plasma levels of their tissue expression. ConclusionsTissue expression of Tie-2, VEGF, and Flt-1 may not be an overly sensitive tool for assessing abnormalities of coagulation, platelet activation, and angiogenesis in human cancer. Plasma markers may not be representative of tumor activity, and may not come wholly from tumor cells. Instead these markers may be indicative of endothelial dysfunction in cancer patients.
Three financial regulators issue reports on product and service innovations

Purpose To summarize developments by the US Consumer Financial Protection Bureau (“CFPB”), the US Office of the Comptroller of the Currency (“OCC”), and the UK Financial Conduct Authority (“FCA”) in their respective efforts to facilitate responsible financial innovation, and to predict what the financial services industry may expect in coming months. Design/methodology/approach This article summarizes financial marketplace developments of particular interest to the CFPB based on the CFPB’s report on its initiative to support responsible financial innovation and CFPB Director Richard Cordray’s speech at the Money 20/20 conference. The article also discusses the OCC’s release of a framework for its “Innovation Initiative”, providing insight to how the agency intends to engage with the fintech industry. Finally, this article explains how the FCA has identified the first cohort of firms to participate in its regulatory sandbox to test new financial products and services as part of the FCA’s wider “Project Innovate” initiative. Findings Financial technology innovators should closely monitor the agencies’ recent regulatory and policy developments to facilitate responsible financial innovation to be aware of new opportunities and regulatory consequences. Originality/value This article provides practical advice for fintech companies and other financial innovators on regulatory and policy updates from experienced financial services lawyers.
Seminal Vesicle Secretion 2 Acts as a Protectant of Sperm Sterols and Prevents Ectopic Sperm Capacitation in Mice1

ABSTRACT Seminal vesicle secretion 2 (SVS2) is a protein secreted by the mouse seminal vesicle. We previously demonstrated that SVS2 regulates fertilization in mice; SVS2 is attached to a ganglioside GM1 on the plasma membrane of the sperm head and inhibits sperm capacitation in in vitro fertilization as a decapacitation factor. Furthermore, male mice lacking SVS2 display prominently reduced fertility in vivo, which indicates that SVS2 protects spermatozoa from some spermicidal attack in the uterus. In this study, we tried to investigate the mechanisms by which SVS2 controls in vivo sperm capacitation. SVS2-deficient males that mated with wild-type partners resulted in decreased cholesterol levels on ejaculated sperm in the uterine cavity. SVS2 prevented cholesterol efflux from the sperm plasma membrane and incorporated liberated cholesterol in the sperm plasma membrane, thereby reversibly preventing the induction of sperm capacitation by bovine serum albumin and methyl-beta-cyclodextrin in vitro. SVS2 enters the uterus and the uterotubal junction, arresting sperm capacitation in this area. Therefore, our results show that SVS2 keeps sterols on the sperm plasma membrane and plays a key role in unlocking sperm capacitation in vivo.
Depressive spectrum disorders in cancer: prevalence, risk factors and screening for depression: a critical review

Abstract Background: Although depression and mood-related disorders are common in persons with cancer, these conditions remain frequently overlooked in clinical practice. Negative consequences of depressive disorder spectrum have been reported (e.g. suicidal ideation, increase physical complications and somatic symptoms, negative influence on prognosis), indicating the need for routine screening, assessment and management. Methods: A search of the major databases (Medline, Embase, PsycLIT, PsycINFO, and the Cochrane Library) was conducted on the reviews and meta-analyses available in order to summarize relevant data concerning depressive disorders spectrum in terms of prevalence, risk factors, and screening and assessment among patients with cancer across the trajectory of the disease. Results: The data show a prevalence of depression and depressive disorders between 5% and 60% according to the different diagnostic criteria, the tools used in the studies (e.g. semi-structured psychiatric interview and psychometric questionnaires), as well as the stage and type of cancer. Furthermore, despite the significant health care resources devoted to cancer care and the importance of addressing depressive symptoms, assessment and management of depressive spectrum disorders in cancer patients remains suboptimal. Conclusions: Routine screening and adequate assessment of depressive spectrum disorders is necessary in patients with cancer in order to effectively manage the multifaceted and complex consequences on cancer care.
Community Engagement Approach

Childhood obesity affects approximately 20% of U.S. preschool children. Early prevention is needed to reduce young children’s risks for obesity, especially among Hispanic preschool children who have one of the highest rates of obesity. Vida Saludable was an early childhood obesity intervention designed to be culturally appropriate for low-income Hispanic mothers with preschool children to improve maternal physical activity and reduce children’s sugar-sweetened beverage consumption. It was conducted at a large southwestern United States urban health center. Presented here are the methods and rationale employed to develop and culturally adapt Vida Saludable, followed by scoring and ranking of the intervention’s cultural adaptations. An empowered community helped design the customized, culturally relevant program via a collaborative partnership between two academic research institutions, a community health center, and stakeholders. Improved health behaviors in the participants may be attributed in part to this community-engagement approach. The intervention’s cultural adaptations were scored and received a high comprehensive rank. Postprogram evaluation of the intervention indicated participant satisfaction. The information presented provides investigators with guidelines, a template, and a scoring tool for developing, implementing, and evaluating culturally adapted interventions for ethnically diverse populations.
Extreme variations in racial rates of total hip arthroplasty for primary coxarthrosis: a population-based study in San Francisco.

OBJECTIVES--To compare the incidence of all total hip arthroplasty, and total hip arthroplasty for primary coxarthrosis, among the Asian, black, Hispanic, and white populations living in one locale. METHODS--We identified all San Francisco residents who underwent total hip replacements (THR) in the 17 hospitals for adults within or near San Francisco County during a five year period. Preoperative pelvic radiographs were read without prior knowledge of the gender or race of the subject, to diagnose the specific hip diseases. Age standardised THR incidence by race and gender was determined, as was the comparative THR incidence for specific diagnosis (primary and secondary osteoarthritis). RESULTS--The greatest annual rate of total hip replacement occurred in white women (97 per 100,000 population), followed by white men, black women, black men, Hispanic women, and Hispanic men. The smallest numbers were found in Asians, whose THR rate was 10% that of whites. A primary coxarthrosis diagnosis was greatest among white subjects (66%), followed by black subjects (54%), Hispanics (53%), and Asians (28%). Age standardised THR rates for primary coxarthrosis per 100,000 population were likewise greatest among whites (43.0) and least among Asians (1.3 for Chinese). Mean age of patients undergoing THR for primary coxarthrosis was 70 years for white subjects and almost a decade younger in all other groups. CONCLUSIONS--THR rates are much lower for Asians, Hispanics, and black subjects than for the white population living in San Francisco. The low rates of total hip arthroplasty in the non-white groups was related to the much lower incidence of THR for primary coxarthrosis among non-whites than among whites. The racial distribution of primary coxarthrosis among patients who underwent THR is consistent with distribution patterns reported internationally.
Gradient metasurfaces: a review of fundamentals and applications

In the wake of intense research on metamaterials the two-dimensional analogue, known as metasurfaces, has attracted progressively increasing attention in recent years due to the ease of fabrication and smaller insertion losses, while enabling an unprecedented control over spatial distributions of transmitted and reflected optical fields. Metasurfaces represent optically thin planar arrays of resonant subwavelength elements that can be arranged in a strictly or quasi periodic fashion, or even in an aperiodic manner, depending on targeted optical wavefronts to be molded with their help. This paper reviews a broad subclass of metasurfaces, viz. gradient metasurfaces, which are devised to exhibit spatially varying optical responses resulting in spatially varying amplitudes, phases and polarizations of scattered fields. Starting with introducing the concept of gradient metasurfaces, we present classification of different metasurfaces from the viewpoint of their responses, differentiating electrical-dipole, geometric, reflective and Huygens’ metasurfaces. The fundamental building blocks essential for the realization of metasurfaces are then discussed in order to elucidate the underlying physics of various physical realizations of both plasmonic and purely dielectric metasurfaces. We then overview the main applications of gradient metasurfaces, including waveplates, flat lenses, spiral phase plates, broadband absorbers, color printing, holograms, polarimeters and surface wave couplers. The review is terminated with a short section on recently developed nonlinear metasurfaces, followed by the outlook presenting our view on possible future developments and perspectives for future applications.
The Stock Market Reaction to Board Changes: The South African Experience

This article investigates the impact of board changes on the share prices of the companies listed on the Johannesburg stock exchange (JSE) during the period 2004–2008. Four types of board changes are investigated: new appointments, resignation, retirement and joint appointments. Market participants consider a change in the composition of a company’s board as having information content and produce statistically significant change in the share prices of the company concerned. In particular, the informational effects of new appointments are perceived differently by the market from resignations from the company board. The results also provide evidence that market reacts more favourably to the appointment of an executive director in comparison to that of a non-executive director board appointment. JEL classification: C58, D22, E44, G10, L22
Novel biomarkers for bipolar disorder.

INTRODUCTION Bipolar disorder is diagnosed on the basis of patient and/or family reports and behavioral observation. Traditionally regarded as an affective disorder involving behavioral changes, bipolar disorder has been reconceptualized as a multisystem disease associated with mood, cognitive, metabolic, autonomic and sleep/wake dysfunctions. Accordingly, recent studies have focused on the identification of biomarkers related to the pathophysiological mechanisms underlying the development, clinical presentation and course of bipolar disorder. AREAS COVERED This article provides an overview of the available literature regarding circulating peripheral and neuroimaging biomarkers in bipolar disorder. Neurotrophic factors, immune parameters, oxidative stress parameters, hormones and neuroimaging findings were taken into consideration. EXPERT OPINION Biomarkers research in bipolar disorder is a new field with an expanding knowledge. Current evidence suggests that a single biomarker will not be able to cover the biological and clinical complexity of bipolar disorder. Alternatively, a composite of biomarkers, including neurotrophic factors, cytokines and oxidative stress molecules, may be promising to identify altered mood states and neuroprogression in bipolar disorder.
Importance of the β12-β13 Loop in Protein Phosphatase-1 Catalytic Subunit for Inhibition by Toxins and Mammalian Protein Inhibitors*

Type-1 protein serine/threonine phosphatases (PP1) are uniquely inhibited by the mammalian proteins, inhibitor-1 (I-1), inhibitor-2 (I-2), and nuclear inhibitor of PP1 (NIPP-1). In addition, several natural compounds inhibit both PP1 and the type-2 phosphatase, PP2A. Deletion of C-terminal sequences that included the β12-β13 loop attenuated the inhibition of the resulting PP1α catalytic core by I-1, I-2, NIPP-1, and several toxins, including tautomycin, microcystin-LR, calyculin A, and okadaic acid. Substitution of C-terminal sequences from the PP2A catalytic subunit produced a chimeric enzyme, CRHM2, that was inhibited by toxins with dose-response characteristics of PP1 and not PP2A. However, CRHM2 was insensitive to the PP1-specific inhibitors, I-1, I-2, and NIPP-1. The anticancer compound, fostriecin, differed from other phosphatase inhibitors in that it inhibited wild-type PP1α, the PP1α catalytic core, and CRHM2 with identical IC50. Binding of wild-type and mutant phosphatases to immobilized microcystin-LR, NIPP-1, and I-2 established that the β12-β13 loop was essential for the association of PP1 with toxins and the protein inhibitors. These studies point to the importance of the β12-β13 loop structure and conformation for the control of PP1 functions by toxins and endogenous proteins.
Cellular restoration in HIV infected persons treated with abacavir and a protease inhibitor: age inversely predicts naive CD4 cell count increase

ObjectiveTo characterize early and later indices of cellular restoration among HIV-1 infected persons treated with abacavir and one protease inhibitor and to identify predictors of CD4 cell increases. MethodsFlow-cytometric analyses of lymphocyte phenotypes among 71 antiretroviral treatment naive adults in a 48 week treatment trial. ResultsDuring the first 4 weeks of therapy, increases in naive and memory CD4 cells and in B cells were seen; naive CD8 cells increased while CD8 cells remained stable as memory CD8 cells decreased. During the second phase total CD4 and naive CD4 and CD8 cells increased while total CD8 and memory CD8 cells decreased. The numbers of CD4 cells that expressed CD28 increased from a median of 308 × 106/l at baseline to 477 × 106/l at week 48. Higher baseline plasma HIV-1 RNA levels predicted the magnitude of early CD4 (r = 0.35;P = 0.01), memory CD4 (r = 0.38;P = 0.001) and CD28 CD4 cell (r = 0.29;P = 0.01) restoration but was not related to second phase changes. Younger age predicted a greater second phase (but not first phase) increase in naive CD4 cells (r = −0.31;P = 0.03). ConclusionsHigher baseline levels of HIV-1 replication determine the magnitude of first phase CD4 cell increases after suppression of HIV-1 replication. Second phase (primarily naive) CD4 cell increases are not related to HIV-1 replication but are inversely relate to age suggesting that thymic potential is a major determinant of long term cellular restoration in HIV-1 infected persons receiving antiretroviral therapy.
Proteome profiling suggests a pro‐inflammatory role for plasma cells through release of high‐mobility group box 1 protein

The final step of B‐cell maturation is to differentiate into plasma cells, a process that is accompanied by gross changes in subcellular organization to enable antibody secretion. To better understand this critical step in mounting a humoral immune response, we analyzed proteome dynamics during plasma cell differentiation with combined 2‐DE/MS. Thirty‐two identified protein spots changed in relative abundance when lipopolysaccharide (LPS)‐stimulated primary B cells differentiated into antibody‐secreting plasma cells. A correlative analysis of protein and transcript abundance suggested that one third of these proteins are post‐transcriptionally regulated. Apart from ER‐resident chaperones, lipid metabolic enzymes, and translation initiation factors, we identified several proteins that had not been previously studied in plasma cells. Among them is the transiently upregulated proteasome activator (PA) 28γ, a component of the putative nuclear proteasome. Additionally, we discovered that the non‐canonical inflammatory cytokine high‐mobility group box 1 (HMG1) was released from plasma cells into the extracellular milieu. This suggests a novel role for plasma cells as pro‐inflammatory mediators, which has important implications for various autoimmune diseases and chronic inflammation.
The Impact of R&D Cooperations and Mergers in Pharmaceuticals on Research Activities and Drugs Offered on the Market

In the last 10 years, the pharmaceutical industry has experienced steep, unprecedented price increases which are frequently attributed to increasing drug development costs. To cope with rocketing development costs, companies engage in Research and Development (R&D) cooperations. We study the impact of R&D cooperations on firms' research activities and drugs offered on the market. Using a comprehensive dataset, we find that R&D cooperations formed at the early stage of the drug development process increase the number of R&D projects and the number of drugs offered on the market. Late stage R&D cooperations, formed among larger firms in technology and product markets, increase firms' research activities, but reduce the number of drugs launched on the product market. Results suggest that large firms cooperating in the late research stage re-optimize their R&D pipelines and eliminate similarly aligned research projects.
Does Sustainability Matter? A Qualitative Study in Tourism Industry in Turkey

Abstract: The main purpose of the study is to analyze the perception of the concept of “sustainability” among undergraduate tourism students in a foundation university in Izmir, Turkey. Structured face to face interviews with 57 respondents revealed that according to 73.7 percent of participants, firms do not pay attention to sustainability in Turkey. However, only 45.6 percent stated that sustainability matters in tourism industry and 24.6 percent said that sustainability is not seen as an essential ingredient for the tourism industry in Turkey. The level of perception of sustainability among the respondents vary and they have different approaches to the concept of sustainability. Specifically, protection of the green environment, cultural, social and society values, natural beauty and recycling outweigh gaining revenue as a firm and having a profitable business. Being innovative and adding value to what you are doing is less considered in terms of describing sustainability. Keywords: Sustainability, Tourism and Hospitality, Sustainable Organization
Internal migration and interregional convergence in Russia 1

In this paper, we study panel data on region-to-region gross migration flows in Russia for 19952010. We find that barriers to labor mobility that hindered internal migration in 1990s, have been generally eliminated by the end of 2000s. In 1990s many poor Russian regions were in a poverty trap: potential workers wanted to leave those regions but could not afford to finance the move. In 2000s (especially in late 2000s), these barriers were no longer binding. Overall economic growth and development of financial markets allowed even poorest Russian regions to grow out of the poverty traps. This resulted in convergence in Russian labor market in 2000s; the interregional gaps in incomes, wages and unemployment rates decreased substantially and are now comparable to those in Europe.
PDGFR‐β‐activated ACK1‐AKT Signaling Promotes Glioma Tumorigenesis

Aberrant PDGF‐PDGFR signaling and its effects on downstream effectors have been implicated in glioma development. A crucial AKT regulator, ACK1 (TNK2) has been shown to be a downstream mediator of PDGF signaling; however, the exact underlying mechanisms in gliomas remain elusive. Here, we report that in glioma cells, PDGFR‐β activation enhanced the interaction between ACK1 and AKT, resulting in AKT activation. PDGF treatment consistently promoted the formation of complexes containing PDGFR‐β and ACK1. Mutational analysis suggested that Y635 of ACK1 is a PDGFR‐β phosphorylation site and that the ACK1 Y635F mutant abrogated the sequential activation of AKT. Moreover, PDK1 interacted with ACK1 during PDGF stimulation, which is required for the binding of ACK1 to PDGFR‐β. Further mutational analysis showed that T325 of ACK1 was crucial for the ACK1 and PDK1 interaction. ACK1 Y635F or T325A mutants abolished PDGFR‐β‐induced AKT activation, the subsequent nuclear translocation of β‐catenin and the expression of cyclin D1. Glioma cell cycle progression, proliferation and tumorigenesis were accordingly blocked by ACK1 Y635F or T325A. In glioblastoma multiforme samples from 51 patients, increased ACK1 tyrosine phosphorylation correlated with upregulated PDGFR‐β activity and AKT activation. Taken together, our data demonstrate that ACK1 plays a pivotal role in PDGF‐PDGFR‐induced AKT signaling in glioma tumorigenesis. This knowledge contributes to our understanding of glioma progression and may facilitate the identification of novel therapeutic targets for future glioma treatment.