Miracle-dz/UniFAR-FTUs huggingface dataset:
Private Equity in Family Firms: Drivers of the Willingness to Cede Control

Our aim is to empirically examine how reasons for using private equity (PE) and prior experience with PE affect the willingness of privately held firms to cede company control. Based on a questionnaire entailing 75 privately held firms backed by PE, we show that family firms cede less control than non-family firms when entering a PE transaction. However, if firms seek funds due to challenges related to ownership changes, the difference between family firms and non-family firms decreases. Moreover, we find that family firms sell more company shares if they are run by a PEexperienced manager.
Are schizophrenia and affective disorder related? A selective literature review.

OBJECTIVE Although most modern investigators accept the Kraepelinian view that schizophrenia and affective disorder are biologically distinct, others have suggested the psychoses are on a continuum of liability. This article is a selective review of evidence for the continuum model. METHOD The author focuses on family, twin, and adoption data that do not support the Kraepelinian view of psychosis. Evidence characterized to a lesser extent includes the frequency of intermediate forms of illness (i.e., schizoaffective disorder), the inability to separate psychoses by classical symptoms into well-defined clusters, and the inability of laboratory measures to clearly define psychotic subgroups. RESULTS The data demonstrate that schizophrenia and affective disorder do co-occur in some families. Whether this co-occurrence reflects true overlap is unclear, and significant pathophysiological heterogeneity may underlie clinical continuity. In some recent studies the inclusion of nonmelancholic depressions in the affective illness category may have masked overlap. CONCLUSIONS The author suggests that the Kraepelinian view of psychoses may need modification. Future research should focus on factors that may reveal overlap between schizophrenia and affective disorder: severity of schizophrenia and affective disorder in probands, severity of depression in relatives, the effect of the unipolar-bipolar disorder relationship on the co-occurrence of affective disorder and schizophrenia, and the relationship of nongenetic factors that might alter the clinical expression of a shared genotype. Also, investigators should not presume a dichotomy or continuum but should examine pure and mixed pedigrees and look for state- and trait-related endophenotypes, the convergence of which would provide the basis for focused molecular genetic study.
Simultaneous and Rapid Analysis of Cyclosporin A and Creatinine in Finger Prick Blood Samples Using Liquid Chromatography Tandem Mass Spectrometry and Its Application in C2 Monitoring

A simple and rapid liquid chromatography tandem mass spectrometry (LC-MS/MS) method for the simultaneous analysis of cyclosporin A (CsA) and creatinine using capillary blood has been developed. Venous and capillary blood samples were taken predose and at C2 from 65 heart and lung transplant recipients (65 × 4 samples). For comparisons, serum creatinine and blood CsA concentrations were measured by the Jaffe and EMIT methods, respectively, using an Olympus AU600 analyzer. For the LC-MS/MS assay, samples were prepared in a 96 × 700-&mgr;L well block by adding 10 &mgr;L of blood (or serum) to 40 &mgr;L of 0.1 mol/L zinc sulphate solution containing deuterated creatinine internal standard. Proteins were precipitated by adding 100 &mgr;L acetonitrile containing ascomycin internal standard. After vigorous mixing and centrifugation, 5 &mgr;L of the supernatant was injected into the LC-MS/MS system. A Waters 2795 high-performance liquid chromatography (HPLC) system was used to elute a C18 cartridge (3 mm × 4 mm) at 0.6 mL/min with a step gradient of 50–100% methanol containing 2 mmol/L ammonium acetate and 0.1% (v/v) formic acid. The column was maintained at 55°C, and the retention times were creatinine, 0.4 minutes; ascomycin, 0.98 minutes; and CsA, 1.2 minutes. Cycle time was 2.5 minutes, injection to injection. The analytes were monitored using a Quattro microtandem mass spectrometer operated in multiple reaction monitoring mode using the following transitions: creatinine, m/z 114>44; d3-creatinine (IS), m/z 117>47; ascomycin (IS), m/z 809>756; and CsA, m/z 1,220>1,203. Assay characteristics were CsA intraassay CV, 3.6–3.0% (33–1,500 &mgr;g/L); CsA interassay CV, 6.7–2.5% (10–5,000 &mgr;g/L); LC-MS/MS capillary [CsA] = 0.99 × LC-MS/MS venous [CsA] − 4.2, R = 0.98; and LC-MS/MS venous [CsA] = 0.93 × EMIT venous [CsA] + 2.9, R = 0.98. Creatinine intraassay CV, 6.6–2.5% (20–720 &mgr;mol/L); interassay CV, 5.7–3.3% (80–590 &mgr;mol/L); LC-MS/MS capillary [creatinine] = 0.99 Jaffe plasma [creatinine] −42.6, R = 0.87. Total time for the preparation and analysis of 30 samples was approximately 2 hours. This assay will provide a flexible, robust, and cost-effective solution for the monitoring of CsA and creatinine in transplant recipients with potential applications in pediatric medicine and pharmacokinetic studies, in which frequent sampling is required.
The impact of disclosing financial ties in research and clinical care: a systematic review.

BACKGROUND Despite increased demand for disclosure of physician and researcher financial ties (FTs) to industry, little is known about patients', research participants', or journal readers' attitudes toward FTs. METHODS We systematically reviewed original, quantitative studies of patients', research participants', or journal readers' views about FTs to pharmaceutical and medical device companies. The MEDLINE, Scopus, and Web of Knowledge databases were searched for English-language studies containing original, quantitative data on attitudes toward FTs. We screened 6561 citations and retrieved 244 potentially eligible abstracts. Of these, 20 met inclusion criteria. RESULTS Eleven studies assessed FTs and perceptions of quality. In clinical care, patients believed FTs decreased the quality and increased the cost of care. In research, FTs affected perceptions of study quality. In 2 studies, readers' perceptions of journal article quality decreased after disclosure of FTs. Eight studies assessed the acceptability of FTs. Patients were more likely to view personal gifts to physicians as unacceptable, compared with professional gifts. In 6 of the 10 studies that assessed the importance of disclosure, most patients and research participants believed FTs should be disclosed; in the other 4, approximately one-quarter believed FTs should be disclosed. Among the 7 studies assessing willingness to participate in research, approximately one-quarter of participants reported less willingness after disclosure of FTs. CONCLUSIONS Patients believe that FTs influence professional behavior and should be disclosed. Patients, physicians, and research participants believe FTs decrease the quality of research evidence, and, for some, knowledge of FTs would affect willingness to participate in research.
C‐terminal domains of general regulatory factors Abf1p and Rap1p in Saccharomyces cerevisiae display functional similarity

Abf1p and Rap1p are global regulatory factors which play an essential role in the transcription activation of yeast ribosomal protein genes. This functional link prompted us to investigate whether these factors may be functionally interchangeable. We focused on the indispensable C‐terminal portions of both factors and performed mutual domain swaps. The functional capacity of the resulting hybrid proteins was subsequently examined using yeast strains conditionally expressing either the ABF1 or the RAP1 gene. Both the Abf1p–Rap1p and the Rap1p–Abf1p fusion proteins were found to be able to complement the growth defect of the respective strains. Furthermore, Abf1p and Rap1p are both able to promote transcription of a reporter gene through a combination of the respective binding site and a T‐rich promoter element. These data strongly suggest that the C‐terminal domains of Abf1p and Rap1p have, at least partially, identical functions. Finally, a deletion analysis of the so far largely uncharacterized C‐terminal domain of Abf1p was performed, which revealed that two regions of 50 amino acids can perform all essential Abf1p functions.
ESG Investing in Emerging and Frontier Markets

The authors discuss the benefits of considering material environmental, social, and governance (ESG) factors when investing in emerging and frontier markets. Companies that operate in these markets face a myriad of operating challenges, and management teams that respond to such challenges effectively can achieve superior financial performance over time. They are able to grow faster, achieve higher profitability, reduce their cost of capital, and manage exogenous risks better than their peers.For investment managers, integrating sustainability into the analysis process provides a differentiated lens to identify companies that possess strong competitive advantages that can drive value creation over time. At the same time, it can help investment managers avoid companies that have embedded risks in their business model or operations that may not be entirely visible to the market.Finally, given the early‐stage nature of many of these markets and the sometimes uneven understanding of sustainability issues at a company level, the authors argue that active ownership can be an important driver of alpha generation by fund managers. Engaging constructively with board members and management teams to improve a company's ESG profile can help drive operational improvements, strengthen the risk management function, and upgrade investors’ perception of the quality of the management team.
Evaluation of Reproductive Compatibility of Interstrain Matings Among Plum Curculio Populations in the Eastern United States

Reproductive compatibility of interstrain matings in plum curculio, Conotrachelus nenuphar (Herbst), was studied during the summers of 2004 and 2006. There was a unidirectional incompatibility in the cross-matings along a rough north to south transect of the range of plum curculio (4 × 4 two-factorial design). There was significantly lower fertility in West Virginia males mated with New York and Virginia females (40 and 29%, respectively), and Florida males had a significantly lower fertility with Virginia and West Virginia females (46 and 37%, respectively), but Florida females were compatible with males of all four populations. Three northern populations were compatible with each other in all cross-mating combinations (New York, Massachusetts, and New Jersey; 3 × 3 two-factorial design). There was a unidirectional reproductive incompatibility in the combination of New Jersey males with Florida females (47%) and a bi-directional incompatibility between Florida and West Virginia reciprocal cross-mating (26 and 21%, respectively). The pattern of the reproductive incompatibility among geographic populations could help us to distinguish plum curculio strains and to clarify their strain distribution range to enrich our knowledge on their population ecology and biosystematics.
Macroeconomic Determinants of Crude Oil Demand in Ghana

This article investigates the macroeconomic determinants of crude oil demand (consumption) in Ghana with annual data from 1980 to 2013. The study applied the vector error correction model (VECM) to estimate the long-run and short-run determinants of crude oil demand in Ghana within the study period. The long-run estimates reveal that price of crude oil, real GDP per capita, real effective exchange rate and energy saving technical progress are significant long-run determinants of crude oil demand. The results also indicate that crude oil demand in Ghana is income and price inelastic. Crude oil price has a positive long-run effect indicating the virtual lack of substitutes and overdependence on crude oil for energy generation and economic activities in Ghana. Based on the variance decomposition and impulse response analyses, the study also found that positive shocks from real effective exchange rate had a dominant and positive impact on crude oil demand in Ghana. We suggest among others that Ghana vigorously explore alternative and sustainable energy sources to curtail the overdependence on crude oil, strategically hedge against volatilities in the exchange rate market, and revive the country’s oil refinery to refine her own crude oil to reduce importation.
Investigation of drug–drug interaction via mechanism‐based inhibition of cytochrome P450 3A by macrolides in dexamethasone‐treated female rats

The in vitro and in vivo inhibition of cytochrome P450 (CYP) 3A with mechanism‐based inhibition (MBI) by macrolides was investigated using dexamethasone‐treated female rats (DEX‐female rats). In the in vitro CYP inhibition studies using erythromycin (ERM) and clarithromycin (CAM), similar inhibition responses were observed between human and DEX‐female rat liver microsomes, however, there were fewer effects in intact male rats. The ex vivo study showed that midazolam (MDZ) metabolism in liver microsomes of DEX‐female rats was reduced by ERM administration and the inhibitory effect was increased with increasing ERM doses, indicating that metabolite intermediate complex formation caused irreversible inhibition of CYP3A activity in DEX‐female rats as well as in humans. In the in vivo studies, ERM and CAM significantly increased the area under the plasma concentration–time curve of MDZ and decreased the total clearance in DEX‐female rats. It was concluded that the DDIs via MBI of CYP3A following macrolide administration in humans could be reproduced in female rats, suggesting that DEX‐female rats can serve as an in vivo model for assessing this DDI in humans. Copyright © 2012 John Wiley & Sons, Ltd.
Nuclear factor-κB p65 small interfering RNA or proteasome inhibitor bortezomib sensitizes head and neck squamous cell carcinomas to classic histone deacetylase inhibitors and novel histone deacetylase inhibitor PXD101

Histone deacetylase inhibitors (HDI) can inhibit proliferation and enhance apoptosis in a wide range of malignancies. However, HDIs show relatively modest activity in head and neck squamous cell carcinomas (HNSCC), in which we have shown the activation of nuclear factor-κB (NF-κB; NF-κB1/RelA or p50/p65), a transcription factor that promotes expression of proliferative and antiapoptotic genes. In this study, we examined if HDIs enhance activation of NF-κB and target genes and if genetic or pharmacologic inhibition of NF-κB can sensitize HNSCC to HDIs. Limited activity of classic HDIs trichostatin A and sodium butyrate was associated with enhanced activation of NF-κB reporter activity in a panel of six HNSCC cell lines. HDIs enhanced NF-κB p50/p65 DNA binding and acetylation of the RelA p65 subunit. Transfection of small interfering RNAs targeting p65 strongly inhibited NF-κB expression and activation, induced cell cycle arrest and cell death, and further sensitized HNSCC cells when combined with HDIs. The p65 small interfering RNA inhibited HDI-enhanced expression of several NF-κB–inducible genes implicated in oncogenesis of HNSCC, such as p21, cyclin D1, and BCL-XL. Bortezomib, an inhibitor of proteasome-dependent NF-κB activation, also increased sensitization to trichostatin A, sodium butyrate, and a novel HDI, PXD101, in vitro, and to the antitumor effects of PXD101 in bortezomib-resistant UMSCC-11A xenografts. However, gastrointestinal toxicity, weight loss, and mortality of the combination were dose limiting and required parenteral fluid administration. We conclude that HDI-enhanced NF-κB activation is one of the major mechanisms of resistance of HNSCC to HDIs. The combination of HDI and proteasome inhibitor produced increased antitumor activity. Low starting dosages for clinical studies combining HDIs with proteasome inhibitors and IV fluid support may be warranted. [Mol Cancer Ther 2007;6(1):37–50]
Flat adenoma in colon: Two decades of debate

The existence of flat adenomas in the colon is well recognized. Whether they represent a distinct disease with a pathogenetic pathway different from that of the classical adenoma‐carcinoma sequence in colorectal tumorigenesis and have higher malignant potential remains a matter of debate. To review the epidemiology, clinical features, detection and management of flat and depressed (non‐polypoid) colonic neoplasm, we performed a thorough literature review on studies focusing on the prevalence, histological features, genetics, detection and treatment of flat and depressed (non‐polypoid) colonic neoplasm. A high percentage of severe dysplasia in flat colonic adenomas has not been consistently demonstrated. Their malignant potential appears to be size‐dependent. Flat adenomas are found to have a lower incidence of major genetic abnormalities involved in the classical adenoma‐carcinoma sequence and that has raised suspicions that they may have a different pathogenesis. The depressed type of colorectal carcinoma is uncommon but shows more aggressive behavior. More advanced colonoscopic techniques, such as chromoendoscopy, may enhance the detection of small and inconspicuous colonic neoplastic lesions that lack a protruding configuration. It is essential for endoscopists to appreciate the existence and clinical significance of flat and depressed colonic lesions as an important variant of colonic neoplasms so that the goal of reducing colorectal carcinoma incidence by polypectomy can be better achieved.
The ketone body metabolite β‐hydroxybutyrate induces an antidepression‐associated ramification of microglia via HDACs inhibition‐triggered Akt‐small RhoGTPase activation

Direct induction of macrophage ramification has been shown to promote an alternative (M2) polarization, suggesting that the ramified morphology may determine the function of immune cells. The ketone body metabolite β‐hydroxybutyrate (BHB) elevated in conditions including fasting and low‐carbohydrate ketogenic diet (KD) can reduce neuroinflammation. However, how exactly BHB impacts microglia remains unclear. We report that BHB as well as its producing stimuli fasting and KD induced obvious ramifications of murine microglia in basal and inflammatory conditions in a reversible manner, and these ramifications were accompanied with microglial profile toward M2 polarization and phagocytosis. The protein kinase B (Akt)‐small RhoGTPase axis was found to mediate the effect of BHB on microglial shape change, as (i) BHB activated the microglial small RhoGTPase (Rac1, Cdc42) and Akt; (ii) Akt and Rac1‐Cdc42 inhibition abolished the pro‐ramification effect of BHB; (iii) Akt inhibition prevented the activation of Rac1‐Cdc42 induced by BHB treatment. Incubation of microglia with other classical histone deacetylases (HDACs) inhibitors, but not G protein‐coupled receptor 109a (GPR109a) activators, also induced microglial ramification and Akt activation, suggesting that the BHB‐induced ramification of microglia may be triggered by HDACs inhibition. Functionally, Akt inhibition was found to abrogate the effects of BHB on microglial polarization and phagocytosis. In neuroinflammatory models induced by lipopolysaccharide (LPS) or chronic unpredictable stress (CUS), BHB prevented the microglial process retraction and depressive‐like behaviors, and these effects were abolished by Akt inhibition. Our findings for the first time showed that BHB exerts anti‐inflammatory actions via promotion of microglial ramification.
CA19-9 antigen levels can distinguish between benign and malignant pancreaticobiliary disease.

BACKGROUND CA19-9 is a carbohydrate tumor-associated antigen which is frequently upregulated in pancreatobiliary neoplasia. However, it may also be elevated in patients with jaundice in the absence of a tumor due to biliary obstruction, and in other non-hepato-pancreatico-biliary conditions. This study aimed to evaluate whether CA19-9 levels could accurately differentiate between benign and malignant pancreatobiliary disease. METHODS All patients referred to a single surgeon for investigation of pancreaticobiliary disease in 2003 in whom a firm diagnosis had been established were included. For malignant disease, a histological diagnosis was required but for benign disease a firm radiological diagnosis was deemed adequate. The patients were divided into 4 categories: pancreatic adenocarcinoma (PCa); cholangiocarcinoma (CCa); chronic pancreatitis (CP) and biliary calculous disease (Calc). Bilirubin and alkaline phosphatase levels corresponding to the point of assessment of CA19-9 were also noted. RESULTS Final diagnoses were made of pancreatic adenocarcinoma (PCa, n=73), cholangiocarcinoma (CCa, n=19), ampullary carcinoma (Amp, n=7), neuroendocrine carcinoma (Neu, n=4), duodenal carcinoma (Duo, n=3), chronic pancreatitis (CP, n=115), and biliary calculous disease (Calc, n=27). Median CA19-9 levels (U/ml) were: PCa, 653; CCa, 408; Duo, 403; Calc, 27; CP, 19; Neu, 10.5; Amp, 8 (reference range: 0-37). The CA19-9 levels were significantly greater for malignant than for benign disease, could differentiate PCa from CCa/Duo, and were significantly higher in unresectable than in resectable PCa. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for CA19-9 were 84.9%, 69.7%, 67.7% and 86.1%, respectively. A ROC analysis provided an area under the curve for CA19-9 of 0.871 (0.820-0.922), giving an optimal CA19-9 of 70.5 U/ml for differentiating benign from malignant pathology. Using this cut-off, the sensitivity was 82.1%, while specificity, PPV and NPV improved to 85.9%, 81.3% and 86.5%, respectively. When standard radiology was included (US/CT/MRCP) in the decision process, the results improved to 97.2%, 88.7%, 86.6%, and 97.7%. For benign disease, the CA19-9 correlated directly with the serum bilirubin, but for malignant disease, CA19-9 levels were elevated independent of the bilirubin level. CONCLUSIONS CA19-9 is useful in the differentiation of pancreatobiliary disease and when using an optimized cut-off and combining with routine radiology, the diagnostic yield is improved significantly, thus stressing the importance of a multi-disciplinary approach to pancreatobiliary disease.
Single minded 2-s (SIM2-s) gene is expressed in human GBM Cells and involved in GBM invasion

The human Single Minded 2 (SIM2) gene is mapped within the Down Syndrome Critical Region (DSCR) of chromosome 21 and its short splice variant SIM2-s is suggested to be a molecular target for cancer therapy. It has been shown that SIM2-s is expressed in colon, pancreatic and prostate tumors but not in their corresponding normal tissues. In present study, we found that SIM2-s was expressed in glioma tissues as well as in glioblastoma (GBM) cell lines but not in other brain tumors or normal cortex. The invasive potential of GBM cells was significantly decreased by RNA interference targeting SIM2-s, while the proliferation was not affected. Further investigation showed that the mRNA and protein levels of matrix metalloproteinase 2 (MMP-2) were down-regulated in cells treated with SIM2-s siRNA, concomitance with the up-regulation of tissue inhibitor of matrix metalloproteinase 2 (TIMP-2). Moreover, the enzymatic activity of MMP-2 was clearly decreased. Our results collectively suggested that SIM2-s expressed in gliomas selectively and played a role in GBM cells invasion, which may be partly associated with the expression of MMP-2 and TIMP-2.