Miracle-dz/UniFAR-FTUs huggingface dataset:
In vitro determination of optimal antifungal combinations against Cryptococcus neoformans and Candida albicans

There is currently no rapid, reliable, and reproducible in vitro technique to describe the growth-inhibitory interactions of antifungal drug combinations over a wide range of drug concentrations. We have developed a microdilution plate assay that was used to determine optimal drug combinations and concentrations of one-, two-, and three-drug regimens of amphotericin B (AmphB), fluconazole (FLU), and 5-fluorocytosine (5FC) for growth inhibition of three isolates each of Cryptococcus neoformans and Candida albicans. These growth inhibition data were then used in a multifactorial design technique to (i) generate contour and surface response plots to aid visual interpretation and (ii) develop mathematical equations describing the growth responses of the fungi to a wide range of antifungal concentrations and ratios. Our data indicated that (i) antifungal drug-drug interactions affecting yeast growth are complex functions of the drugs used in combination, their absolute concentrations, and also their relative (proportional) concentrations; (ii) AmphB-FLU combinations had additive effects against C. albicans over wide concentration ranges for each agent but were indifferent (i.e., were less than additive) in their inhibitory effect on C. neoformans; (iii) other two-drug combinations (FLU-5FC or AmphB-5FC) had indifferent effects on the growth of both fungi; and (iv) three-drug combinations (AmphB-FLU-5FC) showed an additive inhibitory effect on the growth of both C. albicans and C. neoformans. The finding that no antagonism was observed in combinations employing AmphB and FLU in this in vitro model is of critical importance since it argues against the current theoretical concept, based on the individual drug's mode of action, of antagonism between these two drugs. These microdilution techniques provide a method to determine rational regimens of antifungal agents in multidrug combinations for future testing to correlate in vitro activity with in vivo response. The use of this approach has made the evaluation of complex antifungal drug-drug interactions possible and provided important new information to the evolving field of antifungal drug combination.
The presence of melanocytes in the human larynx

During the study of serially sectioned cancerous and irradiated larynges, a unique case of extensive melanosis of the laryngeal mucosa was encountered. While pigmented neoplasms in the larynx had been reported repeatedly, to our knowledge the presence of melanocytes had not been demonstrated at that site; consequently, we initiated a study to ascertain whether melanocytes were present in the human larynx as an explanation for the histogenesis of these neoplasms.
Present but sick: a three‐wave study on job demands, presenteeism and burnout

Purpose – The opposite of absenteeism, presenteeism, is the phenomenon of employees staying at work when they should be off sick. Presenteeism is an important problem for organizations, because employees who turn up for work, when sick, cause a reduction in productivity levels. The central aim of the present study is to examine the longitudinal relationships between job demands, burnout (exhaustion and depersonalization), and presenteeism. We hypothesized that job demands and exhaustion (but not depersonalization) would lead to presenteeism, and that presenteeism would lead to both exhaustion and depersonalization over time.Design/methodology/approach – The hypotheses were tested in a sample of 258 staff nurses who filled out questionnaires at three measurement points with 1.5 years in‐between the waves.Findings – Results were generally in line with predictions. Job demands caused more presenteeism, while depersonalization was an outcome of presenteeism over time. Exhaustion and presenteeism were found to.
Evolving Modalities for Femoropopliteal Interventions

Despite technical advances in balloon design and technique, there has been little improvement of primary patency rates after balloon-based endovascular interventions for all but focal femoropopliteal lesions. Improving on stainless steel models, nitinol stents have been associated with favorable short- and midterm primary patency rates; studies with longer-term follow-up will be required to learn whether restenosis is ongoing, with continued loss of primary patency. Studies in recent years have shown varying incidences of mechanical fatigue leading to nitinol stent fracture. Covered stents are designed to prevent the tissue infiltration and intimal hyperplasia that can lead to bare metal in-stent restenosis. Several clinical studies, mainly single-center registries, have demonstrated a general effectiveness of the Hemobahn/Viabahn polytetrafluoroethylene-covered stent-grafts, approved for femoral arterial occlusive disease, and have helped to distinguish indications for use and to delineate possible failure modes. A multicenter randomized trial, which has completed enrollment, will compare the Viabahn with self-expanding bare nitinol stents. The primary use of drug-eluting stents (DES) has become routine clinical practice for coronary artery disease. The 2-phase multicenter randomized double-blind SIROCCO trials have been completed, with results published through 24 months. Follow-up demonstrated the feasibility and safety of deploying sirolimus-eluting stents in the femoropopliteal segment but failed to show superior efficacy for DES versus bare nitinol stents. However, the restenosis rates with bare metal stents were unexpectedly low. A paclitaxel-eluting stent without a polymer coating is currently being evaluated in the recently enrolled Zilver PTX randomized trial and international registry. A polymer-based everolimus-eluting stent is being evaluated for femoropopliteal use in the nonrandomized European STRIDES trial. Balloons coated with paclitaxel have recently been evaluated for simple femoropopliteal disease with encouraging results through 2 years of follow-up. The bioabsorbable stent concept emerged in response to the potential issues with metal stents, but to date no investigational device has successfully overcome issues such as relatively low radial force and variable degradation rates.
Circulating Tumor DNA is Effective for Detection of KRAS Mutation in Colorectal Cancer: A Meta-Analysis

Background Circulating tumor DNA (ctDNA) offers a novel and minimally invasive approach to the detection of the KRAS oncogene mutation in colorectal cancer. This study was conducted to compare the prognostic value of ctDNA with that of the current gold standard tumor tissue analysis. Methods A systematic literature review was conducted to identify relevant articles published from inception to December 27, 2016; the PubMed, Web of Science, Embase, Wanfang and China National Knowledge Infrastructure databases were searched. Pooled specificity, sensitivity, positive likelihood ratio, negative likelihood ratio and diagnostic odds ratio (DOR) estimates and areas under summary receiver operating characteristic (AUSROC) curves were calculated. We also performed subgroup and sensitivity analyses. Results Twenty-three studies with 1,715 colorectal cancer patients were included. The overall sensitivity and specificity were 0.75 (95% confidence interval [CI], 0.66-0.82) and 0.98 (CI, 0.95-0.99), respectively. The positive likelihood ratio was 31.8 (95% CI, 14.8-68.3), and the negative likelihood ratio was 0.26 (95% CI, 0.19-0.36). In addition, the AUSROC and DOR were 0.96 (95% CI, 0.93-0.97) and 123 (95% CI, 52-291), respectively. Substantial heterogeneity was observed across studies (I2 = 95%, 95% CI, 91-99). None of the subgroups investigated, including those defined by blood sample type, study region, TNM stage, detection site and detection method, could indicate the source of the observed heterogeneity. The results of the sensitivity analysis indicated that the results of our meta-analysis were stable. Conclusions Circulating tumor DNA may serve as a viable alternative to tissue analysis for the detection of KRAS mutations in colorectal cancer.
A multiparametric evaluation of regional brain damage in patients with primary progressive multiple sclerosis

The purpose of this study is to define the topographical distribution of gray matter (GM) and white matter (WM) damage in patients with primary progressive multiple sclerosis (PPMS), using a multiparametric MR‐based approach. Using a 3 Tesla scanner, dual‐echo, 3D fast‐field echo (FFE), and diffusion tensor (DT) MRI scans were acquired from 18 PPMS patients and 17 matched healthy volunteers. An optimized voxel‐based (VB) analysis was used to investigate the patterns of regional GM density changes and to quantify GM and WM diffusivity alterations of the entire brain. In PPMS patients, GM atrophy was found in the thalami and the right insula, while mean diffusivity (MD) changes involved several cortical‐subcortical structures in all cerebral lobes and the cerebellum. An overlap between decreased WM fractional anisotropy (FA) and increased WM MD was found in the corpus callosum, the cingulate gyrus, the left short temporal fibers, the right short frontal fibers, the optic radiations, and the middle cerebellar peduncles. Selective MD increase, not associated with FA decrease, was found in the internal capsules, the corticospinal tracts, the superior longitudinal fasciculi, the fronto‐occipital fasciculi, and the right cerebral peduncle. A discrepancy was found between regional WM diffusivity changes and focal lesions because several areas had DT MRI abnormalities but did not harbor T2‐visible lesions. Our study allowed to detect tissue damage in brain areas associated with motor and cognitive functions, which are known to be impaired in PPMS patients. Combining regional measures derived from different MR modalities may be a valuable tool to improve our understanding of PPMS pathophysiology. Hum Brain Mapp 2009. © 2009 Wiley‐Liss, Inc.
Globalization and Trust: Theory and Evidence from Cooperatives

We study the effect of globalization on the stock of trust in organizations. We present a simple model of endogenous trust and show that contrary to centralized hierarchies (pure limited liability firms), decentralized organizational structures (cooperatives) foster the emergence of trust. We treat organizations as directly observable ? summary statistics? for underlying trust and ask what will be the fate of trust as the world becomes increasingly globalized. Because the cooperative is an intrinsically less efficient organizational form and globalization implies harsher competitive pressures, conventional wisdom suggests that the viability of cooperatives is in jeopardy. We show that this is not necessarily true. If the increase in competition is bundled with an increase in uncertainty and risk, the cooperative may become a more efficient organizational form. We conclude that globalization does not necessarily erode trust. The case of Mondrag? n Corporaci? n Cooperativa is used to motivate assumptions and illustrate the results.
Immunochemical estimations of allergenic activities from outdoor aero‐allergens, collected by a high‐volume air sampler

To quantify airborne allergens in amorphus and morphological particles, a survey with collection of aero‐allergens on glass fibre filters by means of a high‐volume air‐sampler (HIVOL) was conducted. In preliminary laboratory experiments we compared various filter elution techniques, and the pulverizing elution technique was found to be optimal with regard to yield and convenience. When a surfactant, Tween 20 (0.5% v/v), was added to the elution buffer, a recovery of 80% could be obtained. Allergens in eluates were analysed by means of an IgG‐subclass RAST inhibition assay. This immunochemical method for quantification of airborne allergens was validated, as a high recovery of timothy grass pollen allergens was eluted from air filters, and eluates were shown specific by RAST inhibition. The amount of Immunochemically measured airborne timothy and birch allergens collected by means of the HIVOL sampler was highly correlated with pollen counts obtained with a Burkard sampler (pollen trap) situated in the same place.
Biochemical characterization of a beta-lactamase that hydrolyzes penems and carbapenems from two Serratia marcescens isolates

Reexamination of Serratia marcescens isolates obtained in 1982 revealed two organisms that were resistant to the penem FCE 22101 (MIC, 512 micrograms/ml) and imipenem (MIC, 16 micrograms/ml) and that had slightly reduced susceptibilities to meropenem (MIC, 0.12 micrograms/ml). MICs of these agents for typical S. marcescens isolates were 1 to 8, 0.25 to 0.5, and 0.03 micrograms/ml, respectively. The two isolates were fully susceptible to broad-spectrum cephalosporins, and only one was highly resistant to ampicillin and carbenicillin (MICs, greater than 1,024 micrograms/ml). Both isolates had beta-lactamases that focused at pIs 8.2 and 9.7. The penicillin-resistant isolate additionally produced the TEM-1 enzyme. The enzymes with pIs of 8.2 and 9.7 were separated by cation-exchange chromatography. The pI 8.2 beta-lactamase was a class I enzyme of the type found in most S. marcescens isolates. It was almost inactive against carbapenems and penems, as was the class I enzyme from another S. marcescens strain. The pI 9.7 enzyme hydrolyzed penems and carbapenems rapidly: kcat (turnover number) values for FCE 22101, imipenem, and meropenem were 3.4, 26, and 1% of the kcat value for cephaloridine, respectively; kcat/Km values were 140, 915, and 150% of the kcat/Km value for cephaloridine, respectively. Otherwise, the pI 9.7 enzyme had predominantly penicillinase activity. It was inhibited more readily by clavulanate than by tazobactam and was inactivated by the chelating agents EDTA and ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid. Expression of the pI 9.7 enzyme was not associated with any plasmid, and production was not transferred to Escherichia coli K-12 recipients, even after the mobilizing plasmid pUZ8 was inserted into the S. marcecens donor strains.
The relationship between cesarean section and labor induction.

BACKGROUND Numerous study results vary when analyzing the relationship between labor induction and the likelihood of cesarean delivery; and few have accounted for the multiple influences of maternal sociodemographic characteristics combined with the provider and hospital in subsequent birth outcomes such as cesarean section. OBJECTIVE This study evaluated the likelihood of cesarean birth following labor induction while accounting for maternal, hospital, and provider characteristics. METHODS A cross-sectional retrospective descriptive design using secondary data was employed to determine what variation in cesarean births was due to differences of hospitals, providers, and patients using the Quality Health Outcomes Model (QHOM). Data were partitioned by primiparous and multiparous women. The individual demographic, system, and provider outcomes in all hospitals and single birth center for Maricopa County in 2005 (N=62,816) were analyzed, using both random effects and fixed effects models. RESULTS For primiparous women, an increased likelihood of cesarean births was associated with medical inductions, maternal age, being Black, and the number of prenatal visits; and less likely in teaching hospitals and women with higher educational attainment. In multiparous women, cesarean births were associated with increased maternal age and medical inductions; and less likely in for-profit hospitals and following elective induction. DISCUSSION Labor inductions were associated with an increased likelihood of cesarean sections based on parity, age, race, number of prenatal visits, education, and hospital teaching status and ownership. Because the QHOM emphasizes multiple contextual variables that influence the delivery and outcomes of care, it can prove ideal for the study of birth outcomes following interventions such as the induction of labor. CLINICAL RELEVANCE Nurses should be well educated about the risks of elective labor induction prior to term gestation and "elective" cesarean birth.
Effect of gamma interferon on hydrogen peroxide production by cultured mouse peritoneal macrophages

Macrophage activation is thought to be mediated via a number of T-lymphocyte products, including gamma interferon (IFN-gamma). However, our studies indicate that IFN-gamma acts as a regulator molecule rather than solely as an activator. This depends upon the status of the macrophage. IFN-gamma treatment of resting macrophages and those activated or elicited by sodium caseinate, lipopolysaccharide, or Mycobacterium bovis BCG did not result in activation, as measured by hydrogen peroxide production; however, when thioglycolate was used as an eliciting agent, incubation with IFN-gamma resulted in a dramatic increase in hydrogen peroxide production compared with that by untreated controls.
The neurobiology and pharmacology of depression. A comparative overview of serotonin selective antidepressants.

BACKGROUND Over the past decade, targeted drug design has led to significant advances in the pharmacological management of depression. A serendipitous approach to drug discovery has therefore been replaced by the development of drugs acting on predetermined neurobiological targets recognised to be involved in the pathology of depressive illness. The first of these 'designer drugs', were the selective serotonin (5-HT) re-uptake inhibitors (SSRIs), followed more recently by venlafaxine and nefazodone which, in addition to 5-HT uptake, also target noradrenaline (NA) uptake and 5-HT2 receptors, respectively. METHODS This paper reviews the biochemistry and pharmacology of depression. From this foundation, the relevance of 5-HT selectivity is discussed followed by a comparison of the clinical pharmacology and pharmacokinetics of 5-HT-selective antidepressants. RESULTS Despite their common action on synaptic 5-HT uptake, structural heterogeneity among the group allows differences to be observed in kinetic and pharmacological parameters, viz. plasma half-life (T1/2), liver metabolism, protein binding, receptor affinities and selectivity ratios. This not only leeds to different attributes which assist in the successful management of a particular patient, but will also predict subtle difference in drug interaction risks and in side-effect profiles of clinical relevance. CONCLUSION 5-HT-selective antidepressants may be more dissimilar than similar, and these differences can allow the clinician to identify clinically reliable determinates predicting side-effects and, possibly, to identify suitable patients for a particular drug.
The impact of destination personality dimensions on destination brand awareness and attractiveness: Australia as a case study

Destination personality refers to human personality traits associated with a destination. It has become an important construct, as tourism managers attempt to understand people's choices to fi nd ways to diff erentiate their destination in an increasingly complex marketplace. Th e present paper outlines a study in which a destination personality scale was used that provides insight into diff erent destinations' personality dimensions and the distinct infl uence of a destination's perception from the perspective of Chinese tourists. More precisely, the results of this study conducted in mainland China revealed that for the destination personality dimensions of Australia, the results suggest that sincerity, one destination personality dimension, has a more positive impact on perceived destination awareness and attractiveness from the perspective of Chinese tourists than the other three dimensions (excitement, sophistication, and ruggedness) do. Implications and future study directions conclude the study report.
Identification of stathmin 1 expression induced by Epstein–Barr virus in human B lymphocytes

Abstract. Introduction: The Epstein–Barr virus transforms resting B cells into proliferating lymphoblastoid cells, the origin of cell lines. Method and results: Our cDNA microarray analyses led to the identification of 232 up‐regulated and 112 down‐regulated genes with more than a 3‐fold difference in lymphoblastoid cell lines compared to resting B cells. The functional classification of these genes exhibited the distinct expression signature for cell proliferation, cell cycle and an immune response. Among them, we verified the differential expression of several oncogenes such as stathmin 1 (STMN1), RAB27A, RAB9A, BACH1 and BACH2 using quantitative real‐time reverse transcriptase‐polymerase chain reactions or Western blot analysis. Expression of STMN1 (which is involved in regulation of the microtubule filament system, cell growth and S‐phase of cell cycle) was increased in lymphoblastoid cell line as well as in 7‐day post‐Epstein–Barr virus infection B cells, compared to resting B cells. Conclusion: Thus, this study suggests that Epstein–Barr virus infection induces STMN1 expression, which play a role in cell cycle progression and proliferation in the human B lymphocyte.
Activation of p53/p21/PUMA alliance and disruption of PI‐3/Akt in multimodal targeting of apoptotic signaling cascades in cervical cancer cells by a pentacyclic triterpenediol from Boswellia serrata

Cervical carcinoma is a growing menace to women health worldwide. This study reports the apoptotic cell death in human cervical cancer HeLa and SiHa cells by a pentacyclic triterpenediol (TPD) from Boswellia serrata by a mechanism different from reported in HL‐60 cells. It caused oxidative stress by early generation of nitric oxide and reactive oxygen species that robustly up regulated time‐dependent expression of p53/p21/PUMA while conversely abrogating phosphatidylinositol‐3‐kinase (PI3K)/Akt pathways in parallel. TPD also decreased the expression of PI3K/pAkt, ERK1/2, NF‐κB/Akt signaling cascades which coordinately contribute to cancer cell survival through these distinct pathways. The tumor suppressor p53 pathway predominantly activated by TPD further up‐regulated PUMA, which concomitantly decreased the Bcl‐2 level, caused mitochondrial membrane potential loss with attendant translocation of Bax and drp1 to mitochondria and release of pro‐apoptotic factors such as cytochrome c and Smac/Diablo to cytosol leading to caspases‐3 and ‐9 activation. In addition both the phospho‐p53 and p21 were found to accumulate heavily in the nuclear fraction with attendant decrease in topoisomarase II and survivin levels. On the contrary, TPD did not affect the extrinsic signaling transduction pathway effectively through apical death receptors. Interestingly, N‐acetyl cysteine, ascorbate and s‐methylisothiourea (sMIT) rescued cells significantly from TPD induced DNA damage and caspases activation. TPD may thus find usefulness in managing and treating cervical cancer. © 2009 Wiley‐Liss, Inc.
Social skills for teenagers with developmental and autism spectrum disorders: The PEERS treatment manual

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