bluuebunny/crossref_metadata_2025_split huggingface dataset:
Activity of Sanguinarine against Candida albicans Biofilms
Authors: Zhong Hua , Hu Dan-Dan , Hu Gan-Hai , Su Juan , Bi Shuang , Zhang Zhuo-Er , Wang Zheng , Zhang Ri-Li , Xu Zheng , Jiang Yuan-Ying , Wang Yan 
Published: February 2017

ABSTRACT

Candida albicans
biofilms show resistance to many clinical antifungal agents and play a considerable contributing role in the process of
C. albicans
infections. New antifungal agents against
C. albicans
biofilms are sorely needed. The aim of this study was to evaluate sanguinarine (SAN) for its activity against
Candida albicans
biofilms and explore the underlying mechanism. The MIC
50
of SAN was 3.2 μg/ml, while ≥0.8 μg/ml of SAN could suppress
C. albicans
biofilms. Further study revealed that ≥0.8 μg/ml of SAN could decrease cellular surface hydrophobicity (CSH) and inhibited hypha formation. Real-time reverse transcription-PCR (RT-PCR) results indicated that the exposure of
C. albicans
to SAN suppressed the expression of some adhesion- and hypha-specific/essential genes related to the cyclic AMP (cAMP) pathway, including
ALS3
,
HWP1
,
ECE1
,
HGC1
, and
CYR1
. Consistently, the endogenous cAMP level of
C. albicans
was downregulated after SAN treatment, and the addition of cAMP rescued the SAN-induced filamentation defect. In addition, SAN showed relatively low toxicity to human umbilical vein endothelial cells, the 50% inhibitory concentration (IC
50
) being 7.8 μg/ml. Collectively, the results show that SAN exhibits strong activity against
C. albicans
biofilms, and the activity was associated with its inhibitory effect on adhesion and hypha formation due to cAMP pathway suppression.
A Phase I, Randomized, Double-Blinded, Placebo- and Moxifloxacin-Controlled, Four-Period Crossover Study To Evaluate the Effect of Gepotidacin on Cardiac Conduction as Assessed by 12-Lead Electrocardiogram in Healthy Volunteers
Authors: Hossain Mohammad , Zhou Meijian , Tiffany Courtney , Dumont Etienne , Darpo Borje 
Published: February 2017

ABSTRACT
Gepotidacin is a novel, first-in-class triazaacenaphthylene antibiotic in development for treatment of conventional and biothreat infections. This was a single-dose, crossover thorough QT study in healthy subjects who were administered intravenous (i.v.) gepotidacin as a therapeutic (1,000-mg) dose and supratherapeutic (1,800-mg) dose, placebo, and 400 mg oral moxifloxacin in 4 separate treatment periods. Gepotidacin caused a mild effect on heart rate, with a largest placebo-corrected change-from-baseline heart rate of 7 and 10 beats per minute at the end of the 1,000-mg and 1,800-mg infusion, respectively. Gepotidacin caused an increase of change-from-baseline QTcF (ΔQTcF), with a peak effect at the end of infusion. The largest mean placebo-corrected ΔQTcF (ΔΔQTcF) was 12.1 ms (90% confidence interval [CI], 9.5 to 14.8) and 22.2 ms (90% CI, 19.6 to 24.9) after 1,000 mg and 1,800 mg, respectively. ΔΔQTcF rapidly fell after the end of the infusion, with a mean ΔΔQTcF of 6.1 ms 60 min after the 1,800-mg dose. Exposure-response analysis demonstrated a statistically significant positive relationship between gepotidacin plasma levels and ΔΔQTcF, with a slope of 1.45 ms per μg/ml (90% CI, 1.30 to 1.61). Using this model, the effect on ΔΔQTcF can be predicted to be 11 and 20 ms at the observed mean peak plasma concentration after the infusion of gepotidacin at 1,000 mg (7 μg/ml) and 1,800 mg (13 μg/ml), respectively. In conclusion, gepotidacin caused QT prolongation in this thorough QT study, and a mean effect can be predicted to less than 15 ms at the highest expected plasma concentration, 9 μg/ml. (This study has been registered at ClinicalTrials.gov under identifier NCT02257398.)
Complete Genome Sequence of Bacillus subtilis Strain 29R7-12, a Piezophilic Bacterium Isolated from Coal-Bearing Sediment 2.4 Kilometers below the Seafloor
Authors: Wei Yuli , Cao Junwei , Fang Jiasong , Kato Chiaki , Cui Weicheng 
Published: February 2017

ABSTRACT

Here, we report the genome sequence of
Bacillus subtilis
strain 29R7-12, a piezophilic bacterium isolated from coal-bearing sediment down to ~2.4 km below the ocean floor in the northwestern Pacific. The strain is a Gram-positive spore-forming bacterium, closely related to
Bacillus subtilis
within the phylum
Firmicutes
. This is the first complete genome sequence of a
Bacillus subtilis
strain from the deep biosphere. The genome sequence will provide a valuable resource for comparative studies of microorganisms from the surface and subsurface environments.
Draft Genome Sequences of Dermacoccus nishinomiyaensis Strains UCD-KPL2534 and UCD-KPL2528 Isolated from an Indoor Track Facility
Authors: Klein Brian A. , Lemon Katherine P. , Gajare Prasad , Jospin Guillaume , Eisen Jonathan A. , Coil David A. 
Published: February 2017

ABSTRACT

We present here the draft genome sequences of
Dermacoccus nishinomiyaensis
strains UCD-KPL2534 and UCD-KPL2528, which were isolated at an indoor track facility in Medford, MA, USA (42.409716, -71.115169) from an exit door handle and settle dust, respectively. The genome assemblies contain 3,088,111 bp in 58 contigs and 3,162,381 bp in 100 contigs, respectively.
Complete Genome Sequence of a Bovine Viral Diarrhea Virus Subgenotype 1h Strain Isolated in Italy
Authors: Bazzucchi Moira , Bertolotti Luigi , Giammarioli Monica , Casciari Cristina , Rossi Elisabetta , Rosati Sergio , De Mia Gian Mario 
Published: February 2017

ABSTRACT
We sequenced the complete genome of bovine viral diarrhea virus (BVDV) strain UM/126/07. It belongs to subgenotype 1h. The complete genome is composed of 12,196 nucleotides organized as one open reading frame encoding 3,898 amino acids. This is the first report of a full-length sequence of BVDV-1h.
Alectorius: a parasympathomimetic stone?
Authors: Carrasco Joaquin , Duffin Christopher J. 
Published: February 2017

Abstract
Lapidaries, or books on stones, formed a historical literary genre which compiled information on the nature and properties of various stones together with their therapeutic applications. One of the mythical stones described in these lapidaries is the Cock Stone or Alectorius. For the most part, authors agree upon both its origins inside the body and its therapeutic uses, although opinion differs as to the exact organ from which it was obtained. It may represent a biliary calculus. The healing properties cited for the Cock Stone are, at first sight, unrelated. However, when viewed in the light of modern physiological understanding, the pharmacological properties ascribed to Alectorius may be related to the effects of parasympathomimetic substances.
Dysregulated GPCR Signaling and Therapeutic Options in Uveal Melanoma
Authors: Chua Vivian , Lapadula Dominic , Randolph Clinita , Benovic Jeffrey L. , Wedegaertner Philip B. , Aplin Andrew E. 
Published: February 2017

Abstract
Uveal melanoma is the most common primary intraocular malignant tumor in adults and arises from the transformation of melanocytes in the uveal tract. Even after treatment of the primary tumor, up to 50% of patients succumb to metastatic disease. The liver is the predominant organ of metastasis. There is an important need to provide effective treatment options for advanced stage uveal melanoma. To provide the preclinical basis for new treatments, it is important to understand the molecular underpinnings of the disease. Recent genomic studies have shown that mutations within components of G protein–coupled receptor (GPCR) signaling are early events associated with approximately 98% of uveal melanomas.
Implications: This review discusses the alterations in GPCR signaling components (GNAQ and GNA11), dysregulated GPCR signaling cascades, and viable targeted therapies with the intent to provide insight into new therapeutic strategies in uveal melanoma. Mol Cancer Res; 15(5); 501–6. ©2017 AACR.
Apixaban Versus Warfarin for Mechanical Heart Valve Thromboprophylaxis in a Swine Aortic Heterotopic Valve Model
Authors: Lester Patrick A. , Coleman Dawn M. , Diaz Jose A. , Jackson Tatum O. , Hawley Angela E. , Mathues Angela R. , Grant Brandon T. , Knabb Robert M. , Ramacciotti Eduardo , Frost Charles E. , Song Yan , Wakefield Thomas W. , Myers Daniel D. 
Published: February 2017

Objective—
Warfarin is the current standard for oral anticoagulation therapy in patients with mechanical heart valves, yet optimal therapy to maximize anticoagulation and minimize bleeding complications requires routine coagulation monitoring, possible dietary restrictions, and drug interaction monitoring. As alternatives to warfarin, oral direct acting factor Xa inhibitors are currently approved for the prophylaxis and treatment of venous thromboembolism and reduction of stroke and systemic embolization. However, no in vivo preclinical or clinical studies have been performed directly comparing oral factor Xa inhibitors such as apixaban to warfarin, the current standard of therapy.

Approach and Results—

A well-documented heterotopic aortic valve porcine model was used to test the hypothesis that apixaban has comparable efficacy to warfarin for thromboprophylaxis of mechanical heart valves. Sixteen swine were implanted with a bileaflet mechanical aortic valve that bypassed the ligated descending thoracic aorta. Animals were randomized to 4 groups: control (no anticoagulation; n=4), apixaban oral 1 mg/kg twice a day (n=5), warfarin oral 0.04 to 0.08 mg/kg daily (international normalized ratio 2–3; n=3), and apixaban infusion (n=4). Postmortem valve thrombus was measured 30 days post-surgery for control-oral groups and 14 days post-surgery for the apixaban infusion group. Control thrombus weight (mean) was significantly different (1422.9 mg) compared with apixaban oral (357.5 mg), warfarin (247.1 mg), and apixiban 14-day infusion (61.1 mg;
P
<0.05).

Conclusions—
Apixaban is a promising candidate and may be a useful alternative to warfarin for thromboprophylaxis of mechanical heart valves. Unlike warfarin, no adverse bleeding events were observed in any apixaban groups.
“Seeing the World with Fresh Eyes”
Authors: Seamon David 
Published: February 2017

In this article, I draw on Gurdjieff’s philosophy to initiate a phenomenology of aesthetic experience, which I define as any intense emotional engagement that one feels in encountering or creating an artistic work, whether a painting, poem, song, dance, sculpture, or something else. To consider how aesthetic experience might be understood in a Gurdjieffian framework, I begin with an overview of phenomenology, emphasizing the phenomenological concepts of lifeworld and natural attitude, about which Gurdjieff said much, though not using phenomenological language. I then discuss Gurdjieff’s “psychology of human beings” as it might be interpreted phenomenologically, emphasizing three major claims: first, that, human beings are “asleep”; second, that they are “machines”; and, third, that they are “three-centered beings.” I draw on the last claim—human “three-centeredness”—to highlight how aesthetic experiences might be interpreted via Gurdjieff’s philosophy. Drawing on accounts from British philosopher and Gurdjieff associate J. G. Bennett, I end by considering how a Gurdjieffian perspective understands the role of the artistic work in contributing to aesthetic experience.
Tropospheric Waveguide Teleconnections and Their Seasonality
Authors: Branstator Grant , Teng Haiyan 
Published: February 2017

Abstract
One-point correlation maps of the subseasonal variability of 200-hPa meridional wind in nature and an atmospheric general circulation model are systematically analyzed to quantify the impact of the climatological-mean jets on tropospheric covariability as a result of the jets acting as waveguides for the propagation of Rossby waves. As anticipated by linear theory, signatures of jet influence are detected in terms of (i) the geographical position of the strongest teleconnections, (ii) the zonal orientation and extent of prominent patterns of variability, and (iii) the scale of the features that make up those patterns. Further evidence of jet waveguide influence comes from examining the seasonality of these teleconnection attributes. During winter, covariability can be essentially circumglobal, while during summer it tends to be confined within two separate sectors of the globe where the jets are especially strong. Experiments with a multilevel linear planetary wave model confirm that the analyzed characteristics of teleconnections in the waveguides can be attributed to the action of the mean state; no organization to the anomalous forcing of the atmosphere is required to produce these properties. Some attributes, however, depend on the presence of zonal variations in the climatological-mean state that are of similar scale to the teleconnection patterns themselves.
Factors Associated With the Use of Postoperative Analgesics in Patients Undergoing Direct Microlaryngoscopy
Authors: Taliercio Salvatore , Sanders Brian , Achlatis Stratos , Fang Yixin , Branski Ryan , Amin Milan 
Published: February 2017

Objective: Morbidity associated with suspension laryngoscopy has been well documented. However, standard of care with regard to postoperative analgesia has not been described, and anecdotal evidence suggests wide variability with regard to postoperative narcotic and non-narcotic recommendations. We sought to quantify the postoperative course following suspension microlaryngoscopy by relating patient-based and intraoperative measures with analgesic use. Methods: Body mass index (BMI), Friedman tongue position (FTP), and Mallampati scores as well as laryngoscope type, number of attempts required for optimal visualization, and suspension time were documented in 50 consecutive patients undergoing routine suspension microlaryngoscopy. Postoperative symptoms and analgesic use was queried on postoperative days 1, 3, and 10. Results: In this cohort, 62.5% employed postoperative analgesia. However, only 20% required narcotics. No difference in suspension time was identified in those taking analgesics (33.0 vs 37.3 minutes, P = .44). In addition, no relationship between procedure type and the need for analgesia was noted. The majority of patients (76%) described sore throat persisting for 3 postoperative days; 36% reported sore throat persisting beyond postoperative day 3. Conclusions: The majority of patients undergoing microlaryngoscopy reported discomfort, but symptoms were largely ameliorated with over-the-counter analgesics. Routine prescription of narcotics following routine suspension laryngoscopy may be unnecessary.
Association of blood pressure in the supine position with target organ damage in subjects over 60 years old
Authors: Wang Feng , Zhao Hualing , Yang Chao , Kong Guilan , Song Lu , Li Chunhui , Wang Yiming , Chen Shuohua , Wang Jing , Wu Shouling 
Published: February 2017

Objective Toexplore the correlation between blood pressure in the supine position and target organ damage in subjects over 60 years of age. Methods In 2444 individuals, we investigated the association of systolic blood pressure (SBP) in the supine position with the target organ damage indices microalbuminuria (ALBU), brachial–ankle pulse wave velocity (baPWV), and carotid intima–media thickness (IMT). Supine hypertension (SH) is defined as systolic blood pressure ≥ 140 mmHg and/or diastolic blood pressure ≥ 90 mmHg. Subjects were assigned to either the SH group (1275 cases) or the non-SH group (1169 cases). Results The levels of ALBU, baPWV, and IMT, as well as the percentage of participants with ALBU > 30 mg/L, baPWV ≥ 1400 cm/s, and IMT ≥ 1 mm, were significantly higher in the SH group than in the non-SH group. Multivariate logistic regression analysis showed that SH was an independent risk factor for baPWV and IMT, but the relationship with ALBU was not statistically significant after correction for confounding factors. Conclusions SH is a risk factor for target organ damage, as expressed by the indices baPWV and IMT. The association of SH with kidney damage requires further study.
Can Managed Care Really Improve Doctor–Patient Relationship?
Authors: Kit Paul Chan Hong , Rasid Siti Zaleha Abdul , Ismail Wan Khairuzzaman Wan , Mokhber Mozhdeh 
Published: February 2017

Background Managed care has created conflicts in the practice of medicine. Physicians now not only treat patients but are also expected to treat them at the least cost possible; hence, complications may arise. The objective of this study is to examine how managed care has affected the doctor–patient relationship. Methodology For the purpose of this research, 220 doctors/physicians in Malaysia participated in this cross-sectional survey. Results The results show that primary care physicians’ perception on the impact of managed care on doctor–patient relationships is predominantly negative in patients’ expectation, continuity of care, patients’ involvement and obligations on patients’ care. Conclusions and Recommendations Based on the findings of this research, there is an urgent need for managed care companies to work closely with insurance firms as well as the health care providers in the provision of health care services.
Overexpression of p53 protein in a high-risk population of patients with superficial bladder cancer before and after bacillus Calmette-Guérin therapy: correlation to clinical outcome.
Authors: Lacombe L , Dalbagni G , Zhang Z F , Cordon-Cardo C , Fair W R , Herr H W , Reuter V E 
Published: February 2017

PURPOSE We have previously demonstrated that p53 overexpression is predictive of disease progression and survival in Ta, Tis, and T1 tumors. Instillation of Bacillus Calmette-Guérin (BCG) is now accepted to be the most efficient adjuvant therapy for superficial bladder carcinoma. The aim of this study was to determine if p53 status, assessed before and after intravesical BCG therapy, can predict clinical outcome in a high-risk population of patients with superficial bladder carcinoma. MATERIALS AND METHODS We examined 196 tissue specimens from 98 patients, obtained immediately before and after intravesical BCG therapy. The pretherapy population was composed of 22 Ta, 57 Tis, and 19 T1 tumors. After BCG, 66 specimens were TO and 32 had residual tumors. Nuclear p53 overexpression was analyzed in relation to time to disease progression and disease-specific survival. RESULTS The median follow-up duration was 44 months. The detection of nuclear p53 overexpression before BCG therapy did not predict response to BCG therapy. Pre-BCG p53 protein overexpression, response to BCG therapy, and pre-BCG stage were all independent markers of disease progression. In patients with residual disease after BCG therapy (nonresponders), multivariate analysis confirmed that posttherapy p53 overexpression was the only independent marker of disease progression. CONCLUSION In this high-risk population of patients with superficial bladder tumors, patients who have p53 nuclear overexpression in the tumor and stage T1 disease before BCG therapy are at high risk of disease progression. Furthermore, in the group of patients with residual disease after BCG therapy, p53 status is a better predictor of disease progression than post-BCG stage.
Efficacy and tolerance of vinorelbine and fluorouracil combination as first-line chemotherapy of advanced breast cancer: results of a phase II study using a sequential group method.
Authors: Dieras V , Extra J M , Bellissant E , Espie M , Morvan F , Pierga J Y , Mignot L , Tresca P , Marty M 
Published: February 2017

PURPOSE To assess the antitumor efficacy and safety profile of the combination of Fluorouracil (5FU) and vinorelbine given as first-line therapy to patients with advanced breast cancer. PATIENTS AND METHODS As defined in the seven consecutive steps of a phase II group sequential design, 63 patients received 5FU 750 mg/m2/d for 5 consecutive days as a continuous infusion and vinorelbine 30 mg/ m2 on days 1 and 5 as a short intravenous (I/V) infusion every 3 weeks. RESULTS Forty-one of 63 patients achieved an objective response, which allowed us to discontinue the study and reject a response rate less than 50% with a statistical power of 90%. The unbiased estimate of the response rate was 61.6%. Response rate did not differ significantly according to the following: (1) type of prior adjuvant therapy (none, n = 23; without anthracycline, n = 6; with anthracyline, n = 34); (2) site of metastatic disease; and (3) number of metastatic sites. The median time to progression was 8.4 months. The median response duration was 12.3 months, and the median duration of complete response (CR), from the first assessment of CR, was 7.3 months. The median overall survival time was 23 months (28.1 months for patients with a CR). The main toxicities (grades 3 and 4) were neutropenia (90% of patients), infection (12.7%), mucositis (37%), and constipation (9.5%). Nevertheless, treatment could be given on an outpatient basis to the majority of patients, and the median relative dose-intensity was 86%. CONCLUSION This phase II study, which used a group-sequential design, shows that the combination of 5FU and vinorelbine is an active and tolerable regimen for the treatment of first metastatic progression of breast cancer. It provides an alternative regimen for patients who have previously received anthracycline-based adjuvant chemotherapy or in whom anthracyclines cannot be used.
Prognostic significance of abnormal p53 accumulation in primary, resected non-small-cell lung cancers.
Authors: Nishio M , Koshikawa T , Kuroishi T , Suyama M , Uchida K , Takagi Y , Washimi O , Sugiura T , Ariyoshi Y , Takahashi T , Ueda R , Takahashi T 
Published: February 2017

PURPOSE This study was conducted to evaluate the prognostic significance of p53 abnormalities in primary, resected non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS Methodologic validation of immunohistologic detection of p53 abnormalities in routine pathology sections was assessed using 31 lung cancer specimens for which p53 gene status was known from our previous molecular biologic studies. Applying the optimized cutoff value, we evaluated the prognostic significance of p53 abnormalities in an independent cohort of 208 NSCLC patients with complete follow-up data, whose resections were consecutively performed between January 1984 and December 1988. RESULTS Immunohistologic detection of p53 abnormalities appeared to be reliable and showed approximately 90% concordance with the p53 gene status. Using the selected cutoff value of 10%, 46% of 208 NSCLCs showed p53 abnormalities. There was no relationship between p53 abnormalities and clinical outcome in the entire cohort, which represented all histologic subtypes of NSCLC (P = .58). Based on the reasoning that the influence of p53 abnormalities may have been obscured by distinct biologic roles depending on histologic subtypes, we also separately analyzed subsets of patients with adenocarcinomas (n = 100) and with squamous cell carcinomas (n = 88) and found that it may be a useful prognosticator only in adenocarcinoma patients (P = .04). CONCLUSION p53 abnormalities are not a significant prognostic factor in primary, resected NSCLC when all histologic subtypes are combined, but may be a useful prognosticator for adenocarcinomas. Additional studies are warranted for further evaluation, specifically of adenocarcinomas.