bluuebunny/crossref_metadata_2025_split huggingface dataset:
Moguntinones—New Selective Inhibitors for the Treatment of Human Colorectal Cancer
Authors: Maderer Annett , Plutizki Stanislav , Kramb Jan-Peter , Göpfert Katrin , Linnig Monika , Khillimberger Katrin , Ganser Christopher , Lauermann Eva , Dannhardt Gerd , Galle Peter R. , Moehler Markus 
Published: April 2014

Abstract3-Indolyl and 3-azaindolyl-4-aryl maleimide derivatives, called moguntinones (MOG), have been selected for their ability to inhibit protein kinases associated with angiogenesis and induce apoptosis. Here, we characterize their mode of action and their potential clinical value in human colorectal cancer in vitro and in vivo. MOG-19 and MOG-13 were characterized in vitro using kinase, viability, and apoptosis assays in different human colon cancer (HT-29, HCT-116, Caco-2, and SW480) and normal colon cell lines (CCD-18Co, FHC, and HCoEpiC) alone or in combination with topoisomerase I inhibitors. Intracellular signaling pathways were analyzed by Western blotting. To determine their potential to inhibit tumor growth in vivo, the human HT-29 tumor xenograft model was used. Moguntinones prominently inhibit several protein kinases associated with tumor growth and metastasis. Specific signaling pathways such as GSK3β and mTOR downstream targets were inhibited with IC50 values in the nanomolar range. GSK3β signaling inhibition was independent of KRAS, BRAF, and PI3KCA mutation status. While moguntinones alone induced apoptosis only in concentrations &gt;10 μmol/L, MOG-19 in combination with topoisomerase I inhibitors induced apoptosis synergistically at lower concentrations. Consistent with in vitro data, MOG-19 significantly reduced tumor volume and weight in combination with a topoisomerase I inhibitor in vivo. Our in vitro and in vivo data present significant proapoptotic, antiangiogenic, and antiproliferative effects of MOG-19 in different human colon cancer cells. Combination with clinically relevant topoisomerase I inhibitors in vitro and xenograft mouse model demonstrate a high potency of moguntinones to complement and improve standard chemotherapy options in human colorectal cancer. Mol Cancer Ther; 13(6); 1399–409. ©2014 AACR.
Clinical Profile and Prognostic Value of Anemia at the Time of Admission and Discharge Among Patients Hospitalized for Heart Failure With Reduced Ejection Fraction
Authors: Mentz Robert J. , Greene Stephen J. , Ambrosy Andrew P. , Vaduganathan Muthiah , Subacius Haris P. , Swedberg Karl , Maggioni Aldo P. , Nodari Savina , Ponikowski Piotr , Anker Stefan D. , Butler Javed , Gheorghiade Mihai 
Published: April 2014

Background—
Anemia has been associated with worse outcomes in patients with chronic heart failure (HF). We aimed to characterize the clinical profile and postdischarge outcomes of hospitalized HF patients with anemia at admission or discharge.

Methods and Results—

An analysis was performed on 3731 (90%) of 4133 hospitalized HF patients with ejection fraction ≤40% enrolled in the Efficacy of Vasopressin Antagonist in Heart Failure Outcome Study with Tolvaptan (EVEREST) trial with baseline hemoglobin data, comparing the clinical characteristics and outcomes (all-cause mortality and cardiovascular mortality or HF hospitalization) of patients with and without anemia (hemoglobin <12 g/dL for women and <13 g/dL for men) on admission or discharge/day 7. Overall, 1277 patients (34%) were anemic at baseline, which persisted through discharge in 73% and resolved in 27%; 6% of patients without baseline anemia developed anemia by discharge or day 7. Patients with anemia were older, with lower blood pressure, and higher creatinine and natriuretic peptide levels compared with those without anemia (all
P
<0.05). After risk adjustment, anemia at discharge, but not admission, was independently associated with increased all-cause mortality (hazard ratio, 1.30; 95% confidence interval, 1.05–1.60;
P
=0.015; and hazard ratio, 0.94; 95% confidence interval, 0.76–1.15;
P
=0.53, respectively) and cardiovascular mortality plus HF hospitalization early postdischarge (≤100 days; hazard ratio 1.73; 95% confidence interval, 1.37–2.18;
P
<0.001; and hazard ratio, 0.92; 95% confidence interval, 0.73–1.16;
P
=0.47, respectively). Neither baseline nor discharge anemia was associated with long-term cardiovascular mortality plus HF hospitalization (>100 days) on adjusted analysis (both
P
>0.1).

Conclusions—
Among hospitalized HF patients with reduced ejection fraction, modest anemia at discharge but not baseline was associated with increased all-cause mortality and short-term cardiovascular mortality plus HF hospitalization.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00071331.
Surgical Revascularization Is Associated With Maximal Survival in Patients With Ischemic Mitral Regurgitation
Authors: Castleberry Anthony W. , Williams Judson B. , Daneshmand Mani A. , Honeycutt Emily , Shaw Linda K. , Samad Zainab , Lopes Renato D. , Alexander John H. , Mathew Joseph P. , Velazquez Eric J. , Milano Carmelo A. , Smith Peter K. 
Published: April 2014

Background—
The optimal treatment for ischemic mitral regurgitation remains actively debated. Our objective was to evaluate the relationship between ischemic mitral regurgitation treatment strategy and survival.

Methods and Results—

We retrospectively reviewed patients at our institution diagnosed with significant coronary artery disease and moderate or severe ischemic mitral regurgitation from 1990 to 2009, categorized by medical treatment alone, percutaneous coronary intervention, coronary artery bypass grafting (CABG), or CABG plus mitral valve repair or replacement. Kaplan-Meier methods and multivariable Cox proportional hazards analyses were performed to assess the relationship between treatment strategy and survival, with the use of propensity scores to account for nonrandom treatment assignment. A total of 4989 patients were included: medical treatment alone=36%, percutaneous coronary intervention=26%, CABG=33%, and CABG plus mitral valve repair or replacement=5%. Median follow-up was 5.37 years. Compared with medical treatment alone, significantly lower mortality was observed in patients treated with percutaneous coronary intervention (adjusted hazard ratio, 0.83; 95% confidence interval, 0.76–0.92;
P
=0.0002), CABG (adjusted hazard ratio, 0.56; 95% confidence interval, 0.51–0.62;
P
<0.0001), and CABG plus mitral valve repair or replacement (adjusted hazard ratio, 0.69; 95% confidence interval, 0.57–0.82;
P
<0.0001). There was no significant difference in these results based on mitral regurgitation severity.

Conclusions—
Patients with significant coronary artery disease and moderate or severe ischemic mitral regurgitation undergoing CABG alone demonstrated the lowest risk of death. CABG with or without mitral valve surgery was associated with lower mortality than either percutaneous coronary intervention or medical treatment alone.
Self-enhancement Influences Medial Frontal Cortex Alpha Power to Social Rejection Feedback
Authors: Leitner Jordan B. , Hehman Eric , Jones James M. , Forbes Chad E. 
Published: April 2014

AbstractAlthough previous research has demonstrated that individuals are motivated to self-enhance, the neurocognitive mechanisms and temporal dynamics of self-enhancement are poorly understood. The current research examined whether self-enhancing motivations affect the perceptual processing of social feedback. Participants who varied in self-enhancement motivations received accept and reject feedback while EEG was recorded. Following this task, we measured perceptions of feedback by asking participants to estimate the number of times they were rejected. Source localization and time–frequency analyses revealed that alpha power in the medial frontal cortex (MFC) completely mediated the relationship between self-enhancement motivations and rejection estimates. Specifically, greater self-enhancement motivations predicted decreased MFC alpha power to reject compared to accept feedback, which predicted decreased rejection estimates. These findings suggest that self-enhancement motivations decrease perception of social rejection by influencing how the MFC processes social feedback.
Revision of Acrochordonoposthia Reisinger, 1924 (Rhabditophora, Typhloplanidae, Protoplanellinae) with the description of one new species
Authors: HOUBEN ALBRECHT M. , PROESMANS WILLEM , BERT WIM , ARTOIS TOM J. 
Published: April 2014

An overview of the morphology, taxonomy and distribution of all known species of the rhabdocoel taxon Acrochordonoposthia is provided. One new species A. vandeputae n. sp. is described from Graz (Austria). This new species can easily be distinguished from its congeners by the morphology of its copulatory organ, which contains a straight cirrus lined with spines. All species of Acrochordonoposthia are compared with one another, and an updated identification key is provided.
Convective Characteristics of the Madden–Julian Oscillation over the Central Indian Ocean Observed by Shipborne Radar during DYNAMO
Authors: Xu Weixin , Rutledge Steven A. 
Published: April 2014

Abstract
This study investigates the convective population and environmental conditions during three MJO events over the central Indian Ocean in late 2011 using measurements collected from the Research Vessel (R/V) Roger Revelle deployed in Dynamics of the MJO (DYNAMO). Radar-based rainfall estimates from the Revelle C-band radar are first placed in the context of larger-scale Tropical Rainfall Measuring Mission (TRMM) rainfall data to demonstrate that the reduced Revelle radar range captured the MJO convective evolution. Time series analysis and MJO phase-based composites of Revelle measurements both support the “recharge–discharge” MJO theory. Time series of echo-top heights indicate that convective deepening during the MJO onset occurs over a 12–16-day period. Composite statistics show evident recharging–discharging features in convection and the environment. Population of shallow/isolated convective cells, SST, CAPE, and the lower-tropospheric moisture increase (recharge) substantially approximately two to three phases prior to the MJO onset. Deep and intense convection and lightning peak in phase 1 when the sea surface temperature and CAPE are near maximum values. However, cells in this phase are not well organized and produce little stratiform rain, possibly owing to reduced shear and a relatively dry upper troposphere. The presence of deep convection leads the mid- to upper-tropospheric humidity by one to two phases, suggesting its role in moistening these levels. During the MJO onset (i.e., phase 2), the mid- to upper troposphere becomes very moist, and precipitation, radar echo-top heights, and the mesoscale extent of precipitation all increase and obtain peak values. Persistent heavy precipitation in these active periods helps reduce the SST and dry/stabilize (or discharge) the atmosphere.
High-Resolution Probabilistic Projections of Temperature Changes over Ontario, Canada
Authors: Wang Xiuquan , Huang Guohe , Lin Qianguo , Liu Jinliang 
Published: April 2014

Abstract
Planning of mitigation and adaptation strategies to a changing climate can benefit from a good understanding of climate change impacts on human life and local society, which leads to an increasing requirement for reliable projections of future climate change at regional scales. This paper presents an ensemble of high-resolution regional climate simulations for the province of Ontario, Canada, developed with the Providing Regional Climates for Impacts Studies (PRECIS) modeling system. A Bayesian statistical model is proposed through an advance to the method proposed by Tebaldi et al. for generating probabilistic projections of temperature changes at gridpoint scale by treating the unknown quantities of interest as random variables to quantify their uncertainties in a statistical way. Observations for present climate and simulations from the ensemble are fed into the statistical model to derive posterior distributions of all the uncertain quantities through a Markov chain Monte Carlo (MCMC) sampling algorithm. Detailed analyses at 12 selected weather stations are conducted to investigate the practical significance of the proposed statistical model. Following that, maps of projected temperature changes at different probability levels are presented to help understand the spatial patterns across the entire province. The analysis shows that there is likely to be a significant warming trend throughout the twenty-first century. It also suggests that people in Ontario are very likely to suffer a change greater than 2°C to mean temperature in the forthcoming decades and very unlikely to suffer a change greater than 10°C to the end of this century.
Increased expression of astrocyte markers in schizophrenia: Association with neuroinflammation
Authors: Catts Vibeke Sørensen , Wong Jenny , Fillman Stu Gregory , Fung Samantha Jane , Shannon Weickert Cynthia 
Published: April 2014

Objective: While schizophrenia may have a progressive component, the evidence for neurodegenerative processes as indicated by reactive astrocytes is inconclusive. We recently identified a subgroup of individuals with schizophrenia with increased expression of inflammatory markers in prefrontal cortex, and hypothesized that this subgroup would also have reactive astrocytes. Method: We measured glial fibrillary acidic protein (GFAP) mRNA by quantitative real-time reverse transcriptase polymerase chain reaction (RT-PCR) and protein levels by immunoblotting in grey matter homogenate from 37 individuals with schizophrenia and 37 unaffected controls. We examined the morphology of GFAP-positive astrocytes in immunostained sections of middle frontal gyrus. We tested if GFAP expression or astrocyte morphology were altered in people with schizophrenia with increased expression of inflammatory markers. We used RNA-Seq data on a subset of patients and controls ( n=20/group) to ascertain whether mRNA transcripts associated with astrogliosis were elevated in the individuals with active neuroinflammation. Results: GFAP (mRNA and protein) levels and astrocyte morphology were not significantly different between people with schizophrenia and controls overall. However, individuals with schizophrenia with neuroinflammation had increased expression of GFAP mRNA ( t(33)=2.978, p=0.005), hypertrophic astrocyte morphology (χ2(2)=6.281, p=0.043), and statistically significant elevated expression of three mRNA transcripts previously associated with astrogliosis. Conclusions: We found clear evidence of astrogliosis in a subset of people with schizophrenia. We suggest that the lack of astrogliosis reported in previous studies may be due to cohort differences in aetiopathology, illness stage, treatment exposure, or a failure to examine subsets of people with schizophrenia.
Effect of intravenous general anaesthesia with epidural block on the expression of pre-endogenous opioid peptide genes
Authors: Chen Zhi-Yang , Wang Huaqing , Xu Weiping , Xu Hui , Fu Xinchun 
Published: April 2014

Objective To measure the plasma concentrations of three endogenous opioid peptides and the levels of preproenkephalin (PPE) and preprodynorphin (PPD) mRNA in peripheral blood lymphocytes of patients during scheduled surgery performed under intravenous general anaesthesia combined with an epidural block. Methods Patients were anaesthetized and arterial blood was collected at 0 (baseline), 20, 40, 60, and 80 min during surgery. The plasma concentrations of β-endorphin, leucine-enkephalin and dynorphin A were measured using radioimmunoassay. Reverse transcription–polymerase chain reaction was used to measure the levels of PPD and PPE mRNA in peripheral blood lymphocytes collected during surgery. Results Fifteen patients participated in this prospective study. The plasma concentrations of β-endorphin were significantly lower at all time-points compared with the baseline value. The plasma concentrations of leucine-enkephalin and dynorphin A were significantly lower at 40, 60, and 80 min compared with baseline. The PPD/β-actin ratio was significantly lower at 80 min compared with baseline, while the PPE/β-actin ratio showed no significant change. Conclusion The level of mRNA from two pre-endogenous opioid peptide genes either decreased or remained unchanged during surgery under intravenous general anaesthesia with epidural block, suggesting that patients remained pain free during surgery.
Association between obesity, prostate-specific antigen level and prostate-specific antigen density in men with a negative prostate biopsy
Authors: Kim Jae Heon , Lee Sang Wook , Kim Jae Ho , Yang Hee Jo , Doo Seung Whan , Yoon Jong Hyun , Kim Doo Sang , Yang Won Jae , Lee Kwang Woo , Kim Jun Mo , Lee Changho , Kwon Soon-Sun 
Published: April 2014

Objective To determine the association between body mass index (BMI), serum prostate-specific antigen (PSA) level and PSA density (PSAD) in patients with an elevated serum PSA level but a negative prostate biopsy. Methods This retrospective study enrolled men with a negative prostate biopsy but a serum PSA level of 3.0–10 ng/ml. All men underwent anthropometric measurements, serum PSA determination and transrectal ultrasound examination. BMI was grouped according to the Asia-Pacific obesity criteria: nonobese (<25 kg/m2) versus obese (≥25 kg/m2). Partial correlation and linear regression models between PSA, PSAD and BMI were conducted after adjusting for age. Results A total of 907 men were enrolled in this study. On multivariate analyses, PSA showed no significant correlation with age or BMI, whereas PSAD had a negative correlation with age and BMI. Similar results were obtained when patients were categorized as having low (3.0 < PSA ≤ 6.5 ng/ml) or high PSA (6.5 < PSA ≤ 10.0 ng/ml) levels. Conclusion PSAD, but not PSA, demonstrated a significant negative correlation with BMI. This indicates that a new strategy including PSAD rather than simple PSA levels should be adopted in the study of obesity-adjusted PSA cut-offs.
Factors associated with HIV and syphilis co-infection among men who have sex with men in seven Chinese cities
Authors: Das Aritra , Li Jianjun , Zhong Fei , Ouyang Lin , Mahapatra Tanmay , Tang Weiming , Fu Gengfeng , Zhao Jinkou , Detels Roger 
Published: April 2014

Summary HIV-syphilis co-infection is often cited as a major reason behind recent resurgence in syphilis prevalence among men who have sex with men in China. Most published literatures explore factors associated with either HIV or syphilis, but not their co-infection. We analysed data from a cross-sectional survey on men who have sex with men in seven Chinese cities. Snowball sampling was used to recruit participants for the survey. Socio-demographic and behavioural predictors for HIV-syphilis mono/co-infection were examined using ordinal logistic regression. Factor scores were used to summarise (1) HIV-related knowledge and (2) access to HIV preventive services. Prevalence of HIV, syphilis, and their co-infection, among 2936 self-identified men who have sex with men, were 7.7%, 14.3%, and 2.6%, respectively. In the adjusted analysis, the significant positive correlates of poorer diagnoses (co-infection vs mono- and no infection or co- and mono-infection vs no infection) were: 30 to 39 years and ≥40 years age, education up to senior high school, unprotected anal intercourse, recent sexually transmitted infection symptoms, incorrect knowledge about routes of transmission, and access to preventive or counselling/testing services for HIV. For effective control of this dual epidemic, integrated HIV and syphilis surveillance and targeted intervention strategies for Chinese men who have sex with men are needed urgently.
Why a career in psychiatry?
Authors: Kumar Varun 
Published: April 2014

Objectives: To reflect upon the factors that might motivate one to undertake a career in psychiatry from the personal perspective of a current registrar in training. Conclusions: The reasons for choosing a career path in psychiatry are complex, and relate to an individual doctor’s life experience, training experiences and own value system. Dissatisfaction with the traditional “medical model” of illness may be a contributing factor, with a perception that psychiatry may embrace the biopsychosocial model of illness more fully. Beyond this, a particular interest in the poetry inherent to an individual’s story and appreciation of the artistic underpinnings of medicine may also contribute.
Analysis of patient satisfaction and donor-site morbidity after different types of breast reconstruction
Authors: Benditte-Klepetko H. C. , Lutgendorff F. , Kästenbauer T. , Deutinger M. , van der Horst C. M. A. M. 
Published: April 2014

Background and Aims: Breast reconstruction has been shown to improve quality of life. However, factors involved in long-term patient satisfaction are largely unknown. Our aim was to evaluate patient satisfaction and donor-site morbidity in five types of breast reconstruction. Material and Methods: A prospectively collected database of all breast surgery patients at Hospital Rudolfstiftung, Vienna, Austria, was searched for five types of breast reconstruction (2000–2006): implant, latissimus dorsi-flap, latissimus dorsi-flap with implant, free transverse rectus abdominis musculocutaneous-flap, and deep inferior epigastric perforator-flap. Patients were sent a study-specific questionnaire to assess satisfaction. Short-form 36-item health survey was used to analyze (quality of life), and complication data were retrieved from the database and assessed during a follow-up visit. Results: There were 257 patients identified, of whom, 126 responded to the survey (17 implant, 5 latissimus dorsi + implant, 64 latissimus dorsi, 22 transverse rectus abdominis musculocutaneous, and 18 deep inferior epigastric perforator reconstructions). No statistical differences were found in complication or reoperation rates. Deep inferior epigastric perforator–flap patients were significantly more satisfied compared to patients from the implant group ( p = 0.007). However, there was no significant difference regarding quality of life scores among the groups. After logistic regression analysis, only “impairment on daily life” showed to be independently correlated with patient satisfaction. This contrary to both operation type and complication rate which did not correlate with patient satisfaction. Conclusions: Our results indicate that operation type, complication rate, and revision rate did not independently correlate with patient satisfaction. Therefore, to further improve patient satisfaction, future research should be focused on other pro-operative factors, for example, patient education, expectations, and personality characteristics.
Controversies in Initial Management of Open Fractures
Authors: Ryan S. P. , Pugliano V. 
Published: April 2014

Background: Treatment of open fractures continues to be a challenge for orthopedic and trauma surgeons, and early treatment recommendations, which persist in the literature for decades, often do not have supporting data. Methods: This is a critical review of the literature surrounding controversies in the initial management of open fractures. It also focuses on the utility of negative pressure dressings in the care of associated complex wounds. Studies were selected based on their relevance to the treatment of open fractures. Results: A total of 40 studies were included. The following topics were critically discussed: timing of initial debridement, antibiotic coverage, utility of obtaining cultures, and timing of wound closure. Conclusion: The majority of open fractures require urgent, not emergent, irrigation and debridement. Antibiotics are essential in preventing infection in open fractures. Timely wound closure after all necrotic tissue has been debrided decreases complications in open fractures. Finally, negative pressure wound therapy has dramatically changed the care of associated complex wounds.