bluuebunny/crossref_metadata_2025_split huggingface dataset:
Animacroxam, a Novel Dual-Mode Compound Targeting Histone Deacetylases and Cytoskeletal Integrity of Testicular Germ Cell Cancer Cells
Authors: Steinemann Gustav , Dittmer Alexandra , Kuzyniak Weronika , Hoffmann Björn , Schrader Mark , Schobert Rainer , Biersack Bernhard , Nitzsche Bianca , Höpfner Michael 
Published: August 2017

Abstract
Novel approaches for the medical treatment of advanced solid tumors, including testicular germ cell tumors (TGCT), are desperately needed. Especially, TGCT patients not responding to cisplatin-based therapy need therapeutic alternatives, as there is no effective medical treatment available for this particular subgroup. Here, we studied the suitability of the novel dual-mode compound animacroxam for TGCT treatment. Animacroxam consists of an HDAC-inhibitory hydroxamate moiety coupled to a 4,5-diarylimidazole with inherent cytoskeleton disrupting potency. Animacroxam revealed pronounced antiproliferative, cell-cycle arresting, and apoptosis-inducing effects in TGCT cell lines with different cisplatin sensitivities. The IC50 values of animacroxam ranged from 0.22 to 0.42 μmol/L and were not correlated to the cisplatin sensitivity of the tumor cells. No unspecific cytotoxicity of animacroxam was observed in either cisplatin-sensitive or resistant TGCT cells, even at doses as high as 10 μmol/L. Furthermore, animacroxam induced the formation of actin stress fibers in cancer cells, thereby confirming the cytoskeleton-disrupting and antimigratory properties of its imidazole moiety. When compared with the clinically established HDAC inhibitor vorinostat, the novel dual-mode compound animacroxam exhibited superior antitumoral efficacy in vitro. Animacroxam also reduced the tumor size of TGCT tumors in vivo, as evidenced by performing xenograft experiments on tumor bearing chorioallantoic membranes of fertilizes chicken eggs (CAM assay). The in vivo experiments also revealed a very good tolerability of the compound, and hence, animacroxam may be a promising candidate for innovative treatment of TGCT in general and the more so for platinum-insensitive or refractory TGCT. Mol Cancer Ther; 16(11); 2364–74. ©2017 AACR.
Tortuous Microvessels Contribute to Wound Healing via Sprouting Angiogenesis
Authors: Chong Diana C. , Yu Zhixian , Brighton Hailey E. , Bear James E. , Bautch Victoria L. 
Published: August 2017

Objective—
Wound healing is accompanied by neoangiogenesis, and new vessels are thought to originate primarily from the microcirculation; however, how these vessels form and resolve during wound healing is poorly understood. Here, we investigated properties of the smallest capillaries during wound healing to determine their spatial organization and the kinetics of formation and resolution.

Approach and Results—
We used intravital imaging and high-resolution microscopy to identify a new type of vessel in wounds, called tortuous microvessels. Longitudinal studies showed that tortuous microvessels increased in frequency after injury, normalized as the wound healed, and were closely associated with the wound site. Tortuous microvessels had aberrant cell shapes, increased permeability, and distinct interactions with circulating microspheres, suggesting altered flow dynamics. Moreover, tortuous microvessels disproportionately contributed to wound angiogenesis by sprouting exuberantly and significantly more frequently than nearby normal capillaries.

Conclusions—
A new type of transient wound vessel, tortuous microvessels, sprout dynamically and disproportionately contribute to wound-healing neoangiogenesis, likely as a result of altered properties downstream of flow disturbances. These new findings suggest entry points for therapeutic intervention.
Regional Dysfunction After Myocardial Infarction in Rats
Authors: Espe Emil K.S. , Aronsen Jan Magnus , Eriksen Morten , Sejersted Ole M. , Zhang Lili , Sjaastad Ivar 
Published: August 2017

Background—
Detailed understanding of regional function after myocardial infarction (MI) is currently incomplete. We aimed at investigating regional myocardial strain and work in post-MI rats with and without heart failure.

Methods and Results—

Six weeks after induction of MI, 62 male Wistar-Hannover rats with a range of infarct sizes, plus 14 sham-operated rats, were examined by cine and phase-contrast magnetic resonance imaging. After magnetic resonance imaging, the rats were catheterized, and left ventricular pressures were recorded. Regional strain and work were calculated from the magnetic resonance imaging and pressure data. On the basis of end-diastolic left ventricular pressure, 34 MI rats were classified as nonfailing (MI
NF
) and 28 MI rats as failing (MI
CHF
). In the region remote to the infarct, the MI
NF
rats exhibited preserved strain and increased work compared with sham, whereas MI
CHF
had reduced longitudinal strain and no increase in work in this region. In the noninfarcted region adjacent to the infarct, MI
CHF
demonstrated substantially reduced work because of high levels of negative work.

Conclusions—
We have demonstrated a distinct difference in regional work between nonfailing and failing hearts after MI and offer novel insight into the relation between regional function and presence of congestion. Work analysis provided significant added value over strain analysis alone.
Epigenome-Wide Association Study Identifies Cardiac Gene Patterning and a Novel Class of Biomarkers for Heart Failure
Authors: Meder Benjamin , Haas Jan , Sedaghat-Hamedani Farbod , Kayvanpour Elham , Frese Karen , Lai Alan , Nietsch Rouven , Scheiner Christina , Mester Stefan , Bordalo Diana Martins , Amr Ali , Dietrich Carsten , Pils Dietmar , Siede Dominik , Hund Hauke , Bauer Andrea , Holzer Daniel Benjamin , Ruhparwar Arjang , Mueller-Hennessen Matthias , Weichenhan Dieter , Plass Christoph , Weis Tanja , Backs Johannes , Wuerstle Maximilian , Keller Andreas , Katus Hugo A. , Posch Andreas E. 
Published: August 2017

Background:
Biochemical DNA modification resembles a crucial regulatory layer among genetic information, environmental factors, and the transcriptome. To identify epigenetic susceptibility regions and novel biomarkers linked to myocardial dysfunction and heart failure, we performed the first multi-omics study in myocardial tissue and blood of patients with dilated cardiomyopathy and controls.

Methods:
Infinium human methylation 450 was used for high-density epigenome-wide mapping of DNA methylation in left-ventricular biopsies and whole peripheral blood of living probands. RNA deep sequencing was performed on the same samples in parallel. Whole-genome sequencing of all patients allowed exclusion of promiscuous genotype-induced methylation calls.

Results:

In the screening stage, we detected 59 epigenetic loci that are significantly associated with dilated cardiomyopathy (false discovery corrected
P
≤0.05), with 3 of them reaching epigenome-wide significance at
P
≤5×10
−8
. Twenty-seven (46%) of these loci could be replicated in independent cohorts, underlining the role of epigenetic regulation of key cardiac transcription regulators. Using a staged multi-omics study design, we link a subset of 517 epigenetic loci with dilated cardiomyopathy and cardiac gene expression. Furthermore, we identified distinct epigenetic methylation patterns that are conserved across tissues, rendering these CpGs novel epigenetic biomarkers for heart failure.

Conclusions:
The present study provides to our knowledge the first epigenome-wide association study in living patients with heart failure using a multi-omics approach.
The Microphysical Roles of Lower-Tropospheric versus Midtropospheric Aerosol Particles in Mature-Stage MCS Precipitation
Authors: Marinescu Peter J. , van den Heever Susan C. , Saleeby Stephen M. , Kreidenweis Sonia M. , DeMott Paul J. 
Published: August 2017

Abstract
Simulations of two leading-line, trailing-stratiform mesoscale convective system (MCS) events that occurred during the Midlatitude Continental Convective Clouds Experiment (MC3E) have been used to understand the relative microphysical impacts of lower- versus midtropospheric aerosol particles (APs) on MCS precipitation. For each MCS event, four simulations were conducted in which the initial vertical location and concentrations of cloud droplet nucleating APs were varied. These simulations were used to determine the precipitation response to AP vertical location. Importantly, the total integrated number and mass of the initial aerosol profiles used in the sensitivity simulations remained constant, such that differences in the simulations could be directly attributable to changes in the vertical location of cloud droplet nucleating APs. These simulations demonstrate that lower-tropospheric APs largely influenced the precipitation response directly rearward of the leading cold pool boundary. However, farther rearward in the MCS, the relative impact of lower- versus midtropospheric APs largely depended on the MCS structure, which varied between the two events because of differences in line-normal wind shear. Midtropospheric APs were able to activate new cloud droplets in the midtropospheric levels of convective updrafts and to enhance mixed-phase precipitation through increased cloud riming, and this microphysical pathway had a more significant impact on mixed-phase precipitation in weaker line-normal wind shear conditions. This result exposes the importance of properly representing midtropospheric APs when assessing aerosol effects on clouds. This study also demonstrates the utility of assessing aerosol effects within the different regions of MCSs.
Generation of Subsurface Anticyclones at Arctic Surface Fronts due to a Surface Stress
Authors: Brannigan Liam , Johnson Helen , Lique Camille , Nycander Jonas , Nilsson Johan 
Published: August 2017

AbstractIsolated anticyclones are frequently observed below the mixed layer in the Arctic Ocean. Some of these subsurface anticyclones are thought to originate at surface fronts. However, previous idealized simulations with no surface stress show that only cyclone–anticyclone dipoles can propagate away from baroclinically unstable surface fronts. Numerical simulations of fronts subject to a surface stress presented here show that a surface stress in the same direction as the geostrophic flow inhibits dipole propagation away from the front. On the other hand, a surface stress in the opposite direction to the geostrophic flow helps dipoles to propagate away from the front. Regardless of the surface stress at the point of dipole formation, these dipoles can be broken up on a time scale of days when a surface stress is applied in the right direction. The dipole breakup leads to the deeper anticyclonic component becoming an isolated subsurface eddy. The breakup of the dipole occurs because the cyclonic component of the dipole in the mixed layer is subject to an additional advection because of the Ekman flow. When the Ekman transport has a component oriented from the anticyclonic part of the dipole toward the cyclonic part then the cyclone is advected away from the anticyclone and the dipole is broken up. When the Ekman transport is in other directions relative to the dipole axis, it also leads to deviations in the trajectory of the dipole. A scaling is presented for the rate at which the surface cyclone is advected that holds across a range of mixed layer depths and surface stress magnitudes in these simulations. The results may be relevant to other regions of the ocean with similar near-surface stratification profiles.
Evaluation of vascular invasion in patients with musculoskeletal tumors of lower extremities: use of time-resolved 3D MR angiography at 3-T
Authors: Jin Teng , Wu Gang , Li Xiaoming , Feng Xiaoyuan 
Published: August 2017

Background Time-resolved angiography with stochastic trajectories (TWIST) sequence makes considerable progress in temporal and spatial resolution, which presents high potential in evaluation of vascular diseases. Purpose To assess magnetic resonance imaging (MRI) using TWIST MR angiography (MRA) sequence in the assessment of vascular invasion for bone and soft-tissue tumors in comparison to computed tomography angiography (CTA) as the reference standard. Material and Methods Thirty-three patients with lower extremity musculoskeletal tumors were imaged with conventional MR and TWIST MRA. CTA was performed 48 h later. The signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) of the femoral artery were calculated. Vascular invasion as determined by MRA and CTA was separately analyzed. Vascular invasion by MRA and CTA were analyzed with kappa coefficients to determine agreement between the imaging methods. Results Seven cases of bone and 26 cases of soft tissue tumors were examined. SNR and CNR of the femoral artery were excellent for TWIST MRA (mean ± SD values of 317 ± 80 and 276 ± 76, respectively). Based on the TWIST sequence, the vessels were free of tumor in 16 cases. Vascular displacement was found in 11 cases and vascular stenosis in six cases. The MRA findings conflicted with CTA findings in only one case. The kappa value was 0.953 ( P < 0.01). In five cases, vascular malformations were found with TWIST MRA but not CTA. Conclusion TWIST MRA enables accurate delineation of anatomical structures and tumor arterial involvement, providing reliable preoperative imaging information with respect to lower extremity musculoskeletal tumors.
Pneumatic retinopexy combined with scleral buckling in the management of relatively complicated cases of rhegmatogenous retinal detachment: A multicenter, retrospective, observational consecutive case series*
Authors: Zhou Chuandi , Lin Qiurong , Wang Yuxin , Qiu Qinghua 
Published: August 2017

Objective To evaluate the efficacy of maximal pneumatic retinopexy (PR) and subretinal fluid (SRF) drainage combined with scleral buckling (SB) in the treatment of complicated rhegmatogenous retinal detachment (RRD). Methods Patients with RRD who underwent maximal PR and SRF drainage combined with SB from June 2007 to June 2012 were included in this multicenter retrospective study. The outcome measures were the primary and final operation success rates and best-corrected visual acuity (BCVA). Results In total, 159 consecutive patients were included. The mean follow-up period was 13.76 ± 1.97 months. Primary operation success was achieved in 146/159 (91.82%) eyes. After salvage management, the final reattachment rate increased to 98.11%. All eyes had improved BCVA, with 62/159 (38.99%) attaining BCVA of ≥20/40. Conclusions Maximal PR and SRF drainage combined with SB achieved satisfactory anatomical and visual recovery in relatively complicated cases of RRD. The decreased need for vitrectomy makes this surgical approach more widely available.
Pacifiers and Exclusive Breastfeeding: Does Risk for Postpartum Depression Modify the Association?
Authors: Sipsma Heather L. , Kornfeind Katelin , Kair Laura R. 
Published: August 2017

Background: Postpartum depression is associated with lower rates of breastfeeding. Evidence describing the effect of pacifiers on breastfeeding is inconsistent, and previous research suggests that pacifiers may help vulnerable mothers breastfeed. Research aim: This study aimed to determine (a) how receiving a pacifier in the hospital affects exclusive breastfeeding (EBF) at 1 week and 3 months postpartum and (b) whether this association is modified by risk for postpartum depression (PPD). Methods: Data were derived from Listening to Mothers III. We included participants ( n = 1,349) who intended to breastfeed and delivered at term. Mothers were considered at high risk for PPD if they reported feeling the need to receive treatment for depression during pregnancy. We used weighted multivariable logistic regression models to adjust for covariates. Results: Receiving a pacifier in the hospital was not significantly associated with EBF at 1 week (odds ratio [ OR] = 0.84, 95% confidence interval [CI] [0.62, 1.12]) but was significantly associated with lower odds of EBF at 3 months postpartum ( OR = 0.72, 95% CI [0.54, 0.95]). Risk for PPD modified this association. Among mothers at high risk for PPD, receiving a pacifier was significantly associated with increased odds of EBF ( OR = 3.31, 95% CI [1.23, 8.97] at 1 week and OR = 5.27, 95% CI [1.97, 14.12] at 3 months); however, among mothers who were at lower risk for PPD, receiving a pacifier was associated with decreased odds of EBF ( OR = 0.75, 95% CI [0.56, 1.02] at 1 week and OR = 0.62, 95% CI [0.46, 0.82] at 3 months). Conclusion: Pacifiers may help protect against early cessation of EBF among mothers at high risk for depression. Additional research is needed to better understand this association.
Implementation and evaluation of medicine and therapeutic information service by clinical pharmacists in oncology care setting
Authors: Patel Himanshu , Gurumurthy Parthasarathi 
Published: August 2017

Background This study was conducted to explore the role of clinical pharmacists in providing medicine and therapeutic information service in oncology care setting. Methods It was a prospective study conducted for a period of three years after implementation of medicine and therapeutic information service as an integral part of oncology pharmacy services. The medicine and therapeutic information queries were received during ward rounds, at ambulatory care and via telephone by clinical pharmacists. All the medicine and therapeutic information requests were reviewed and answered to the concerned requester(s). Answered medicine and therapeutic information requests were electronically documented in the hospital drug information database and analyzed further. Results A total of 484 medicine and therapeutic information requests were received by clinical pharmacists during period of August 2013 to June 2016. Majority of medicine and therapeutic information queries were requested by radiation oncologists (27.2%) followed by medical oncologists (26.4%), general physicians (14.04%), resident medical officers (11.7%), ambulatory care nurses (8.6%), in-patient nurses (5.1%) and patients and care takers (6.6%). Majority of the medicine and therapeutic information queries were asked for the purpose of improving patient care (48.3%) followed by to update knowledge (30.9%) and training sessions to nurses (6.6%). The most common categories of medicine and therapeutic information were adverse drug reactions and its management (21.4%) followed by dosage adjustments of chemotherapy and biologicals (15.5%), supportive care related (14.6%), contraindications (14%), drug–drug interactions (11.9%), management of co-morbidities (7.8%), chemotherapy selection in special populations (4.5%). Conclusion The provision of medicine and therapeutic information was found to be useful in providing medicine information to improve patient care and to update knowledge of health care professionals at the study hospital.
Feline leprosy due to Candidatus ‘Mycobacterium lepraefelis’: Further clinical and molecular characterisation of eight previously reported cases and an additional 30 cases
Authors: O’Brien Carolyn R , Malik Richard , Globan Maria , Reppas George , McCowan Christina , Fyfe Janet A 
Published: August 2017

Objectives: This paper, the last in a series of three on ‘feline leprosy’, provides a detailed description of disease referable to the previously unnamed species, Candidatus ‘Mycobacterium lepraefelis’, a close relative of the human pathogens Mycobacterium leprae and Mycobacterium lepromatosis. Methods: Cases were sourced retrospectively and prospectively for this observational study, describing clinical, geographical and molecular microbiological data for cats definitively diagnosed with Candidatus ‘M lepraefelis’ infection. Results: A total of 145 cases of feline leprosy were scrutinised; 114 ‘new’ cases were sourced from the Victorian Infectious Diseases Reference Laboratory (VIDRL) records, veterinary pathology laboratories or veterinarians, and 31 cases were derived from six published studies. Thirty-eight cats were definitively diagnosed with Candidatus ‘M lepraefelis’ infection. Typically, cats tended to be middle-aged or older when first infected, with a male predilection. Affected cats typically had widespread cutaneous lesions, in some cases after initially localised disease. Advanced cases were often systemically unwell. All cats had outdoor access. The histological picture was lepromatous in the majority of patients, although two cases had tuberculoid disease. In one case that underwent necropsy, lesions were evident in the liver, spleen and lungs. Treatment was varied, although most cats received a combination of oral clarithromycin and rifampicin. Prognosis for recovery was variable, but typically poor. Conclusions and relevance: Candidatus ‘M lepraefelis’ typically causes high bacterial index (lepromatous) feline leprosy that in some cases progresses to systemic mycobacteriosis. The disease has a variable clinical course and prognosis. Many cases either died or were euthanased due to the infection. Multilocus sequence analysis reveals a heterogeneous picture and further analysis of draft genome sequencing may give clues to the taxonomy and epidemiology of this organism. Prospective treatment trials and/or additional drug susceptibility testing in specialised systems would further inform treatment recommendations. Comparative aspects: This paper finishes with a discussion of comparative aspects of infection caused by the three feline leproid disease agents that have been the subject of this series: Candidatus ’Mycobacterium tarwinense’, Mycobacterium lepraemurium and Candidatus ‘M lepraefelis’.
Development and psychometric evaluation of the Thirst Distress Scale for patients with heart failure
Authors: Waldréus Nana , Jaarsma Tiny , van der Wal Martje HL , Kato Naoko P 
Published: August 2017

Background: Patients with heart failure can experience thirst distress. However, there is no instrument to measure this in patients with heart failure. The aim of the present study was to develop the Thirst Distress Scale for patients with Heart Failure (TDS-HF) and to evaluate psychometric properties of the scale. Methods and results: The TDS-HF was developed to measure thirst distress in patients with heart failure. Face and content validity was confirmed using expert panels including patients and healthcare professionals. Data on the TDS-HF was collected from patients with heart failure at outpatient heart failure clinics and hospitals in Sweden, the Netherlands and Japan. Psychometric properties were evaluated using data from 256 heart failure patients (age 72±11 years). Concurrent validity of the scale was assessed using a thirst intensity visual analogue scale. Patients did not have any difficulties answering the questions, and time taken to answer the questions was about five minutes. Factor analysis of the scale showed one factor. After psychometric testing, one item was deleted. For the eight item TDS-HF, a single factor explained 61% of the variance and Cronbach’s alpha was 0.90. The eight item TDS-HF was significantly associated with the thirst intensity score ( r=0.55, p<0.001). Regarding test-retest reliability, the intraclass correlation coefficient was 0.88, and the weighted kappa values ranged from 0.29–0.60. Conclusion: The eight-item TDS-HF is valid and reliable for measuring thirst distress in patients with heart failure.