bluuebunny/crossref_metadata_2025_split huggingface dataset:
Toward a direct and scalable identification of reduced models for categorical processes
Authors: Gerber Susanne , Horenko Illia 
Published: April 2017

Significance
We derive a computational framework that allows highly scalable identification of reduced Bayesian and Markov relation models, their uncertainty quantification, and inclusion of a priori physical information. It does not rely on the prior knowledge or a necessity of estimation of the full matrix of system’s relations in any step. Application to a molecular dynamics (MD) example showed that this methodology opens possibilities for a robust construction of reduced Markov state models directly from the MD data—providing ways of bridging the gap toward longer simulation times and larger systems in computational MD.
Comparative genomic analysis of SET domain family reveals the origin, expansion, and putative function of the arthropod-specific SmydA genes as histone modifiers in insects
Authors: Jiang Feng , Liu Qing , Wang Yanli , Zhang Jie , Wang Huimin , Song Tianqi , Yang Meiling , Wang Xianhui , Kang Le 
Published: April 2017

Abstract
The SET domain is an evolutionarily conserved motif present in histone lysine methyltransferases, which are important in the regulation of chromatin and gene expression in animals. In this study, we searched for SET domain–containing genes (SET genes) in all of the 147 arthropod genomes sequenced at the time of carrying out this experiment to understand the evolutionary history by which SET domains have evolved in insects. Phylogenetic and ancestral state reconstruction analysis revealed an arthropod-specific SET gene family, named SmydA, that is ancestral to arthropod animals and specifically diversified during insect evolution. Considering that pseudogenization is the most probable fate of the new emerging gene copies, we provided experimental and evolutionary evidence to demonstrate their essential functions. Fluorescence in situ hybridization analysis and in vitro methyltransferase activity assays showed that the SmydA-2 gene was transcriptionally active and retained the original histone methylation activity. Expression knockdown by RNA interference significantly increased mortality, implying that the SmydA genes may be essential for insect survival. We further showed predominantly strong purifying selection on the SmydA gene family and a potential association between the regulation of gene expression and insect phenotypic plasticity by transcriptome analysis. Overall, these data suggest that the SmydA gene family retains essential functions that may possibly define novel regulatory pathways in insects. This work provides insights into the roles of lineage-specific domain duplication in insect evolution.
Risk Factors for Intracranial Aneurysm Rupture: A Systematic Review
Authors: Kleinloog Rachel , de Mul Nikki , Verweij Bon H , Post Jan Andries , Rinkel Gabriel J E , Ruigrok Ynte M 
Published: April 2017

Abstract

BACKGROUND
Intracranial aneurysm rupture prediction is poor, with only a few risk factors for rupture identified and used in clinical practice.

OBJECTIVE
To provide an overview of all the risk factors (including genetic, molecular, morphological, and hemodynamic factors) that have potential for use in clinical practice.

METHODS
We systematically searched PubMed and EMBASE and focused on factors that can be easily assessed in clinical practice, might be used for rupture prediction in clinical practice, and/or are potential targets for further research. Studies were categorized according to methodological quality, and a meta-analysis was performed, if possible.

RESULTS
We included 102 studies describing 144 risk factors that fulfilled predefined criteria. There was strong evidence for the morphological factors irregular shape (studied in 4 prospective cohort studies of high-quality, pooled odds ratio [OR] of 4.8 [95% confidence interval 2.7-8.7]), aspect ratio (pooled OR 10.2 [4.3-24.6]), size ratio, bottleneck factor, and height-to-width ratio to increase rupture risk. Moderate level of evidence was found for presence of contact with the perianeurysmal environment (pooled OR 3.5 [1.4-8.4]), unbalanced nature of this contact (pooled OR 17.8 [8.3-38.5]), volume-to-ostium ratio, and direction of the aneurysm dome (pooled OR 1.5 [1.2-1.9]).

CONCLUSION
Irregular aneurysm shape was identified as a risk factor with potential for use in clinical practice. The risk factors aspect ratio, size ratio, bottleneck factor, height-to-width ratio, contact with the perianeurysmal environment, volume-to-ostium ratio, and dome-direction should first be confirmed in multivariate analysis and incorporated in prediction models.
The Four-Tier Continuum of Academic and Behavioral Support (4T-CABS) Model: An Integrated Model for Medical Student Success
Authors: Stegers-Jager Karen M. , Cohen-Schotanus Janke , Themmen Axel P.N. 
Published: April 2017

Not all students cope successfully with the demands of medical school, and students’ struggles may result in study delay or dropout. To prevent these outcomes, medical schools need to identify students who are experiencing academic difficul ties and provide them with timely interventions through access to support programs. Although the importance of early identification and intervention is well recognized, less is known about successful strategies for identifying and supporting struggling students.
Building on the literature and their own empirical findings, the authors propose an integrated, school-wide model for medical student success comprising a continuum of academic and behavioral support. This Four-Tier Continuum of Academic and Behavioral Support (4T-CABS) model focuses on improving both academic and behavioral outcomes by offering support for students at four levels, which range from adequate instruction for all, to targeted small-group interventions, to individualized support, and also include exit support for students who might be better off in another degree program. Additionally, medical schools should provide both academic and behavioral support; set high, yet realistic expectations and clearly communicate these to students; and intervene early, which requires timely identification of at-risk students who would benefit from the different types and tiers of support. Finally, interventions should be evidence based and fit the needs of the identified groups of students. The authors argue that adopting the core principles of the 4T-CABS model will enable medical schools to maximize academic engagement and performance for all students.
DNA Hydroxymethylation by Ten-eleven Translocation Methylcytosine Dioxygenase 1 and 3 Regulates Nociceptive Sensitization in a Chronic Inflammatory Pain Model
Authors: Pan Zhiqiang , Xue Zhou-Ya , Li Guo-Fang , Sun Meng-Lan , Zhang Ming , Hao Ling-Yun , Tang Qian-Qian , Zhu Li-Jiao , Cao Jun-Li 
Published: April 2017

Abstract

Background
Ten-eleven translocation methylcytosine dioxygenase converts 5-methylcytosine in DNA to 5-hydroxymethylcytosine, which plays an important role in gene transcription. Although 5-hydroxymethylcytosine is enriched in mammalian neurons, its regulatory function in nociceptive information processing is unknown.

Methods
The global levels of 5-hydroxymethylcytosine and ten-eleven translocation methylcytosine dioxygenase were measured in spinal cords in mice treated with complete Freund’s adjuvant. Immunoblotting, immunohistochemistry, and behavioral tests were used to explore the downstream ten-eleven translocation methylcytosine dioxygenase-dependent signaling pathway.

Results
Complete Freund’s adjuvant-induced nociception increased the mean levels (± SD) of spinal 5-hydroxymethylcytosine (178 ± 34 vs. 100 ± 21; P = 0.0019), ten-eleven translocation methylcytosine dioxygenase-1 (0.52 ± 0.11 vs. 0.36 ± 0.064; P = 0.0088), and ten-eleven translocation methylcytosine dioxygenase-3 (0.61 ± 0.13 vs. 0.39 ± 0.08; P = 0.0083) compared with levels in control mice (n = 6/group). The knockdown of ten-eleven translocation methylcytosine dioxygenase-1 or ten-eleven translocation methylcytosine dioxygenase-3 alleviated thermal hyperalgesia and mechanical allodynia, whereas overexpression cytosinethem in naïve mice (n = 6/group). Down-regulation of spinal ten-eleven translocation methylcytosine dioxygenase-1 and ten-eleven translocation methylcytosine dioxygenase-3 also reversed the increases in Fos expression (123 ± 26 vs. 294 ± 6; P = 0.0031; and 140 ± 21 vs. 294 ± 60; P = 0.0043, respectively; n = 6/group), 5-hydroxymethylcytosine levels in the Stat3 promoter (75 ± 16.1 vs. 156 ± 28.9; P = 0.0043; and 91 ± 19.1 vs. 156 ± 28.9; P = 0.0066, respectively; n = 5/group), and consequent Stat3 expression (93 ± 19.6 vs. 137 ± 27.5; P = 0.035; and 72 ± 15.2 vs. 137 ± 27.5; P = 0.0028, respectively; n = 5/group) in complete Freund’s adjuvant-treated mice.

Conclusions
This study reveals a novel epigenetic mechanism for ten-eleven translocation methylcytosine dioxygenase-1 and ten-eleven translocation methylcytosine dioxygenase-3 in the modulation of spinal nociceptive information via targeting of Stat3.
Resuscitation With Balanced Fluids Is Associated With Improved Survival in Pediatric Severe Sepsis*
Authors: Emrath Elizabeth T. , Fortenberry James D. , Travers Curtis , McCracken Courtney E. , Hebbar Kiran B. 
Published: April 2017

Objective:
To evaluate outcomes in patients receiving balanced fluids for resuscitation in pediatric severe sepsis.

Design:
Observational cohort review of prospectively collected data from a large administrative database.

Setting:
PICUs from 43 children’s hospitals.

Patients:
PICU patients diagnosed with severe sepsis.

Interventions:
None.

Measurements and Main Results:
We reviewed data from the Pediatric Health Information System database from 2004 to 2012. Children with pediatric severe sepsis receiving balanced fluids for resuscitation in the first 24 and 72 hours of treatment were compared to those receiving unbalanced fluids. Thirty-six thousand nine hundred eight patients met entry criteria for analysis. Two thousand three hundred ninety-eight patients received exclusively balanced fluids at 24 hours and 1,641 at 72 hours. After propensity matching, the 72-hour balanced fluids group had lower mortality (12.5% vs 15.9%; p = 0.007; odds ratio, 0.76; 95% CI, 0.62–0.93), lower prevalence of acute kidney injury (16.0% vs 19.2%; p = 0.028; odds ratio, 0.82; 95% CI, 0.68–0.98), and fewer vasoactive infusion days (3.0 vs 3.3 d; p < 0.001) when compared with the unbalanced fluids group.

Conclusions:
In this retrospective analysis carried out by propensity matching, exclusive use of balanced fluids in pediatric severe sepsis patients for the first 72 hours of resuscitation was associated with improved survival, decreased prevalence of acute kidney injury, and shorter duration of vasoactive infusions when compared with exclusive use of unbalanced fluids.
NPY Impairs Cell Viability and Mitochondrial Membrane Potential Through Ca2+ and p38 Signaling Pathways in Neonatal Rat Cardiomyocytes
Authors: Hu Jun , Xu Xuehua , Zuo Yuanyi , Gao Xiangting , Wang Yun , Xiong Cunquan , Zhou Hongcheng , Zhu Shaohua 
Published: April 2017

Abstract:
NPY is involved in stress cardiomyopathy. However, the associated mechanism for NPY-induced stress cardiomyopathy remains unclear. In this study, we aimed to explore potential cell signaling pathways that are related to NPY-mediated cell viability in neonatal rat cardiomyocytes. We found that NPY induced cell viability suppression in cultured cardiomyocytes in a dose-dependent manner. After NPY treatment, expression of CaN and p-CAMKII increased significantly, and phosphorylation of p38 but not ERK and JNK was changed. Moreover, NPY treatment significantly increased PGC-1α (the key factor of mitochondrial biogenesis and energy metabolism) expression but decreased mitochondrial membrane potential in cultured cardiomyocytes. More importantly, the blockage of CaN, CAMKII, and p38 signaling pathways by their inhibitors could rescue the reduced cell viability and mitochondrial membrane potential in NPY-treated cardiomyocytes. Collectively, our data demonstrated that NPY mediated cell viability and mitochondrial membrane potential in cardiomyocytes through CaN, CAMKII, and p38 signaling pathways.
Inhibition of Mid-chain HETEs Protects Against Angiotensin II–induced Cardiac Hypertrophy
Authors: Elkhatali Samya , Maayah Zaid H. , El-Sherbeni Ahmed A. , Elshenawy Osama H. , Abdelhamid Ghada , Shoieb Sherif M. , El-Kadi Ayman O. S. 
Published: April 2017

Abstract:
Recent data demonstrated the role of CYP1B1 in cardiovascular disease. It was, therefore, necessary to examine whether the inhibition of CYP1B1 and hence inhibiting the formation of its metabolites, using 2,4,3′,5′-tetramethoxystilbene (TMS), would have a cardioprotective effect against angiotensin II (Ang II)-induced cardiac hypertrophy. For this purpose, male Sprague Dawley rats were treated with Ang II with or without TMS (300 μg/kg every third day i.p.). Thereafter, cardiac hypertrophy and the formation of mid-chain HETEs and arachidonic acid were assessed. In vitro, RL-14 cells were treated with Ang II (10 μM) in the presence and absence of TMS (0.5 μM). Then, reactive oxygen species, mitogen-activated protein kinase phosphorylation levels, and nuclear factor-kappa B–binding activity were determined. Our results demonstrated that TMS protects against Ang II-induced cardiac hypertrophy as indicated by the improvement in cardiac functions shown by the echocardiography as well as by reversing the increase in heart weight to tibial length ratio caused by Ang II. In addition, the cardioprotective effect of TMS was associated with a significant decrease in cardiac mid-chain HETEs levels. Mechanistically, TMS inhibited reactive oxygen species formation, the phosphorylation of ERK1/2, p38 mitogen-activated protein kinase, and the binding of p65 NF-κB.
Pharmacodynamic and -kinetic Behavior of Low-, Intermediate-, and High-Dose Landiolol During Long-Term Infusion in Whites
Authors: Krumpl Günther , Ulč Ivan , Trebs Michaela , Kadlecová Pavla , Hodisch Juri , Maurer Gabriele , Husch Bernhard 
Published: April 2017

Abstract:
Pharmacokinetics, pharmacodynamics, safety, and tolerability of long-term administration of landiolol, a fast-acting cardioselective β-blocker, were investigated for the first time in white subjects in a prospective clinical trial. Blood concentrations of landiolol and its metabolites, heart rate (HR), blood pressure (BP), and electrocardiogram parameters were studied in 12 healthy volunteers receiving continuous infusions of a new 12-mg/mL formulation of landiolol using a dose-escalation regimen (10 μg/kg BW/min for 2 hours, 20 μg/kg BW/min for 2 hours, 40 μg/kg BW/min for 20 hours, 6 hours follow-up). Landiolol blood concentrations were dose proportional. Time until steady state decreased with increasing doses. Pharmacokinetic parameters were t1/2 = 4.5 minutes, VD = 366 mL/kg, and total body clearance = 53 mL·kg−1·min−1. Maximal blood concentrations of the inactive main metabolite M1 were 10-fold higher than those of landiolol, with t1/2 = 126 minutes, VD = 811 mL/kg, and total body clearance = 4.5 mL·kg−1·min−1. HR reduction from baseline was fast (significant after 16 minutes) and sustained throughout the administration period. Systolic and diastolic BP reductions and electrocardiogram parameter changes were less pronounced and became significant only occasionally. Recovery after discontinuation of infusion was fast with little (HR) or no (BP) rebound. The new formulation showed excellent local and general tolerability.
Inhibition of Rho-kinase Attenuates Left Ventricular Remodeling Caused by Chronic Intermittent Hypoxia in Rats via Suppressing Myocardial Inflammation and Apoptosis
Authors: Wang Zhi-hua , Zhu Die , Xie Sheng , Deng Yan , Pan Yueying , Ren Jie , Liu Hui-guo 
Published: April 2017

Abstract:
Chronic intermittent hypoxia (CIH), the hallmark of obstructive sleep apnea syndrome (OSAS), has been reported to play a key role in the development of OSAS-associated cardiovascular diseases including cardiac remodeling. RhoA/Rho-kinase (ROCK) pathway has also been implicated in myocardial remodeling, but the exact mechanisms are not fully elucidated. This study's purpose is to investigate the influence of fasudil, a selective ROCK inhibitor, on CIH-induced left ventricular remodeling in rats and its possible mechanisms. Adult male Sprague-Dawley rats suffered from CIH or normoxia stimulus and were intervened with vehicle or fasudil (10 mg·kg−1·d−1, intraperitoneal injection) for 6 weeks. In this study, treatment with fasudil significantly reversed intermittent hypoxia-induced histopathological transformations and ultrastructural changes in rat myocardium. Moreover, fasudil downregulated the protein levels of RhoA and phosphorylation of myosin phosphatase targeting subunit-1 (MYPT1), thus effectively inhibited the activation of RhoA/ROCK signaling pathway. Simultaneously, activity of nuclear factor (NF)-kB was suppressed by fasudil, which was accompanied by reduced NF-kB downstream inflammatory genes including interleukin-6, tumor necrosis factor-a and monocyte chemotactic protein-1, and apoptosis. These results suggest that fasudil attenuates myocardial remodeling in CIH rats, at least partly by suppressing activation of NF-kB. Inhibition of the RhoA/ROCK pathway could become an important therapeutic target in the prevention of OSAS-related cardiomyopathy.
β-adrenergic Receptor-stimulated Cardiac Myocyte Apoptosis: Role of Cytochrome P450 ω-hydroxylase
Authors: Jiang Shan , Huo Dan , Wang Xueying , Zhao Huan , Tan Jiang , Zeng Qinghua , O'Rourke Stephen T. , Sun Chengwen 
Published: April 2017

Abstract:
Prolonged or excessive β-adrenergic activation leads to cardiac myocyte loss and heart dysfunction; however, the underlying cellular mechanisms are still unclear. Therefore, we first confirmed the effect of isoproterenol (ISO), a β-adrenergic receptor agonist, on cardiac toxicity using TUNEL and caspase activity assays in cultured rat cardiomyocytes. ISO treatment significantly increased cardiomyocyte apoptosis. Persistent ISO stimulation of cardiomyocytes also increased the expression of CYP4A3, a major CYP450 ω-hydroxylase that produces 20-hydroxyeicosatetraenoic acid (20-HETE) in a time-dependent manner. Next, we examined the effect of ISO and 20-HETE on cardiomyocyte apoptosis using annexin V and propidium iodide staining. Treatment with either 20-HETE or ISO significantly increased cardiomyocyte apoptosis, and inhibition of 20-HETE production using 17-ODYA, a CYP450 ω-hydroxylase inhibitor, dramatically attenuated ISO-induced cardiomyocyte apoptosis. To determine the apoptotic pathway involved, the mitochondrial membrane potential (ΔΨm) was measured by detecting the ratio of JC-1 green/red emission intensity. The results demonstrated that 17-ODYA significantly abolished ISO-induced disruption of ΔΨm and that 20-HETE alone induced a marked disruptive effect on ΔΨm in cardiomyocytes. In addition, 20-HETE–induced disruption of ΔΨm and apoptosis was significantly attenuated by KN93, a CaMKII inhibitor. Taken together, these results demonstrate that 20-HETE treatment induces significant apoptosis via mitochondrial-dependent pathways, and that inhibition of 20-HETE production using 17-ODYA attenuates ISO-induced cardiomyocyte apoptosis.
Pyoderma Gangrenosum after Deep Inferior Epigastric Perforator Breast Reconstruction: Systematic Review and Case Report
Authors: Zelones Justin T. , Nigriny John F. 
Published: April 2017

Background:
Pyoderma gangrenosum (PG) is a rare skin disorder of the neutrophilic dermatoses spectrum that can mimic wound infections in surgical patients. PG after breast surgery has been reported but in limited amounts in autologous breast reconstruction patients. We present the first case of PG after a delayed bilateral deep inferior epigastric perforator flap breast reconstruction in the setting of systemic disease along with a systematic review.

Methods:
PubMed, Ovid, and Web of Science were systematically searched to obtain cases of PG after autologous breast reconstruction. Sixty articles were identified but only 16 were relevant to this study.

Results:
Systemic disease was present in 2 patients (13%). Wound onset occurred typically 5 days after surgery. Fever and/or leukocytosis was observed in 10 patients (63%). Wound cultures were positive in 2 patients (13%). Donor-site wounds were present in 9 patients (56%). Bilateral breast wounds were present in 67% of bilateral cases. Debridement was performed in 10 cases (63%). Skin graft or substitute was performed in 6 cases (38%). Resection of autologous flap was performed in 3 cases (19%). All patients were treated with systemic steroids (81%) and/or immunosuppressive medications (50%). Complete wound healing occurred by 4 months on average.

Conclusion:
If early ulcerative wounds develop at multiple sites after autologous breast reconstruction with worsening after debridement and antibiotic therapy, then PG should be considered. It is imperative that an early diagnosis and subsequent treatment with steroids and/or immunosuppressive medications be initiated so further surgical procedures, flap loss, and scarring can be minimized.
Prediction of Skin Necrosis after Mastectomy for Breast Cancer Using Indocyanine Green Angiography Imaging
Authors: Gorai Katsuya , Inoue Keita , Saegusa Noriko , Shimamoto Ryo , Takeishi Meisei , Okazaki Mutsumi , Nakagawa Masahiro 
Published: April 2017

Background:
In immediate tissue expander reconstruction following total mastectomy for breast cancer, indocyanine green angiography (ICGA)–guided skin trimming is useful for the prevention of complications. However, instances of unclear ICGA contrast can occur with this method, which are difficult to judge as to whether preventive trimming is warranted. To further improve the mastectomy flap necrosis rate, more accurate objective parameters are necessary.

Methods:
The degree of clinical improvement was compared between 81 patients trimmed according to the surgeon’s judgment (non-ICGA group) and 100 patients with ICGA-guided trimming (ICGA group). We then retrospectively measured 3 parameters [relative perfusion (RP); time (T) to reach RPmax; and slope (S = RP/T) reflecting the rate of increase to RPmax] by using region of interest analysis software and examined their relationships with skin necrosis.

Results:
The rate of grade III necrosis (reaching the subcutaneous fat layer) was significantly lower in the ICGA group (4.8%) than in the non-ICGA group (17.8%; P < 0.05). The specificity of RP for the diagnosis of skin necrosis was high (98.5%; cutoff value, 34). However, the sensitivities of slope parameters were higher than RP.

Conclusions:
ICGA-guided trimming decreased the rate of deep skin necrosis requiring additional surgical treatment. Region of interest analysis indicated that a relatively low percentage luminescence (RP < 34) was indicative of the need for skin trimming, combined with a slow increase in the perfusion of the mastectomy skin flaps.