bluuebunny/crossref_metadata_2025_split huggingface dataset:
Morpholine as a privileged structure: A review on the medicinal chemistry and pharmacological activity of morpholine containing bioactive molecules
Authors: Kourounakis Angeliki P. , Xanthopoulos Dimitrios , Tzara Ariadni 
Published: September 2019

AbstractMorpholine is a heterocycle featured in numerous approved and experimental drugs as well as bioactive molecules. It is often employed in the field of medicinal chemistry for its advantageous physicochemical, biological, and metabolic properties, as well as its facile synthetic routes. The morpholine ring is a versatile and readily accessible synthetic building block, it is easily introduced as an amine reagent or can be built according to a variety of available synthetic methodologies. This versatile scaffold, appropriately substituted, possesses a wide range of biological activities. There are many examples of molecular targets of morpholine bioactive in which the significant contribution of the morpholine moiety has been demonstrated; it is an integral component of the pharmacophore for certain enzyme active‐site inhibitors whereas it bestows selective affinity for a wide range of receptors. A large body of in vivo studies has demonstrated morpholine's potential to not only increase potency but also provide compounds with desirable drug‐like properties and improved pharamacokinetics. In this review we describe the medicinal chemistry/pharmacological activity of morpholine derivatives on various therapeutically related molecular targets, attempting to highlight the importance of the morpholine ring in drug design and development as well as to justify its classification as a privileged structure.
High expression of PRKDC promotes breast cancer cell growth via p38 MAPK signaling and is associated with poor survival
Authors: Zhang Yan , Yang Wei‐kang , Wen Guo‐ming , Tang Hongping , Wu Chuan‐an , Wu Yan‐xia , Jing Zhi‐liang , Tang Min‐shan , Liu Guang‐long , Li Da‐zhou , Li Yan‐hua , Deng Yong‐Jian 
Published: September 2019

AbstractBackgroundDNA‐Dependent Protein Kinase Catalytic Subunit (PRKDC), a key component of the DNA damage repair pathway, is associated with chemotherapy resistance and tumor progression.MethodsHere we analyzed transcriptome data of ~2,000 breast cancer patients and performed functional studies in vitro to investigate the function of PRKDC in breast cancer.ResultsOur results revealed overexpression of PRKDC in multiple breast cancer subtypes. Consistent with patients’ data, overexpression of PRKDC was also observed in breast cancer cell lines compared to normal breast epithelial cells. Knockdown of PRKDC in MCF‐7 and T47D breast cancer cell lines resulted in proliferation inhibition, reduced colony formation and G2/M cell cycle arrest. Furthermore, we showed that PRKDC knockdown induced proliferation inhibition through activation of p38 MAPK, but not ERK MAPK, signaling pathway in breast cancer cells. Blockage of p38 MAPK signaling could largely rescue proliferation inhibition and cell cycle arrest induced by PRKDC knockdown. Moreover, we analyzed gene expression and clinical data from six independent breast cancer cohorts containing ~1,000 patients. In all cohorts, our results consistently showed that high expression of PRKDC was significantly associated with poor survival in both treated and untreated breast cancer patients.ConclusionTogether, our results suggest that high expression of PRKDC facilitates breast cancer cell growth via regulation of p38 MAPK signaling, and is a prognostic marker for poor survival in breast cancer patients.
Rett and Rett‐like syndrome: Expanding the genetic spectrum to KIF1A and GRIN1 gene
Authors: Wang Jiaping , Zhang Qingping , Chen Yan , Yu Shujie , Wu Xiru , Bao Xinhua 
Published: September 2019

AbstractBackgroundThis study aimed to investigate the new genetic etiologies of Rett syndrome (RTT) or Rett‐like phenotypes.MethodsTargeted next‐generation sequencing (NGS) was performed on 44 Chinese patients with RTT or Rett‐like phenotypes, in whom genetic analysis of MECP2, CDKL5, and FOXG1 was negative.ResultsThe detection rate was 31.8% (14/44). A de novo pathogenic variant (c.275_276ins AA, p. Cys92*) of KIF1A was identified in a girl with all core features of typical RTT. A patient with atypical RTT was detected having de novo GRIN1 pathogenic variant (c.2337C > A, p. Val793Phe). Additionally, compound heterozygous pathogenic variants of PPT1 gene were detected in a girl, who initially displayed typical RTT features, but progressed into neuronal ceroid lipofuscinoses (NCL) afterwards. Pathogenic variants in KCNQ2, MEF2C, WDR45, TCF4, IQSEC2, and SDHA were also found in our cohort.ConclusionsIt is the first time that pathogenic variants of GRIN1 and KIF1A were linked to RTT and Rett‐like profiles. Our findings expanded the genetic heterogeneity of Chinese RTT or Rett‐like patients, and also suggest that some patients with genetic metabolic disease such as NCL, might displayed Rett features initially, and clinical follow‐up is essential for the diagnosis.
Current status of simulation and training models in microsurgery: A systematic review
Authors: Javid Pernia , Aydın Abdullatif , Mohanna Pari‐Naz , Dasgupta Prokar , Ahmed Kamran 
Published: September 2019

AbstractWith the prolific uptake of simulation‐based training courses, this systematic review aims to identify the available microsurgical simulation and training models, their status of validation, associated studies, and levels of evidence (LoE) for each training model, thereby establishing a level of recommendation (LoR). MEDLINE, Embase, and the Cochrane Library databases were searched for English language articles, describing microsurgery simulators and/or validation studies. All studies were assessed for LoE, and each model was subsequently awarded a LoR using a modified Oxford Centre for Evidence‐Based Medicine classification, adapted for education, with 1 being the highest and 4 the lowest score. A total of 86 studies were identified describing 64 models and simulators ranging from bench models, cadaveric animal tissue, cadaveric human tissue, live animal models, virtual reality simulators, and training curricula. Of these, 49 simulators had at least one validation study. Models were assessed for face (n= 42), content (n= 31), construct (n= 25), transfer (n= 10), and concurrent validity (n= 1) by these studies. The most commonly identified modality was bench models (n= 28) followed by cadaveric animal tissue (n= 24). The cryopreserved rat aorta model received the highest LoR followed by chicken wing, chicken thigh and practice cardboard models. Microsurgery simulation is a growing field and increasing numbers of models are being produced. However, there are still only a few validation studies with a high LoE. It is therefore imperative that training models and/or programs are evaluated for validity and efficacy in order to allow utilization in microsurgical skills acquisition.
Diffusion maps‐based surrogate modeling: An alternative machine learning approach
Authors: Kalogeris I. , Papadopoulos V. 
Published: September 2019

SummaryIn this work, an alternative machine learning methodology is proposed, which utilizes nonlinear manifold learning techniques in the frame of surrogate modeling. Under the assumption that the solutions of a parametrized physical system lie on a low‐dimensional manifold embedded in a high‐dimensional Euclidean space, the goal is to unveil the manifold's intrinsic dimensionality and use it for the construction of a surrogate model, which will be used as a cost‐efficient emulator of the high‐dimensional physical system. To this purpose, a computational framework based on the diffusion maps algorithm is put forth herein, where a set of system solutions is used to identify the geometry of a low‐dimensional space called the diffusion maps space. This space is completely described by a low‐dimensional basis, which is constructed from the eigenvectors and eigenvalues of a diffusion operator on the data. The proposed approach exploits the diffusion maps space's reduced dimensionality for the construction of locally clustered interpolation schemes between the parameter space, the diffusion maps space, and the solution space, which are cheap to evaluate and highly accurate. This way, the need to formulate and solve the governing equations of the system is eliminated. In addition, a sampling methodology is proposed based on the metric of the diffusion maps space to efficiently sample the parameter space, thus ensuring the quality of the surrogate model. Even though it is exploited herein in the premises of uncertainty quantification, this methodology is applicable to any other problem type that depends on some parametric space (ie, optimization, sensitivity analysis, etc). In the numerical examples, it is shown that the proposed surrogate model is capable of high levels of accuracy, as well as significant computational gains.
Multi‐Relaxation Test to Characterize PE Pipe Performance
Authors: Tan Na , Jar P‐Y Ben 
Published: September 2019

AbstractA new concept is proposed, which uses results from a multi‐relaxation test to characterize transition of deformation mechanisms in polyethylene (PE) pipes, for plastic deformation from the amorphous phase only to the involvement of the crystalline phase. The former mechanism is believed to lead to brittle fracture, while the latter to ductile fracture. This phenomenon is believed to be related to the transition from ductile to brittle (DB) fracture that has been observed in creep tests of PE pipes by reducing the applied stress below a critical level. This paper presents results from 6 PE pipes of different density and molecular weight distribution. The results suggest that high‐density PE pipes require a higher deformation level for the DB transition than the medium‐density PE pipes. The results also suggest that the trend of change in the critical stress level for the DB transition is close to the trend of change in the hydrostatic design base, but the former takes less than two weeks to complete, while the latter more than 1 year. Therefore, the multi‐relaxation test can be used as an alternative method to characterize PE pipe performance, as a means for preliminary screening or in‐service monitoring of pipe performance.
Peramivir for Influenza A and B Viral Infections: A Pharmacokinetic Case Series
Authors: Cies Jeffrey J. , Moore Wayne S. , Enache Adela , Chopra Arun 
Published: September 2019

ObjectiveTo describe the peramivir (PRV) pharmacokinetics in critically ill children treated for influenza A or B viral infections.DesignRetrospective electronic medical record review of prospectively collected data from critically ill children receiving peramivir for influenza A or B viral infections in the pediatric intensive care unit (PICU).SettingA 189‐bed, freestanding children's tertiary care teaching hospital in Philadelphia, PA.PatientsCritically ill children admitted to the PICU who were infected with influenza between January 1, 2016 and March 31, 2018.InterventionsNone.ResultsEleven patients, two females (18%) and nine males (82%), accounted for 24 peramivir samples for therapeutic drug management. The median age was 5 years (interquartile range 1.5–6.5 yrs) with a median weight of 16.4 kg (interquartile range 14–24 kg). Ten (91%) patients demonstrated a larger volume of distribution, 11 (100%) patients demonstrated an increase in clearance, and 11 (100%) patients demonstrated a shorter half‐life estimate as compared with the package insert and previous pediatric trial data for peramivir. Eight (73%) patients tested positive for a strain of influenza A and 3 (27%) patients tested positive for influenza B; 4 of 11 (36%) patients tested positive for multiple viruses. All patients had adjustments made to their dosing interval to a more frequent interval. Ten (91%) patients were adjusted to an every‐12‐hour regimen and 1 (9%) patient was adjusted to an every‐8‐hour regimen. No adverse events were associated with peramivir treatment.ConclusionThe pharmacokinetics of PRV demonstrated in this PICU cohort differs in comparison to healthy pediatric and adult patients, and alterations to dosing regimens may be needed in PICU patients to achieve pharmacodynamic exposures. Additional investigations in the PICU population are needed to confirm these findings.
Brexanolone for Postpartum Depression: Clinical Evidence and Practical Considerations
Authors: Leader Lauren D. , O'Connell Megan , VandenBerg Amy 
Published: September 2019

Our aim was to review the efficacy, safety, and pharmacology of brexanolone (Zulresso), a new antidepressant with a novel mechanism of action, in the treatment of postpartum depression (PPD). Pertinent data and information were obtained via PubMed (1993 to August 2018). Articles published in English that evaluated the safety and efficacy of brexanolone and other off‐label PPD treatments were included. Literature regarding epidemiology and pathophysiology of PPD was also selected. Brexanolone, administered as an intravenous infusion over 60 hours, produced a statistically significant and clinically meaningful reduction in Hamilton Depression Rating Scale (HAM‐D) scores compared with placebo at both 60 and 90 μg/kg/hour in patients with moderate to severe PPD. Brexanolone groups had higher response and remission rates compared with placebo. Common adverse effects were somnolence, dizziness, and headache. A small percentage (4%) of patients required cessation of therapy due to excessive sedation or loss of consciousness. Although the evidence for brexanolone as a novel treatment for PPD looks promising, a Risk Evaluation and Mitigation Strategies (REMS) program requirement and the logistics of prolonged infusions serve as barriers to treatment. A discussion of these obstacles as well as pharmacokinetics, monitoring, and dosing is provided. Brexanolone is a novel antidepressant indicated for the treatment of PPD. Clinical trials demonstrated that brexanolone significantly reduces depression scores in women with moderate to severe PPD. Due to risk of oversedation and loss of consciousness, a REMS program will be put in place to mitigate the risk of adverse events.
A model study of the effect of clustering on the last stage of drizzle formation
Authors: Madival Deepak G. 
Published: September 2019

AbstractIn the final stage of growth, settling cloud drops become drizzle by collision and coalescence with the smaller droplets in their path. We study the impact of droplet clustering on the growth of settling collector drops by modelling it as an exponentially decaying correlation. Enhancement in collector drop growth is measured by the reduction in time needed for drizzle formation in the last stage. The effect of clustering is characterized by two dimensionless parameters C = δλL and K = (λ0L)−1, where δλ is the enhancement in the collision rate inside the clusters, L is the cluster size perceived by the settling collector drop and λ0 is the initial collision rate. Increasing C or K reduces the time needed for drizzle formation compared to the unclustered case. We find that for K ≥ 5, C ≤ 2 even a small increase in droplet concentration inside clusters can cause a significant enhancement in the collector drop growth. Further even for low turbulence intensities (low K) significant reduction in the time for drizzle formation is achieved for moderate values of C. These findings are relevant to the debate on the intensity of clustering needed to explain rapid drizzle formation.
Toward Arbitrary Control of Lattice Interactions in Nonequilibrium Condensates
Authors: Kalinin Kirill P. , Berloff Natalia G. 
Published: September 2019

AbstractThere is a growing interest in investigating new states of matter using out‐of‐equilibrium lattice spin models in two dimensions. However, a control of pairwise interactions in such systems has been elusive as due to their nonequilibrium nature they maintain nontrivial particle fluxes even at the steady state. Here it is suggested how to overcome this problem and formulate a method for engineering reconfigurable networks of nonequilibrium condensates with control of individual pairwise interactions. Representing spin by condensate phase, the effective two spin interactions are created with nonresonant pumping, are directed with dissipative channels, and are further controlled with dissipative gates. The dissipative barriers are used to block unwanted interactions between condensates. Together, spatial anisotropy of dissipation and pump profiles allow an effective control of sign and intensity of the coupling strength between any two neighbouring sites independent of the rest of the spins, which is demonstrated with a 2D square lattice of polariton condensates. Experimental realization of such fully controllable networks offers great potential for reservoir computing, modelling of the systems of coupled oscillators, simulation of the new state of matters, studying the phase transitions in large‐scale systems, and optimization.
Ten years later: The progress and future of integrating sustainable principles, practices, and metrics into remediation projects
Authors: Favara Paul , Raymond Dick , Ambrusch Matthew , Libera Arianna , Wolf Gerlinde , Simon John A. , Maco Barbara , Collins Elizabeth R. , Harclerode Melissa A. , McNally Amanda D. , Ridsdale Reanne , Smith Maile , Howard Lyndsey 
Published: September 2019

AbstractIn 2009, the Sustainable Remediation Forum released a white paper entitled “Integrating sustainable principles, practices, and metrics into remediation projects” (Ellis & Hadley, 2009, Remediation, 19, pp. 5–114). Sustainable remediation was a relatively new concept, and the white paper explored a range of approaches on how sustainability could be integrated into traditional remediation projects. This paper revisits the 2009 white paper, providing an overview of the early days of the evolving sustainable remediation practice and an assessment of the progress of sustainable remediation over the last 10 years with a primary focus on the United States. The current state of the sustainable remediation practice includes published literature, current practices and resources, applications, room for improvement, international progress, the virtuous cycle that applying sustainable remediation creates, and the status of the objectives cited in the 2009 white paper. Over the last decade, several sustainable remediation frontiers have emerged that will likely be a focus in advancing the practice. These frontiers include climate change and resiliency, weighting and valuation to help better consolidate different sustainable remediation metrics, programmatic implementation, and better integration of the societal impacts of sustainable remediation. Finally, as was the case for the 2009 white paper, this paper explores how sustainable remediation may evolve over the next 10 years and focuses on the events and drivers that can be significant in the pace of further development of the practice. The events and drivers include transformation impacts, societal influences, and the continued development of new technologies, approaches, and tools by remediation practitioners. The remediation industry has made significant progress in developing the practice of sustainable remediation and has implemented it successfully into hundreds of projects. While progress has been significant, an opportunity exists to implement the tenets of sustainable remediation on many more projects and explore new frontiers to help improve the communication, integration, and derived benefits from implementing sustainable remediation into future remediation projects.
Practical considerations for kriging groundwater surfaces
Authors: Uetrecht Rachel M. , Elmore Andrew C. , Guggenberger Joe D. , Helwig Zane D. 
Published: September 2019

AbstractKriging is an accepted method of characterizing the groundwater elevation surface at sites where the water level data are available but where there may be insufficient additional data necessary for groundwater flow modeling. Groundwater surface interpolation via kriging is readily performed using commercial, state of the practice software, but some practitioners may not be able to justify such efforts because the process is not validated within studies documented in the peer‐reviewed literature. This paper describes the available kriging software and literature studies and then uses a case study to compare practical groundwater surface modeling to the studies available in the scientific literature. The literature review shows that the state of the practice as represented by the commercial software approach is consistent with the literature. Specifically, cokriging with groundwater elevation as the primary variable with trend removal and ground‐surface elevation as the secondary variable is an appropriate point of departure in practice. The literature review‐based summary of variogram model parameters (model type, nugget, sill, range, and trend model) was not useful as a quality‐control step to assess the reasonableness of variogram parameters identified by the standard practice of software‐assisted iteration when applied to the case‐study data set. The literature review indicated that groundwater elevation kriging has been performed using as few as 10 data points but a comparison of the case‐study simulated groundwater elevations and groundwater gradient magnitudes and directions indicated that the 30‐well threshold more commonly found in the literature was an appropriate minimum at the study site.
Perfluoroalkyl and polyfluoroalkyl substances thermal desorption evaluation
Authors: Crownover Emily , Oberle Daniel , Kluger Mark , Heron Gorm 
Published: September 2019

AbstractPer‐ and polyfluoroalkyl substances (PFAS) are highly resistant to biotic and abiotic degradation and can withstand very high temperatures before breaking down. The storage of PFAS‐impacted water and sediments in a holding pond or stockpiled investigation or remedial action‐derived waste is occurring on an increasing number of sites. The most common PFAS water treatment options include granular‐activated carbon and resins and the most common soil treatment options have been primarily limited to excavation, offsite incineration, and, in some cases, soil stabilization. An increasing number of states across the United States are establishing part per trillion PFAS guidance levels for drinking water. Removing PFAS from soils removes PFAS source impacts to groundwater. In this study, volatilization of PFAS from soil treated using in situ thermal heating is evaluated as a treatment method to achieve a high degree of PFAS removal from soils. The evaluation of temperatures needed to achieve removal is described. To minimize vapor treatment required for PFAS thermal remediation, a scrubber was incorporated into the treatment train to transfer PFAS to the liquid phase in a concentrated, low‐volume solution. Vapor‐liquid equilibrium behavior and the extent of PFAS volatilization from impacted soil over a range of temperatures were evaluated. Results showed that heating soil to 350°C and 400°C reduces PFAS soil concentrations by 99.91% and 99.998%, respectively. It was also confirmed that sulfonate‐based PFAS generally required higher temperatures for volatilization to occur than carboxylate‐based PFAS.