bluuebunny/crossref_metadata_2025 huggingface dataset:
Seneciphylline, a main pyrrolizidine alkaloid in Gynura japonica, induces hepatotoxicity in mice and primary hepatocytes via activating mitochondria‐mediated apoptosis
Authors: Wang Weiqian , Yang Xiao , Chen Yan , Ye Xuanling , Jiang Kaiyuan , Xiong Aizhen , Yang Li , Wang Zhengtao
Published: July 2020

Herbal drug‐induced liver injury has been reported worldwide and gained global attention. Thousands of hepatic sinusoidal obstruction syndrome (HSOS) cases have been reported after consumption of herbal medicines and preparations containing pyrrolizidine alkaloids (PAs), which are natural phytotoxins globally distributed. And herbal medicines, such as Gynura japonica, are the current leading cause of PA‐induced HSOS. The present study aimed to reveal the mechanism underlying the hepatotoxicity of seneciphylline (Seph), a main PA in G. japonica. Results showed that Seph induced severe liver injury through apoptosis in mice (70 mg/kg Seph, orally) and primary mouse and human hepatocytes (5–50 μM Seph). Further research uncovered that Seph induced apoptosis by disrupting mitochondrial homeostasis, inducing mitochondrial depolarization, mitochondrial membrane potential (MMP) loss, and cytochrome c (Cyt c) release and activating c‐Jun N‐terminal kinase (JNK). The Seph‐induced apoptosis in hepatocytes could be alleviated by Mdivi‐1 (50 μM, a dynamin‐related protein 1 inhibitor), as well as SP600125 (25 μM, a specific JNK inhibitor) and ZVAD‐fmk (50 μM, a general caspase inhibitor). Moreover, the Seph‐induced MMP loss in hepatocytes was also rescued by Mdivi‐1. In conclusion, Seph induced liver toxicity via activating mitochondrial‐mediated apoptosis in mice and primary hepatocytes. Our results provide further information on Seph detoxification and herbal medicines containing Seph such as G. japonica.
Automated red blood cell depletion: Results from a validation trial of the Fenwal Amicus new red blood cell depletion program
Authors: Sanderson Frederick , Cauchois Raphaël , Berda‐Haddad Yael , Poullin Pascale
Published: July 2020

Purpose

A new software release of the Fenwal Amicus device is now available for red blood cell (RBC) apheresis, offering RBC exchange, RBC depletion (RBCd)/RCB exchange, and RBCd procedures. The main goal of this study was to validate the new RBCd program through the accuracy of the patient's postprocedure hematocrit (HCT) (actual end HCT) to the HCT reported by the device at the end of the procedure (target end HCT). Secondary objectives were to assess the device‐related significant adverse events, the patient's cellular losses, and the degree of device induced hemolysis.

Methods

The study was an open‐label, single‐center, prospective trial in adult patients eligible for RBCd. Patients were enrolled between October 2015 and June 2016. In all procedures, saline was used as replacement fluid. Blood samples were collected from the patient before and after the procedure. Device settings, adverse events, and procedure results were recorded.

Results

Thirty‐nine patients were enrolled (34 treated for iron storage disease and 5 for polycythemia vera); only 36 were evaluable for the primary objective. The mean actual end HCT was 34.6 ± 2.79% and the mean target end HCT was 35.8 ± 2.25%. The ratio (actual end to target end HCT) was 0.97 ± 0.05 with a 95% CI demonstrating the accuracy of the target HCT. One patient experienced a vasovagal event not related to the device. Cellular losses were not clinically relevant.

Conclusion

The RBCd Amicus program met all RBCd efficiency and safety requirements with high accuracy of the target HCT.
SuSMoST: Surface Science Modeling and Simulation Toolkit
Authors: Akimenko Sergey S. , Anisimova Galina D. , Fadeeva Anastasiya I. , Fefelov Vasiliy F. , Gorbunov Vitaliy A. , Kayumova Tatyana R. , Myshlyavtsev Alexander V. , Myshlyavtseva Marta D. , Stishenko Pavel V.
Published: July 2020

We present to the scientific community the Surface Science Modeling and Simulation Toolkit (SuSMoST), which includes a number of utilities and implementations of statistical physics algorithms and models. WithSuSMoSTit is possible to predict or explain the structure and thermodynamic properties of adsorption layers.SuSMoSTautomatically builds formal graph and tensor‐network models based on atomic description of adsorption complexes and helps to do ab initio calculations of interactions between adsorbed species. Using methods of various natureSuSMoSTgenerates representative samples of adsorption layers and computes its thermodynamic quantities such as mean energy, coverage, density, and heat capacity. From these data one can plot phase diagrams of adsorption systems, assess thermal stability of self‐assembled structures, simulate thermal desorption spectra, and so forth.
Evaluation of methods to detect and quantify the bimodal precipitation over Central America and Mexico
Authors: Zhao Zijie , Zhang Xihan
Published: July 2020

Bimodal precipitation is a globally observed and regionally significant event that has a significant influence on the agriculture, public health, and insurance needs of associated regions. Many studies have focused on the mechanisms behind the generation and development of this event; however, little research into its characteristics exists due to a lack of a widely accepted method for accurate detection and quantification. Using a function collection containing various methods, different methods can be compared in terms of their performance in the detection and quantification of bimodal precipitation signals, allowing the proposal of appropriate criteria for method choice in various study types. Five methods (Mosiño and García, 1966; Curtis, 2002; Angeles et al., 2010; Karnauskas et al., 2013; Zhao et al., 2020) are adapted to the Climate Prediction Centre data during 1979–2017 in the domain of southern Mexico and Central America, and their performances are evaluated and compared. While outputs from the five methods reach general consistence for strong bimodal features over the Pacific side of Central America and Yucatán Peninsula, some biases are identified, specifically shown by the fact that methods using monthly climatological data demonstrates bimodal precipitation over the Caribbean side of Central America, while those using daily annual data indicate the existence of bimodal precipitation over the Pacific side of southern Mexico. By comparing two typical algorithms, we determined that this bias was induced by the limitation of temporal resolution in monthly climatological data and the nature of algorithms applying daily annual data. As part of a case study, a cluster algorithm was applied to outputs from an algorithm using daily annual precipitation, and a classification algorithm was used to test clustering performance. The resultant general high accuracy shows that annual bimodal signals offer good adaption to cluster and other potential machine learning algorithms.
Assessing the risk of bias in choice of search sources for environmental meta‐analyses
Authors: Konno Ko , Pullin Andrew S.
Published: July 2020

Results of meta‐analyses are potentially valuable for informing environmental policy and practice decisions. However, selective sampling of primary studies through searches exclusively using widely used bibliographic platform(s) could bias estimates of effect sizes. Such search strategies are common in environmental evidence reviews, and if risk of bias can be detected, this would provide the first empirical evidence that comprehensiveness of searches needs to be improved. We compare the impact of using single and multiple bibliographic platform(s) searches vs more comprehensive searches on estimates of mean effect sizes. We used 137 published meta‐analyses, based on multiple source searches, analyzing 9388 studies: 8095 sourced from commercially published articles; and 1293 from grey literature and unpublished data. Single‐platform and multiple‐platform searches missed studies in 100 and 80 of the meta‐analyses, respectively: 52 and 46 meta‐analyses provided larger‐effect estimates; 32 and 28 meta‐analyses provided smaller‐effect estimates; eight and four meta‐analyses provided opposite direction of estimates; and two each were unable to estimate effects due to missing all studies. Further, we found significant positive log‐linear relationships between proportions of studies missed and the deviations of mean effect sizes, suggesting that as the number of studies missed increases, deviation of mean effect size is likely to expand. We also found significant differences in mean effect sizes between indexed and non‐indexed studies for 35% of meta‐analyses, indicating high risk of bias when the searches were restricted. We conclude that the restricted searches are likely to lead to unrepresentative samples of studies and biased estimates of true effects.
Monolayer Conveyor for Stably Trapping and Transporting Sub‐1 nm Particles
Authors: Danesh Mohammad , Zadeh Mehdi Jafary , Zhang Tianhang , Zhang Xiaohe , Gu Bing , Lu Jin‐Sheng , Cao Tun , Liu Zhengtong , Wee Andrew T. S. , Qiu Min , Bao Qiaoliang , Maier Stefan , Qiu Cheng‐Wei
Published: July 2020

Efficient manipulation of nanoparticles and single molecules has always been of great interest and potential in nanotechnology. However, many challenges still remain in effectively functionalizing structures for this purpose. In this work, taking advantage of graphene's Dirac plasmon for its extreme confinement and tunability, a monolayer conveyor along which the position of optical potential well can be dynamically controlled is theoretically proposed. It is shown that by tuning a single voltage, one can manipulate the resonance along the graphene nanoribbon by changing graphene's effective surface plasmons wavelength. A configuration of monolayer graphene conveyor is proposed and Langevin dynamics reveals that a prototypical nanoparticle (1 nm size) can be effectively confined and transported along the device with proper external bias voltage. Hence, this work successfully proposes a promising avenue toward reconfigurable nanomanipulation of sub‐1 nm nanoparticles, and goes beyond the current state‐of‐the‐art of optical micrometer/nanometer‐sized particles manipulation with optical tweezers and nanoplasmonic tweezers.
Multiple solutions for superlinear Klein–Gordon–Maxwell equations†
Authors: Wu Dong‐Lun , Lin Hongxia
Published: July 2020

In this paper, we consider the following Klein–Gordon–Maxwell equations
where is a constant, u, , is a potential function. By assuming the coercive condition on V and some new superlinear conditions on f, we obtain two nontrivial solutions when h is nonzero and infinitely many solutions when f is odd in u and for above equations.
Glutaredoxin 1 Downregulation in the Substantia Nigra Leads to Dopaminergic Degeneration in Mice
Authors: Verma Aditi , Ray Ajit , Bapat Deepti , Diwakar Latha , Kommaddi Reddy Peera , Schneider Bernard L. , Hirsch Etienne C. , Ravindranath Vijayalakshmi
Published: July 2020

Background

Parkinson's disease (PD) is characterized by a severe loss of the dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc). Perturbation of protein thiol redox homeostasis has been shown to play a role in the dysregulation of cell death and cell survival signaling pathways in these neurons. Glutaredoxin 1 (Grx1) is a thiol/disulfide oxidoreductase that catalyzes the deglutathionylation of proteins and is important for regulation of cellular protein thiol redox homeostasis.

Objectives

We evaluated if the downregulation of Grx1 could lead to dopaminergic degeneration and PD‐relevant motor deficits in mice.

Methods

Grx1 was downregulated unilaterally through viral vector‐mediated transduction of short hairpin RNA against Grx1 into the SNpc. Behavioral assessment was performed through rotarod and elevated body swing test. Stereological analysis of tyrosine hydroxylase–positive and Nissl‐positive neurons was carried out to evaluate neurodegeneration.

Results

Downregulation of Grx1 resulted in contralateral bias of elevated body swing and reduced latency to fall off, accelerating rotarod. This was accompanied by a loss of tyrosine hydroxylase–positive neurons in the SNpc and their DA projections in the striatum. Furthermore, there was a loss Nissl‐positive neurons in the SNpc, indicating cell death. This was selective to the SNpc neurons because DA neurons in the ventral tegmental area were unaffected akin to that seen in human PD. Furthermore, Grx1 mRNA expression was substantially decreased in the SNpc from PD patients.

Conclusions

Our study indicates that Grx1 is critical for the survival of SNpc DA neurons and that it is downregulated in human PD. © 2020 International Parkinson and Movement Disorder Society
Simultaneous proton density, T1, T2, and flip‐angle mapping of the brain at 7 T using multiparametric 3D SSFP imaging and parallel‐transmission universal pulses
Authors: Leroi Lisa , Gras Vincent , Boulant Nicolas , Ripart Mathilde , Poirion Emilie , Santin Mathieu D. , Valabregue Romain , Mauconduit Franck , Hertz‐Pannier Lucie , Le Bihan Denis , de Rochefort Ludovic , Vignaud Alexandre
Published: July 2020

Purpose

Performing simultaneous quantitative MRI at ultrahigh field is challenging, as B0 and heterogeneities as well as specific absorption rate increase. Too large deviations of flip angle from the target can induce biases and impair SNR in the quantification process. In this work, we use calibration‐free parallel transmission, a dedicated pulse‐sequence parameter optimization and signal fitting to recover 3D proton density, flip angle, T1, and T2 maps over the whole brain, in a clinically suitable time.

Methods

Eleven optimized contrasts were acquired with an unbalanced SSFP sequence by varying flip‐angle amplitude and RF phase‐cycling increment, at a 1.0 × 1.0 × 3.0 mm3 resolution. Acquisition time was 16 minutes 36 seconds for the whole brain. Parallel transmission and universal pulses were used to mitigate heterogeneity, to improve the results’ reliability over 6 healthy volunteers (3 females/3 males, age 22.6 ± 2.7 years old). Quantification of the physical parameters was performed by fitting the acquired contrasts to the simulated ones using the Bloch‐Torrey equations with a realistic diffusion coefficient.

Results

Whole‐brain 3D maps of effective flip angle, proton density, and relaxation times were estimated. Parallel transmission improved the robustness of the results at 7 T. Results were in accordance with literature and with measurements from standard methods.

Conclusion

These preliminary results show robust proton density, flip angle, T1, and T2 map retrieval. Other parameters, such as ADC, could be assessed. With further optimization in the acquisition, scan time could be reduced and spatial resolution increased to bring this multiparametric quantification method to clinical research routine at 7 T.
Exogenous Dietary Ketone Ester Decreases Body Weight and Adiposity in Mice Housed at Thermoneutrality
Authors: Deemer Sarah E. , Davis Rachel A. H. , Roberts Brandon M. , Smith Daniel L. , Koutnik Andrew P. , Poff Angela M. , D’Agostino Dominic P. , Plaisance Eric P.
Published: July 2020

Objective

The aim of this study was to examine the effects of a ketone ester (KE)‐supplemented diet on energy expenditure (EE) and adiposity in mice housed at 23 °C versus thermoneutrality (30 °C), in which sympathetic nervous system activity is diminished.

Methods

Thirty‐two 10‐week‐old male C57BL/6J mice were assigned to 1 of 4 groups (n = 8 per group): 30% KE diet + 23 °C (KE23), control (CON) diet + 23 °C (CON23), 30% KE diet + 30 °C (KE30), or CON diet + 30 °C (CON30). CON mice were pair‐fed to the average intake of mice consuming the KE diet (ad libitum) for 8 weeks. Body composition and components of energy balance were measured at completion of the study.

Results

CON23 (mean ± SD, 26.0 ± 1.6 g) and CON30 (29.7 ± 1.4 g) mice weighed more than KE groups (P < 0.03 for both) and were also different from each other (CON23 vs. CON30, P < 0.01). However, KE23 (23.4 ± 2.7 g) and KE30 (23.1 ± 1.9 g) mice were not different in body weight. As expected, food intake at 30 °C (2.0 ± 0.3 g/d) was lower than at 23 °C (2.6 ± 0.3 g/d, P < 0.01). Diet did not influence resting and total EE, but mice housed at 30 °C had lower EE compared with mice at 23 °C (P < 0.01).

Conclusions

Dietary KEs attenuate body weight gain at standard (23 °C) and thermoneutral (30 °C) housing temperatures, and this effect is not mediated by increased EE under these conditions.
Testicular transposition in children before scrotal external radiotherapy
Authors: Le Bon Marielle , Lejeune Herve , Helfre Sylvie , Bolle Stéphanie , Padovani Laetitia , Mengue Laurence , Corradini Nadege , Hameury Frédéric , Claude Line
Published: July 2020

Testicular transposition (TT) before scrotal external radiotherapy (RT) is poorly reported in children with cancer, with only rare case reports published. TT surgical techniques, dosimetric parameters, and testicular functions are retrospectively reported in 12 children, median age 12.8 years, after scrotal RT for sarcomas. TT has low morbidity and allows a dramatic RT dose decrease in the healthy testicle. Endocrine functions seem preserved while more follow‐up is needed to assess fertility. Though a rare situation, TT should be discussed in children and young adult cases when a scrotal high‐dose RT is needed.
Plasticization mechanism in polybenzimidazole membranes for organic solvent nanofiltration: Molecular insights from in situ FTIR spectroscopy
Authors: Loianno Valerio , Bye Kelly P. , Galizia Michele , Musto Pellegrino
Published: July 2020

Despite substantial research efforts being devoted to design polymer membranes for organic solvent nanofiltration (OSN) exhibiting enhanced plasticization resistance, detailed studies of membrane structural stability in chemically challenging environments are rare. This study sets forth a multiscale method, which combines in situ FTIR measurements in the transmission mode with sorption and transport measurements, to investigate the molecular mechanism of polymer plasticization upon exposure to organic species. We recently reported that polybenzimidazole (PBI), a polymer that has been considered for OSN application, experiences severe plasticization upon exposure to methanol. FTIR measurements suggest that the mechanism of PBI plasticization relies on competitive hydrogen bonding. According to this mechanism, methanol molecules disrupt the hydrogen bonded network characteristic of dry PBI, by forming mutual polymer/penetrant hydrogen bonds, which enhances polymer chain mobility and favors polymer plasticization. The analysis of the isosteric heat of sorption supports the picture sketched above. The method developed in this study can be readily extended to many other systems of practical interest in membrane science, to shed fundamental light on the phenomenon of plasticization, whose molecular aspects are still largely unknown. Equally important, this study provides some useful guidelines to design OSN membrane materials.
Video conference vs face‐to‐face group psychotherapy for distressed cancer survivors: A randomized controlled trial
Authors: Lleras de Frutos María , Medina Joan Carles , Vives Jaume , Casellas‐Grau Anna , Marzo Jose Luis , Borràs Josep M. , Ochoa‐Arnedo Cristian
Published: July 2020

Objective

This study assesses the effectiveness of face‐to‐face group positive psychotherapy for cancer survivors (PPC) compared to its online adaptation, online group positive psychotherapy for cancer survivors (OPPC), which is held via videoconference. A two‐arm, pragmatic randomized controlled trial was conducted to examine the effects of both interventions on emotional distress, post‐traumatic stress symptoms (PTSS), and post‐traumatic growth (PTG) among cancer survivors and analyze attrition to treatment.

Methods

Adult women with a range of cancer diagnoses were invited to participate if they experienced emotional distress at the end of their primary oncological treatment. Emotional distress, PTSS, and PTG were assessed at baseline, immediately after treatment, and 3 months after treatment. Intention‐to‐treat analyses were carried out using general linear mixed models to test the effect of the interventions overtime. Logistic regressions were performed to test differential adherence to treatment and retention to follow‐up.

Results

A total of 269 individuals participated. The observed treatment effect was significant in both modalities, PPC and OPPC. Emotional distress (b = −2.24, 95% confidence interval [CI] = −3.15 to −1.33) and PTSS (b = −3.25, 95% CI = −4.97 to −1.53) decreased significantly over time, and PTG (b = 3.08, 95% CI = 0.38‐5.78) increased significantly. Treatment gains were sustained across outcomes and over time. Analyses revealed no significant differences between modalities of treatment, after adjusting for baseline differences, finding that OPPC is as effective and engaging as PPC.

Conclusions

The OPPC treatment was found to be effective and engaging for female cancer early survivors. These results open the door for psycho‐oncology interventions via videoconference, which are likely to lead to greater accessibility and availability of psychotherapy.
Study on the Improvement of Adhesion Strength between Composite Solid Propellant, Liner, and Heat‐Resistant Material
Authors: Park Sungjun J. , Choi Sunghan H. , Lee Sangwon W. , Jeon Jongwon J. , Park Jungho H.
Published: July 2020

This study was conducted to improve the adhesion strength between a propellant, liner, and heat‐resistant material. As the drying time of the heat‐resistant material increased, the adhesion strength between the propellant, liner, and heat‐resistant material improved. Further, the surface of the heat‐resistant material was subjected to buffing treatment to improve the adhesion strength. In addition, as the thickness of the heat‐resistant material increased, the adhesion strength degraded. Moreover, the adhesion strength was improved by increasing the thickness of the liner on the heat‐resistant material. Besides, the adhesion strength slightly reduced with an increase in the plasticizer content. The liner curing time was an important factor affecting the adhesion strength, and an optimum liner curing time was obtained. In this study, the adhesion strength was improved by applying a barrier coat between the heat‐resistant material and liner. The adhesion was further improved when the heat‐resistant material was buffed.
Polypharmacy, potentially serious clinically relevant drug‐drug interactions, and inappropriate medicines in elderly people with type 2 diabetes and their impact on quality of life
Authors: AL‐Musawe Labib , Torre Carla , Guerreiro Jose Pedro , Rodrigues Antonio Teixeira , Raposo Joao Filipe , Mota‐Filipe Helder , Martins Ana Paula
Published: July 2020

The aim of the study is to investigate the patterns of polypharmacy, clinical‐relevant drug‐drug interactions (DDIs), and potentially inappropriate medicines (PIMs), and whether polypharmacy, potential serious clinically‐relevant DDIs, or PIMs can be associated with low quality of life (QoL) index scores of older adults with type 2 diabetes (T2D). A cross‐sectional study was conducted using data of 670 elderly T2D sub‐cohort from a nationwide pharmacy‐based intensive monitoring study of inception cohort of T2D in Portugal. 72.09% were found on polypharmacy (≥5 medicines). Participants on polypharmacy were mostly females (P = .0115); more obese (P = .0131); have more comorbid conditions (P < .0001); more diabetes complications (P < .0001); and use more of glucose lowering drugs (P = .0326); insulin (P < .0001); chronic medicines (P < .0001); and have higher diabetes duration (P = .0088) than those without polypharmacy. 10.59% of the participants were found to have potential serious clinically relevant DDIs. The most frequent drug‐combinations were angiotensin‐converting enzyme (ACE) inhibitors with angiotensin‐receptor blockers (ARBs), aspirin with Selective serotonin reuptake inhibitors (SSRIs), and clopidogrel with calcium channel blockers. PIMs are found in 36.11% of the participants. The most common PIMs were benzodiazepines, long‐acting sulfonylureas, and iron overdose. The adjusted multivariate models show that Polypharmacy, PIMs, and potential serious clinically relevant DDIs were associated with lower QoL index scores (OR 1.80 95% CI 1.15‐2.82), (OR 1.57 95% CI 1.07‐2.28), and (OR 1.34 95% CI 0.73‐2.48) respectively. The study shows that polypharmacy, potential serious clinical‐relevant DDIs, and PIMs may correlate with risk of reduced health related QoL outcome of older adults with T2D.
QSP‐IO: A Quantitative Systems Pharmacology Toolbox for Mechanistic Multiscale Modeling for Immuno‐Oncology Applications
Authors: Sové Richard J. , Jafarnejad Mohammad , Zhao Chen , Wang Hanwen , Ma Huilin , Popel Aleksander S.
Published: July 2020

Immunotherapy has shown great potential in the treatment of cancer; however, only a fraction of patients respond to treatment, and many experience autoimmune‐related side effects. The pharmaceutical industry has relied on mathematical models to study the behavior of candidate drugs and more recently, complex, whole‐body, quantitative systems pharmacology (QSP) models have become increasingly popular for discovery and development. QSP modeling has the potential to discover novel predictive biomarkers as well as test the efficacy of treatment plans and combination therapies through virtual clinical trials. In this work, we present a QSP modeling platform for immuno‐oncology (IO) that incorporates detailed mechanisms for important immune interactions. This modular platform allows for the construction of QSP models of IO with varying degrees of complexity based on the research questions. Finally, we demonstrate the use of the platform through two example applications of immune checkpoint therapy.
Effect of an aqueous extract of Terminalia chebula on endothelial dysfunction, systemic inflammation, and lipid profile in type 2 diabetes mellitus: A randomized double‐blind, placebo‐controlled clinical study
Authors: Pingali Usharani , Sukumaran Deepasree , Nutalapati Chandrasekhar
Published: July 2020

Endothelial dysfunction is a crucial complication in type 2 diabetic patients, related to cardiovascular risk. Terminalia chebula (TC), a traditional ayurvedic herb, is known for its antioxidant and antihyperlipidemic activity. A prospective, randomized, double‐blind, placebo‐controlled clinical study was undertaken to evaluate the effects of an aqueous extract of T. chebula 250 and 500 mg versus placebo on endothelial dysfunction and biomarkers of oxidative stress in type 2 diabetic patients. A total of 60 eligible patients were randomized to receive either T. chebula 250 mg, T. chebula 500 mg, or placebo twice daily for 12 weeks. The subjects were assessed based on the endothelial function, the levels of nitric oxide, malondialdehyde, glutathione, high sensitivity C‐reactive protein, glycosylated hemoglobin, and lipid profile at baseline and after 12 weeks of treatment. Treatment with T. chebula 250 mg and T. chebula 500 mg for 12 weeks significantly improved the endothelial function (reflection index) compared to placebo (absolute changes: ‐ T. chebula 250: −2.55 ± 1.82% vs. T. chebula 500: −5.21 ± 2.41% vs. placebo: 1.40 ± 2.11%). Other cardiovascular risk indicators were also significantly ameliorated in the treatment groups compared to placebo. In conclusion, T. chebula (especially, 500 mg BID dose) significantly minimized the cardiovascular risk factors in patients with type 2 diabetes compared to placebo.
1H and 13C NMR spectra of Strychnos alkaloids: Selected NMR updates
Authors: Semenov Valentin A. , Samultsev Dmitry O. , Krivdin Leonid B.
Published: July 2020

The PBE0/pcSseg‐2//pcseg‐2 calculations of 1H and 13C NMR chemical shifts were performed for a classical series of 12 Strychnos alkaloids (except for the earlier studied parent strychnine), namely akuammicine, isostrychnine, rosibiline, tsilanine, spermostrychnine, diaboline, cyclostrychnine, henningsamide, strychnosilidine, strychnobrasiline, holstiine, and icajine. It was found that the calculated 1H and 13C NMR chemical shifts show markedly good correlations with available experimental data, as characterized by a mean absolute error of 0.22 ppm for the range of 8 ppm for protons and 1.97 ppm for the range of 180 ppm for carbons. Complementarily, the present results provide essential NMR update and fill a gap in the NMR data of this distinguished group of vitally important natural products.
Umbilical cord blood: The promise and the uncertainty
Authors: Kindwall-Keller Tamila L. , Ballen Karen K.
Published: July 2020

Unfortunately, many patients referred for hematopoietic cell transplant will not have a fully matched related donor, and finding matched unrelated donors through the registry may be difficult, especially if the recipient is not of Northern European descent [N Engl J Med 2014;371:339-348]. Umbilical cord blood (UCB) has been an available graft source for hematopoietic cell transplant for more than 30 years, since the first UCB transplant was performed in the late 1980s [N Engl J Med 1989;321:1174-1178]. UCB is readily available, has low immunogenicity, and does not require as strict of human leukocyte antigen (HLA) matching compared to other graft sources [N Engl J Med 2004;351:2265-2275]. According to data from the Center for International Blood and Marrow Transplant Research (CIBMTR), an estimated 500 patients in the US will have received a UCB transplant in 2018. Since 2014, haploidentical transplants have surpassed UCB transplants performed in the United States (CIBMTR Summary Slides, 2018, available at https://www.cibmtr.org). Increased use of haploidentical transplants has brought to light concerns about UCB transplants, including delayed engraftment and graft failure, increased nonrelapse mortality, increased infection risk, and UCB acquisition costs [Lancet Oncol 2010;11:653-660; Biol Blood Marrow Transplant 2019;1456-1464]. These concerns will need to be addressed for UCB to remain a viable option as a graft source for hematopoietic cell transplant. Other promising therapeutic benefits for UCB, in addition to hematopoietic cell transplant, is its use in regenerative medicine and immune modulation, which is currently being evaluated in ongoing clinical trials.
CIRM tools and technologies: Breaking bottlenecks to the development of stem cell therapies
Authors: Collins Lila R. , Shepard Kelly A.
Published: July 2020

The California Institute for Regenerative Medicine (CIRM) has a mission to accelerate stem cell treatments to patients with unmet medical needs. This perspective describes successful examples of work funded by CIRM’s New Cell Lines and Tools and Technologies Initiatives, which were developed to address bottlenecks to stem cell research and translation. The tools developed through these programs evolved from more discovery-oriented technologies, such as disease models, differentiation processes, and assays, to more translation focused tools, including scalable good manufacturing processes, animal models, and tools for clinical cell delivery. These tools are available to the research community and many are facilitating translation of regenerative therapeutics today.
Stereochemistry of the Kabachnik‐Fields Condensation of Terpenic Amino Oximes with Aldehydes and Dimethyl Phosphite
Authors: Marenin Konstantin S. , Agafontsev Alexander M. , Bryleva Yuliya A. , Gatilov Yuri V. , Glinskaya Ludmila A. , Piryazev Dmitry A. , Tkachev Alexey V.
Published: July 2020

Three‐component condensation of aldehydes and dimethyl phosphite with α‐amino oximes derived from (−)‐α‐pinene and (+)‐3‐carene (Kabachnik‐Fields reaction) resulted in amino phosphonates as pairs of diastereomers. Diastereomeric ratio depends on the catalyst used (SnCl2×2H2O, SiO2, Al2O3‐H+) and the heating type (conventional or microwave). The best results were achieved by MW irradiation with simultaneous cooling. Stereochemical assignment of the key derivatives was made by X‐ray diffractometry. According to quantum chemical calculations (DFT PBE0/def2‐TZVPP) and spectroscopic data, the terpenic α‐amino phosphonates should be conformationally inhomogeneous, exhibiting a tendency to form H‐bonded dimers (DFT M06/def2‐SVP, IR). One‐bond spin‐spin coupling 1JP–C was found to be diagnostic for the configuration assignment since the value 1JP–C depends on the dihedral angle between bond C−P and axis of the electron lone pair at the neighboring nitrogen (NMR, DFT PBE0/aug‐cc‐pVTZ−J).
An empirical comparison of commercial and open‐source web vulnerability scanners
Authors: Amankwah Richard , Chen Jinfu , Kudjo Patrick Kwaku , Towey Dave
Published: July 2020

Web vulnerability scanners (WVSs) are tools that can detect security vulnerabilities in web services. Although both commercial and open‐source WVSs exist, their vulnerability detection capability and performance vary. In this article, we report on a comparative study to determine the vulnerability detection capabilities of eight WVSs (both open and commercial) using two vulnerable web applications: WebGoat and Damn vulnerable web application. The eight WVSs studied were: Acunetix; HP WebInspect; IBM AppScan; OWASP ZAP; Skipfish; Arachni; Vega; and Iron WASP. The performance was evaluated using multiple evaluation metrics: precision; recall; Youden index; OWASP web benchmark evaluation; and the web application security scanner evaluation criteria. The experimental results show that, while the commercial scanners are effective in detecting security vulnerabilities, some open‐source scanners (such as ZAP and Skipfish) can also be effective. In summary, this study recommends improving the vulnerability detection capabilities of both the open‐source and commercial scanners to enhance code coverage and the detection rate, and to reduce the number of false‐positives.
Set‐based design: The state‐of‐practice and research opportunities
Authors: Shallcross Nicholas , Parnell Gregory S. , Pohl Ed , Specking Eric
Published: July 2020

Increasing system complexity has provided the impetus to develop new and novel systems engineering methodologies. One of these methodologies is set‐based design (SBD), a concurrent design methodology well suited for complex systems subject to significant uncertainty. Since the 1990s, numerous private, public, and defense sector design programs have successfully implemented SBD. However, concerns regarding SBD's complexity, tendency toward qualitative methods, and lack of quantitative tools have limited its use. To address these issues, our research surveys 122 refereed journal articles and conference papers to assess SBD's state‐of‐practice and identify relevant research opportunities. To accomplish these tasks, we perform a structured literature review to identify and assess relevant and influential research. We found that SBD's state‐of‐practice relies heavily upon decision and tradespace analysis with increasing emphasis on uncertainty modeling and MBSE. We found that the majority of SBD research consists of quantitative methodologies focusing on component and small system applications. We also found that complex system applications used mostly qualitative methodologies. We identify SBD research opportunities for requirements development, MBSE, uncertainty modeling, multiresolution modeling, adversarial analysis, and program management. Finally, we recommend the development of a comprehensive SBD methodology and toolkit, suited for complex system design across all stages of the product development life cycle.
Discriminatory job advertisements for English language teachers in Colombia: An analysis of recruitment biases
Authors: Mackenzie Lee
Published: July 2020

Numerous studies have explored the persistence of discrimination against nonnative‐English‐speaking teachers (NNESTs) of English as a foreign or second language in various contexts. However, the author of this article could find no study that explores the prevalence of “native‐speakerism” and other forms of discrimination in English language teacher recruitment in South America. The current study thus investigated the extent to which online postings for English language teachers in Colombia expressed a preference for native‐English‐speaking teachers (NESTs) and how this discrimination intersects with other inequitable hiring practices. The author conducted content analysis on job ads found on two prominent Facebook groups for English language teachers in Colombia. The findings reveal evidence of discrimination in nearly half of the 95 job ads analysed. These ads discriminate based on age, gender, nationality, variety of English, the location where a prospective teacher gained their qualifications, and “nativeness.” The study tentatively concludes that this discrimination has several dimensions, with those further from the colonial “centre” facing greater degrees of discrimination. The mutually reinforcing constructs of coloniality and native‐speakerism help account for the persistence of such discrimination, which is also reflected in the Colombian governments’ linguistic policies.
Humanizing TESOL Research Through the Lens of Complexity Thinking
Authors: Pinner Richard S. , Sampson Richard J.
Published: July 2020

Humanizing complexity research is already strongly advocated by much of the literature on complexity (Kramsch, 2011; Larsen‐Freeman, 2011; Sampson, 2016) and yet there is a recent trend towards a potentially alienating approach, which could confound readers, utilising a dense vocabulary and overly technical methods. We advocate a more practical approach to complexity thinking, which continues on from McKinley’s (2019) paper on the teaching‐research nexus by advocating more practitioner‐based research which can provide emic and contextually situated insights into the language classroom.
A model of puppy growth during the first three weeks
Authors: Alves Isabel
Published: July 2020

Neonatal mortality in puppies is highly variable, with large scale surveys still reporting average values around 10% –15%. Weight measurement is the simplest way to monitor the development of the puppies, and a weight loss during the first 48 hr has been recognized as one of the factors that puts puppies at a higher risk of neonatal mortality. However, little is known about what constitutes optimum growth up to 3 weeks. In this study, a mathematical formula with the formP = P0exp (0.13084x‐ 0.001616x2), wherePis weight on DayxandP0is weight on Day 0, obtained by multiple linear regression, is presented and validated with data from 345 puppies belonging to 60 litters of 19 different breeds, from toy to giant size, showing that it appropriately describes maximum puppy growth rate during the neonatal period for all breeds. This formula is in agreement with previous studies and generic recommendations that can be found in the literature on puppy growth from birth to 21 days regarding relative daily weight gain. It can be easily introduced in a spreadsheet or used to build growth charts that can help the breeder or the veterinarian in monitoring and evaluating puppy growth during the neonatal period. Although deviations from the maximum growth rate can now be quantified, there is still a need to determine the limits beyond which supplementary feeding is advised/required.
Representation Learning and NLP
Authors: Liu Zhiyuan , Lin Yankai , Sun Maosong
Published: July 2020

Natural languages are typical unstructured information. Conventional Natural Language Processing (NLP) heavily relies on feature engineering, which requires careful design and considerable expertise. Representation learning aims to learn representations of raw data as useful information for further classification or prediction. This chapter presents a brief introduction to representation learning, including its motivation and basic idea, and also reviews its history and recent advances in both machine learning and NLP.
Dualities of 5d gauge theories from S-duality
Authors: Bhardwaj Lakshya
Published: July 2020

Abstract

We describe a general method to determine dualities between supersymmetric 5d gauge theories. The method is based on performing local S-dualities in the geometry associated to the gauge theory. We find that often a duality can be obtained by adding matter to both sides of a more primitive duality. This allows us to define the notion of irreducible dualities which cannot be obtained from more primitive dualities. More general dualities then are obtained by adding matter to both sides of an irreducible duality. The geometric method described in this paper allows us to systematically construct irreducible dualities. As an application, we explicitly determine a special class of irreducible dualities classified by removal and addition of edges into a Dynkin diagram. This class of dualities vastly generalizes many of the known 5d dualities in the literature.
Serum levels of the IL-6 family of cytokines predict prognosis in renal cell carcinoma (RCC)
Authors: Gudbrandsdottir Gigja , Aarstad Helene H. , Bostad Leif , Hjelle Karin M. , Aarstad Hans J. , Bruserud Øystein , Tvedt Tor Henrik Anderson , Beisland Christian
Published: July 2020

Purpose

An improved understanding of RCC immunology should shed further light on RCC tumor biology. Our objective was to study to what extent serum levels of the IL-6 family of cytokines at diagnosis were relevant to survival.

Methods

A total of 118 consecutively patients with RCC, in which the tumor was surgically removed at Haukeland University Hospital during the period from 2007 to 2010, were included. The patients were followed-up for 10 years. The morning before surgery blood was sampled and serum frozen, with levels of IL-6, IL-27, IL-31, OSM, CNTF, IL-6Rα and gp130 determined.

Results

Among patients with the highest quartile of IL-6 (> 8 pg/ml) (n = 29), six of nine who had metastasis at diagnosis had such high IL-6 values. Among presumed radically treated patients, a high IL-6 and IL-27 strongly predicted recurrence. In particular, the predictions among patients with large (diameter > 7 cm) tumors were excellent regarding both IL-6 and IL-27 values. High gp130 serum levels predicted an overall survival (OS) among RCC patients with large tumors. Patients with a high IL-6 exhibited a strong expression of IL-6 in endothelial- and vascular smooth muscle cells. Moreover, the level of intra-tumoral CD3-positive cells predicted survival.

Conclusions

IL-6 and IL-27 seem to play a role in RCC biology. IL-6 enables the pinpointing of metastatic condition at diagnosis, as well as together with IL-27, the predicting of survival and recurrence. Endothelial cells and vascular smooth muscle cells are both suggested as important sources of IL-6.
Thermodynamics of the system Fe–Si–O under high pressure and temperature and its implications for Earth’s core
Authors: Komabayashi Tetsuya
Published: July 2020

The thermodynamics of the system Fe–Si–O under high pressure (P) and temperature (T) was examined, starting with modelling the phase transition between a face-centred cubic (fcc) and hexagonal close-packed (hcp) structure in Fe–Si alloy which was previously examined by experiment under high P–T conditions. The mixing properties of Fe and Si for the iron phases were found to be approximated by ideal mixing under high P and T conditions. The entropy changes upon melting of the end-members of the system are fairly large, and therefore the melting temperature of the Si-bearing fcc or hcp phases needs to be insensitive to the Si content, to account for the reported close compositions of coexisting liquid and solid (< 1 wt%Si at P > 50 GPa). The solidus and liquidus temperatures of Fe–Si iron alloy would therefore, not significantly be changed by the presence of Si at the inner core-outer core boundary, which enables us to evaluate the melting curve of Fe–Si fcc and hcp phases. From thus-constrained melting curve, I assessed a thermal equation of state of Si-bearing iron liquid. I then estimated a seismologically consistent outer core composition as a function of Si and O contents using the EoS for liquids constructed in this study and the literature. The best-fit composition is Fe-5.8(0.6) wt%Si–0.8(0.6) wt%O, which however does not precipitate a solid iron phase that is consistent with the inner core density. Therefore, Earth’s core cannot be fully represented by the system Fe–Si–O and it should include another light element.
Rotatable microfluidic device for simultaneous study of bilateral chemosensory neurons in Caenorhabditis elegans
Authors: Chung Jinyang , Brittin Christopher A. , Evans Stephen D. , Cohen Netta , Shim Jung-uk
Published: July 2020

The nematode Caenorhabditis elegans is a leading model system in genetics, development and neurobiology; its transparent body and small size make it particularly suitable for fluorescent imaging of cells and neurons within microfluidic setups. Simultaneously recording activity in bilaterally symmetric cells has proved difficult in C. elegans because the worm enters the chip and is then immobilised when it is lying on one side of the body. We developed a side-view rotatable microfluidic device that allows us to image a pair of bilateral neurons in a single focal plane of an epi-fluorescence microscope. We demonstrated the utility of the device by recording the responses of immobilised worms to controlled stimuli, focusing on the responses of two classes of head sensory neurons to changes in NaCl concentration. The results indicate that responses of ASE left and right and ASH left and right sensory neurons are stochastic. Simultaneous recordings of ASH left and right neurons tend to synchronise, pointing to a role of gap junctional connectivity. The anatomy of the C. elegans nerve ring makes this microfluidic approach ideally suited for the study of spatially extended pairs of neurons or larger neuronal circuits that lie within a limited depth of field.
Licensing, Educational Credentialing, and Wages Among Foreign Skilled Workers in Germany
Authors: Rohrbach-Schmidt Daniela
Published: July 2020

The article studies whether foreign skilled workers have similar access to licensed and more credentialed occupations, and whether they profit from these regulations in terms of similar wages in these occupations to comparable domestic skilled workers. The theoretical foundations of this article are concepts of signaling and occupational closure. The analyses use a sample of 60,000 employed persons from the 2006, 2012 and 2018 Employment Surveys of the German Federal Institute for Vocational Education and Training (BIBB) and the Federal Institute for Occupational Safety and Health (BAuA), and a reweighting approach to account for the selection on observables. Results show an ambivalent picture of the regulation of occupations: on the one hand, at least foreign skilled men earn similar wages to domestic skilled men in more closed occupations; on the other hand, foreign skilled workers are less likely to enter these positions and they have monetary disadvantages compared with domestic skilled workers in less closed occupations.