bluuebunny/crossref_metadata_2025 huggingface dataset:
A New Look on Octet‐Compliant Macrocyclic Organoaluminum Carboxylates as Dormant Poly‐Lewis Acids
Authors: Terlecki Michał , Justyniak Iwona , Prochowicz Daniel , Lewiński Janusz
Published: December 2019

A more in‐depth understanding of the multi‐faceted chemistry of organoaluminum complexes is continually vital for the comprehension and development of new reagents and catalytic systems as well as molecular building blocks for modern functional materials. In this report we utilize a macrocyclic tetranuclear organoaluminum derivative of 2,3‐naphthalenedicarboxylic acid (naphtha‐H2), [(Me2Al)2(naphtha)]2, as a model complex to probe both the dormant Lewis acidity and self‐assembly processes of octet‐compliant multinuclear macrocyclic organoaluminum compounds in the presence of mono‐ or bidentate pyridine ligands. The results nicely demonstrate that multinuclear octet‐compliant organoaluminum clusters may effectively act as so‐called poly‐Lewis acids, utilizing their dormant Lewis acidity with the preservation or cleavage of the parent macrocycle depending on the character of both donor ligands and aromatic subunits of the dicarboxylate ligands.
Synthesis of Carbamates from Alkyl Bromides and Secondary Amines Using Silver Carbonate
Authors: Acharya Vanitha , Mal Sanjib , Kilaru Jagadeesh P. , Montgomery Mark G. , Deshpande Sudhindra H. , Sonawane Ravindra P. , Manjunath Bhanu N. , Pal Sitaram
Published: December 2019

Synthesis of alkyl carbamates from alkyl bromides and secondary amines using silver carbonate as a carbonate source under mild condition is described. Various secondary amines and bromo derivatives were converted into alkyl carbamate derivatives in 33 to 62 % yield.
Opioids for chronic low back pain: An updated systematic review and meta‐analysis of efficacy, tolerability and safety in randomized placebo‐controlled studies of at least 4 weeks of double‐blind duration
Authors: Petzke Frank , Klose Petra , Welsch Patrick , Sommer Claudia , Häuser Winfried
Published: December 2019

Background and Objective

This updated systematic review evaluated the efficacy, tolerability and safety of opioids compared to placebo in non‐malignant chronic low back pain.

Databases and Data Treatment

Clinicaltrials.gov, CENTRAL, MEDLINE and PsycINFO were searched from October 2013 to May 2019. Randomized controlled trials comparing opioids with placebo and at least 4 weeks of double‐blinded duration were analysed. Primary outcomes were pain relief of 50% or greater, disability, tolerability and safety. Effects were summarized by a random effects model using risk differences or standardized mean differences. We added nine new studies with 2,980 participants for a total of 21 studies with 7,650 participants. Study duration ranged between 4 and 15 weeks. Studies with a parallel and cross‐over design: Based on very low to low‐quality evidence, opioids provided no clinically relevant pain relief of 50% or greater, but a clinically relevant reduction of disability compared to placebo. Enriched enrolment randomized withdrawal (EERW) design: Based on very low to low‐quality evidence, opioids provided a clinically relevant pain relief of 50% or greater, but not a clinically relevant reduction of disability compared to placebo. There was no clinically relevant harm with regard to serious adverse events by opioids compared to placebo in studies with parallel/cross‐over and EERW design. There was a relevant harm with regard to drop out rates due to adverse events in studies with parallel/cross‐over, but not in studies with EERW design.

Conclusions

Opioids may provide a safe and clinically relevant pain relief for 4–15 weeks in highly selected patients.

Significance

Within the context of randomized controlled trials of 4–15 weeks, opioids provided a clinically relevant pain relief of 30% or greater and a clinically relevant reduction of disability compared to placebo in non‐malignant chronic low back pain. Number needed to treat for an additional drop out due to side effects was 11 (95% confidence interval: 6–33). Assessment of abuse and addiction was incomplete. The frequency of serious adverse events including deaths did not differ from placebo.
Application of polydopamine‐coated nylon capillary‐channeled polymer fibers as a stationary phase for mass spectrometric phosphopeptide analysis
Authors: Trang Hung K. , Marcus R. Kenneth
Published: December 2019

Capillary‐channeled polymer (C‐CP) fibers are demonstrated as a selective stationary phase for phosphopeptide analysis via LC–MS. Taking advantage of the oxidative self‐polymerization of dopamine under alkaline conditions, a simple system involving a dilute aqueous solution of 0.2% w/v dopamine hydrochloride in 0.15% w/v TRIS buffer, pH 8.5 was utilized to coat polydopamine onto nylon 6 C‐CP fibers. Confirmation of the polydopamine coating on the fibers (nylon‐PDA) was made through attenuated total reflection‐FTIR (ATR‐FTIR) analysis. Imaging using SEM was also performed to examine the morphology and topography of the nylon‐PDA. Subsequent loading of Fe3+ to the nylon‐PDA matrix was confirmed by SEM/energy dispersive X‐ray spectroscopy (SEM/EDX). The Fe3+‐bound nylon‐PDA fibers packed in a microbore column format were tested in the off‐line preconcentration of phosphopeptides from a 1:100 mixture of β‐casein/BSA digests for MALDI‐TOF analysis. The packed column was also installed onto an HPLC system as a platform for the online sample clean‐up and enrichment of phosphopeptides from a 1:1000 mixture of β‐casein/BSA protein digests that were determined by subsequent ESI–MS analysis.
A method to determine nuclear magnetic resonanceT2cutoff value of tight sandstone reservoir based on multifractal analysis
Authors: Hu Yunbing , Guo Yinghai , Zhang Junjian , Shangguan Jingwen , Li Mi , Quan Fangkai , Li Guanlin
Published: December 2019

Nuclear magnetic resonance (NMR)T2cutoff value is an important parameter for pore structure evaluation. It is complicated and uneconomical to obtainT2cutoff value by an experimental method; therefore, it is necessary to explore a prediction method ofT2cutoff value. In this paper, 10 samples of tight gas reservoirs in the eastern Ordos Basin were selected, and then saturation and centrifugal experiments of nuclear magnetic resonance were carried out. On this basis, multifractal theory was introduced to calculate the multifractal characteristics of the NMRT2spectrum of each sample, and the relationship between multifractal parameters andT2value was analyzed. The influencing factors of theT2cutoff value were clarified, and the prediction model of theT2cutoff value was constructed accordingly. The results show that theT2spectra of sandstones in the study area can be divided into three types: single steeple peak, double steeple peak, and irregular double peak. The pore diameter of the three types is 1 nm ~ 3×104 nm, 1 nm ~ 104 nm and 1 nm ~ 4×103 nm, respectively. TheT2cutoff value ranges from 9.72 to 35.16 ms. The correlation analysis suggests that the symmetrical fractal dimension difference and symmetrical multifractal dimension ratio (Dmin−Dmax, Dmin/Dmax) shows a positive linear correlation with theT2cutoff value. The value ofT2cutoff gradually decreases with the increase of the flow zone indicator (FZI). Therefore, three parameters, including symmetrical fractal dimension difference, symmetrical multifractal number ratio, andFZIare optimized, and the prediction model for the NMRT2cutoff value of sandstone samples in the study area is proposed. The introduction of porosity‐related parameters compensates for the shortcomings of previousT2cutoff value prediction models. At the same time, the prediction model is proven to be accurate and reliable by testing the measured data of the samples near the study area. The results of this paper can be used for further study of the NMRT2cutoff value prediction of tight sandstone reservoirs in different areas.
CACC: Context‐aware congestion control approach for lightweight CoAP/UDP‐based Internet of Things traffic
Authors: Akpakwu Godfrey A. , Hancke Gerhard P. , Abu‐Mahfouz Adnan M.
Published: December 2019

With the emerging applications of the Internet of Things (IoT), a congestion control mechanism becomes a critical phenomenon for efficient communication in networks of constrained devices. The Internet Engineering Task Force developed the constrained application protocol (CoAP) as a standard communication protocol that favors lightweight interoperability for accommodating resource‐constrained devices. However, the base CoAP specification congestion control is insensitive to various network conditions. Thus, differentiating the scenario of packet loss due to bit error rate and congestion, and identifying correct round trip time (RTT) of retransmitted message‐acknowledgement is quite essential to adapt the CoAP behavior based on the network status. In this paper, we present a context‐aware congestion control (CACC) approach for lightweight CoAP/user datagram protocol–based IoT traffic. The CACC proposes mechanisms that include retransmission timeout (RTO) estimator, retransmission count–based smoothed round‐trip‐time observation, lower bound RTO restriction approach, and aging concept. The proposed RTO estimators utilize the strong, weak, and failed RTT to identify exact network status and provide adaptive congestion control. The CACC incorporates the variable of retransmission count in request‐response interaction model to mitigate the negative variation in RTT due to the fluctuation in the IoT environment. Moreover, with lower bound RTO restriction approach, the unnecessary spurious retransmissions are avoided, and the aging mechanism limits the validity of the RTO value to improve the efficiency of the proposed scheme. The proposed model is validated against baseline CoAP and CoCoA+ using Contiki OS and the Cooja simulator. The results are impressive under different network topologies.
In vitro study of the antioxidative and antiproliferative capabilities of Lactobacillus casei 16‐fermented soymilk
Authors: Qian Fang , Zhang Jiang , Hou Kairong , Zhang Yuqing , Wang Zifei , Luo Pengjie , Tuo Yanfeng
Published: December 2019

In this study, soymilk was fermented with Lactobacillus casei 16. The contents of aglycone isoflavones, saponins, total phenolic, and free amino acid in the fermented soymilk, and the protection for the HepG2 cells against 2,2'‐azobis(2‐amidinopropane) dihydrochloride (ABAP) damage and the antiproliferative effects of the fermented soymilk on the HT‐29 cells and Caco‐2 cells were studied. The results showed that the levels of total phenolic, aglycone isoflavones, and free amino acids in the L. casei 16‐fermented soymilk were enhanced. The ethanol extract and the water extract of the L. casei 16‐fermented soymilk showed protection for HepG2 cells against ABAP damage and inhibited the proliferation of the HT‐29 cells and Caco‐2 cells, which may be attributed to the enhanced level of total phenolic, aglycone isoflavones, and free amino acids in the L. casei 16‐fermented soymilk.
Sustained post‐seismic effects on groundwater flow in fractured carbonate aquifers in Central Italy
Authors: Mastrorillo Lucia , Saroli Michele , Viaroli Stefano , Banzato Francesca , Valigi Daniela , Petitta Marco
Published: December 2019

A sustained increase in spring discharges was monitored after the 2016 Central Italy seismic sequence in the fractured carbonate aquifer of Valnerina–Sibillini Mts. The groundwater surplus recorded between August 2016 and November 2017 was determined to be between 400 and 500 × 106 m3. In fractured aquifers, the post‐seismic rise in spring discharges is generally attributed to an increase in bulk permeability caused by the fracture cleaning effect, which is induced by pore pressure propagation. In the studied aquifers, the large amount of additional discharge cannot only be attributed to the enhanced permeability, which was evaluated to be less than 20% after each main seismic event. A detailed analysis of the spring discharge hydrographs and of the water level at five gauging stations was carried out to determine the possible causes of this sudden increase in groundwater outflow. Taking into account the geological and structural framework, a conceptual model of a basin‐in‐series has been adopted to describe the complex hydrogeological setting, where the thrusts and extensional faults have clearly influenced the groundwater flow directions before and after the seismic sequence. The prevalent portion of the total post‐seismic discharge surplus not explained by the increase in permeability has been attributed to changes in the hydraulic gradient that caused seismogenic fault rupture and the disruption in the upgradient sector of the aquifer. The additional flow calculated through the breach of the pre‐existing hydrostructural barrier corresponds to approximately 470 × 106 m3. This value is consistent with the total discharge increase measured in the whole study area, validating the proposed conceptual model. Consequently, a shift in the piezometric divide of the hydrogeological system has been induced, causing a potentially permanent change that lowers the discharge amount of the eastern springs.
Clinical and Biochemical Phenotypes in a Family With ENPP1 Mutations
Authors: Kotwal Anupam , Ferrer Alejandro , Kumar Rajiv , Singh Ravinder J , Murthy Vishakantha , Schultz-Rogers Laura , Zimmermann Michael , Lanpher Brendan , Zimmerman Kristin , Stabach Paul R , Klee Eric , Braddock Demetrios T , Wermers Robert A
Published: December 2019

Inactivating mutations of the ENPP1 gene are associated with generalized arterial calcification of infancy (GACI) and less often autosomal-recessive hypophosphatemic rickets type 2 (ARHR2). We aimed to investigate the spectrum of phenotypes in a family with monoallelic and biallelic mutations of ENPP1 after identification through whole exome sequencing of a 54-year-old female with biallelic mutation of ENPP1, c.323G > T; p.Cys108Phe and c.1441C > T; p.Arg481Trp. Including the proband, 2 subjects had biallelic mutations, 5 had monoallelic mutations, and 2 had no mutation of ENPP1. The maternal mutation, a known pathogenic variant associated with GACI, was found in 3 subjects with monoallelic mutations, while the paternal mutation, which was not previously reported, was present in 2 subjects with monoallelic mutations. Both subjects with biallelic mutations had bowing of bilateral femurs, periarticular mineral deposition, normocalcemic primary hyperparathyroidism with multigland parathyroidectomy, increased carotid intima-media thickness, and enthesopathy was also noted in one subject. Intact FGF23 was elevated in both subjects with biallelic mutations, while C-terminal FGF23 was only elevated in one and PPi was reduced in one. Subjects with monoallelic mutations did not have periarticular calcifications or bone deformities. To conclude, patients with biallelic GACI causing mutations can survive well into adulthood, and despite the same biallelic ENPP1 pathogenic variants, clinical and biochemical manifestations can significantly differ, and include enthesopathy and primary hyperparathyroidism, which have not been previously described. Although carriers of monoallelic ENPP1 variants appear unaffected by classic disease manifestations, there may be subtle biochemical and clinical findings that warrant further investigation. © 2019 American Society for Bone and Mineral Research.
LIGHT/TNFSF14 Promotes Osteolytic Bone Metastases in Non-small Cell Lung Cancer Patients
Authors: Brunetti Giacomina , Belisario Dimas C , Bortolotti Sara , Storlino Giuseppina , Colaianni Graziana , Faienza Maria F , Sanesi Lorenzo , Alliod Valentina , Buffoni Lucio , Centini Elisa , Voena Claudia , Pulito Roberta , Novello Silvia , Ingravallo Giuseppe , Rizzi Rita , Mori Giorgio , Reseland Janne E , Ware Carl F , Colucci Silvia , Ferracini Riccardo , Grano Maria , Roato Ilaria
Published: December 2019

Tumor necrosis factor superfamily member 14 (TNFSF14), LIGHT, is a component of the cytokine network that regulates innate and adaptive immune responses, which promote homeostasis of lymphoid organs, liver, and bone. Metastatic tumors often disrupt the tissue microenvironment, thus altering the homeostasis of the invaded organ; however, the underlying mechanisms required further studies. We investigated the role of LIGHT in osteolytic bone disease induced by metastatic non-small cell lung cancer (NSCLC). Patients diagnosed with NSCLC bone metastasis show significantly higher levels of LIGHT expressed in monocytes compared with non-bone metastatic tumors and healthy controls. Serum LIGHT levels were also higher in patients with bone metastases than in controls, suggesting a role for LIGHT in stimulating osteoclast precursors. In bone metastatic patients, we also detected increased RNA expression and serum RANKL levels, thus by adding anti-LIGHT or RANK–fragment crystallizable region (RANK-Fc) in PBMC cultures, a significant inhibition of osteoclastogenesis was observed. To model this observation in mice, we used the mouse lung cancer cell line LLC-1. After intratibial implantation, wild-type mice showed an increased number of osteoclasts but reduced numbers of osteoblasts and decreased osteoid formation. In contrast, Tnfsf14−/− mice showed no significant bone loss or other changes in bone homeostasis associated with this model. These data indicate LIGHT is a key control mechanism for regulating bone homeostasis during metastatic invasion. Thus, LIGHT may be a novel therapeutic target in osteolytic bone metastases. © 2019 American Society for Bone and Mineral Research.
Irisin Prevents Disuse-Induced Osteocyte Apoptosis
Authors: Storlino Giuseppina , Colaianni Graziana , Sanesi Lorenzo , Lippo Luciana , Brunetti Giacomina , Errede Mariella , Colucci Silvia , Passeri Giovanni , Grano Maria
Published: December 2019

Previous results showed that intermittently administered irisin improves bone mass in normal mice and prevents the development of disuse-induced osteoporosis and muscular atrophy in hindlimb-suspended mice, a murine model able to mimic the absence of mechanical loading. A recent study showed that irisin increases survival of osteocytes acting through integrin αV/β5 receptors. To better understand the action of irisin on these cells, we investigated the downstream signaling cascades in osteocyte-like cells (MLO-Y4) treated with recombinant irisin (rec-irisin) in vitro and we analyzed survival of osteocytes and caspase activation in cortical bone of osteoporotic mice treated with rec-irisin in vivo. Our results revealed that rec-irisin activated the MAP kinases Erk1 and Erk2 and increased the expression of the transcription factor Atf4 (2.5-fold, p < .05) through an Erk-dependent pathway in osteocytes. Some key genes expressed by MLO-Y4 cells were modulated by long-term irisin treatment, either continuously administered or given with intermittent short pulses. Interestingly, Sost mRNA was severely downregulated only upon intermittent irisin administration (10-fold, p < .001). Furthermore, rec-irisin upregulated Tfam mRNA (fourfold, p < .05) and Bcl2/Bax ratio (twofold, p < .05) in MLO-Y4 cells. By detecting caspase-9 and caspase-3, we also found that rec-irisin inhibited apoptosis induced by hydrogen peroxide and dexamethasone, respectively. In cortical bone of unloading C57BL6 mice treated with vehicle (unload-veh), irisin prevented disuse-induced reduction of viable osteocytes (+30% versus unload-veh, p < .05) and increase of empty lacunae (+110% versus unload-veh, p < .05), as well as caspase-9 (threefold, p < .05) and caspase-3 (twofold, p < .05) activations. Our findings revealed underlying mechanisms of irisin action on osteocytes, which increases their functions and exerts anti-apoptotic effects, confirming that mechanosensor cells of bone are sensitive to the exercise-mimetic myokine irisin. © 2019 American Society for Bone and Mineral Research.

Abstract

Schematic representation of irisin's action on osteocytes to activate ERK phosphorylation, which in turn stimulates the increase of Atf4 mRNA levels. A recent study showed that irisin increases survival of osteocytes acting through integrin αV/β5 receptors. To elucidate the action of irisin on osteocytes, we investigated the downstream signaling cascades in MLO-Y4 cells treated with recombinant irisin (rec-irisin). We found that rec-irisin activated the MAP kinases Erk1 and Erk2 and increased the expression of the transcription factor Atf4 through an Erk-dependent pathway in osteocytes.
Theoretical molecular predictions and antimicrobial activities of newly synthesized molecular hybrids of norfloxacin and ciprofloxacin
Authors: Kaur Gurmeet , Kaur Manpreet , Sharad Lakhvir , Bansal Manisha
Published: December 2019

Antibiotics such as norfloxacin and ciprofloxacin are used to treat numerous bacterial infections. The present research work involves the molecular prediction, synthesis, characterization and in vitro antimicrobial activities of molecular hybrids of norfloxacin and ciprofloxacin. First set of compounds involve the substitutions of various amines at third position of ciprofloxacin and norfloxacin. On the other hand, second set of molecular hybrids include the substitution of different amines at seventh position along with linker (─COCH2─). These synthesized compounds were identified by TLC technique and well characterized by various spectroscopic techniques such as IR, NMR, and ESI‐MS. Molecular prediction of these newly synthesized compounds have been carried out using the SwissADME, ADMETLab software. Their cytotoxicity parameters have also been studied using Osiris software. It was observed that almost all these molecular hybrids suitable for their drug likeness properties. Further, these newly synthesized compounds were subjected to study their antimicrobial activities in vitro. The third substituted as well as most of seventh substituted molecular hybrids have shown 10‐folds increase in their antibacterial activity as compared to the standard drug ciprofloxacin. Some of these compounds have also shown their potency when subjected to study their cytotoxicity test against Escherichia coli AB 1157, proficient to prepare damage in DNA.
Examining overlap of included studies in meta‐reviews: Guidance for using the corrected covered area index
Authors: Hennessy Emily A. , Johnson Blair T.
Published: December 2019

Overlap in meta‐reviews results from the use of multiple identical primary studies in similar reviews. It is an important area for research synthesists because overlap indicates the degree to which reviews address the same or different literatures of primary research. Current guidelines to address overlap suggest that assessing and documenting the degree of overlap in primary studies, calculated via the corrected covered area (CCA) is a promising method. Yet, the CCA is a simple percentage of overlap and current guidelines do not detail ways that reviewers can use the CCA as a diagnostic tool while also comprehensively incorporating these findings into their conclusions. Furthermore, we maintain that meta‐review teams must address non‐independence via overlap more thoroughly than by simply estimating and reporting the CCA. Instead, we recommend and elaborate five steps to take when examining overlap, illustrating these steps through the use of an empirical example of primary study overlap in a recently conducted meta‐review. This work helps to show that overlap of primary studies included in a meta‐review is not necessarily a bias but often can be a benefit. We also highlight further areas of caution in this task and potential for the development of new tools to address non‐independence issues.
Comparative study of physicochemical and functional properties of flours from kidney bean (Phaseolus vulgaris L.) and green gram (Vigna radiata L.) cultivars grown in Indian temperate climate
Authors: Wani Idrees Ahmed , Andrabi Syed Nowsheen , Sogi Dalbir Singh , Hassan Ifra
Published: December 2019

The present work was conducted to study the physicochemical, functional, and morphological characteristics of flours obtained from two kidney bean (Shalimar Rajmah‐1 and Shalimar Rajmah 132) and two green gram cultivars (Shalimar Moong‐1 [Shal Moong‐1] and Shalimar Moong‐2 [Shal Moong‐2]). Moisture, protein, fat, ash, and carbohydrate contents of flours varied at 13.00–14.00, 14.78–25.02, 1.00–2.00, 3.00–4.00, and 56.98–66.22 g/100 g, respectively. Hunter colour “L,” “a,” and “b” values varied in the range of 71.22–82.65, −1.80 to −0.12, and 15.20–22.85, respectively. Swelling index increased from 2.48 at 50°C to 3.76 at 90°C (bean flour) and 2.5 at 50°C to 5.83 at 90°C (green gram flour). Increase in syneresis and decrease in transmittance of flour gels were observed at 4°C during 120h storage period. A significant (p ≤ .05) variation was observed in the peak viscosity (282.0–772.0 cP), trough viscosity (211.0–620 cP), setback viscosity (20.0–112.0 cP), and pasting temperature (67.48–94.93°C). Fourier transform infrared analysis of the flours revealed main absorption bands around 3,275 and 992 cm−1. The lowest and highest gelatinization temperatures were reported in Shal M‐2 and Shal Moong‐1, respectively. G′ and G″ of the flours increased with the increase in frequency depicting gel‐like behaviour. The flour particles were oval or elliptical with rough and irregular surfaces. The study concluded that the green gram flours had higher protein, swelling index, solubility index, syneresis, and pasting properties than had the kidney bean flours. However, higher functional properties like water absorption, foaming, and emulsifying capacities were observed in kidney bean than in green gram flours.
Temporal bone histopathology: Superior semicircular canal dehiscence
Authors: Lin Brian M. , Reinshagen Katherine , Nadol Joseph , Quesnel Alicia M.
Published: December 2019

Objectives

To present a histopathological case of a 91‐year‐old woman who was diagnosed with superior semicircular canal dehiscence postmortem.

Methods

The patient was a registered donor with the National Temporal Bone Donor Program at the NIDCD National Temporal Bone, Hearing and Balance Pathology Resource Registry. Computed tomography imaging was performed on each temporal bone. The temporal bones were decalcified with ethylenediaminetetracetate and embedded in celloidin, and tissue sections were stained with hematoxylin and eosin. Horizontal sections were taken through the left temporal bone, and vertical sections were taken through the right temporal bone.

Results

Histopathological sections taken through the right temporal bone demonstrated no bone between the membranous wall of the superior semicircular canal and the middle fossa dura. There was no histopathological evidence of superior semicircular canal dehiscence in the left temporal bone; however, a small dehiscence would not be identified on horizontal sections. Microcavitations were observed in the common crus of the left temporal bone.

Conclusion

This reports describes the case of a woman who was diagnosed with superior semicircular canal dehiscence postmortem. The presence of microcavitations in the temporal bone is consistent with osteoclastic activity, which may play a role in the development of superior canal dehiscence.
Long‐term forecast of water temperature and dissolved oxygen profiles in deep lakes using artificial neural networks conjugated with wavelet transform
Authors: Saber Ali , James David E. , Hayes Donald F.
Published: December 2019

Forecasting water quality in inland waters can improve management practices to protect water resources. This study proposes a novel data‐driven framework to forecast water quality profiles over long time periods in Boulder Basin of Lake Mead, a deep monomictic subtropical lake. Hourly meteorological data were used to estimate lake–atmosphere heat exchange. Heat fluxes combined with 6‐hourly measured water quality profiles up to 106 m depth were used to train six different artificial neural networks to forecast water temperature, dissolved oxygen, and conductivity profiles up to 240 d ahead. A model incorporating heat fluxes, winds, and stationary wavelet decomposition generated correlation coefficients > 0.88 and relative errors < 4% throughout the water column for up to 240‐d ahead forecasts. Internal wave motions at the thermocline resulted in larger relative errors of forecasts in the metalimnion compared to other depths. Greater atmospheric influences on water temperature and dissolved oxygen resulted in larger forecast errors compared to conductivity. An autocovariance method successfully determined appropriate forecasting lead times at different depths, improving forecast accuracies.
Mid‐Infrared Photonics Using 2D Materials: Status and Challenges
Authors: Fang Yuanrong , Ge Yanqi , Wang Cong , Zhang Han
Published: December 2019

In recent years, a variety of 2‐dimensional (2D) materials including graphene, topological insulators, transition metal dichalcogenides, and black phosphorus have been utilized in photonics and optoelectronics applications. Since the mid‐infrared (MIR) region has a significant role in various fields, rapid progress has been made on photonics and optoelectronics applications using 2D materials. Herein, the progress in the photonics devices that exploit the unique properties of 2D materials for a range of MIR applications is summarized, focusing on ultrafast light generation, MIR light modulation, and photodetection. By taking advantage of ultrafast light response, broadband absorption, and high carrier mobility of 2D materials, femtosecond lasers, broadband optical modulators, and high‐responsivity photodetectors are achieved. Some perspectives on 2D material‐based MIR photonics are highlighted. Due to their MIR bandgaps, small size, high carrier mobility, and easy integration, 2D materials are appealing for MIR photonics applications. Moreover, the availability of an increasingly broad library of 2D materials with variable electronic and optical properties, and the ability to be thinned and restacked into functional and complex assembled structures, enable the development of a highly integrated MIR photonic chip, which will make information technology greener, faster, and lower in energy consumption.
Building and maintaining trust in clinical decision support: Recommendations from the Patient‐Centered CDS Learning Network
Authors: Richardson Joshua E. , Middleton Blackford , Platt Jodyn E. , Blumenfeld Barry H.
Published: December 2019

Knowledge artifacts in digital repositories for clinical decision support (CDS) can promote the use of CDS in clinical practice. However, stakeholders will benefit from knowing which they can trust before adopting artifacts from knowledge repositories. We discuss our investigation into trust for knowledge artifacts and repositories by the Patient‐Centered CDS Learning Network's Trust Framework Working Group (TFWG). The TFWG identified 12 actors (eg, vendors, clinicians, and policy makers) within a CDS ecosystem who each may play a meaningful role in prioritizing, authoring, implementing, or evaluating CDS and developed 33 recommendations distributed across nine “trust attributes.” The trust attributes and recommendations represent a range of considerations such as the “Competency” of knowledge artifact engineers and the “Organizational Capacity” of institutions that develop and implement CDS. The TFWG findings highlight an initial effort to make trust explicit and embedded within CDS knowledge artifacts and repositories and thus more broadly accepted and used.
The sup‐norm vs. the norm of the coefficients: equivalence constants for homogeneous polynomials
Authors: Galicer Daniel , Mansilla Martín , Muro Santiago
Published: December 2019

Let be the best constant that fulfills the following inequality: for every m‐homogeneous polynomial in n complex variables,
For every degree m, and a wide range of values of (including any r in the case , and any r and p for the 2‐homogeneous case), we give the correct asymptotic behavior of these constants as n (the number of variables) tends to infinity. Remarkably, in many cases, extremal polynomials for these inequalities are not (as traditionally expected) found using classical random unimodular polynomials, and special combinatorial configurations of monomials are needed. Namely, we show that Steiner polynomials (i.e., m‐homogeneous polynomials such that the multi‐indices corresponding to the nonzero coefficients form partial Steiner systems), do the work for certain range of values of . As a byproduct, we present some applications of these estimates to the interpolation of tensor products of Banach spaces, to the study of (mixed) unconditionality in spaces of polynomials and to the multivariable von Neumann's inequality.
Meteorological drought analysis using copula theory and drought indicators under climate change scenarios (RCP)
Authors: Mesbahzadeh Tayyebeh , Mirakbari Maryam , Mohseni Saravi Mohsen , Soleimani Sardoo Farshad , Miglietta Mario M.
Published: December 2019

The study was carried out to assess meteorological drought on the basis of the standardized precipitation index (SPI) and standardized precipitation evapotranspiration index (SPEI) evaluated in future climate scenarios. Yazd province, located in an arid region in the centre of Iran, was chosen for analysis. The study area has just one synoptic station with a long‐term record (56 years). The impact of climate change on future drought was examined by using the CanESM2 of the CMIP5 model under three scenarios, that is, representative concentration pathways RCP2.6, RCP4.5 and RCP8.5. Given that a drought is defined by several dependent variables, the evaluation of this phenomenon should be based on a multivariate analysis. For this purpose, two main characteristics of drought (severity and duration) were extracted by run theory in a past (1961–2016) and future (2017–2100) period based on the SPI and SPEI, and studied using copula theory. Three functions, that is, Frank, Gaussian and Gumbel copula, were selected to fit with drought severity and duration. The results of the bivariate analysis using copula showed that, according to both indicators, the study area will experience droughts with greater severity and duration in future as compared with the historical period, and the drought represented by the SPEI is more severe than that associated with the SPI. Also, drought simulated using the RCP8.5 scenario was more severe than when using the other two scenarios. Finally, droughts with a longer return period will become more frequent in future.
MiR‐338 regulates NFATc1 expression and inhibits the proliferation and epithelial‐mesenchymal transition of human non‐small‐cell lung cancer cells
Authors: He Wei , Lu Jibin
Published: December 2019

Background

It is well known that nuclear factor of activated T cells c1 (NFATc1) expression is closely associated with progression of many cancers. And we found that miR‐338 could directly target the NFATc1. However, the precise mechanisms of miR‐338 in non‐small‐cell lung cancer (NSCLC) have not been well clarified. Our study aimed to explore the interaction between NFATc1 and miR‐338 in NSCLC.

Methods

Quantitative RT‐PCR was utilized to determine the expressions of NFATc1 and miR‐338 in NSCLC tissues and cell lines. And the cell proliferation and epithelial‐mesenchymal transition (EMT) were assessed to determine the functional roles of miR‐338 and NFATc1 in NSCLC cells. NFATc1 expression was detected using quantitative RT‐PCR and western blotting, respectively. Luciferase reporter assays were performed to validate NFATc1 as a target of miR‐338 in NSCLC cells.

Results

In this study, our results showed that NFATc1 expression was significantly up‐regulated in NSCLC tissues and cell lines, and the miR‐338 level was dramatically down‐regulated. Moreover high NFATc1 expression was closely associated with low miR‐338 level in NSCLC tissues. Moreover introduction of miR‐338 significantly inhibited proliferation and EMT of NSCLC cells. Bioinformatics analysis predicted that the NFATc1 was a potential target gene of miR‐338. We demonstrated that miR‐338 could directly target NFATc1 by using luciferase reporter assay. Besides, knockdown of NFATc1 had the similar effects with miR‐338 overexpression on NSCLC cells. Up‐regulation of NFATc1 in NSCLC cells partially abolished the inhibitory effects of miR‐338 mimic.

Conclusions

Overexpression of miR‐338 inhibited cell proliferation and EMT of NSCLC cells by directly down‐regulating NFATc1 expression.
Artificial neural network for Slice Encoding for Metal Artifact Correction (SEMAC) MRI
Authors: Seo Sunghun , Do Won‐Joon , Luu Huan Minh , Kim Ki Hwan , Choi Seung Hong , Park Sung‐Hong
Published: December 2019

Purpose

To develop new artificial neural networks (ANNs) to accelerate slice encoding for metal artifact correction (SEMAC) MRI.

Methods

Eight titanium phantoms and 77 patients after brain tumor surgery involving metallic neuro‐plating instruments were scanned using SEMAC at a 3T Skyra scanner. For the phantoms, proton‐density, T1‐, and T2‐weighted images were acquired for developing both multilayer perceptron (MLP) and convolutional neural network (CNN). For the patients, T2‐weighted images were acquired for developing CNN. All networks were trained with the SEMAC factor 4 or 6 as input and the factor 12 as label, yielding an acceleration factor of 3 or 2. Performance of the CNN model was compared against parallel imaging and compressed sensing on the phantom datasets. Two extra T1‐weighted in vivo sets were acquired to investigate generalizability of the models to different contrasts.

Results

Both multilayer perceptron and CNN provided artifact‐suppressed images better than the input images and comparable to the label images visually and quantitatively, a trend observable regardless of input SEMAC factor and image type (P < .01). CNN suppressed the artifacts better than multilayer perceptron, parallel imaging, and compressed sensing (P < .01). Tests on the patient datasets demonstrated clear metal artifact suppression visually and quantitatively (P < .01). Tests on T1 datasets also demonstrated clear visual metal artifact suppression.

Conclusion

Our study introduced a new effective way of artificial neural networks to accelerate SEMAC MRI while maintaining the comparable quality of metal artifact suppression. Application on the preliminary patient datasets proved the feasibility in clinical usage, which warrants further investigation.
Synthesis and Antitumor Evaluation of Novel Hybrids of Phenylsulfonylfuroxan and Estradiol Derivatives
Authors: Wan Qi , Deng Yan , Huang Yaoqing , Yu Zhihui , Wang Chunli , Wang Ke , Dong Jibin , Chen Ying
Published: December 2019

Fifteen novel furoxan‐based nitric oxide (NO) releasing hybrids of estradiol derivatives were synthesized and evaluated in vitro anti‐proliferative activity in MDA‐MB‐231, A2780, Hela and HUVEC cell lines. Most of them displayed potent anti‐proliferative effects. Among the compounds, 4‐bromo‐3‐((phenylsulfonyl)‐1,2,5‐oxadiazole 2‐oxide)‐oxy‐propoxy‐estradiol (11 b) exhibited the best activity with IC50 values of 3.58–0.0008 μM. Preliminary pharmacological studies showed that 11 b induced apoptosis and hardly affected the cell cycle of MDA‐MB‐231 cell line. NO‐releasing capacity and inhibition of ERK/MAPK pathway signaling might explain the potent antineoplastic activity of these compounds. The preliminary structure‐activity relationship (SAR) showed that steroidal scaffolds with a linker in 3‐position were favorable moieties to evidently increase the bioactivities of these hybrids. Overall, these results implied that 11 b merited to be further investigated as a promising anti‐cancer candidate.
A novel nitrogen, phosphorus, and boron ionic pair compound toward fire safety and mechanical enhancement effect for epoxy resin
Authors: Tang Hao , Zhou Hong
Published: December 2019

In this work, a novel nitrogen, phosphorus and boron ionic pair compound (DTPA[AZB]), composed of a protonated flame retardant (DTPA) 6,6'‐(1,4‐phenylenebis((pyrazin‐2‐ylamino)methylene))bis(dibenzo[c,e][1,2]oxaphosphinine 6‐oxide) and a counter anion alizarin borate (AZB), has been prepared and fully characterized, AZB was synthesized by the reaction of alizarin with boric acid. DTPA was produced in two steps. First, terephthalaldehyde was condensed with aminopyrazine to form the corresponding imine. This was treated with 9,10‐dihydro‐9‐oxa‐10‐phosphaphenanthrene‐10‐oxide (DOPO) to generate DTPA. Blending with DTPA greatly reduced the flammability of epoxy resin. When the amount of DTPA added was 4%, a modified epoxy resin passed the V‐0 rating and the limiting oxygen index (LOI) reached 32.5%. With the introduction of 3% AZB into the EP/DTPA material, the LOI reached 33.5%. Simultaneously, compared with that of neat EP, the peak heat release rate and smoke production rate for EP/DTPA‐4 was decreased by 24.1% and 40.7%, respectively, and the peak heat release rate and smoke production rate for EP/DTPA[AZB]‐3 was decreased by 32.9% and 43.4%, respectively. The results indicate that AZB and DTPA show good cooperative flame retardant effects. The flame retardancy of the modified epoxy is improved with greater heat release suppression combustion of the resin. A mode of flame retardant action has been proposed based on analysis results from Py‐GC/MS for DTPA, and SEM, IR and Raman for the residual carbon from cone calorimeter and UL‐94 tests, respectively. Importantly, the tensile strength, fexural strength, and fexural modulus of the EP/DTPA[AZB] increased compared with the same properties of neat EP.
Trial designs using real‐world data: The changing landscape of the regulatory approval process
Authors: Baumfeld Andre Elodie , Reynolds Robert , Caubel Patrick , Azoulay Laurent , Dreyer Nancy A.
Published: December 2019

Purpose

There is a need to develop hybrid trial methodology combining the best parts of traditional randomized controlled trials (RCTs) and observational study designs to produce real‐world evidence (RWE) that provides adequate scientific evidence for regulatory decision‐making.

Methods

This review explores how hybrid study designs that include features of RCTs and studies with real‐world data (RWD) can combine the advantages of both to generate RWE that is fit for regulatory purposes.

Results

Some hybrid designs include randomization and use pragmatic outcomes; other designs use single‐arm trial data supplemented with external comparators derived from RWD or leverage novel data collection approaches to capture long‐term outcomes in a real‐world setting. Some of these approaches have already been successfully used in regulatory decisions, raising the possibility that studies using RWD could increasingly be used to augment or replace traditional RCTs for the demonstration of drug effectiveness in certain contexts. These changes come against a background of long reliance on RCTs for regulatory decision‐making, which are labor‐intensive, costly, and produce data that can have limited applicability in real‐world clinical practice.

Conclusions

While RWE from observational studies is well accepted for satisfying postapproval safety monitoring requirements, it has not commonly been used to demonstrate drug effectiveness for regulatory purposes. However, this position is changing as regulatory opinions, guidance frameworks, and RWD methodologies are evolving, with growing recognition of the value of using RWE that is acceptable for regulatory decision‐making.
Synthesis and properties of a novel bio‐based benzoxazine resin with excellent low‐temperature curing ability
Authors: Zhan Zuo‐min , Yan Hong‐qiang , Yin Ping , Cheng Jie , Fang Zheng‐ping
Published: December 2019

A novel bio‐based benzoxazine resin (diphenolic acid/furfurylamine benzoxazine resin, PDPA‐F‐Boz) was prepared by using bio‐based diphenolic acid, furfurylamine and paraformaldehyde as raw materials. The structure of DPA‐F‐Boz monomer was characterized by Fourier transform infrared spectroscopy, 1H NMR and 13C NMR, and then its curing reaction and the thermal stability of the cured PDPA‐F‐Boz were analyzed. Compared with the traditional fossil‐based benzoxazine (bisphenol A/aniline benzoxazine, BPA‐A‐Boz) and the bio‐based benzoxazine (diphenolic acid/aniline benzoxazine, DPA‐A‐Boz), DPA‐F‐Boz monomer showed the lowest curing temperature, and PDPA‐F‐Boz had the highest residual char ratio at 800 °C and the lowest degradation rate at the peak temperature. Meanwhile, the total heat release, peak heat release rate and heat release capacity of PDPA‐F‐Boz were much lower than those of PBPA‐A‐Boz and PDPA‐A‐Boz. Thus, PDPA‐F‐Boz showed excellent low‐temperature curing ability and thermal stability. © 2019 Society of Chemical Industry
Peace of mind among adolescents and young adults with cancer
Authors: Gittzus Jordan A. , Fasciano Karen M. , Block Susan D. , Mack Jennifer W.
Published: December 2019

Objective

Adolescents and young adults (AYAs) with cancer have high rates of psychological distress and unmet support needs. Peace of mind is an important construct among older cancer patients and parents of children with cancer but has not been explored in AYAs. We sought to evaluate the extent to which AYAs with cancer experience peace of mind and to identify factors associated with greater peace of mind.

Methods

We surveyed 193 AYAs with cancer aged 15 to 29 years within 12 weeks of diagnosis; 137 patients completed the same measures again 4 and 12 months after diagnosis. Patients were asked to report peace of mind, measured using items from the Functional Assessment of Chronic Illness, Spiritual Well‐being scale (FACIT‐Sp); anxiety and depression, using the Hospital Anxiety and Depression Scale (HADS); and experiences surrounding medical communication and decision making.

Results

Mean scores for peace of mind were 3.59 at diagnosis (range 1‐5, standard deviation 0.84), with similar scores at 4 (3.53, P = .34) and 12 (3.59, P = .94) months. In a multivariable model adjusted for age and gender, patients who reported receiving high‐quality information about their cancer had greater peace of mind at diagnosis (β = .25, P = .03), whereas those who reported holding a passive role in treatment decision making (β = −.47, P < .0001) or who had anxiety (β = −.64, P = .0003) or depression (β = −.51, P = .04) had lower peace of mind.

Conclusion

Peace of mind did not improve significantly over time for AYAs with cancer. While high‐quality communication may be associated with heightened peace of mind, further study is needed to clarify relationships between peace of mind and other psychological variables.
Prostate cancer research: The next generation; report from the 2019 Coffey‐Holden Prostate Cancer Academy Meeting
Authors: Miyahira Andrea K. , Sharp Adam , Ellis Leigh , Jones Jennifer , Kaochar Salma , Larman H. Benjamin , Quigley David A. , Ye Huihui , Simons Jonathan W. , Pienta Kenneth J. , Soule Howard R.
Published: December 2019

Introduction

The 2019 Coffey‐Holden Prostate Cancer Academy (CHPCA) Meeting, “Prostate Cancer Research: The Next Generation,” was held 20 to 23 June, 2019, in Los Angeles, California.

Methods

The CHPCA Meeting is an annual conference held by the Prostate Cancer Foundation, that is uniquely structured to stimulate intense discussion surrounding topics most critical to accelerating prostate cancer research and the discovery of new life‐extending treatments for patients. The 7th Annual CHPCA Meeting was attended by 86 investigators and concentrated on many of the most promising new treatment opportunities and next‐generation research technologies.

Results

The topics of focus at the meeting included: new treatment strategies and novel agents for targeted therapies and precision medicine, new treatment strategies that may synergize with checkpoint immunotherapy, next‐generation technologies that visualize tumor microenvironment (TME) and molecular pathology in situ, multi‐omics and tumor heterogeneity using single cells, 3D and TME models, and the role of extracellular vesicles in cancer and their potential as biomarkers.

Discussion

This meeting report provides a comprehensive summary of the talks and discussions held at the 2019 CHPCA Meeting, for the purpose of globally disseminating this knowledge and ultimately accelerating new treatments and diagnostics for patients with prostate cancer.