bluuebunny/crossref_metadata_2025 huggingface dataset:
Chemotherapy is associated with increased survival from colorectal signet ring cell carcinoma with distant metastasis: A Surveillance, Epidemiology, and End Results database analysis
Authors: Shi Tao , Huang Mengxi , Han Dong , Tang Xinyi , Chen Yanyan , Li Zhiping , Liu Chao , Xiang Dan , Wang Ting , Chen Yitian , Wang Rui , Lei Zengjie , Chu Xiaoyuan
Published: March 2019

Background

Colorectal signet ring cell carcinoma (SRCC) is a rare histological subtype of colorectal adenocarcinoma with high metastatic frequency compared to non‐SRCC colorectal cancer (NOS). The aim of this study was to analyze prognostic factors of colorectal SRCC with different metastatic sites and evaluate impacts of various therapies for metastatic colorectal SRCC.

Methods

Patients with NOS and SRCC were from the Surveillance, Epidemiology, and End Results (SEER) database during 2010‐2014. χ2 tests were used to compare data significance. Kaplan‐Meier and COX models were used to analyze the differences in the survival. Propensity‐matched analyses were used to adjust numerical differences.

Results

Among the 173 460 patients, 1932 (1.11%) patients had colorectal SRCC. In univariate analysis, older age, male sex, and peritoneum metastasis were associated with higher mortality risk. The peritoneum was both the site with the highest metastatic frequency and the site with the worst prognosis in SRCC. In the COX regression model, peritoneum‐metastatic SRCC patients receiving chemotherapy had better survival than patients treated with surgery.

Conclusions

Our study analyzed the unique metastatic pattern of colorectal SRCC toward different sites and found that compared to surgery, chemotherapy was associated with better survival for colorectal SRCC patients with distant metastasis, which provided insights for future SRCC patient treatment.
Facile in Vitro Biocatalytic Production of Diverse Tryptamines
Authors: McDonald Allwin D. , Perkins Lydia J. , Buller Andrew R.
Published: March 2019

Tryptamines are a medicinally important class of small molecules that serve as precursors to more complex, clinically used indole alkaloid natural products. Typically, tryptamine analogues are prepared from indoles through multistep synthetic routes. In the natural world, the desirable tryptamine synthon is produced in a single step by l‐tryptophan decarboxylases (TDCs). However, no TDCs are known to combine high activity and substrate promiscuity, which might enable a practical biocatalytic route to tryptamine analogues. We have now identified the TDC from Ruminococcus gnavus as the first highly active and promiscuous member of this enzyme family. RgnTDC performs up to 96 000 turnovers and readily accommodates tryptophan analogues with substituents at the 4, 5, 6, and 7 positions, as well as alternative heterocycles, thus enabling the facile biocatalytic synthesis of >20 tryptamine analogues. We demonstrate the utility of this enzyme in a two‐step biocatalytic sequence with an engineered tryptophan synthase to afford an efficient, cost‐effective route to tryptamines from commercially available indole starting materials.
A case report of a ruptured subclavian artery aneurysm presenting to the emergency department
Authors: Ramtoola Mohammad Tariq , Bhatti Mubashir , Shetty Ritesh
Published: March 2019

Key Clinical Message

Subclavian artery aneurysms are uncommon and present a diagnostic dilemma. Our patient attended with life‐threatening rupture, requiring prompt management. However, lack of on‐site facilities and specialist input posed a logistical challenge. The patient was stable enough to allow an urgent transfer to a specialist unit for successful endovascular repair.
Electrochemical Decarboxylative Trifluoromethylation of α, β‐Unsaturated Carboxylic Acids with CF3SO2Na
Authors: Li Fang‐Yuan , Lin Dian‐Zhao , He Tian‐Jun , Zhong Wei‐Qiang , Huang Jing‐Mei
Published: March 2019

A new method for the synthesis of vinyl trifluoromethyl compounds from α, β‐unsaturated carboxylic acids and CF3SO2Na has been developed. This electrochemical decarboxylative trifluoro‐methylation was found to be highly stereoselective and afforded products in good yields with wide substrate scope under metal‐free and external chemical oxidant‐free conditions.
Ultrasmall Iron Fluoride Nanoparticles Embedded in Graphitized Porous Carbon Derived from Fe‐Based Metal Organic Frameworks as High‐Performance Cathode Materials for Li Batteries
Authors: Zhang Qi , Liu Nan‐Nan , Sun Cheng‐Zhi , Fan Li‐Shuang , Zhang Nai‐Qing , Sun Ke‐Ning
Published: March 2019

Iron‐based metal organic framework (MOF) MIL‐53 is used as a precursor and self‐template to synthesize a 3D porous carbon/FeF3 ⋅ 0.33 H2O composite in situ. We find that the organic ligands in iron‐containing MOFs can convert into highly graphitized carbon with the catalysis of central Fe atoms. The FeF3 ⋅ 0.33 H2O nanoparticles formed after fluorination and dehydration are surrounded by highly graphitized carbon. In the composite, the graphitized 3D porous carbon can provide passageways for electron transport and ultrasmall FeF3 ⋅ 0.33 H2O nanoparticles facilitate the diffusion of Li ions. The composite shows excellent performance for the Li storage. A capacity of 86 mAh g−1 can be reached at an ultra‐high rate of 20 C. Even after 300 charge−discharge cycles at 5 C, the capacity remains at 113 mAh g−1.
Highly Sensitive Method to Isolate Photocurrent Signals from Large Background Redox Currents on Protein‐Modified Electrodes
Authors: Jun Daniel , Beatty J. Thomas , Bizzotto Dan
Published: March 2019

The high quantum efficiency in converting light energy into a charge‐separated state is a major advantage in using photosynthetic proteins in biophotovoltaic applications. Photocurrents are typically measured at open circuit potential (OCP), where the electrochemical redox or faradaic currents are minimized. However, at potentials far from the OCP, the photocurrents produced by the proteins may be impossible to measure against the large background current, owing to electrochemical redox reactions of charge‐transfer mediators and/or sacrificial electron donors. Demonstrated here is a highly sensitive method using a sinusoidal‐modulated intensity of an LED excitation light source to isolate the protein‐based photocurrent component from the total current irrespective of electrode surface coverage. Using a genetically modified photochemical reaction center from Rhodobacter sphaeroides as a proof‐of‐concept, photocurrents up to 104–105 orders of magnitude smaller than the background electrochemical redox current (due to redox reactions directly on the electrode surface) were measured at applied voltages >0.4 V from the OCP. The phase relationship between the optical excitation and photocurrent response was also measured and shown to be analytically useful.
One Stone for Three Birds‐Rhodium‐Catalyzed Highly Diastereoselective Intramolecular [4+2] Cycloaddition of Optically Active Allene‐1,3‐dienes
Authors: Han Yulin , Qin Anni , Ma Shengming
Published: March 2019

Summary of main observation and conclusion

RhCl(PPh3)3‐catalyzed [4+2] intramolecular cycloaddition of optically active axially chiral allene‐dienes afforded cis‐fused [3.4.0]‐bicyclic products with three chiral centers in good yields with an excellent chemo‐ and diastereoselectivity. A pair of enantiomers of such products was generated highly selectively from both enantiomers of starting allene‐dienes, indicating that the axial chirality dictated the absolute configurations of the three in situ generated chiral centers with a very high efficiency of chirality transfer.
Ancestral characterization of 1018 cancer cell lines highlights disparities and reveals gene expression and mutational differences
Authors: Kessler Michael D. , Bateman Nicholas W. , Conrads Thomas P. , Maxwell George L. , Dunning Hotopp Julie C. , O’Connor Timothy D.
Published: March 2019

Background

Although cell lines are an essential resource for studying cancer biology, many are of unknown ancestral origin, and their use may not be optimal for evaluating the biology of all patient populations.

Methods

An admixture analysis was performed using genome‐wide chip data from the Catalogue of Somatic Mutations in Cancer (COSMIC) Cell Lines Project to calculate genetic ancestry estimates for 1018 cancer cell lines. After stratifying the analyses by tissue and histology types, linear models were used to evaluate the influence of ancestry on gene expression and somatic mutation frequency.

Results

For the 701 cell lines with unreported ancestry, 215 were of East Asian origin, 30 were of African or African American origin, and 453 were of European origin. Notable imbalances were observed in ancestral representation across tissue type, with the majority of analyzed tissue types having few cell lines of African American ancestral origin, and with Hispanic and South Asian ancestry being almost entirely absent across all cell lines. In evaluating gene expression across these cell lines, expression levels of the genes neurobeachin line 1 (NBEAL1), solute carrier family 6 member 19 (SLC6A19), HEAT repeat containing 6 (HEATR6), and epithelial cell transforming 2 like (ECT2L) were associated with ancestry. Significant differences were also observed in the proportions of somatic mutation types across cell lines with varying ancestral proportions.

Conclusions

By estimating genetic ancestry for 1018 cancer cell lines, the authors have produced a resource that cancer researchers can use to ensure that their cell lines are ancestrally representative of the populations they intend to affect. Furthermore, the novel ancestry‐specific signal identified underscores the importance of ancestral awareness when studying cancer.
A Thermodynamic Model of Auto‐regulated Protein Assembly by a Supramolecular Scaffold
Authors: Rennie Martin L. , Crowley Peter B.
Published: March 2019

Ligand‐mediated regulation of protein assembly occurs frequently in different cellular contexts. Auto‐regulated assembly, where a ligand acts as its own competitive inhibitor, provides a mechanism for exquisite control of assembly. Unlike simple protein‐ligand systems a quantification of the binding thermodynamics is not straightforward. Here, we characterize the interactions of a recently identified model system in which the oligomerization of cytochrome c is controlled by sulfonato‐calix[8]arene, an anionic supramolecular scaffold. Isothermal titration calorimetry and thermodynamic modelling, in combination with Bayesian fitting, were used to quantify the ligand binding and assembly equilibria for this system. The approach and variations of this model may prove useful for the analysis of auto‐regulated protein assembly in general.
Laser Spectroscopy and Lifetime Measurements of the S1 State of Tetracyanoquinodimethane (TCNQ) in a Cold Gas‐Phase Free‐Jet
Authors: Chaki Nobumasa , Muramatsu Satoru , Iida Yuji , Kenjo Seiya , Inokuchi Yoshiya , Iimori Toshifumi , Ebata Takayuki
Published: March 2019

The S1 electronic state of 7,7,8,8‐Tetracyanoquinodimethane (TCNQ) has been investigated by laser induced fluorescence (LIF), dispersed fluorescence (DF) spectroscopy, and lifetime measurements under jet‐cooled conditions in the gas‐phase. The LIF spectrum showed a weak origin band at 412.13 nm (24262 cm−1) with prominent progression and combination bands involving vibrations of 327, 1098, and 2430 cm−1. In addition, very strong bands appeared at ∼363.6 nm (3300 cm−1 above the origin). Both the LIF and DF spectra indicate considerable geometric change in the S1 state. The fluorescence lifetime of S1 at zero‐point level was obtained to be 220 ns. This lifetime is 40 times longer than the radiative lifetime estimated from the S1−S0 oscillator strength. Furthermore, the lifetimes of the vibronic bands exhibited drastic energy dependence, indicating a strong mixing with the triplet (T1) or intramolecular charge‐transfer (CT) state. This study is thought to disclose intrinsic nature of TCNQ, which has been well known as a component of organic semiconductors and a versatile p‐type dopant.
Rat Left Ventricular Cardiomyocytes Characterization in the Process of Postinfarction Myocardial Remodeling
Authors: Baidyuk Ekaterina V. , Sakuta Galina A. , Vorobev Mikhail L. , Stepanov Andrei V. , Karpov Andrei A. , Rogoza Olga V. , Kudryavtsev Boris N.
Published: March 2019

Ischemic lesions of the heart, including myocardial infarction, are the most common pathologies of human cardiovascular system. Despite all the research and achievements of medicine in this field, the mortality from this disease remains heavy. Therefore, studying of processes occurring in the myocardium in the early and late postinfarction periods remains important. Rat left ventricular cardiomyocyte (CMC) ploidy, hypertrophy, hyperplasia, and ultrastructure were investigated in 2, 6, and 26 weeks after experimental myocardial infarction, caused by permanent ligation of left coronary artery. Cytofluorimetric study of CMC ploidy revealed no difference between normal, sham‐operated, and infarcted animals for all the tested stages. However, interference microscopy indicated significant changes in cells size. CMC dry mass of infarcted rats in 2 weeks after surgery was 1.5 times lower than in control and sham operated groups. Electron microscopy analysis of CMC revealed disruption of sarcomere structure. However, in 6 weeks after surgery CMC dry mass was 1.6 times higher than in control. In 26 weeks after myocardial infarction CMC dry mass exceeded control only in peri‐infarction zone. Cell counting showed that the number of left ventricular CMC, reduced as a result of myocardial infarction, was not restored during myocardial remodeling. © 2019 International Society for Advancement of Cytometry
Gold‐Catalyzed Post‐Ugi Cascade Transformation for the Synthesis of 2‐Pyridones
Authors: Du Xiaochen , Yu Jiafeng , Gong Jing , Zaman Manzoor , Pereshivko Olga P. , Peshkov Vsevolod A.
Published: March 2019

A gold‐catalyzed post‐Ugi cascade transformation for the synthesis of 2‐pyridones is described. The process involves furan–alkyne cyclization followed by furan ring‐opening and cleavage of the isocyanide‐originated fragment. The initially formed cis double bond can isomerize into a more stable trans double bond upon prolonged exposure to a strong Brønsted acid. Thus, the overall strategy provides a viable access towards two types of 2‐pyridones.
Organocatalytic Asymmetric Synthesis of Bridged O,O‐Ketals with Spirooxindole Motif
Authors: Balha Megha , Soni Chintan , Pan Subhas Chandra
Published: March 2019

The first organocatalytic enantioselective synthesis of bridged O,O‐ketals embedded with spirooxindoles has been developed. Dioxindoles and ortho‐hydroxy‐benzylidene acetones were engaged as the reaction partners in this method. The desired products were obtained via epi‐cinchonine primary amine catalyzed Michael reaction followed by ketal formation with TFA.
Six‐Component Azido‐Ugi Reaction: from Cyclic Ketimines to Bis‐Tetrazole‐Derived 5–7‐Membered Amines
Authors: Kutovaya Irina V. , Zarezin Danil P. , Shmatova Olga I. , Nenajdenko Valentine G.
Published: March 2019

A new six‐component azido‐Ugi reaction was investigated. Using cyclic ketimines as starting materials highly efficient, synthesis of 5‐, 6‐ and 7‐membered cyclic amines connected with two tetrazole rings was elaborated. The influence of different components (ketimine, aldehyde, isocyanide) on the reaction was studied. It was demonstrated that bis‐tetrazoles derived from benzyl isocyanide can be converted efficiently to NH‐tetrazoles by hydrogenolysis.
An application of paired quasilinearization on double‐diffusive convection flow over a cone embedded in a porous medium in the presence of nanoparticles
Authors: Otegbeye Olumuyiwa , Motsa Sandile S. , Ansari Md. Sharifuddin
Published: March 2019

Mixed convection flow of a nanofluid near a vertical cone embedded in a a porous medium with Soret and Dufour effects is exercised. The bearing of a porous medium is recounted by the Darcy model. The partial differential equations, modeling the concerned problem, is nondimensionalised by implementing compatible transformations, which results in a similar form. A new paired spectral quasilinearization method is adopted to get the accurate numerical solution. Convergence and accuracy of the solution is elaborated by analyzing the norm of residual and solution errors. Alteration of velocity, temperature, nanoparticle and solute concentration profiles due to flow controlling parameters, namely, Brownian motion, thermophoresis, Soret, Dufour, Lewis number, and buoyancy ratio is outlined by reproducing the obtained numerical solution in graphs and tables. Analysis reveals that the flow profiles are greatly influenced by the physical parameters under investigation.
Relationships between microbial communities and groundwater chemistry in two pristine confined groundwater aquifers in central China
Authors: Ma Jie , Liu Hui , Tong Lei , Wang Yan , Chen Rong , Liu Shan , Zhao Lei , Li Zhimin , Cai Liegang
Published: March 2019

This study explores linkages between the microbial composition and hydrochemical variables of pristine groundwater to identify active redox conditions and processes. Two confined aquifers underlying the city of Qianjiang in the Jianghan Plain in China were selected for this study, having different recharge sources and strong hydrochemical gradients. Typical methods for establishing redox processes according to threshold concentration criteria for geochemical parameters suggest iron or sulphate reduction processes. High‐throughput 16S rRNA sequencing was used to obtain diversity and taxonomic information on microbial communities. Instead of revealing iron‐ and sulphate‐reducing bacteria, salt‐ and alkali‐tolerant bacteria, such as the phylum Firmicutes and the class Gammaproteobacteria, and in particular, the family Bacillaceae, were dominant in the downstream groundwater of the first aquifer that had high ion concentrations caused by the dissolution of calcite and dolomite; meanwhile, the heterotrophic microaerophilic families Comamonadaceae and Rhodocyclaceae prevailed in the upstream groundwater of the first aquifer. Sulphate‐reducing bacteria were extremely abundant in the upstream groundwater of the second aquifer, as the SO42− concentration was especially high. Methanogens and methanotrophs were predominant in the downstream groundwater of the second aquifer even though the concentration of SO42− was much higher than 0.5 mg L−1. The microbial communities, together with the geochemical parameters, indicated that the upstream region of the first aquifer was suboxic, that Fe(III) and Mn(IV) reductions were not the main redox processes in the downstream groundwater of the first aquifer with high Fe and Mn concentrations, and that the redox processes in the upstream and downstream regions of the second confined aquifer were SO42− reduction and methanogenesis, respectively. This study expands understanding of the linkages between microbial communities and hydrogeochemistry in pristine groundwaters and provides more evidence for identifying active redox conditions and processes.
Association of a genetic variant in ATP‐binding cassette sub‐family B member 1 gene with poor prognosis in patients with squamous cell carcinoma of the esophagus
Authors: Rastgar‐Moghadam Azam , Mehramiz Mehrane , Shahidsales Soodabeh , Entezari Malihe , Hassanian Seyed Mahdi , Talebian Sahar , Nourbakhsh Mahnaz , Ferns Gordon A. , Avan Amir
Published: March 2019

Esophageal cancer is a common cause of death from cancer in men and the eighth most prevalent cancer globally. The morbidity and mortality rates are four times higher in men than in women. Genetic factors are among the susceptibility factors for squamous cell carcinoma of the esophagus. The rs2032582 polymorphism is a triallelic missense variant of the ABCB1 gene, that has been reported to be associated with several cancers. Here we have explored the association of the ABCB1 rs2032582 polymorphism with esophageal squamous cell carcinoma (ESCC) for the first time in a total of 251 subjects, with and without ESCC. Data from patient's record were obtained from the Mashhad University of Medical Sciences, and were used to recruit ESCC patients into the study. A total of 89 ESCC patients and 162 healthy controls were included. DNAs were extracted and genotyped using a TaqMan real‐time PCR‐based method. Caplan Meier method was applied to analyze patients overall survival, and progression‐free survival and log‐rank were used in order to compare the results. Logistic regression was used to calculate the association between risk of ESCC and different genotypes. Our data showed that patients with ESCC had a higher frequency of a T/A (TT/TA/AA) genotype for rs2032592 than individuals with GG‐genotype. There were no associations between BMI and genotypic frequencies. Furthermore patients with TT/TA/AA genotypes had a poorer disease‐free survival (P = 0.016) in comparison with GG genotype. We found a significant association of the ABCB1 rs2032582 polymorphism with prognosis, although further studies in a larger and multicenter setting are needed to value these findings. © 2019 IUBMB Life, 71(9):1252–1258, 2019
Counselor Supervision: A Comparison Across States and Jurisdictions
Authors: Henriksen Richard C. , Henderson Susan E. , Liang Ya‐Wen (Melissa) , Watts Richard E. , Marks Danielle F.
Published: March 2019

Counselor licensure portability models have focused primarily on academic training with only little discussion concerning postgraduate supervision. Using a qualitative content analysis, the authors analyzed the supervision rules and laws in all 53 licensing jurisdictions. The results of this study reflect the lack of a consistent set of supervision guidelines across all 53 jurisdictions. Further study and reflection on these results could lead to the development of a supervision model for postgraduate supervision.
N‐Inversion in N‐phenyloxaziridine: substituent and solvent effects via density functional theory
Authors: Jalali Hamideh , Ali‐Asgari Safa , Hosseini Seyyed Javad , Izadi Nia Jafar
Published: March 2019

In this work, using density functional theory, the kinetic effects of the substitution of a t‐butyl group and\or the incorporation of an oxygen atom, and both, at the aziridine ring moiety were investigated for N‐inversion in N‐phenylaziridine. Then, for N‐inversion in 3‐t‐butyl‐N‐phenyloxaziridine, the kinetic Hammett substituent effects were studied using the different para‐substituted groups on the N‐phenyl ring moiety. The natural bond orbital (NBO) study was the last case in this work. The calculations were performed in the gas phase and solution (in carbon tetrachloride and dichloromethane). The incorporation of an oxygen atom in the aziridine ring strongly weakens the N‐inversion process. In addition, while both t‐butyl substituent and solvent slightly reinforce the N‐inversion of N‐phenyloxaziridine, in N‐phenylaziridine, they decrease the N‐inversion rate to some extent. In both phases, more pronounced in solution and especially in dichloromethane, and in agreement with the NBO results, the electron‐withdrawing groups on para position of the N‐phenyl ring strongly increase the rate of N‐inversion of 3‐t‐butyl‐N‐phenyloxaziridine molecule.
Kidney graft failure induced by BKPyV replication despite a strong reduction of the immunosuppressive therapy
Authors: Anselmo Alessandro , Prezioso Carla , Saccà Filippo Antonino , Di Lella Federica Maria , Palmieri Giampiero , Tisone Giuseppe , Pietropaolo Valeria , Ciotti Marco
Published: March 2019

BKPyV replication is a risk factor for the development of polyomavirus‐associated nephropathy in kidney transplant recipients. Here, the case of a 42 years old Caucasian patient is described who developed a kidney allograft failure because of uncontrolled BKPyV replication 7 months after transplant despite a strong reduction of the immunosuppressive therapy. The genetic analysis of the noncoding control region did not show rearrangement but two point mutations at nucleotide positions 18 and 31 within P block. The mutation at position 31 involved the nuclear factor‐1 site. Sequencing of the VP1 region revealed a subtype I/subgroup b‐1.
Determinants of Quality of Life in Patients With Intestinal Failure Receiving Long‐Term Parenteral Nutrition Using the SF‐36 Questionnaire: A German Single‐Center Prospective Observational Study
Authors: Blüthner Elisabeth , Bednarsch Jan , Stockmann Martin , Karber Mirjam , Pevny Sophie , Maasberg Sebastian , Gerlach Undine A. , Pascher Andreas , Wiedenmann Bertram , Pratschke Johann , Pape Ulrich‐Frank
Published: March 2019

Background

Parenteral nutrition (PN) is a life‐sustaining therapy for patients with chronic intestinal failure (IF) but inevitably has an impact on patients’ quality of life (QoL). The purpose of this study was to examine multiple aspects of QoL by utilizing the standardized Short Form 36 (SF‐36) health survey.

Methods

Between 2014 and 2017, a total of 90 adult patients with IF who were receiving PN were prospectively enrolled in an observational study. All subjects underwent nutrition status assessment, liver assessment, blood tests, and QoL assessment based on the SF‐36. Univariate and multivariable analyses were performed to identify determinants of 8 domains and 2 summary scales of the SF‐36.

Results

Analysis of the SF‐36 questionnaire data showed that QoL was significantly worse compared with the general German population across all categories. Multivariable analysis revealed that bioelectrical impedance analysis of phase angle (1/10 categories), stoma/fistula (4/10 categories), oral intake (4/10 categories), infusions per week (1/10 categories), duration of PN (1/10 categories), citrulline (4/10 categories), and hemoglobin levels (1/10 categories) are independent risk factors affecting QoL.

Conclusion

This study uses the largest cohort of IF patients assessed by the standardized SF‐36 questionnaire to comprehensively analyze QoL. Presence of oral intake, presence of ostomy, and citrulline levels were independently correlated with 4 of 10 categories of the SF‐36. These results indicate that to improve QoL for IF patients, clinical care should focus on addressing the social and emotional value of oral intake, educational interventions, early stoma closure, and application of new targeted therapies.
Early Postnatal Changes of Bone Turnover Biomarkers in Very Low‐Birth‐Weight Neonates—The Effect of Two Parenteral Lipid Emulsions with Different Polyunsaturated Fatty Acid Content: A Randomized Double‐Blind Study
Authors: Papandreou Panos , Agakidis Charalampos , Scouroliakou Maria , Karagiozoglou‐Lampoudi Thomai , Kaliora Adriana , Kalogeropoulos Nick , Siahanidou Tania
Published: March 2019

Background

ω‐3 polyunsaturated fatty acids (n‐3 PUFAs) are reported to have beneficial effect on bone mineral density. This study aimed to evaluate early changes of bone turnover biomarkers in very low‐birth‐weight (VLBW) neonates and the effect of 2 parenteral lipid emulsions (PLEs) with different PUFA composition.

Methods

This is a randomized double‐blind study with parallel design. VLBW neonates (n = 66) receiving parenteral nutrition (PN)>70% of daily energy requirements for >14 days were assigned into 2 groups that were prescribed soybean oil–based (n = 35) and n‐3–enriched PLE (n = 31), respectively. Osteoprotegerin (OPG), soluble receptor activator of nuclear factor‐kB ligand (sRANKL), osteocalcin (OC), interleukin‐6 (enzyme‐linked immunoblot assay kits), Ca, and P plasma levels were assessed before PLE implementation (T1) and on day 20 of life (T2).

Results

In the total population, sRANKL and OC significantly increased, whereas OPG and the OPG/sRANKL ratio decreased from T1 to T2. Within each group, T1‐to‐T2 changes of OC were significant in both groups, whereas those of OPG/sRANKL were significant only in the soybean‐based group. Multiple regressions showed an independent effect of group allocation on OPG change. Significant associations were observed between PN duration and sRANKL change (negatively), n‐6/n‐3 and OC changes (positively), and OPG and sRANKL changes (positively).

Conclusions

A high bone‐turnover rate in VLBW neonates with predominance of bone resorption is confirmed. The lower rate of OPG/sRANKL reduction in the n‐3–enriched PLE group indicates that n‐3 PUFA–enriched PLEs may help to attenuate early bone loss in VLBW neonates.
Biological detoxification of Monascus purpureus pigments by heat‐treated Saccharomyces cerevisiae
Authors: Davoudi Moghadam Hediyeh , Shahidi Fakhri , Tabatabaei Yazdi Farideh , Sarabi Jamab Mahboobe , Eshaghi Zarrin
Published: March 2019

BACKGROUND

Today, there is an increasing concern about the consumption of synthetic colorants in food because of their possible health hazards. Monascus purpureus has attracted a great deal of attention as it produces various coloured pigments with high chemical stability, but it also produces citrinin, a secondary toxic metabolite, along with the pigments. This study aims to investigate the amount of pigment and citrinin reduction by different treatments with Saccharomyces cerevisiae such as heat treatment and suspension concentration.

RESULTS

The results indicated that the ability of S. cerevisiae regarding citrinin adsorption increased with increase of temperature and yeast concentration. The maximum extent of citrinin adsorption was related to heat treatment at 121 °C and a yeast concentration of 105 cells mL−1, for which citrinin reduced from 4.43 mg L−1 in control to 0.1 mg L−1. Heat treatment of 103 cells mL−1 suspension of S. cerevisiae cells at 50 °C, with 0.56 mg L−1 citrinin remaining in the medium, showed the lowest ability for citrinin binding. The optimum absorbance of all red, orange and yellow pigments was observed for the heat treatment at 50 °C and yeast concentrations of 103 and 104 cells mL−1 which was greater than that for the control.

CONCLUSIONS

We can conclude from this study that heat treatment with S. cerevisiae can be a useful way to reduce citrinin to below the standard limits. © 2019 Society of Chemical Industry
Cytoreduction and hyperthermic intraperitoneal chemotherapy in metastatic colorectal cancer
Authors: Eng Oliver S. , Turaga Kiran K.
Published: March 2019

As the management of metastatic colorectal cancer (CRC) has evolved over the past decades, optimal management of CRC with peritoneal metastases remains controversial, especially about cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. In this review, we highlight the current data on this challenging disease process, as well as comment on its limitations.
Ongoing and future directions in the management of metastatic colorectal cancer: Update on clinical trials
Authors: Advani Shailesh , Kopetz Scott
Published: March 2019

Metastatic colorectal cancer (mCRC) continues to show poor outcomes, with many patients exhausting effective standard‐of‐care therapy. To explore the current landscape of clinical trials for mCRC, we reviewed over 600 clinical trials that are currently ongoing for mCRC patients. Immunotherapeutic agents form approximately 39% (includes monoclonal antibodies, viruses, vaccines, and immunomodulators) of all agents and targeted therapy forms 45% (tyrosine kinase inhibitors, epigenetic modulators, and others) of all agents being investigated for mCRC.
Ecology of a polymetallic nodule occurrence gradient: Implications for deep‐sea mining
Authors: Simon‐Lledó Erik , Bett Brian J. , Huvenne Veerle A. I. , Schoening Timm , Benoist Noelie M. A. , Jones Daniel O. B.
Published: March 2019

Abyssal polymetallic nodule fields constitute an unusual deep‐sea habitat. The mix of soft sediment and the hard substratum provided by nodules increases the complexity of these environments. Hard substrata typically support a very distinct fauna to that of seabed sediments, and its presence can play a major role in the structuring of benthic assemblages. We assessed the influence of seafloor nodule cover on the megabenthos of a marine conservation area (area of particular environmental interest 6) in the Clarion Clipperton Zone (3950–4250 m water depth) using extensive photographic surveys from an autonomous underwater vehicle. Variations in nodule cover (1–20%) appeared to exert statistically significant differences in faunal standing stocks, some biological diversity attributes, faunal composition, functional group composition, and the distribution of individual species. The standing stock of both the metazoan fauna and the giant protists (xenophyophores) doubled with a very modest initial increase in nodule cover (from 1% to 3%). Perhaps contrary to expectation, we detected little if any substantive variation in biological diversity along the nodule cover gradient. Faunal composition varied continuously along the nodule cover gradient. We discuss these results in the context of potential seabed‐mining operations and the associated sustainable management and conservation plans. We note in particular that successful conservation actions will likely require the preservation of areas comprising the full range of nodule cover and not just the low cover areas that are least attractive to mining.
Trump Board Narrows Definition of Protected Concerted Activity
Authors: DeMaria Alfred T.
Published: March 2019

In another decision that is a boon for employers, the NLRB recently overruled an Obama era precedent and substantially narrowed what is considered “protected concerted activities” by workers. Alstate Maintenance, 367 NLRB No. 68 (2019). The decision expressly overturned a prior ruling which held that a single employee who gripes in a group setting is per se speaking on behalf of other employees and is therefore engaged in protected activity under the NLRA without regard to whether the employee intends to raise a group complaint or is seeking to initiate, induce, or prepare for group action.
Comparative study of hybrid artificial neural network methods under stationary and nonstationary data in stock market
Authors: Dosdoğru Ayşe Tuğba
Published: March 2019

In this study, a new methodology is proposed to automatically determine six parameters of artificial neural network using population‐based metaheuristics. We considered following three issues: What is the effect of used metaheuristic on performance? Which parameters are mostly selected? Is there a difference between the forecasting results when using stationary or nonstationary dataset that are selected according to the augmented Dickey–Fuller test statistics? Based upon results of performance measures, proposed method leads to significant opportunities to forecast stock market more effectively. We also expect proposed methodology can provide remarkable advantages for other complex, dynamic, and nonlinear forecasting problems.
Occurrence of CYP2B6 516G>T polymorphism in patients with ARV‐associated hepatotoxicity
Authors: Singh HariOm , Lata Sonam , Dhole T. N. , Gangakhedkar Raman R.
Published: March 2019

Background

Hepatic enzyme cytochrome P450 2B6 (CYP2B6) plays a role in the metabolism of efavirenz drugs. CYP2B6 516G>T variation showed an implication for HIV treatment.

Methods

CYP2B6 516G>T polymorphism was genotyped in a total 165 HIV patients that include 34 with and 131 without hepatotoxicity and 155 healthy individuals by the PCR‐RFLP.

Results

In patients with hepatotoxicity, the prevalence of CYP2B6 516TT genotype was higher as compared to healthy individuals (35.3% vs. 30.5%, OR = 1.74). Patients with hepatotoxicity using tobacco had a higher prevalence of genotypes CYP2B6 516GT, 516TT, 516GT+TT as compared to healthy individuals (28.57% vs. 25.93%; 57.14% vs. 29.63%; 85.71% vs. 55.56%). Likewise, hepatotoxicity in patients consuming alcohol showed higher distributions of CYP2B6 516GT, 516TT, 516GT+TT genotypes (57% vs. 25.93%; 42.86% vs. 33.33%; 71.43% vs. 59.26%). Nevirapine users with hepatotoxicity overrepresented genotypes CYP2B6 TT and 516GT+TT as compared to efavirenz users (47.83% vs. 45.45%, OR = 6.88, 65.22% vs. 54.55%, OR = 1.56). Similarly, in nevirapine +alcohol users with hepatotoxicity, the frequency of CYP2B6 516GT, 516GT+TT genotypes was higher than with nevirapine +alcohol nonusers (40.0% vs. 11.11%, OR = 8.00, 80.0% vs. 27.78%, OR = 4.00). In HIV patients, nevirapine users had higher frequency of CYP2B6 516GT, 516GT+TT genotypes as compared to efavirenz users (42.02% vs. 25.00%, OR = 2.53; 72.27% vs. 58.33%, OR = 1.86). Likewise, in HIV patients, genotypes CYP2B6 516GT, 516GT+TT were predominant with nevirapine +alcohol users as compared to nevirapine +alcohol nonusers (57.89% vs. 34.57%, OR = 2.46; 78.95% vs. 69.14%, OR = 1.67). In multivariate logistic regression, taking nevirapine had a protection for severity of ARV‐associated hepatotoxicity (OR = 0.23, p = 0.005).

Conclusions

No significant association was detected between CYP2B6 516G>T polymorphism and susceptibility to ARV‐associated hepatotoxicity.
Landmark MH ruling finds insurer illegally denied coverage to patients
Authors: Canady Valerie A.
Published: March 2019

In a case that may have national implications and has been called “groundbreaking,” a San Francisco federal court ruled March 5 that United Behavioral Health (UBH) used flawed and overly restrictive guidelines when it denied mental health and substance use disorder coverage claims for tens of thousands of patients, including children.
RAND: Effective training in psychotherapy critical to high‐quality care
Authors: Canady Valerie A.
Published: March 2019

Observing advances in mental health care and, subsequently, the many effective treatments available for mental health conditions, including certain types of medications and psychotherapy, RAND officials have developed a training tool to help clinicians determine which trainings in psychotherapy best meet the needs of trainer and trainee.
Nasal spray treatment for adults with TRD approved by FDA
Authors: Canady Valerie A.
Published: March 2019

Less than a month after a Food and Drug Administration (FDA) advisory committee recommended the approval of a ketamine nasal spray treatment for adults with treatment‐resistant depression (TRD), the agency formally approved it March 6, with officials citing a “long‐standing need” for additional effective treatments for people who have not benefited from other antidepressant medications.
Stiffness pathologies in discrete granular systems: Bifurcation, neutral equilibrium, and instability in the presence of kinematic constraints
Authors: Kuhn Matthew R. , Prunier Florent , Daouadji Ali
Published: March 2019

The paper develops the stiffness relationship between the movements and forces among a system of discrete interacting grains. The approach is similar to that used in structural analysis, but the stiffness matrix of granular material is inherently nonsymmetric because of the geometrics of particle interactions and of the frictional behavior of the contacts. Internal geometric constraints are imposed by the particles' shapes, in particular, by the surface curvatures of the particles at their points of contact. Moreover, the stiffness relationship is incrementally nonlinear, and even small assemblies require the analysis of multiple stiffness branches, with each branch region being a pointed convex cone in displacement space. These aspects of the particle‐level stiffness relationship give rise to three types of microscale failure: neutral equilibrium, bifurcation and path instability, and instability of equilibrium. These three pathologies are defined in the context of four types of displacement constraints, which can be readily analyzed with certain generalized inverses. That is, instability and nonuniqueness are investigated in the presence of kinematic constraints. Bifurcation paths can be either stable or unstable, as determined with the Hill–Bažant–Petryk criterion. Examples of simple granular systems of three, 16, and 64 disks are analyzed. With each system, multiple contacts were assumed to be at the friction limit. Even with these small systems, microscale failure is expressed in many different forms, with some systems having hundreds of microscale failure modes. The examples suggest that microscale failure is pervasive within granular materials, with particle arrangements being in a nearly continual state of instability.
Investigation on interlayer phase morphology evolution of “Ex‐Situ” toughened composite laminate
Authors: Ding Yanyu , Yao Xinglong , Gong Chenchen , Chen Qifeng , Ren Baosheng
Published: March 2019

The numerical simulation on the interlayer phase morphology evolution of “Ex‐Situ” toughened laminate was performed in this study. Specifically, the diffusion process of thermoset (TS) resin into thermoplastic (TP) resin was modeled incorporating the negative effect of resin curing reactions. The dynamic process of polymerization‐induced phase separation in TP/TS blends was predicted by the modified Cahn–Hilliard equation, in which the concentration‐dependent mobility was used to describe dynamic asymmetry between TP resin and TS resin, and the mixing free energy of the blends contained the contribution of resin curing reactions. The phase morphology evolution of polysulfone/epoxy blends in the interlaminar region was analyzed numerically, and the results indicated that the diffusion process resulted in the concentration‐gradient distribution of epoxy resin in interlayer, and when the concentration‐gradient decreased, the interlayer phase morphology developed from the coexistence of different microstructures to the presence of a single structural form. The post‐curing temperature played a more important role in the phase separation than that in resin curing reaction, and the separated structures were only observed in the local region of interlayer under low post‐curing temperature, due to small driving force of phase separation. Moreover, the movements of epoxy molecules dominated the microstructure formation process. POLYM. COMPOS., 40:3644–3656, 2019. © 2019 Society of Plastics Engineers
Cover Image, Volume 68, Issue 4
Authors: Jagtap Siddheshwar , Dalvi Vishal , Sankar Kalleta , Ratna Debdatta
Published: March 2019

The cover image is based on the Research Article Enhancement of orientation of rigid polymer blocks by incorporating rod‐coil block copolymer chains into metal‐organic frameworks by Jin Wang et al. DOI: 10.1002/pi.5766.

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Proteomic Analysis of Stromal and Epithelial Cell Communications in Human Endometrial Cancer Using a Unique 3D Co‐Culture Model
Authors: Al‐Juboori Aminah Ali Abid , Ghosh Arnab , Jamaluddin Muhammad Fairuz Bin , Kumar Manish , Sahoo Subhransu Sekhar , Syed Shafiq Mukhtar , Nahar Pravin , Tanwar Pradeep Singh
Published: March 2019

Epithelial and stromal communications are essential for normal uterine functions and their dysregulation contributes to the pathogenesis of many diseases including infertility, endometriosis, and cancer. Although many studies have highlighted the advantages of culturing cells in 3D compared to the conventional 2D culture system, one of the major limitations of these systems is the lack of incorporation of cells from non‐epithelial lineages. In an effort to develop a culture system incorporating both stromal and epithelial cells, 3D endometrial cancer spheroids are developed by co‐culturing endometrial stromal cells with cancerous epithelial cells. The spheroids developed by this method are phenotypically comparable to in vivo endometrial cancer tissue. Proteomic analysis of the co‐culture spheroids comparable to human endometrial tissue revealed 591 common proteins and canonical pathways that are closely related to endometrium biology. To determine the feasibility of using this model for drug screening, the efficacy of tamoxifen and everolimus is tested. In summary, a unique 3D model system of human endometrial cancer is developed that will serve as the foundation for the further development of 3D culture systems incorporating different cell types of the human uterus for deciphering the contributions of non‐epithelial cells present in cancer microenvironment.
Management of skin sarcoidosis with minocycline monotherapy
Authors: Sasaki Shinichi , Kato Motoyasu , Nakamura Kota , Namba Yukiko , Nagashima Osamu , Takahashi Kazuhisa
Published: March 2019

A 46‐year‐old woman with severe skin sarcoidosis, mainly on the back of the trunk, persisting for >15 years, was followed up without systemic treatment. In 2014, she was started on minocycline monotherapy owing to worsening of the skin sarcoid lesions. Surprisingly, after approximately 1 year of the monotherapy, nearly all skin lesions resolved with only light residual scars, despite the poor efficacy of the monotherapy for pulmonary sarcoidosis. The patient's serum angiotensin‐converting enzyme levels also decreased to the normal range. The presence of Propionibacterium acnes was confirmed when a retrospectively immunostained epithelioid granuloma, obtained from skin biopsy, demonstrated staining with monoclonal antibodies specific for P. acnes. Minocycline monotherapy, thus, appears to be a possible treatment modality for skin sarcoidosis.
Architecting federations of systems: A framework for capturing synergy
Authors: Lluch Ignasi , Golkar Alessandro
Published: March 2019

This paper defines Federations of Systems, introduces a tailored architecting framework, and demonstrates it in a satellite design case study. While certainly not being new concepts in the literature, federations are a class of Systems of Systems (SoS) that have not been extensively explored due to the scarcity of applied examples and still few practitioners facing their specific design challenges. This is expected to change with the advent of the Internet of Things, Machine to Machine applications, collaborative consumption, and Federated Satellite Systems. It has become henceforth necessary to develop approaches in design and architecting capable of addressing such interconnected sets of systems.

Federations are SoS characterized by the absence of global goals and stakeholders, and cooperation enabled only on an opportunistic basis. Systems engage in federations when the perceived benefit exceeds the costs of the necessary interfaces. The proposed framework quantifies the upper limits to the net benefits of cooperation between systems through the concept of synergy. Using synergy as a heuristic to navigate federated design spaces, the framework predicts the appearance and evolution of federations.

The demonstration of the framework in a six‐satellite federation shows that advantages of federating emerge with the collaboration between just two systems. Interface costs, architectural cost preferences, and network topology drive the achievable benefits. Specifically, when considering communication architectures under 80 MUSD for satellite systems, federating is advantageous when the interface lifecycle costs are below 15 MUSD. This demonstration case exemplifies how federating can assist systems in achieving design points that dominate the solutions of their local tradespace.