bluuebunny/crossref_metadata_2025 huggingface dataset:
Improved production, purification, and characterization of biosurfactants produced by Serratia marcescens SM3 and its isogenic SMRG‐5 strain
Authors: Rosas‐Galván Nashbly Sarela , Martínez‐Morales Fernando , Marquina‐Bahena Silvia , Tinoco‐Valencia Raunel , Serrano‐Carreón Leobardo , Bertrand Brandt , León‐Rodríguez Renato , Guzmán‐Aparicio Josefina , Alvaréz‐Berber Laura , Trejo‐Hernández María R.
Published: February 2018

In this study, the biosurfactants (Bs) production of two Serratia marcescens strains (SM3 and its isogenic SMRG‐5 strain) was improved and the tenso‐active agents were purified and characterized. A 23 factorial design was used to evaluate the effect of nitrogen and carbon sources on the surface tension (ST) reduction and emulsion index (EI24) of the produced Bs. Optimum Bs production by SM3 was achieved at high concentrations of carbon and nitrogen, reducing ST to 26.5 ± 0.28 dynes/cm, with an EI24 of 79.9 ± 0.2%. Meanwhile, the best results for SMRG‐5 were obtained at low concentrations, reducing the ST to 25.2 ± 0.2 dynes/cm, with an EI24 of 89.7 ± 0.28%. The optimal conditions for Bs production were scaled up in a 2‐L reactor, yielding 4.8 and 5.2 g/L for SM3 and SMRG‐5, respectively. Gas Chromatography–Mass Spectrometry (GC–MS) analysis revealed the presence of two different lipopeptides (hidrofobic fractions: octadecanoic and hexadecanoic acid for SM3 and SMRG5, respectively). Both strains were capable of benzo [a] pyrene removal (59% after 72 H of culture).
Application of adaptive laboratory evolution to overcome a flux limitation in an Escherichia coli production strain
Authors: Tokuyama Kento , Toya Yoshihiro , Horinouchi Takaaki , Furusawa Chikara , Matsuda Fumio , Shimizu Hiroshi
Published: February 2018

Gene deletion strategies using flux balance analysis (FBA) have improved the growth‐coupled production of various compounds. However, the productivities were often below the expectation because the cells failed to adapt to these genetic perturbations. Here, we demonstrate the productivity of the succinate of the designed gene deletion strain was improved by adaptive laboratory evolution (ALE). Although FBA predicted deletions of adhE‐pykAF‐gldA‐pflB lead to produce succinate from glycerol with a yield of 0.45 C‐mol/C‐mol, the knockout mutant did not produce only 0.08 C‐mol/Cmol, experimentally. After the ALE experiments, the highest succinate yield of an evolved strain reached to the expected value. Genome sequencing analysis revealed all evolved strains possessed novel mutations in ppc of I829S or R849S. In vitro enzymatic assay and metabolic profiling analysis revealed that these mutations desensitizing an allosteric inhibition by L‐aspartate and improved the flux through Ppc, while the activity of Ppc in the unevolved strain was tightly regulated by L‐aspartate. These result demonstrated that the evolved strains achieved the improvement of succinate production by expanding the flux space of Ppc, realizing the predicted metabolic state by FBA.
Structural and metabolic responses of Staphylococcus aureus biofilms to hyperosmotic and antibiotic stress
Authors: Kiamco Mia M. , Mohamed Abdelrhman , Reardon Patrick N. , Marean‐Reardon Carrie L. , Aframehr Wrya M. , Call Douglas R. , Beyenal Haluk , Renslow Ryan S.
Published: February 2018

Biofilms alter their metabolism in response to environmental stress. This study explores the effect of a hyperosmotic agent–antibiotic treatment on the metabolism of Staphylococcus aureus biofilms through the use of nuclear magnetic resonance (NMR) techniques. To determine the metabolic activity of S. aureus, we quantified the concentrations of metabolites in spent medium using high‐resolution NMR spectroscopy. Biofilm porosity, thickness, biovolume, and relative diffusion coefficient depth profiles were obtained using NMR microimaging. Dissolved oxygen concentration was measured to determine the availability of oxygen within the biofilm. Under vancomycin‐only treatment, the biofilm communities switched to fermentation under anaerobic condition, as evidenced by high concentrations of formate (7.4 ± 2.7 mM), acetate (13.1 ± 0.9 mM), and lactate (3.0 ± 0.8 mM), and there was no detectable dissolved oxygen in the biofilm. In addition, we observed the highest consumption of pyruvate (0.19 mM remaining from an initial 40 mM concentration), the sole carbon source, under the vancomycin‐only treatment. On the other hand, relative effective diffusion coefficients increased from 0.73 ± 0.08 to 0.88 ± 0.08 under vancomycin‐only treatment but decreased from 0.71 ± 0.04 to 0.60 ± 0.07 under maltodextrin‐only and from 0.73 ± 0.06 to 0.56 ± 0.08 under combined treatments. There was an increase in biovolume, from 2.5 ± 1 mm3 to 7 ± 1 mm3, under the vancomycin‐only treatment, while the maltodextrin‐only and combined treatments showed no significant change in biovolume over time. This indicated that physical biofilm growth was halted during maltodextrin‐only and combined treatments.
Peptide ligand‐mediated endocytosis of nanoparticles to cancer cells: Cell receptor‐binding‐ versus cell membrane‐penetrating peptides
Authors: Jo Eunji , Heo June Seok , Lim Ja‐Yun , Lee Bo‐Ram , Yoon Chul Joo , Kim Jinkwan , Lee Jeewon
Published: February 2018

The endocytosis‐mediating performances of two types of peptide ligands, cell receptor binding peptide (CRBP) and cell membrane penetrating peptide (CMPP), were analyzed and compared using a common carrier of peptide ligands‐human ferritin heavy chain (hFTH) nanoparticle. Twenty‐four copies of a CMPP(human immunodeficiency virus‐derived TAT peptide) and/or a CRBP (peptide ligand with strong and specific affinity for either human integrin(αvβ3) or epidermal growth factor receptor I (EGFR) that is overexpressed on various cancer cells) were genetically presented on the surface of each hFTH nanopariticle. The quantitative level of endocytosis and intracellular localization of fluorescence dye‐labeled CRBP‐ and CMPP‐presenting nanoparticles were estimated in the in vitro cultures of integrin‐ and EGFR‐overexpressing cancer and human dermal fibroblast cells(control). From the cancer cell cultures treated with the CMPP‐ and CRBP‐presenting nanoparticles, it was notable that CRBPs resulted in quantitatively higher level of endocytosis than CMPP (TAT) and successfully transported the nanoparticles to the cytosol of cancer cells depending on concentration and treatment period of time, whereas TAT‐mediated endocytosis localized most of the nanoparticles within endosomal vesicles under the same conditions. These novel findings provide highly useful informations to many researchers both in academia and in industry who are interested in developing anticancer drug delivery systems/carriers.
Baseline factors predicting a response to neoadjuvant chemotherapy with implications for non-surgical management of triple-negative breast cancer
Authors: van la Parra R F D , Tadros A B , Checka C M , Rauch G M , Lucci A , Smith B D , Krishnamurthy S , Valero V , Yang W T , Kuerer H M
Published: February 2018

Background

Patients with triple-negative breast cancer (TNBC) and a pathological complete response (pCR) after neoadjuvant chemotherapy may be suitable for non-surgical management. The goal of this study was to identify baseline clinicopathological variables that are associated with residual disease, and to evaluate the effect of neoadjuvant chemotherapy on both the invasive and ductal carcinoma in situ (DCIS) components in TNBC.

Methods

Patients with TNBC treated with neoadjuvant chemotherapy followed by surgical resection were identified. Patients with a pCR were compared with those who had residual disease in the breast and/or lymph nodes. Clinicopathological variables were analysed to determine their association with residual disease.

Results

Of the 328 patients, 36·9 per cent had no residual disease and 9·1 per cent had residual DCIS only. Patients with residual disease were more likely to have malignant microcalcifications (P = 0·023) and DCIS on the initial core needle biopsy (CNB) (P = 0·030). Variables independently associated with residual disease included: DCIS on CNB (odds ratio (OR) 2·46; P = 0·022), T2 disease (OR 2·40; P = 0·029), N1 status (OR 2·03; P = 0·030) and low Ki-67 (OR 2·41; P = 0·083). Imaging after neoadjuvant chemotherapy had an accuracy of 71·7 (95 per cent c.i. 66·3 to 76·6) per cent and a negative predictive value of 76·9 (60·7 to 88·9) per cent for identifying residual disease in the breast and lymph nodes. Neoadjuvant chemotherapy did not eradicate the DCIS component in 55 per cent of patients.

Conclusion

The presence of microcalcifications on imaging and DCIS on initial CNB are associated with residual disease after neoadjuvant chemotherapy in TNBC. These variables can aid in identifying patients with TNBC suitable for inclusion in trials evaluating non-surgical management after neoadjuvant chemotherapy.
Dejerine–Sottas disease in childhood—Genetic and sonographic heterogeneity
Authors: Hobbelink Sanne M. R. , Brockley Cain R. , Kennedy Rachel A. , Carroll Kate , de Valle Katy , Rao Padma , Davis Mark R. , Laing Nigel G. , Voermans Nicol C. , Ryan Monique M. , Yiu Eppie M.
Published: February 2018

Introduction

The nerve sonographic features of Dejerine‐Sottas disease (DSD) have not previously been described.

Methods

This exploratory cross‐sectional, matched, case–control study investigated differences in nerve cross‐sectional area (CSA) in children with DSD compared to healthy controls and children with Charcot–Marie–Tooth disease type 1A (CMT1A). CSA of the median, ulnar, tibial, and sural nerves was measured by peripheral nerve ultrasound. The mean difference in CSA between children with DSD, controls, and CMT1A was determined individually and within each group.

Results

Five children with DSD and five age‐ and sex‐matched controls were enrolled. Data from five age‐matched children with CMT1A was also included. Group comparison showed no mean difference in nerve CSA between children with DSD and controls. Individual analysis of each DSD patient with their matched control indicated an increase in nerve CSA in three of the five children. The largest increase was observed in a child with a heterozygous PMP22 point mutation (nerve CSA fivefold larger than a control and twofold larger than a child with CMT1A). Nerve CSA was moderately increased in two children—one with a heterozygous mutation in MPZ and the other of unknown genetic etiology.

Conclusions

Changes in nerve CSA on ultrasonography in children with DSD differ according to the underlying genetic etiology, confirming the variation in underlying pathobiologic processes and downstream morphological abnormalities of DSD subtypes. Nerve ultrasound may assist in the clinical phenotyping of DSD and act as an adjunct to known distinctive clinical and neurophysiologic findings of DSD subtypes. Larger studies in DSD cohorts are required to confirm these findings.
Substrate Binding Drives Active‐Site Closing of Human Blood Group B Galactosyltransferase as Revealed by Hot‐Spot Labeling and NMR Spectroscopy Experiments
Authors: Weissbach Sophie , Flügge Friedemann , Peters Thomas
Published: February 2018

Crystallography has shown that human blood group A (GTA) and B (GTB) glycosyltransferases undergo transitions between “open”, “semiclosed”, and “closed” conformations upon substrate binding. However, the timescales of the corresponding conformational reorientations are unknown. Crystal structures show that the Trp and Met residues are located at “conformational hot spots” of the enzymes. Therefore, we utilized 15N side‐chain labeling of Trp residues and 13C‐methyl labeling of Met residues to study substrate‐induced conformational transitions of GTB. Chemical‐shift perturbations (CSPs) of Met and Trp residues in direct contact with substrate ligands reflect binding kinetics, whereas the CSPs of Met and Trp residues at remote sites reflect conformational changes of the enzyme upon substrate binding. Acceptor binding is fast on the chemical‐shift timescale with rather small CSPs in the range of less than approximately 20 Hz. Donor binding matches the intermediate exchange regime to yield an estimate for exchange rate constants of approximately 200–300 Hz. Donor or acceptor binding to GTB saturated with acceptor or donor substrate, respectively, is slow (<10 Hz), as are coupled protein motions, reflecting mutual allosteric control of donor and acceptor binding. Remote CSPs suggest that substrate binding drives the enzyme into the closed state required for catalysis. These findings should contribute to better understanding of the mechanism of glycosyl transfer of GTA and GTB.
MSN‐on‐a‐Chip: Cell‐Based Screenings Made Possible on a Small‐Molecule Microarray of Native Natural Products
Authors: Peng Bo , Yu Changmin , Du Shubo , Liew Si S. , Mao Xin , Yuan Peiyan , Na Zhenkun , Yao Shao Q.
Published: February 2018

Standard small‐molecule microarrays (SMMs) are not well‐suited for cell‐based screening assays. Of the few attempts made thus far to render SMMs cell‐compatible, all encountered major limitations. Here we report the first mesoporous silica nanoparticle (MSN)‐on‐a‐chip platform capable of allowing high‐throughput cell‐based screening to be conducted on SMMs. By making use of a glass surface on which hundreds of MSNs, each encapsulated with a different native natural product, were immobilized in spatially defined manner, followed by on‐chip mammalian cell growth and on‐demand compound release, high‐content screening was successfully carried out with readily available phenotypic detection methods. By combining this new MSN‐on‐a‐chip system with small interfering RNA technology for the first time, we discovered that (+)‐usniacin possesses synergistic inhibitory properties similar to those of olaparib (an FDA‐approved drug) in BRCA1‐knockdown cancer cells.
Angelica sinensis polysaccharide inhibits proliferation, migration, and invasion by downregulating microRNA‐675 in human neuroblastoma cell line SH‐SY5Y
Authors: Yang Jing , Shao Xiaojun , Jiang Jian , Sun Yan , Wang Lingzhen , Sun Lirong
Published: February 2018

Neuroblastoma is the most common tumor diagnosed in children and infants, with high recurrence and poor prognosis. Angelica sinensis polysaccharide (AP) whose average molecular weight is 72,900 Da possesses various bioactivities. We aimed to explore the effects of AP on neuroblastoma SH‐SY5Y cells as well as the underlying mechanisms. Effects of AP on cell viability, proliferation, apoptosis, migration, invasion, and expressions of long noncoding RNA H19 (lncRNA‐H19), microRNA (miR)‐675, and CD44 were assessed. Then, effects of miR‐675 overexpression on AP‐treated cells were analyzed. Next, expression of key kinases in the PI3K/AKT and JAK/ STAT pathways was detected. The possible target gene of miR‐675 was finally explored. Cell viability was reduced by 200–500 µg/mL AP. Meanwhile, AP repressed cell proliferation, migration, and invasion, but induced apoptosis. Expressions of lncRNA‐H19 and miR‐675 were upregulated in neuroblastoma cells, and were downregulated by AP. AP was also identified to upregulate CD44. We next found AP affected SH‐SY5Y cells through downregulating miR‐675. Key kinases in the PI3K/AKT and JAK/STAT pathways were downregulated by AP stimulation, while these downregulations were abrogated by miR‐675 overexpression. KIF1B isoform β (KIF1Bβ) is proved to be a target of miR‐675. In conclusion, AP was first identified to inhibit proliferation, migration, and invasion but induce apoptosis. Furthermore, AP might repress tumorigenesis of SH‐SY5Y cells through miR‐675‐mediated inactivation of the PI3K/AKT and JAK/STAT pathways. Besides, KIF1Bβ might be a target of miR‐675.
A superelderly case of TAFRO syndrome treated effectively using corticosteroid hormones
Authors: Shimada Yoshitaka , Adachi Mizuho , Kobayashi Noritada , Okada Takemichi , Yamazaki Hitoshi , Nagaba Yasushi , Yokomori Hiroaki
Published: February 2018

Key Clinical Message

Peripheral lymphocyte subsets may be less time‐consuming and are a prognostic tool for managing thrombocytopenia, anasarca, myelofibrosis, renal dysfunction, and organomegaly (TAFRO) syndrome. Here, we report a superelderly case of plasma cell type TAFRO syndrome treated effectively using corticosteroid hormones.
Coccidioides immitis soft tissue infection mimicking pseudofolliculitis barbae
Authors: Gerstein Wendy , Ilieva Valeria
Published: February 2018

Key Clinical Message

Endemic fungal infections can present atypically and should be considered in the differential diagnosis of any soft tissue infection not responding appropriately to antibiotic therapy. Diagnosis can be confirmed with a biopsy. Most fungal soft tissue infections require extended duration of treatment.
Successful treatment of refractory TAFRO syndrome with elevated vascular endothelial growth factor using thyroxine supplements
Authors: Oka Satoko , Ono Kazuo , Nohgawa Masaharu
Published: February 2018

Key Clinical Message

Although the clinical significance of hypothyroidism in TAFRO syndrome is unknown, vascular endothelial growth factor (VEGF) levels decreased with improvements in the condition of our refractory TAFRO cases after thyroxine supplement therapy. Our results indicate that elevated VEGF levels are a potential factor in the pathogenesis and anasarca of TAFRO syndrome with hypothyroidism.
Parapelvic cysts mimicking hydronephrosis
Authors: Koratala Abhilash , Alquadan Kawther F.
Published: February 2018

Key Clinical Message

Point‐of‐care renal ultrasonography performed by physicians at bedside assists in rapid evaluation of hydronephrosis, nephrolithiasis and other structural abnormalities, and guides management. As such, it is important to differentiate between various renal pathologies that can mimic one another and herein, we present a case where parapelvic cysts mimicked hydronephrosis.
Fever in a transplant recipient: think beyond infection
Authors: Kamboj Mayanka , Chornyy Volodymyr , Koratala Abhilash , Santos Alfonso H.
Published: February 2018

Key Clinical Message

Immune reconstitution inflammatory syndrome (IRIS) is an exaggerated inflammatory cascade initiated in response to immune recovery during the resolution of an infection. Reduction in calcineurin inhibitor levels in organ transplant recipients due to enhanced metabolism from interaction with rifampin can predispose these individuals to develop IRIS during the treatment of tuberculosis and mimic sepsis.
Removal of brilliant green and malachite green from aqueous solution by a viable magnetic polymeric nanocomposite: Simultaneous spectrophotometric determination of 2 dyes by PLS using original and first derivative spectra
Authors: Bagtash Maryam , Zolgharnein Javad
Published: February 2018

Here, we describe the successful synthesis of a new magnetic nanocomposite and investigate simultaneous removal of 2 cationic dyes, brilliant green (BG) and malachite green (MG), from aqueous solutions. The nanocomposite is characterized by
scanning electron microscopy, energy‐dispersive X‐ray spectroscopy, thermal gravimetric analysis, and Fourier‐transform infrared spectrophotometry. The spectra of BG and MG in their mixture show severe overlapping. Therefore, partial least square (PLS) regression is applied for simultaneous determination of target dyes. The original and first derivative spectra of the binary mixtures are used to perform the optimization of the calibration matrices by the PLS method. According to statistical values, PLS on first derivative spectral data has given better results with respect to the original data. The coefficients of determination (R2) for the test data set were 0.998 and 0.9996; root mean square error of prediction values for BG and MG were 0.12 and 0.19, respectively. Furthermore, adsorption kinetics and effects of various variables such as solution pH, adsorbent amount, and initial dye concentration are investigated. Under optimized conditions (adsorbent mass, 0.08 g; solution pH, 8; and contact time, 60 min), equilibrium experimental data are represented by Langmuir, Freundlich, and Sips isotherms. Results briefly show that adsorption of dyes by nanocomposite obeys pseudo–second‐order kinetic model and Sips isotherm.
(Multi‐)Metallic Cluster Growth
Authors: Weinert Bastian , Mitzinger Stefan , Dehnen Stefanie
Published: February 2018

This review article provides a survey of contemporary investigations on main group metal cluster formation, addressing homo‐ and heterometallic clusters (including small numbers of transition metal atoms), with or without an external ligand shell, thereby excluding clusters with non‐metal atoms as bridging ligands. Most of the studies reflected herein represent insights into the formation of intermediates from the starting material, or the final cluster formation from established intermediates. In rare cases, the entire process was suggested as a result of comprehensive, multi‐method elucidations. The article is to be understood as a state‐of‐the‐art report, as the subject matter is currently a rising field of research, which is still in its infancy, despite some early activities that date back to the 1980s. At the same time, the article intends to point toward both the importance and the feasibility of according studies, in order to encourage researchers to gain even more knowledge in this field. Only deep understanding of cluster formation will allow for design, and ultimately control, of their syntheses, with the long‐term goal of their optimization and purposeful application in catalysis or novel material synthesis.
Reactions of Metal–Carbon Bonds within Six‐Membered Metallaaromatic Rings
Authors: Zhou Xiaoxi , Zhang Hong
Published: February 2018

Metallaaromatics represent a distinct and attractive class of heterocycles, which have greatly expanded the library of known aromatics. They have garnered extensive research interest on account of their unique properties, organometallic reactivity, and aromaticity. The metal–carbon bonds have been regarded as the most active reaction sites of metallaaromatics and a variety of related reactions have been demonstrated in the literature. This Minireview summarized recent findings on the reactivity of the metal–carbon bonds, mainly relevant to the representative metallaaromatics with six‐membered ring scaffolds. A series of reactions occurred on the metal–carbon bonds, including the nucleophilic addition reactions, nucleophilic aromatic substitution reactions, electrophilic addition reactions, reactions with unsaturated compounds, and migratory insertion reactions, have been classified. These reactions demonstrate that the metal–carbon bonds of metallaaromatics can undergo typical reactions for both aromatic species and metal carbene/carbyne complexes. Meanwhile, the reactivity trends of the metal–carbon bonds are strongly affected by the metal centers and the effect of the corresponding substituents of metallacycles.
Ullazine Donor–π bridge‐Acceptor Organic Dyes for Dye‐Sensitized Solar Cells
Authors: Zhang Yanbing , Cheema Hammad , McNamara Louis , Hunt Leigh Anna , Hammer Nathan I. , Delcamp Jared H.
Published: February 2018

A series of four ullazine‐donor based donor–π bridge‐acceptor (D–π–A) dyes have been synthesized and compared to a prior ullazine donor‐acceptor (D–A) dye as well as a triphenylamine donor with an identical π–bridge and acceptor. The D–π–A ullazine series demonstrates an unusually uniform‐in‐intensity panchromatic UV/Vis absorption spectrum throughout the visible region. This is in part due to the introduction of strong high‐energy bands through incorporation of the ullazine building block as shown by computational analysis. The dyes were characterized on TiO2 films and in DSC devices. Performances of 5.6 % power conversion efficiency were obtained with IPCE onsets reaching 800 nm.
A Variety of Bond Analysis Methods, One Answer? An Investigation of the Element−Oxygen Bond of Hydroxides HnXOH
Authors: Fugel Malte , Beckmann Jens , Jayatilaka Dylan , Gibbs Gerald V. , Grabowsky Simon
Published: February 2018

There is a great variety of bond analysis tools that aim to extract information on the bonding situation from the molecular wavefunction. Because none of these can fully describe bonding in all of its complexity, it is necessary to regard a balanced selection of complementary analysis methods to obtain a reliable chemical conclusion. This is, however, not a feasible approach in most studies because it is a time‐consuming procedure. Therefore, we provide the first comprehensive comparison of modern bonding analysis methods to reveal their informative value. The element−oxygen bond of neutral HnXOH model compounds (X=Li, Be, B, C, N, O, F, Na, Mg, Al, Si, P, S, Cl) is investigated with a selection of different bond analysis tools, which may be assigned into three different categories: i) real space bonding indicators (quantum theory of atoms in molecules (QTAIM), the electron localizability indicator (ELI‐D), and the Raub–Jansen index), ii) orbital‐based descriptors (natural bond orbitals (NBO), natural resonance theory (NRT), and valence bond (VB) calculations), and iii) energy analysis methods (energy decomposition analysis (EDA) and the Q‐analysis). Besides gaining a deep insight into the nature of the element−oxygen bond across the periodic table, this systematic investigation allows us to get an impression on how well these tools complement each other. Ionic, highly polarized, polarized covalent, and charge‐shift bonds are discerned from each other.
Clinical and mutational spectrum of highly differentiated, paired box 3:forkhead box protein o1 fusion–negative rhabdomyosarcoma: A report from the Children's Oncology Group
Authors: Teot Lisa A. , Schneider Michaela , Thorner Aaron R. , Tian Jing , Chi Yueh‐Yun , Ducar Matthew , Lin Ling , Wlodarski Marcin , Grier Holcombe E. , Fletcher Christopher D. M. , van Hummelen Paul , Skapek Stephen X. , Hawkins Douglas S. , Wagers Amy J. , Rodriguez‐Galindo Carlos , Hettmer Simone
Published: February 2018

BACKGROUND

Pediatric paired box 3:forkhead box protein O1 fusion–negative (PF–) rhabdomyosarcoma (RMS) represents a diverse spectrum of tumors with marked differences in histology, myogenic differentiation, and clinical behavior.

METHODS

This study sought to evaluate the clinical and mutational spectrum of 24 pediatric PF– human RMS tumors with high levels of myogenic differentiation. Tumors were sequenced with OncoPanel v.2, a panel consisting of the coding regions of 504 genes previously linked to human cancer.

RESULTS

Most of the tumors (19 of 24) arose at head/neck or genitourinary sites, and the overall survival rate was 100% with a median follow‐up time of 4.6 years (range, 1.4‐8.6 years). RAS pathway gene mutations were the most common mutations in PF–, highly differentiated RMS tumors. In addition, Hedgehog (Hh) and mechanistic target of rapamycin (mTOR) gene mutations with evidence for functional relevance (high‐impact) were identified in subsets of tumors. The presence of Hh and mTOR pathway gene mutations was mutually exclusive and was associated with high‐impact RAS pathway gene mutations in 3 of 4 Hh‐mutated tumors and in 1 of 6 mTOR‐mutated tumors.

CONCLUSIONS

Interestingly, Hh and mTOR gene mutations were previously associated with rhabdomyomas, which are also known to preferentially arise at head/neck and genitourinary sites. Findings from this study further support the idea that PF–, highly differentiated RMS tumors and rhabdomyomas may represent a continuous spectrum of tumors. Cancer 2018;124:1973‐81. © 2018 American Cancer Society.
Impact of the affordability of novel agents in patients with multiple myeloma: Real‐world data of current clinical practice in Mexico
Authors: Tarín‐Arzaga Luz , Arredondo‐Campos Daniela , Martínez‐Pacheco Victor , Martínez‐González Odra , Ramírez‐López Alba , Gómez‐De León Andrés , Gutiérrez‐Aguirre Cesar Homero , Cantú‐Rodríguez Olga , Jaime‐Pérez José Carlos , Gómez‐Almaguer David
Published: February 2018

BACKGROUND

The treatment of multiple myeloma (MM) has become costly and difficult to access for patients living in low‐income to middle‐income countries.

METHODS

The current retrospective study included 148 patients in Mexico with newly diagnosed MM, and was performed to compare the outcomes of patients with and without access to novel agents. The records of 77 patients admitted to a public hospital (PubC) and 71 patients cared for within private health systems (PrivC) from November 2007 to July 2016 were reviewed.

RESULTS

Compared with those treated in PrivC, patients receiving care at PubC were more likely to be diagnosed with advanced disease. A thalidomide‐based regimen was the most common induction treatment used at PubC, whereas a bortezomib‐based regimen was used most often in PrivC. The median follow‐up was 41 months. Patients in PrivC demonstrated better response rates and survival; 65% of patients treated in PrivC versus 41% treated at PubC achieved a very good partial response or better (P = .005). The median progression‐free survival and median overall survival were 23 months and 51 months, respectively, for patients treated at PubC and 41 months and 79 months, respectively, for those treated in PrivC (P<.001). More patients underwent autologous stem cell transplantation in PrivC. When adjustments were made for covariates, patients treated at PubC experienced a higher risk of death compared with patients receiving care in PrivC (hazard ratio, 2.0; 95% confidence interval, 1.0‐4.3 [P = .04]).

CONCLUSIONS

Stage at diagnosis, induction regimen, and autologous stem cell transplantation were found to be contributors to survival disparities between patients with MM treated at PubC compared with PrivC in Mexico. These findings underscore the need to improve access to novel agents and stem cell transplantation in public health systems. Cancer 2018;124:1946‐53. © 2018 American Cancer Society.
Postoperative cytological findings from the use of the Integran microfibrillar collagen hemostatic matrix in conization
Authors: Toyoda Shinji , Okada Hiroshi , Tsujino Hideo , Takeda Yoshinori , Sugiura Atsushi , Itani Yoshio , Kita Tsunekazu , Ishida Eiwa
Published: February 2018

The Integran microfibrillar collagen hemostatic matrix is one form of microfibrillar collagen hemostat. This form has a sheet‐type structure and has explicitly been used in Japan. In gynecology, this sheet‐type matrix has helped effect uterine surface hemostasis, especially in myomectomy and cervical conization. However, cytotechnologists and pathologists have overlooked the foreign materials used for conization in postoperative cervical cytology. We report two cases describing the characteristic cervical cytology findings when Integran was used in conization. The first case was a 67‐year‐old woman who underwent conization because of cervical intraepithelial neoplasia (CIN) 3. Thirty‐six days after the surgery, many cylindrical fragments of glossy acellular materials appeared in the cervical cytology. Fortunately, the content did not impede the diagnosis of NILM. The patient then underwent hysterectomy two months after conization. Surgical specimen revealed a high degree of inflammation and granulation without malignancy. Following surgery, the cylindrical fragments disappeared from microscopic findings. The second case was a 45‐year‐old woman who underwent conization because of CIN3. Thirty‐four days after the surgery, many tubular pieces of glossy acellular materials appeared in cervical cytology, as seen in the first case. The cytological diagnosis was NILM. One hundred days after surgery, cervical cytology revealed many clue cells but no cylindrical fragments. These clusters of cylindrical fragments of glossy acellular materials in cervical cytology after conization might induce a delay in diagnosing the persistence and recurrence of cervical cancer. This article is the first report describing cervical cytology findings associated with Integran use.
Validation of a blood marker for plasma volume in endurance athletes during a live‐high train‐low altitude training camp
Authors: Lobigs Louisa M. , Garvican‐Lewis Laura A. , Vuong Victor L. , Tee Nicolin , Gore Christopher J. , Peeling Peter , Dawson Brian , Schumacher Yorck O.
Published: February 2018

Altitude is a confounding factor within the Athlete Biological Passport (ABP) due, in part, to the plasma volume (PV) response to hypoxia. Here, a newly developed PV blood test is applied to assess the possible efficacy of reducing the influence of PV on the volumetric ABP markers; haemoglobin concentration ([Hb]) and the OFF‐score. Endurance athletes (n=34) completed a 21‐night simulated live‐high train‐low (LHTL) protocol (14 h.d‐1 at 3000 m). Bloods were collected twice pre‐altitude; at days 3, 8, and 15 at altitude; and 1, 7, 21, and 42 days post‐altitude. A full blood count was performed on the whole blood sample. Serum was analysed for transferrin, albumin, calcium, creatinine, total protein, and low‐density lipoprotein. The PV blood test (consisting of the serum markers, [Hb] and platelets) was applied to the ABP adaptive model and new reference predictions were calculated for [Hb] and the OFF‐score, thereby reducing the PV variance component. The PV correction refined the ABP reference predictions. The number of atypical passport findings (ATPFs) for [Hb] was reduced from 7 of 5 subjects to 6 of 3 subjects. The OFF‐score ATPFs increased with the PV correction (from 9 to 13, 99% specificity); most likely the result of more specific reference limit predictions combined with the altitude‐induced increase in red cell production. Importantly, all abnormal biomarker values were identified by a low confidence value. Although the multifaceted, individual physiological response to altitude confounded some results, the PV model appears capable of reducing the impact of PV fluctuations on [Hb].
Inferring species interactions through joint mark–recapture analysis
Authors: Yackulic Charles B. , Korman Josh , Yard Michael D. , Dzul Maria
Published: February 2018

Introduced species are frequently implicated in declines of native species. In many cases, however, evidence linking introduced species to native declines is weak. Failure to make strong inferences regarding the role of introduced species can hamper attempts to predict population viability and delay effective management responses. For many species, mark–recapture analysis is the more rigorous form of demographic analysis. However, to our knowledge, there are no mark–recapture models that allow for joint modeling of interacting species. Here, we introduce a two‐species mark–recapture population model in which the vital rates (and capture probabilities) of one species are allowed to vary in response to the abundance of the other species. We use a simulation study to explore bias and choose an approach to model selection. We then use the model to investigate species interactions between endangered humpback chub (Gila cypha) and introduced rainbow trout (Oncorhynchus mykiss) in the Colorado River between 2009 and 2016. In particular, we test hypotheses about how two environmental factors (turbidity and temperature), intraspecific density dependence, and rainbow trout abundance are related to survival, growth, and capture of juvenile humpback chub. We also project the long‐term effects of different rainbow trout abundances on adult humpback chub abundances. Our simulation study suggests this approach has minimal bias under potentially challenging circumstances (i.e., low capture probabilities) that characterized our application and that model selection using indicator variables could reliably identify the true generating model even when process error was high. When the model was applied to rainbow trout and humpback chub, we identified negative relationships between rainbow trout abundance and the survival, growth, and capture probability of juvenile humpback chub. Effects on interspecific interactions on survival and capture probability were strongly supported, whereas support for the growth effect was weaker. Environmental factors were also identified to be important and in many cases stronger than interspecific interactions, and there was still substantial unexplained variation in growth and survival rates. The general approach presented here for combining mark–recapture data for two species is applicable in many other systems and could be modified to model abundance of the invader via other modeling approaches.
Deacylative Reactions: Synthetic Applications
Authors: Ortega‐Martínez Aitor , Molina Cynthia , Moreno‐Cabrerizo Cristina , Sansano José M. , Nájera Carmen
Published: February 2018

Herein we introduce the recent developments of a new strategy based on deacylative alkylation (DaA) reactions for the generation of quaternary stereocenters based on the in situ preparation and functionalization of enolates under very mild reaction conditions. Palladium‐catalyzed deacylative allylation and benzylation reactions of carbon nucleophiles are performed with the corresponding alcohols. This methodology has been applied to the synthesis of the calcium ion channel blocker verapamil, the antiviral (+)‐hamigeran B, several oxindole precursors of esermethole, horsfiline, physostigmine, phenserine, meso‐folicanthine, meso‐chinonanthine and the dimer cyclotriptamine alkaloids. Base‐promoted deacylative reactions enable the functionalization of 2‐oxindole enolates at the 3‐position with alkyl halides and electrophilic alkenes. In the presence of oxygen or air, 3‐hydroxy‐2‐oxindoles are prepared by deacylative oxidation. Detrifluoroacylative reactions are promoted by a base generating fluoroenolates, which can participate in aldol, Mannich and Michael reactions for the preparation of important fluorinated intermediates. Finally, palladium‐catalyzed deacylative cross‐coupling of acetyl diazoacetates and phosphonates with aryl iodides let to the formation of aryl diazoacetates and phosphonates, respectively. The same process, with 2‐iodoazoarenes and 2‐iodoaryltriazenes, gives 2H‐indazoles, which are important pharmacophores.
Pressurized hot water extraction of β‐glucans from Cantharellus tubaeformis
Authors: Rodríguez‐Seoane Paula , González‐Muñoz María Jesús , Falqué Elena , Domínguez Herminia
Published: February 2018

Cantharellus tubaeformis was processed by pressurized hot water extraction (80–240°C) with the aim of maximizing the extraction of oligomeric fractions, β‐glucans, and the in vitro antioxidant properties of the extracts. Increased severity of treatment enhanced the extraction yields above 62% at temperatures of 210ºC or higher, corresponding to the maximum β‐glucan yields. The highest antioxidant capacity was obtained at 170ºC, although the highest content of phenolic compounds was obtained at the highest severity studied. This hydrothermal treatment can be considered a suitable process to obtain extracts with antioxidant properties and rich in β‐glucans.
Excavation of subglacial bedrock channels by seasonal meltwater flow
Authors: Beaud Flavien , Venditti Jeremy G. , Flowers Gwenn E. , Koppes Michele
Published: February 2018

Subglacial water flow drives the excavation of a variety of bedrock channels including tunnel valleys and inner gorges. Subglacial floods of various magnitudes – events occurring once per year or less frequently with discharges larger than a few hundred cubic metres per second – are often invoked to explain the erosive power of subglacial water flow. In this study we examine whether subglacial floods are necessary to carve bedrock channels, or if more frequent melt season events (e.g. daily production of meltwater) can explain the formation of substantial bedrock channels over a glacial cycle. We use a one‐dimensional numerical model of bedrock erosion by subglacial meltwater, where water flows through interacting distributed and channelized drainage systems. The shear stresses produced drive bedrock erosion by bed‐ and suspended‐load abrasion. We show that seasonal meltwater discharge can incise an incipient bedrock channel a few tens of centimetres deep and several metres wide, assuming abrasion is the only mechanism of erosion, a particle size of D=256 mm and a prescribed sediment supply per unit width. Using the same sediment characteristics, flood flows yield wider but significantly shallower bedrock channels than seasonal meltwater flows. Furthermore, the smaller the shear stresses produced by a flood, the deeper the bedrock channel. Shear stresses produced by seasonal meltwater are sufficient to readily transport boulders as bedload. Larger flows produce greater shear stresses and the sediment is carried in suspension, which produces fewer contacts with the bed and less erosion. We demonstrate that seasonal meltwater discharge can excavate bedrock volumes commensurate with channels several tens of metres to a few hundred metres wide and several tens of metres deep over several thousand years. Such simulated channels are commensurate with published observations of tunnel valleys and inner gorges. Copyright © 2018 John Wiley & Sons, Ltd.
Preparation of Stable Silver Nanoparticles Having Wide Red‐To‐Near‐Infrared Extinction
Authors: Kawamura Shiori , Matsubara Kazuki , Sakai Sotaro , Sasaki Kazuhisa , Saito Masataro , Saito Kenji , Yagi Masayuki , Norimatsu Wataru , Sasai Ryo , Kusunoki Michiko , Eguchi Miharu , Yin Shu , Asakura Yusuke , Yui Tatsuto
Published: February 2018

The synthesis of silver nanoparticles (AgNPs) within the interlayer space of transparent layered titania nanosheet (TNS) films is investigated. A considerable number of silver ions (≈70% against the cation exchange capacity of the TNS) are intercalated in the TNS films using methyl‐viologen‐containing TNSs as a precursor. The silver ion (Ag+)‐containing TNS films are treated with aqueous sodium tetrahydroborate (NaBH4), resulting in a gradual color change to bright blue. Various structural analyses clearly show that crystalline AgNPs are generated within the interlayer space of the TNSs. The NaBH4‐treated films show intense and characteristic near‐infrared (NIR) extinction spectra up to 1800 nm. The stability of the AgNPs within the TNS against oxygen and moisture is also investigated, and 96% and 82% of the AgNPs remain after standing in air for 1 month and 1 year, respectively. The NIR extinctions of the AgNP‐containing TNS films are further extended by employing different preparation procedures, for example, using sintered TNS films as starting materials and irradiating the Ag+‐containing TNSs with ultraviolet (UV) light. The obtained AgNP‐containing TNS films exhibit photochemical activities in the production of hydrogen from ammonia borane under visible‐light irradiation and the decomposition of nitrogen monoxide under UV‐light irradiation.
Genetic and environmental (physical fitness and sedentary activity) interaction effects on cardiometabolic risk factors in Mexican American children and adolescents
Authors: Arya Rector , Farook Vidya S. , Fowler Sharon P. , Puppala Sobha , Chittoor Geetha , Resendez Roy G. , Mummidi Srinivas , Vanamala Jairam , Almasy Laura , Curran Joanne E. , Comuzzie Anthony G. , Lehman Donna M. , Jenkinson Christopher P. , Lynch Jane L. , DeFronzo Ralph A. , Blangero John , Hale Daniel E. , Duggirala Ravindranath , Diego Vincent P.
Published: February 2018

Knowledge on genetic and environmental (G × E) interaction effects on cardiometabolic risk factors (CMRFs) in children is limited.  The purpose of this study was to examine the impact of G × E interaction effects on CMRFs in Mexican American (MA) children (n = 617, ages 6–17 years). The environments examined were sedentary activity (SA), assessed by recalls from “yesterday” (SAy) and “usually” (SAu) and physical fitness (PF) assessed by Harvard PF scores (HPFS). CMRF data included body mass index (BMI), waist circumference (WC), fat mass (FM), fasting insulin (FI), homeostasis model of assessment—insulin resistance (HOMA‐IR), high‐density lipoprotein cholesterol (HDL‐C), triglycerides (TG), systolic (SBP) and diastolic (DBP) blood pressure, and number of metabolic syndrome components (MSC). We examined potential G × E interaction in the phenotypic expression of CMRFs using variance component models and likelihood‐based statistical inference. Significant G × SA interactions were identified for six CMRFs: BMI, WC, FI, HOMA‐IR, MSC, and HDL, and significant G × HPFS interactions were observed for four CMRFs: BMI, WC, FM, and HOMA‐IR. However, after correcting for multiple hypothesis testing, only WC × SAy, FM × SAy, and FI × SAu interactions became marginally significant. After correcting for multiple testing, most of CMRFs exhibited significant G × E interactions (Reduced G × E model vs. Constrained model). These findings provide evidence that genetic factors interact with SA and PF to influence variation in CMRFs, and underscore the need for better understanding of these relationships to develop strategies and interventions to effectively reduce or prevent cardiometabolic risk in children.
Powerful and robust cross‐phenotype association test for case‐parent trios
Authors: Fischer S. Taylor , Jiang Yunxuan , Broadaway K. Alaine , Conneely Karen N. , Epstein Michael P.
Published: February 2018

There has been increasing interest in identifying genes within the human genome that influence multiple diverse phenotypes. In the presence of pleiotropy, joint testing of these phenotypes is not only biologically meaningful but also statistically more powerful than univariate analysis of each separate phenotype accounting for multiple testing. Although many cross‐phenotype association tests exist, the majority of such methods assume samples composed of unrelated subjects and therefore are not applicable to family‐based designs, including the valuable case‐parent trio design. In this paper, we describe a robust gene‐based association test of multiple phenotypes collected in a case‐parent trio study. Our method is based on the kernel distance covariance (KDC) method, where we first construct a similarity matrix for multiple phenotypes and a similarity matrix for genetic variants in a gene; we then test the dependency between the two similarity matrices. The method is applicable to either common variants or rare variants in a gene, and resulting tests from the method are by design robust to confounding due to population stratification. We evaluated our method through simulation studies and observed that the method is substantially more powerful than standard univariate testing of each separate phenotype. We also applied our method to phenotypic and genotypic data collected in case‐parent trios as part of the Genetics of Kidneys in Diabetes (GoKinD) study and identified a genome‐wide significant gene demonstrating cross‐phenotype effects that was not identified using standard univariate approaches.