bluuebunny/crossref_metadata_2025_split huggingface dataset:
Investigation of the effects of oxidative stress‐inducing factors on culturing and productivity of Bordetella pertussis
Authors: Zavatti Vanessa , Budman Hector , Legge Raymond L. , Tamer Melih 
Published: September 2019

AbstractThe stress response of Bordetella pertussis during fermentation was assessed by means of fluorescence‐based techniques. During the manufacturing of vaccines, B. pertussis is subjected to stress during adaptation to a new environment and operating conditions in the bioreactor, which can have harmful consequences on growth and protein yield. In this study, stress was imposed by varying the percentage of dissolved oxygen (DO) and inoculum size, and by adding rotenone and hydrogen peroxide. In this study, fluorescence spectroscopy is used as a tool for measuring oxidative stress. High levels of DO during fed‐batch operation had no detrimental effect on growth, but the specific productivity of pertactin (PRN) decreased. Cultures that were started with an inoculum size that was 10 times smaller than the control resulted in significantly less PRN as compared to controls where reduction was more significant in flasks as compared to bioreactors. A comparison of filtered to heat‐sterilized media revealed that filtered media offered a protective effect against H2O2. Heat sterilization of the media might result in the destruction of components that offer protection against oxidative stress. Nonetheless, filter sterilization on its own would be insufficient for large‐scale manufacturing. It should be emphasized that the effects of these stressors while investigating for other microorganisms have not been studied for B. pertussis.
Peritoneal mesothelioma in Sweden: A population‐based study
Authors: Cashin Peter H. , Jansson Palmer Gabriella , Asplund Dan , Graf Wilhelm , Syk Ingvar 
Published: September 2019

AbstractThe study aim was to report survival and morbidity of all patients in Sweden with peritoneal mesothelioma treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) as well as investigate whether the survival has increased on a population level since this treatment was nationalized 2011. Study data were collected from the Swedish HIPEC registry and the Swedish National Cancer Registry. All patients with peritoneal mesothelioma scheduled for CRS/HIPEC treatment in Sweden January 2011 to March 2018 were retrieved from the Swedish HIPEC registry. Clinicopathological and survival data were collected. For population‐level analysis, all patients with diffuse malignant peritoneal mesothelioma (DMPM) were identified from the Swedish National Cancer Registry and data were retrieved from two separate 5‐year time periods: 1999‐2003 and 2011‐2015. Thirty‐two patients were accepted for CRS/HIPEC. Four were open/close cases. Two‐year survival rate was 84% or 59% when excluding borderline peritoneal mesotheliomas (n = 17). Median overall survival was not reached. Grade III‐IV Clavien‐Dindo events occurred in 22% with no mortality. From the national cancer registry, 102 DMPM cases were retrieved: 40 cases between 1999 and 2003, and 62 cases between 2011 and 2015 (corresponding to an increase from 0.9 to 1.24/million/year, P = .04). Six patients (10%) received CRS/HIPEC in the second period. Median OS increased between periods from 7 to 15 months and 5‐year survival from 14% to 29% (P = .03). Peritoneal mesothelioma of both borderline and DMPM subtypes undergoing CRS/HIPEC have good long‐term survival. The incidence of DMPM in Sweden has increased. Overall survival has increased alongside the introduction of CRS/HIPEC, which may be a contributing factor.
Association of health insurance status with presentation, treatment and outcomes in soft tissue sarcoma
Authors: Jain Varsha , Venigalla Sriram , Sebro Ronnie A. , Karakousis Giorgos C. , Wilson Robert J. , Weber Kristy L. , Shabason Jacob E. 
Published: September 2019

AbstractBackgroundNumerous studies across a variety of malignancies have demonstrated that health insurance status is associated with differences in clinical presentation, type of treatments received, and survival. The effect of insurance status on the management of soft tissue sarcoma is unknown. We assessed the association of insurance on (a) stage at diagnosis, (b) receipt of neoadjuvant/adjuvant radiation therapy, and (c) overall survival (OS) in patients with soft tissue sarcoma.MethodsThe study cohort was identified from the National Cancer Database (NCDB) and consisted of patients with stage I‐IV soft tissue sarcoma of various histologies diagnosed from 2004 to 2015. The patients were stratified by age (<65 and ≥65 years) and by insurance status (commercial, Medicare, Medicaid and uninsured). Using multivariable logistic regression analysis, we evaluated the association between insurance status and (a) stage at diagnosis (Stage I‐III vs IV), and (b) receipt of neoadjuvant/adjuvant radiation therapy in patients with locally advanced disease. The association of insurance status on OS was assessed using Kaplan‐Meier and multivariable Cox proportional hazards analyses. A propensity score matched survival analysis was performed to account for measured confounders.Results49 754 patients were identified of whom 23 677 (48%) had commercial insurance, 20 867 (42%) had Medicare, 3229 (6%) had Medicaid, and 1981 (4%) were uninsured. In patients <65 years, those with Medicaid (OR = 1.74, 95% CI: 1.57‐1.93, P < .001) and the uninsured (OR = 1.71, 95% CI: 1.51‐1.94, P < .001) were more likely to present with stage IV vs Stage I‐III disease. Furthermore, among patients with locally advanced disease treated with limb sparing surgery, those with Medicaid (OR = 0.87, 95% CI: 0.77‐ 0.98, P = .021) and the uninsured (OR = 0.73, 95% CI: 0.63‐0.85, P < .001) were less likely to receive neoadjuvant or adjuvant radiotherapy as compared to those with commercial insurance. Lastly, having Medicaid (HR = 1.26, 95% CI: 1.17‐1.34, P < .001) and no insurance (HR = 1.30, 95% CI: 1.20‐1.41, P < .001) was associated with worse OS compared to having commercial insurance, a finding which remained significant after propensity score matching. In contrast, in patients ≥65 years, there were no statistically significant differences between those with Medicare and commercial insurance with regards to disease presentation, receipt of radiotherapy, or survival.ConclusionsIn a large modern cohort identified from the NCDB, commercial insurance status in patients <65 years was associated early diagnosis, receipt of neoadjuvant/adjuvant radiation therapy, and overall survival for patients with soft tissue sarcoma. Further efforts are warranted to understand disparities in care based on health insurance in the United States.
Lymph node metastasis in lung squamous cell carcinoma and identification of metastasis‐related genes based on the Cancer Genome Atlas
Authors: Dong Ming , Gong Hao , Li Tong , Li Xin , Liu Jinghao , Zhang Hongbing , Liu Minghui , Chen Gang , Liu Hongyu , Chen Jun 
Published: September 2019

AbstractSquamous cell carcinoma (SCC) is a unique clinical and histological category that accounts for about 30% of total lung cancer. To identify risk factors for lymph node metastasis and analyze the molecular features of these metastases in lung SCC, a retrospective study was performed for 170 lung SCC patients who underwent surgical treatment. The overall survival of these patients with or without lymph node metastasis (LM/NLM) was analyzed using the Kaplan‐Meier method. We also used the TCGA database to compare the differentially expressed genes (DEGs) in patients with stage T1‐2 and T3‐4 lung SCC. Data from both our retrospective study and the TCGA database demonstrated a correlation between age and stage T1‐T2 LM (P = .002). There were significant differences between the LM and NLM groups in both mean survival time and median survival time for different T‐stages (P = .031). There were 176 upregulated and 177 downregulated DEGs between the LM and NLM groups in the stage T1‐2 group and 93 upregulated and 34 downregulated DEGs in the stage T3‐T4 group. These differentially expressed genes were predicted to participate in five cellular components, five molecular functions, and five biological processes. There were 20 genes, including GCG, CASR, NPY, CGA, TAC1, ALB, APOA1, CRH, CHRH, TRH, and GHSR, located at the core of the protein‐protein interaction network in the stage T1‐2 group and 11 genes, including F2, CASR, GRM1, GNRHR, GRPR, NTSR1, PROKR2, UTS2D, PTH, ALB, and FGA, in the stage T3‐4 group. Overall, LM plays a key role in the treatment response and prognosis of SCC patients. Several risk factors, including age and stage, were identified for LM. There was a previously undiscovered enrichment of significant novel genes in lung SCC between the LM and NLM groups, which may have the potential for predicting prognosis and targeting.
Cultures of Care in Primary Schools in Ireland that Support Child Protection Work
Authors: Nohilly Margaret 
Published: September 2019

This paper presents the results of a qualitative study completed with 16 designated liaison persons (DLPs) for child protection in Ireland. The care practices and systems in place in Irish primary schools that support child protection work are the particular focus of this paper. Recent changes in legislation, following the publication of the Children First Act 2015 (Government of Ireland, Irish Statute Book; Office of the Attorney General), are considered. The Act recognises all teachers registered with the Teaching Council as mandated persons. Mandated persons are recognised as persons who work with children and young people and are required to report child abuse, above a defined threshold, which comes to their attention in the course of their professional or employment duties. Semi‐structured interviews were completed with the DLPs, and an exploratory approach using interpretative phenomenologial analysis was deemed the most suitable method of analysis for the study. Five superordinate themes emerged from the findings, alongside a number of subordinate themes; the theme ‘The School Story’ which focuses on the care practices that are undertaken in schools daily is illuminated throughout this paper. The findings highlight the need for formal acknowledgement of this work in schools and also for greater interagency communication and collaboration in the area of child protection.‘This paper presents the results of a qualitative study completed with 16 designated liaison persons (DLPs) for child protection in Ireland’Key Practitioner Messages

Teachers, in their day‐to‐day work in schools and through the care structures in place in schools, contribute in a significant way to the safety and protection of children.
There is a need for greater communication and collaboration between schools and the Child and Family Agency to support children at risk of abuse effectively.
There should be formal recognition in the evaluations undertaken by the Department of Education of the care practices that exist in schools.
Recent Advances of Natural Polyphenols Activators for Keap1‐Nrf2 Signaling Pathway
Authors: Zhou Yanping , Jiang Zhongliang , Lu Haiying , Xu Zhuyu , Tong Rongsheng , Shi Jianyou , Jia Guiqing 
Published: September 2019

AbstractThe Keap1‐Nrf2/ARE signaling pathway is an important defense system against exogenous and endogenous oxidative stress injury. The dysregulation of the signaling pathway is associated with many diseases, such as cancer, diabetes, and respiratory diseases. Over the years, a wide range of natural products has provided sufficient resources for the discovery of potential therapeutic drugs. Among them, polyphenols possess Nrf2 activation, not only inhibit the production of ROS, inhibit Keap1‐Nrf2 protein–protein interaction, but also degrade Keap1 and regulate the Nrf2 related pathway. In fact, with the continuous improvement of natural polyphenols separation and purification technology and further studies on the Keap1‐Nrf2 molecular mechanism, more and more natural polyphenols monomer components of Nrf2 activators have been gradually discovered. In this view, we summarize the research status of natural polyphenols that have been found with apparent Nrf2 activation and their action modes. On the whole, this review may guide the design of novel Keap1‐Nrf2 activator.
Probing the Membrane Vibration of Single Living Cells by Using Nanopipettes
Authors: Chen Bin‐Bin , Lv Jian , Wang Xiao‐Yuan , Qian Ruo‐Can 
Published: September 2019

AbstractThe vibration of a cell membrane plays a key role in the regulation of cell shape and the behavior of cells. However, most existing approaches for the measurement of cell vibration require either exogenous modification or sophisticated techniques, and the main challenge lies in developing methods that can monitor membrane vibration of living cells directly. Herein, a noninvasive strategy based on ultrasmall quartz nanopipettes is introduced. With a tip size of less than 100 nm, nanopipettes can be spatially controlled for precision targeting of a specific location on the membrane of single living cells. Surprisingly, by employing a constant voltage, stable cyclic oscillations are observed from the continuous current versus time traces. The time‐domain current can be decomposed into two basic waves: the high‐frequency one indicates the local membrane vibration driven by the electro‐osmotic flow from the nanopipette, whereas the low‐frequency one indicates the natural frequency of the whole cell. This provides a simple but reliable method to test local and global membrane vibration of single living cells simultaneously with little damage, which provides a tool for the quantification of drugs, disease, or mutations of the cell structure.
Enhanced Charge Transfer Process in Morphology Restructured TiO2 Nanotubes via Hydrochloric Acid Assisted One Step In‐Situ Hydrothermal Approach
Authors: Woo An Gil , Dhandole Love Kumar , Park Hyunwoong , Sub Bae Ho , Mahadik Mahadeo A. , Suk Jang Jum 
Published: September 2019

AbstractIn this study, we demonstrate the enhanced photoelectrochemical (PEC) performance of the titanium foil based TiO2 nanotube (TNT) array through a simple hydrothermal (HT) acid treatment method. The influence of hydrochloric acid (HCl) concentration variation in HT method on morphology and the photoelectrochemical performances of TNTs nanostructures were studied. Field Emission Scanning Electron Microscopy and X‐ray powder diffraction results confirmed the morphology and crystal structure easily restructured during HCl assisted one step in‐situ hydrothermal approach. The photocurrent density of optimized acid treated TiO2 nanotube (TH‐40) electrode was observed to be 2‐times higher than the pristine TNT electrode. Thereafter, TH‐40 sample exhibited noticeably photoelectrochemical solar hydrogen production of 66 μmol and 82 μmol in NaOH and Na2S/Na2SO3 electrolytes respectively than the pristine TNT. The enhancement of photocatalytic activity was ascribed to the restructured morphology, as well as the efficient charge separation at rutile‐anatase interface in the TH‐40 sample as well as at the electrode‐electrolyte interface. A hydrochloric acid assisted one step in‐situ hydrothermal approach tailors the crystal structure and morphological features, which enhanced the photoelectrochemical properties of TiO2 nanotube.
G‐Quadruplex‐Based Photooxidase Driven by Visible Light
Authors: Gao Longlong , Tong Xingyu , Ye Ting , Gao Heng , Zhang Qingqing , Yan Chenxiao , Yu Yali , Fei Yifan , Zhou Xiaoshun , Shao Yong 
Published: September 2019

AbstractThe G‐quadruplex (G4)/hemin entity has been widely used as a peroxidase‐mimic DNAzyme to catalyze the substrate oxidation with exogenous and concentrated H2O2 as oxidant for developing various devices. Herein, a G4‐based oxidase‐mimic DNAzyme that can be driven by visible light was developed. The oxidant is in situ produced by light irradiation. As a natural photosensitizer, Hypericin (Hyp) alone in solution is inactive because of aggregation. However, the binding with G4 triggers the fluorescence emission and activates Hyp to produce singlet oxygen (1O2) by energy transfer to the dissolved oxygen. Therefore, the G4/Hyp entity can serve as a photooxidase via the 1O2 pathway to catalyze the substrate oxidation. Since the G4‐bound Hyp can be excited by almost the whole range of visible light, the photooxidase should cover a wide range of photocatalytic applications. Similar to the peroxidase‐mimic DNAzyme, the G4 sequence can regulate the photooxidase activity and metal ions can serve as efficient cofactors to activate the photooxidase capacity for an inactive G4 structure. This work provides an alternative to build a versatile G4‐based photooxidase with straightforward tunability of its activity.
Drug Syntheses Beyond the Rule of 5
Authors: Tyagi Mohit , Begnini Fabio , Poongavanam Vasanthanathan , Doak Bradley C. , Kihlberg Jan 
Published: September 2019

AbstractDrugs in the chemical space beyond the rule of 5 (bRo5) can modulate targets with difficult binding sites while retaining cell permeability and oral absorption. Reviewing the syntheses of bRo5 drugs approved since 1990 highlights synthetic chemistry's contribution to drug discovery in this space. Initially, bRo5 drugs were mainly natural products and semi‐synthetic derivatives. Later, peptidomimetics and de novo designed compounds, that include up to seven chiral centres and macrocyclic rings became dominant. These drugs are prepared by total synthesis, sometimes by routes of more than 25 steps with stereocentres originating from the chiral pool, or being installed by chiral induction or enzymatic resolution. Interestingly, ring‐closing metathesis proved to be the method of choice for macrocyclisation in hepatitis C virus protease inhibitors. We conclude that structural simplification, planning of synthetic routes regarding incorporation of stereocentres and macrocyclisation, as well as incorporation of structural knowledge and consideration of chameleonic properties in design, should facilitate drug discovery in bRo5 space.
Photoinitiated Reactions of Haloperfluorocarbons with Gold(I) Organometallic Complexes: Perfluoroalkyl Gold(I) and Gold(III) Complexes
Authors: Portugués Alejandro , López‐García Inmaculada , Jiménez‐Bernad Javier , Bautista Delia , Gil‐Rubio Juan 
Published: September 2019

AbstractThe study of perfluoroalkyl metal complexes is key to understand and improve metal‐promoted perfluoroalkylation reactions. Herein, we report the synthesis of the first gold complexes with primary or secondary perfluoroalkyl ligands by photoinitiated reactions between AuI organometallic complexes and iodoperfluoroalkanes. Complexes of the types LAuRF (L=PPh3 or N,N‐bis(2,6‐diisopropylphenyl)imidazol‐2‐ylidene; RF=n‐C4F9, n‐C6F13, i‐C3F7, c‐C6F11) and [Au(RF)(Ar)I(PPh3)] (Ar=2,4,6‐trimethylphenyl) have been isolated and characterized. Alkynes RFC≡CR were formed by reaction of Ph3PAuC≡CR (R=Ph, nHex) with IRF (RF=n‐C4F9, i‐C3F7). According to the evidences obtained, this transformation undergoes through a photoinitiated radical mechanism. AuIII complexes [Au(n‐C4F9)(X)(Y)L] (X=Y=Cl, Br, I, Me; X=Me, Y=I) have been prepared or in situ generated, and their thermal or photochemical decomposition reactions have been studied.
Integrated Bismuth Oxide Ultrathin Nanosheets/Carbon Foam Electrode for Highly Selective and Energy‐Efficient Electrocatalytic Conversion of CO2 to HCOOH
Authors: Meng Fan‐Lu , Zhang Qi , Liu Kai‐Hua , Zhang Xin‐Bo 
Published: September 2019

AbstractElectroreduction of CO2 into formic acid (HCOOH) is of particular interest as a hydrogen carrier and chemical feedstock. However, its conversion is limited by a high overpotential and low stability due to undesirable catalysts and electrode design. Herein, an integrated 3D bismuth oxide ultrathin nanosheets/carbon foam electrode is designed by a sponge effect and N‐atom anchor for energy‐efficient and selective electrocatalytic conversion of CO2 to HCOOH for the first time. Benefitting from the unique 3D array foam architecture for highly efficient mass transfer, and optimized exposed active sites, as confirmed by density functional theory calculations, the integrated electrode achieves high electrocatalytic performance, including superior partial current density and faradaic efficiency (up to 94.1 %) at a moderate overpotential as well as a high energy conversion efficiency of 60.3 % and long‐term durability.
Low‐Energy Electronic Excitations of N‐Substituted Heteroacene Molecules: Matrix Isolation Spectroscopy in Concert with Quantum‐Chemical Calculations
Authors: Thusek Jean , Hoffmann Marvin , Hübner Olaf , Tverskoy Olena , Bunz Uwe H. F. , Dreuw Andreas , Himmel Hans‐Jörg 
Published: September 2019

AbstractN‐Heteropolycycles are attractive as materials in organic electronic devices. However, a detailed understanding of the low‐energy electronic excitation characteristics of these species is still lacking. In this work, the matrix isolation technique is applied to obtain high‐resolution absorbance spectra for a series of tetracene and core‐substituted N‐analogues. The experimental electronic excitation spectra obtained for matrix‐isolated molecules are then analysed with the help of quantum‐chemical calculations. Additional lower energy excitation bands in the spectrum of the core‐substituted N‐derivatives of tetracene could be explained in terms of intensity borrowing from dipole‐forbidden transitions due to Herzberg–Teller vibronic coupling. In the case of tetracene, evidence for the additional formation of London dimers (J aggregates) is found at higher tetracene concentrations in the matrix.
Turning DNA Binding Motifs into a Material for Flow Cells
Authors: Feldner Tobias , Wolfrum Manpreet , Richert Clemens 
Published: September 2019

AbstractNanoscale assemblies of DNA strands are readily designed and can be generated in a wide range of shapes and sizes. Turning them into solids that bind biomolecules reversibly, so that they can act as active material in flow cells, is a challenge. Among the biomolecular ligands, cofactors are of particular interest because they are often the most expensive reagents of biochemical transformations, for which controlled release and recycling are desirable. We have recently described DNA triplex motifs that bind adenine‐containing cofactors, such as NAD, FAD and ATP, reversibly with low micromolar affinity. We sought ways to convert the soluble DNA motifs into a macroporous solid for cofactor binding. While assemblies of linear and branched DNA motifs produced hydrogels with undesirable properties, long DNA triplexes treated with protamine gave materials suitable for flow cells. Using exchangeable cells in a flow system, thermally controlled loading and discharge were demonstrated. Employing a flow cell loaded with ATP, bioluminescence was induced through thermal release of the cofactor. The results show that materials generated from functional DNA structures can be successfully employed in macroscopic devices.
Generation and Reaction of Functional Alkyllithiums by Using Microreactors and Their Application to Heterotelechelic Polymer Synthesis
Authors: Nagaki Aiichiro , Yamashita Hiroki , Tsuchihashi Yuta , Hirose Katsuyuki , Takumi Masahiro , Yoshida Jun‐ichi 
Published: September 2019

AbstractInvited for the cover of this issue is the group of Aiichiro Nagaki at Kyoto University. The image depicts the reaction in the flow microreactor reported in the paper. Read the full text of the article at 10.1002/chem.201902867.