bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical efficacy of daratumumab, pomalidomide, and dexamethasone in patients with relapsed or refractory myeloma: Utility of re‐treatment with daratumumab among refractory patients
Authors: Nooka Ajay K. , Joseph Nisha S. , Kaufman Jonathan L. , Heffner Leonard T. , Gupta Vikas A. , Gleason Charise , Boise Lawrence H. , Lonial Sagar
Published: May 2019

Background

The efficacy of daratumumab (DARA) both as a monotherapy and in combination with standard‐of‐care regimens in multiple myeloma (MM) has been established in clinical trials. This article presents a retrospective analysis of the safety and efficacy of DARA in combination with pomalidomide (POM) and dexamethasone (ie, daratumumab, pomalidomide, and dexamethasone [DARA‐POM‐D]) and, more importantly, the long‐term follow‐up of a cohort that was naive to DARA and POM as well as a cohort in which the utility of re‐treatment was evaluated among patients who were DARA‐ and/or POM‐refractory.

Methods

Thirty‐four consecutive patients with relapsed and/or refractory MM treated with DARA‐POM‐D at the Winship Cancer Institute of Emory University from January 2015 through July 2016 were included in the analysis. The study was approved by Emory University's institutional review board. All received prior proteasome inhibitors and immunomodulatory drugs (IMiDs) and were refractory to their last line of therapy.

Results

All patients were lenalidomide‐refractory, and 91% were bortezomib‐refractory. Two cohorts were identified on the basis of prior exposure to DARA and/or POM. Cohort 1 (12 patients) was DARA‐ and POM‐naive, and cohort 2 (22 patients) was DARA‐ and/or POM‐refractory. A subgroup of 12 patients in cohort 2 (cohort 3) was DARA‐ and POM‐refractory. The combination's tolerability was consistent with the results of the published phase 1b study (EQUULES) that evaluated the combination and no new safety signals were observed. The overall response rates (ORRs) were 91.7%, 40.9%, and 33.3% in cohorts 1, 2, and 3, respectively. Deep responses, including 4 stringent complete responses, were observed in cohort 1. In cohort 2, the ORR comprised 8 partial responses (PRs) and 1 very good PR. The median progression‐free survival (PFS) was not reached in cohort 1 at a median follow‐up of 41 months, and it was 3.2 months in cohort 2. DARA‐POM‐D not only was effective in DARA‐ and POM‐naive patients but also produced clinical responses in a third of patients re‐treated with these drugs.

Conclusions

A better than quadrupled PFS benefit observed in cohort 1 in comparison with the previously reported benefit in the EQUULEUS trial (which led to US Food and Drug Administration approval of the DARA‐POM‐D combination) highlights the fact that the introduction of monoclonal antibody combination strategies and IMiDs as earlier lines of therapeutic options potentially could deliver better clinical outcomes. One‐third of patients refractory to separate lines of DARA and/or POM responded when they were re‐treated with a combination, and this resulted in survival benefits equivalent to those of other antimyeloma agents/combinations available for DARA‐refractory patients.
Rapid research autopsy is a stealthy but growing contributor to cancer research
Authors: Duregon Eleonora , Schneider Jowaly , DeMarzo Angelo M. , Hooper Jody E.
Published: May 2019

Rapid autopsy has been shown to be a powerful tool for advancing research at essentially no risk and with no distress to the contributing patient. Academic and health centers with a substantial investment in cancer research should consider using this emerging research support modality.
Generation of T Cell Receptor Retrogenic Mice
Authors: Kong Yuelin , Jing Yi , Bettini Maria
Published: May 2019

The ability to express and study a single T cell receptor (TCR) in vivo is an important aspect of both basic and translational immunological research. Traditionally, this was achieved by using TCR transgenic mice. In the past decade, a more efficient approach for single TCR expression was developed. This relatively rapid and accessible method utilizes retrovirus‐mediated stem cell–based gene transfer and is commonly referred to as the TCR retrogenic approach. In this approach, hematopoietic bone marrow precursors are transduced with retroviral vector carrying both alpha and beta chains of a T cell receptor. After successful transduction, bone marrow is injected into recipient mice, in which T cell development is driven by expression of the vector‐encoded TCR. This article details the materials and methods required to generate TCR retrogenic mice. It is divided into three sections and provides detailed methods for generation of stable retroviral producer cell lines, isolation and optimal transduction of hematopoietic bone marrow cells, and subsequent analysis of TCR retrogenic T cells. A detailed example of such analysis is provided. The current protocol is a culmination of many years of optimization and is the most efficient approach to date. Bone marrow transduction and transfer into recipient mice can now be achieved in a short period of four days. The protocol can be followed in most laboratories with standard biomedical equipment, and is supported by a troubleshooting guide that covers potential pitfalls and unexpected results. © 2019 by John Wiley & Sons, Inc.
Regioselective Oxidative Ring Cleavage of Antiaromatic Nickel(II) Norcorrole to Dialkoxybis(dipyrrin)s
Authors: Shafie Siham A. , Kawashima Hiroyuki , Miyake Yoshihiro , Shinokubo Hiroshi
Published: May 2019

Invited for this month's cover is the group of Prof. Dr. Hiroshi Shinokubo at Nagoya University, Japan. The front cover shows the oxidative ring opening reaction of an antiaromatic porphyrinoid, norcorrole, into dipyrrin dimers. The background with the map of Japan represents the venue of ISNA‐18, which will be held in Sapporo, Japan in July 2019. Read the full text of the article at 10.1002/cplu.201900068.
The value of cytology in diagnosis of serous effusions in malignant lymphomas: An experience of a tertiary care center
Authors: Patel Trupti , Patel Priya , Mehta Shailee , Shah Majal , Jetly Dhaval , Khanna Nisha
Published: May 2019

Background

Malignant lymphomas (ML) are often complicated by serous effusions. The present study is an attempt to cytologically assess a large series of serous effusions associated with ML, identify the immunoreactivity of cells and to evaluate the role of various ancillary methods in confirming and subtyping these cases.

Methods

A cross‐sectional study of 4612 serous effusions was undertaken at the Department of Cytology, Gujarat Cancer and Research Institute by retrieving data from the year 2015 to 2017. Total 169 cases of ML, clinically suspicious, were included. All cerebrospinal fluids, serous effusions involved by myeloid neoplasms, and cases of primary effusion lymphomas were excluded from our study. Pap stained smears of all these serous effusions were examined. Ancillary methods such as immunohistochemistry were used to further subtype the positive cases using the WHO classification of hematopoietic and lymphoid neoplasms (2016).

Results

Out of total 169 clinically suspicious cases, 109 cases were cytologically positive for ML which included 73 (66.9%) pleural effusions, 34 (31.1%) ascitic fluids, and 2 (1.8%) pericardial effusions. T‐lymphoblastic lymphoma (36.9%) and Burkitt's lymphoma (38.2%) were the most common ML involving the pleural and ascitic fluids respectively. Non‐Hodgkin's lymphoma (NHL) more frequently involved the serous cavities than Hodgkin's lymphoma. (P value <.0001). Among the NHL, T‐cell lymphomas more commonly lead to serous effusions than B‐cell lymphomas (P value <.0048).

Conclusion

Cytological examination of serous effusions is an accurate, prompt, affordable technique having diagnostic and therapeutic implications. With the help of ancillary methods, we can identify the phenotype of cells, classify as well as confirm our diagnosis.
Dicarboxylate‐Induced Structural Diversity of Luminescent Zn(II)/Cd(II) Metal–Organic Frameworks Based on the 2,5‐Bis(4‐pyridyl)thiazolo[5,4‐d]thiazole Ligand
Authors: Zhai Zhi‐Wei , Yang Shuang‐Hua , Luo Peng , Li Lin‐Ke , Du Chen‐Xia , Zang Shuang‐Quan
Published: May 2019

Constructed from rigid 2,5‐bis(4‐pyridyl)thiazolo[5,4‐d]thiazole (Py2TTz) and various dicarboxylic acids [2‐methyl‐1,4‐benzenedicarboxylic acid (2‐CH3‐H2BDC), 5‐methyl‐1,3‐benzenedicarboxylic acid (5‐CH3‐H2BDC), 2,5‐dimethyl‐1,4‐benzenedicarboxylic acid (2,5‐di‐CH3‐H2BDC), 2,5‐dihydroxyl‐1,4‐benzenedicarboxylic acid (2,5‐di‐OH‐H2BDC), 1,4‐naphthalenedicarboxylic acid (1,4‐H2NDC), and 2,6‐naphthalenedicarboxylic acid (2,6‐H2NDC)], nine novel Zn(II)/Cd(II) MOFs have been synthesized under solvothermal conditions. They possess diverse structures, which mainly result from the different shapes and sizes of the auxiliary dicarboxylate ligands. Linear dicarboxylate ligands (2‐CH3‐BDC, 2,5‐di‐CH3‐BDC, 1,4‐NDC, 2,6‐NDC) generate 3D multi‐fold interpenetrated structures, while the V‐shaped dicarboxylate ligand (5‐CH3‐BDC) affords a 2D layer structure. However, linear 2,5‐di‐OH‐BDC results in a 2D layer structure owing to the influence of the hydroxy group. Luminescence properties of compounds 1–9 have been investigated systematically. They display structure‐dependent emission ranging from blue to blue‐white and blue‐green.
Hollow Au‐ZnO/CN Nanocages Derived from ZIF‐8 for Efficient Visible‐Light‐Driven Hydrogen Evolution from Formaldehyde Alkaline Solution
Authors: Yang Hongchen , Zhang Shengbo , Li Mei , Liu Xiao , Han Jinyu , Zhu Xinli , Ge Qingfeng , Wang Hua
Published: May 2019

Hollow carbon nanostructured materials incorporating metals or metal oxides have attracted considerable interest in photocatalysis. Herein, novel hollow N‐doped carbon nanocages incorporating Au and ZnO nanoparticles derived from ZIF‐8 were successfully synthesized. Firstly, ZIF‐8 nanocrystals were treated with chloroauric acid solution (HAuCl4) to produce hollow AuX@ZIF‐8 cubes through acid etching of cores and cation exchange. Then, the AuX@ZIF‐8 cubes were used as precursors to obtain AuX‐ZnO/CN after pyrolysis in a N2 atmosphere. The resulting Au0.40‐ZnO/CN had a uniform hollow structure with ≈ 30 nm shells conformal to ZIF‐8 dimension while incorporating ≈ 5 nm nanoparticles of Au and ZnO and exhibited remarkable photocatalytic activity and excellent recyclability for hydrogen production from formaldehyde (HCHO) alkaline solution under visible light irradiation. The results demonstrated that incorporation of Au greatly improves the visible light absorption and charge separation via SPR effect. Furthermore, the ZIF‐8‐derived hollow N‐doped carbon cages can expose more uniformly disperse active sites with conductive support. The methodology used here provides a novel approach for preparing hollow hybrid carbon materials with visible‐light‐driven photocatalytic applications.
One‐Pot Synthesis of Cycloocta[b]indole Through Formal [5+3] Cycloaddition Using Donor–Acceptor Cyclopropanes
Authors: Okabe Akito , Harada Shinji , Takeda Takuya , Nishida Atsushi
Published: May 2019

A new approach to cycloocta[b]indole through formal [5+3] cycloaddition was developed. This methodology was realized by using an indole derivative as a C5 unit and a cyclopropane derivative as a C3 unit. These two units have both donor and acceptor properties. Two carbon–carbon bonds were formed stepwise by the successive addition of a Lewis acidic catalyst and a Brønsted base. The reaction could be performed as a one‐pot process. Optically active cycloocta[b]indole was also synthesized by using this methodology with a chiral cyclopropane as a C3 substrate.
Techno‐economic analysis of metal hydride‐based energy storage system in microgrid
Authors: Kumar Kuldeep , Alam Mohd , Dutta Viresh
Published: May 2019

Hydrogen can be a promising option as an energy storage medium in renewable power generator‐based microgrid. However, the technologies used for the hydrogen storage such as high pressure in gaseous form and solid storages can significantly affect the cost performance of the hydrogen‐based microgrid. In this study, a techno‐economic assessment for solid hydrogen storage (metal hydride [MH])‐based microgrid in Indian operating conditions has been carried out in terms of levelized cost of electricity (LCOE), net present cost, and avoided environmental emissions. In the present microgrid, excess photovoltaic (PV) generator electricity is used to generate hydrogen using the alkaline water electrolyzer (EL). This generated hydrogen is stored in the MH cylinder. The stored hydrogen is converted back into electricity by fuel cell (FC) in case of insufficiency of PV electricity. The sizing of the microgrid components such as PV, FC, EL, and hydrogen storage tank are obtained for given load profile using HOMER optimization tool. An attempt has been made for the cost evaluation of the solid and high‐pressure gaseous storages in the microgrid. A comparative study between two energy storage mediums such as battery and hydrogen in microgrid is also performed. In case of battery and hydrogen storages, the LCOE is found to be 0.1293 and 0.383 $/kWh, respectively. It was found that battery storage system is more economical than hydrogen storage in microgrid. Nonetheless, the difference between the LCOE in hydrogen‐based microgrid is reduced considerably with optimized cost scenario of the EL, FC, and H2 storage tank as compared to the battery storage. Such technical, economic, and environmental assessment of the MH‐based microgrid system provides a firm basis to policymakers for shaping energy and environment policies for hydrogen activities.
Review of solid particle materials for heat transfer fluid and thermal energy storage in solar thermal power plants
Authors: Calderón Alejandro , Barreneche Camila , Palacios Anabel , Segarra Mercè , Prieto Cristina , Rodriguez‐Sanchez Alfonso , Fernández Ana Inés
Published: May 2019

Current concentrated solar power (CSP) plants that operate at the highest temperature use molten salts as both heat transfer fluid (HTF) and thermal energy storage (TES) medium. Molten salts can reach up to 565°C before becoming chemically unstable and highly corrosive. This is one of the higher weaknesses of the technology. Solid particles have been proposed to overcome current working temperature limits, since the particle media can be stable for temperatures close to 1000°C. This work presents a review of solid particles candidates to be used as HTF and TES in CSP plants in open receivers. In addition, the interactions between solid particles with major system components are described in this review, for example, with TES system or heat exchanger. The parameters and properties of solid particles are identified from the material science point of view explaining their nature and the relation to the power plant efficiency and lifetime durability. Finally, future development is proposed; such as material selection according to each specific design, materials characterization, or durability test.
Simplex space‐time meshes in compressible flow simulations
Authors: von Danwitz Max , Karyofylli Violeta , Hosters Norbert , Behr Marek
Published: May 2019

Employing simplex space‐time meshes enlarges the scope of compressible flow simulations. The simultaneous discretization of space and time with simplex elements extends the flexibility of unstructured meshes from space to time. In this work, we adapt a finite element formulation for compressible flows to simplex space‐time meshes. The method obtained allows, for example, flow simulation on spatial domains that change topology with time. We demonstrate this with the two‐dimensional simulation of compressible flow in a valve that fully closes and opens again. Furthermore, simplex space‐time meshes facilitate local temporal refinement. A three‐dimensional transient simulation of blow‐by past piston rings is run in parallel on 120 cores. The timings point out savings of computation time gained from local temporal refinement in four‐dimensional space‐time meshes.
Effects of Pleurotus eryngii (mushroom) powder and soluble polysaccharide addition on the rheological and microstructural properties of dough
Authors: Nie Yuanyang , Zhang Penghui , Deng Chujun , Xu Linshuang , Yu Mingjun , Yang Wei , Zhao Renyong , Li Bo
Published: May 2019

Adding a certain proportion of Pleurotus eryngii can improve the nutritional value of wheat‐flour foods and enhance the utilization of this mushroom. In this research, partial wheat flour was substituted with P. eryngii powder (PEP) or soluble polysaccharide (SPPE) at different addition levels, and the effects of PEP and SPPE on the rheological and microstructural properties of dough were investigated. Farinographic assay results suggested that PEP significantly (p < 0.05) increased the water absorption of wheat flour but decreased the development time and stability of dough significantly (p < 0.05). Furthermore, it was capable of providing weaker extensographic characteristics and harder dough with the increasing of PEP addition levels. The dynamic oscillatory tests indicated that the PEP addition approximately increased the storage (G′) and loss (G″) moduli in the entire frequency range, while the tan δ roughly decreased with the increasing of PEP addition levels, which could be attributed to the low solubility and strong water‐trapping capacity of the dietary fiber in PEP. Due to the good water solubility and easy formation of hydrogen bonds, the addition of SPPE had inconsistent results with the PEP addition. The inner microstructure of dough showed that the continuity of gluten networks had been disrupted by PEP and SPPE addition and then resulted in a weaker extension and harder dough. This research could provide a foundation for the application of PEP in wheat‐flour foods, and PEP addition levels of 2.5%–5.0% are recommended.
Establishing a method of HPLC involving precolumn derivatization by 2,2′‐dithiobis (5‐nitropyridine) to determine the sulfites in shrimps in comparison with ion chromatography
Authors: Yang Kai , Zhou Cheng , Yang Zhenhuan , Yu Lan , Cai Ming , Wu Changqing , Sun Peilong
Published: May 2019

Although sulfites are widely used in shrimp processing, the contents of residual sulfite need to be strictly controlled due to their potential toxicity. In this paper, a novel method was developed for determination of the free and total sulfites in shrimps. Major procedures of the method includes separation of free and total sulfites with ultrasound‐assisted extraction and pH adjustment for 20 min, then a precolumn derivatization was conducted by 2,2′‐Dithiobis (5‐nitropyridine) and verified by LC‐MS, and finally HPLC coupled with an ultraviolet (UV) detector was carried out. Results indicated that the UV absorption wavelength shifted from 213 (sulfites) to 320 nm (new disulfide compounds), significantly reducing the interference of natural occurring compounds and solvents in the matrix. The standard curves exhibited a good linear range of 3.2–51.2 mg/L (R2 = 0.9996). The limit of detection (LOD) and limit of quantification (LOQ) were 0.3 and 1.0 mg/L, respectively. The contents of free and total sulfite in frozen shrimps were 26.58 ± 0.48 and 31.44 ± 0.83 mg/kg calculated by SO2, respectively. These were similar (p > 0.05) to the data obtained by the method of ion chromatography. In conclusion, the new developed method has been proved to be a reliable and economic method for effective determination of free and total sulfites in the shrimps, and the method could be expanded in determination of the sulfites in other food products.
Domestic cooking methods affect nutrient, phytochemicals, and flavor content in mushroom soup
Authors: Sun Yujing , Lv Feiyan , Tian Jinhu , Ye Xing qian , Chen Jianchu , Sun Peilong
Published: May 2019

The effects of different cooking methods, including autoclaving, microwaving, sous vide, and stewing, on the nutritional quality of mushroom (Hypsizygus marmoreus) soup were investigated. The results showed that all four cooking methods increased the polysaccharide, polyphenol, and amino acid levels compared to uncooked soup. Stewing increased protein content with the other cooking methods showing no change when compared with uncooked soup. Sous vide increased nucleotide content with the other methods decreasing nucleotide levels, and this method was also the best for increasing polyphenol and flavor compounds. Autoclaving generated the highest levels of polysaccharides. In summary, each method had a characteristic effect on mushroom soup properties, and cooking improved the nutritional value of mushrooms by the increase in releasing macro‐ and micronutrients.
Survival Network
Authors: Rössler Patrick , Droste Magdalena , Blümm Anke
Published: May 2019

Founded 100 years ago, the Bauhaus was Germany's most successful cultural export of the 20th century. New research reveals how the communicative links between members of the Bauhaus enabled the institution to continue functioning after its closure in 1933 as an early form of “virtual community”. The study steps away from a more conventional stylistic examination to take a fresh look at the movement.
Secrets of the Deep
Authors: Erbacher Jochen
Published: May 2019

The International Ocean Discovery Program, the world's largest research collaboration in the geosciences, is celebrating its 50th anniversary. With significant scientific and financial participation from Germany, the IODP expeditions and their core samples are providing fundamental insights into the Earth's structure and climate history.
The Cupboard in the East Wall
Authors: Perlich Barbara , Hurlbeck Julia
Published: May 2019

The discovery of a private Jewish prayer room in Erfurt dating from the 13th century came as a complete surprise to building archaeologists and conservators. The first confirmed ensemble of this kind north of the Alps reveals a fascinating insight into everyday Jewish piety in the Middle Ages.
Health system performance assessment in small countries: The case study of Latvia
Authors: Noto Guido , Corazza Ilaria , Kļaviņa Kristīne , Lepiksone Jana , Nuti Sabina
Published: May 2019

Managing the complexity that characterizes health systems requires sophisticated performance assessment information to support the decision‐making processes of healthcare stakeholders at various levels. Accordingly, in the past few decades, many countries have designed and implemented health system performance assessment (HSPA) programmes. Literature and practice agree on the key features that performance measurement in health should have, namely, multidimensionality, evidence‐based data collection, systematic benchmarking of results, shared design, transparent disclosure, and timeliness.

Nevertheless, the specific characteristics of different countries may pose challenges in the implementation of such programmes. In the case of small countries, many of these challenges are common and related to their inherent characteristics, eg, small populations, small volumes of activity for certain treatments, and lack of benchmarks.

Through the development of the case study of Latvia, this paper aims at discussing the challenges and opportunities for assessing health system performance in a small country.

As a result, for each of the performance measurement features identified by the literature, the authors discuss the issues emerging when adopting them in Latvia and set out the potential solutions that have been designed during the development of the case study.
Low‐intensity pulsed ultrasound promotes the proliferation of human bone mesenchymal stem cells by activating PI3K/AKt signaling pathways
Authors: Xie Shucai , Jiang Xili , Wang Rui , Xie Shaowei , Hua Yongyong , Zhou Shuai , Yang Yijun , Zhang Jianquan
Published: May 2019

Low‐intensity pulsed ultrasound (LIPUS) is a promising therapy that is widely used in clinical applications and fundamental research. Previous research has shown that LIPUS exposure has a positive effect on stem cell proliferation. However, the impact of LIPUS exposure on human bone marrow mesenchymal stem cells (hBMSCs) remains unknown. In our study, the effect and mechanism of LIPUS exposure on the proliferation of hBMSCs were investigated, and the optimal parameters of LIPUS were determined. hBMSCs were obtained and identified by flow cytometry, and the proliferation of hBMSCs was measured using the Cell Counting Kit‐8 assay to determine cell cycle and cell count. Expression levels of the phosphoinositide 3‐kinase (PI3K)/protein kinase B (AKt) pathway proteins and cyclin D1 were determined by western blot analysis. Next, hBMSCs were successfully cultured and identified as multipotent mesenchymal stem cells. We found that LIPUS could promote the proliferation of hBMSCs when the exposure time was 5 or 10 minutes per day. Furthermore, 50 or 60 mW/cm2 LIPUS had a more significant effect on cell proliferation, but if cells were irradiated by LIPUS for 20 minutes once a day, an intensity of at least 50 mW/cm2 could markedly inhibit cell growth. Cell cycle analysis demonstrated that LIPUS treatment drives cells to enter S and G2/M phases from the G0/G1 phase. LIPUS exposure increased phosphorylation of PI3K/AKt and significantly upregulated expression of cyclin D1. However, these effects were inhibited when cells were treated with PI3K inhibitor (LY294002), which in turn reduced LIPUS‐mediated proliferation of hBMSCs. These results suggest that LIPUS exposure may be involved in the proliferation of hBMSCs via activation of the PI3K/AKt signaling pathway and high expression of cyclin D1, and the intensity of 50 or 60 mW/cm2 and exposure time of 5 minutes were determined to be the optimal parameters for LIPUS exposure.
Screening candidate microRNA‐mRNA network for predicting the response to chemoresistance in osteosarcoma by bioinformatics analysis
Authors: Dai Penggao , He Yancheng , Luo Guosong , Deng Jiaqi , Jiang Nan , Fang Tingting , Li Yujuan , Cheng Ying
Published: May 2019

The search for biomarkers is important for providing more targeted treatments for osteosarcoma patients with chemoresistance. In this study, differentially expressed microRNAs (miRNAs) were identified from miRNA expression profiles. And the target messenger RNAs (mRNAs) of miRNA were obtained from two websites in public domains. Analysis of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway by these miRNA targets suggests that they may have potential links to osteosarcoma chemoresistance. In the protein‐protein interaction (PPI) network, we screened three subnetworks and 10 hub RNAs, and analyzed through KEGG pathway and searched the PubMed database, indicating that they were significantly associated with drug resistance. Then we found 12 key mRNAs by analyzing the mRNA expression profile. Survival analyses showed that most of the 10 hub mRNAs and 12 key mRNAs had a significant influence on the prognosis of patients with chemoresistance osteosarcoma. A miRNA‐mRNA network is constructed by integrating mRNAs and miRNAs information. The network biomarkers in this study have an advantage over traditional single‐molecule biomarkers in terms of predictive power. And the mRNAs in this network biomarkers are supported by survival analysis or by existing theories. These results will contribute to the choice of chemotherapy before treatment and the prediction of patient prognosis.
Development of an ATP force field for coarse‐grained simulation of ATPases and its application to the maltose transporter
Authors: Hirano Ryosuke , Yabuchi Tsubasa , Sakurai Minoru , Furuta Tadaomi
Published: May 2019

The biological functions of ATPases, such as myosin, kinesin, and ABC transporter, are due to large conformational motions driven by energy obtained from ATP. Elucidation of the mechanisms underlying these ATP‐driven movements is one of the greatest challenges in computational chemistry. It has been shown that the MARTINI coarse‐grained method is a promising tool for the investigation of large conformational motions in various proteins. However, this method has not yet been applied to ATPases because of the lack of a force field for the ATP molecule. Here, we developed force field parameters for the ATP molecule and conducted simulations using these parameters for the subunits (MalK2) and the full‐length structure (MalFGK2‐E) of a maltose transporter. It was found for both targets that the dimerization of the nucleotide binding domains (NBDs) is induced upon ATP binding. Moreover, for the full‐length transporter, the conformational transition from the pre‐translocation state to the outward‐facing state was observed and was accompanied by an initial transport motion of the substrate. It is expected that coarse‐grained simulations utilizing the parameters for the ATP molecule developed here will serve as a powerful tool for investigating other ATPases as well. © 2019 Wiley Periodicals, Inc.
Performance evaluation of thrombomodulin, thrombin‐antithrombin complex, plasmin‐α2‐antiplasmin complex, and t‐PA: PAI‐1 complex
Authors: Chen Qian , Shou Weiling , Wu Wei , Wang Geng , Cui Wei
Published: May 2019

Background

To conduct a comprehensive performance evaluation of a fully automated analyzer for measuring thrombomodulin (TM), thrombin‐antithrombin complex (TAT), plasmin‐α2‐antiplasmin complex (PAP), and t‐PA: PAI‐1 complex (tPAI‐C).

Methods

According to the Clinical and Laboratory Standards Institute (CLSI) EP05‐A2, EP06‐A specifications, TM, TAT, PAP, and tPAI‐C were analyzed to evaluate intraassay variability and interassay variability, linear range, carryover rate, reference range, sample stability, and interferences.

Results

The intraassay variability and interassay variability of the four factors were all below 5%. The carryover rates were below 1%. Linear verification analysis revealed correlation coefficients of 0.998‐0.999. The recommended reference ranges of TM, TAT, and PAP were appropriate for our laboratory, whereas the reference of tPAI‐C should be established by each laboratory. Stability assessment revealed that TM is stable for 2 days at room temperature but lacks stability at colder temperatures. In contrast, TAT is stable for 5 days at 4°C and −20°C but has poor stability at room temperature. PAP and tPAI‐C are stable for 3 days at all three temperatures. The measurement of TM, TAT, PAP, and tPAI‐C is not altered by the presence of 510 mg/dL hemoglobin, 1490 FTU triglycerides, or 21.1 mg/dL conjugated and free bilirubin.

Conclusion

The determination of TM, TAT, PAP, and tPAI‐C using a high‐sensitivity chemiluminescence analyzer performs well in terms of precision, carryover rate, linear range, and interference. Thus, this method is suitable for the detection of these substances in clinical specimens.
Copper Salt Catalyzed Synthesis of Functionalized 2H‐Pyranes
Authors: Varmazyar Alireza , Sedaghat Sajjad , Goli‐Kand Ahmad Nozad , Khalaj Mehdi , Arab‐Salmanabadi Samira
Published: May 2019

A copper‐catalyzed reaction between terminal alkynes, oxiranes, and malonitrile has been described. In this transformation, copper acetylide was attacked on oxiranes to form homopropargyl alkoxy‐copper intermediate that was further transferred to 2H‐pyrane skeletons by reaction with malonitrile. We found that the reaction was not productive without hexafluoroisopropanol.
Epidemiological and clinical suspicion of congenital Zika virus infection: Serological findings in mothers and children from Brazil
Authors: Venturi Giulietta , Fortuna Claudia , Alves Rita Maria , Passos do Prado Paschoal Ana Gabriela , da Silva Júnior Pedro José , Remoli Maria Elena , Benedetti Eleonora , Amendola Antonello , da Silva Batista Everton , Gama Deijamile Virginia Novais , Barros Davi Hasselmann , Fiorentini Cristiano , Rezza Giovanni , Leite Primo Chagas Janeusa Rita
Published: May 2019

The emergence of Zika virus in the Americas has caused an increase of babies born with microcephaly or other neurological malformations. The differential diagnosis of Zika infection, particularly serological diagnosis, is an important but complex issue. In this study, we describe clinical manifestations of 94 suspected cases of congenital Zika from Bahia state, Brazil, and the results of serological tests performed on children and/or their mothers at an average of 71 days after birth. Anti‐Zika immunoglobulin M (IgM) antibodies were detected in 44.4% and in 7.1% of samples from mothers and children, respectively. Nearly all the IgM, and 92% of immunoglobulin G positive results were confirmed by neutralization test. Zika specific neutralizing antibodies were detected in as much as 90.4% of the cases. Moreover, dengue specific neutralizing antibodies were detected in 79.0% of Zika seropositive mothers. In conclusion, Zika IgM negative results should be considered with caution, due to a possible rapid loss of sensitivity after birth, while the NS1‐based Zika IgM enzyme‐linked immunosorbent assay test we have used has demonstrated to be highly specific. In a high percentage of cases, Zika specific neutralizing antibodies were detected, which are indicative of a past Zika infection, probably occurred during pregnancy in this population.
Are Current Protein Recommendations for the Critically Ill Adequate for Patients on VV ECMO: Experience From a High‐Volume Center
Authors: Pelekhaty Stacy L. , Galvagno Samuel M. , Lantry James H. , Dolly Katelyn N. , Herr Daniel L. , Kon Zachary N. , Deatrick Kristopher B. , Cornachione Christopher R. , Scalea Thomas M. , Menaker Jay
Published: May 2019

Background

The nutrition needs of patients requiring extracorporeal membrane oxygenation (ECMO) have not been established in the literature. The purpose of this study is to investigate if current protein recommendations are adequate to achieve nitrogen equilibrium in patients on venovenous ECMO (VV ECMO).

Methods

Patients aged ≥18 years on VV ECMO admitted November 2016 through January 2018 with a documented nitrogen balance (NB) study were included. Patients were stratified by body mass index (BMI) into obese (BMI ≥ 30 kg/m2) and nonobese (BMI < 30 kg/m2) categories for analysis.

Results

After exclusions, 55 NB studies in 29 patients were analyzed. Twelve nonobese patients received a median of 2.1 g protein/kg actual body weight (ABW) (interquartile range [IQR]: 1.7–2.5), and median NB was −2.2 g/d (IQR: −7.4 to 2.8). In 17 obese patients, median protein delivery of 2 g protein/kg ideal body weight (IBW) (IQR: 1.7–2.5) achieved a median NB of −7.3 g/d (IQR: −12.6 to −2.8). Obese patients exhibited greater urinary urea nitrogen excretion than nonobese patients did (24.6 vs 17.6 g/d, P < 0.0001).

Conclusions

Obese and nonobese patients undergoing VV ECMO may require more protein than is currently recommended for critical illness. Monitoring nutrition delivery and serial NB to assess prescription adequacy should be incorporated into routine patient care. Further research is needed to confirm these findings and create specific guidelines for patients on VV ECMO.
Universal detection of body fluid traces in situ with Raman hyperspectroscopy for forensic purposes: Evaluation of a new detection algorithm (HAMAND) using semen samples
Authors: McLaughlin Gregory , Fikiet Marisia A. , Ando Masahiro , Hamaguchi Hiro‐o , Lednev Igor K.
Published: May 2019

Towards closing the technological gaps in forensic science, Raman spectroscopy has been a boon to the field. One area that this technique shows exceptional promise is in body fluid identification and characterization, but substrate interference remains a major impediment to its practical implementation. Here, we present an approach for the universal detection of body fluids regardless of the substrate. This approach, which is based on Raman hyperspectroscopy and multivariate curve resolution, was applied to datasets representing simulated semen evidence. In every instance, the signal of the fluid was extracted and matched to a reference of semen. This approach has immediate application for body fluid detection and allows for a universal, automatic, nondestructive, on‐field method for confirmatory identification of body fluid traces at a crime scene. This approach is applicable where an analyte is either a minor contributor or spatially distributed on a strongly interfering substrate.
Time‐gated Raman and laser‐induced breakdown spectroscopy in mapping of eudialyte and catapleiite
Authors: Romppanen Sari , Häkkänen Heikki , Kekkonen Jere , Nissinen Jan , Nissinen Ilkka , Kostamovaara Juha , Kaski Saara
Published: May 2019

Raman analysis of rock samples containing rare earth elements (REEs) is challenging due to the strong fluorescence, which may mask the weaker Raman signal. In this research, time‐gated (TG) Raman has been applied to the construction of the mineral distribution map from REE‐bearing rock. With TG Raman, material is excited with a short subnanosecond laser pulse, and the Raman signal is collected within a picosecond‐scale time window prior to the formation of a strong fluorescent signal by means of single‐photon avalanche diode array. This allows signal readout with a significantly reduced fluorescence background. TG Raman maps are used to reveal the location of valuable minerals and are compared with the elemental distribution given by laser‐induced breakdown spectroscopy. The analysis was carried out from a REE‐bearing rock, nepheline syenite sample from the Norra Kärr deposit, where REEs are mainly hosted in eudialyte and catapleiite. The combination of these two complimentary laser spectroscopic methods offers valuable elemental and mineralogical information about rocks.
Pediatric airway tumors: A report from the International Network of Pediatric Airway Teams (INPAT)
Authors: Pio Luca , Varela Patricio , Eliott Martin J. , Couloigner Vincent , Guillén Burrieza Gabriela , Paraboschi Irene , Virgone Calogero , Maunsell Rebecca , Rachkov Victor , Rutter Michael J. , Boglione Mariano , Penchyna Grub Jaime , Bellía Munzón Gastón , Sarnacki Sabine , Irtan Sabine , Schweiger Claudia , Larroquet Michèle , Khen Dunlop Naziha , Ramaswamy Madhavan , Pistorio Angela , Cecchetto Giovanni , Ferrari Andrea , Bisogno Gianni , Torre Michele
Published: May 2019

Objective

Primary tracheobronchial tumors (PTTs) are rare heterogeneous lesions arising from any part of the tracheobronchial tree. Nonspecific symptoms may lead to delayed diagnosis that requires more aggressive surgical treatment. An analysis of cases collected by the International Network of Pediatric Airway Team was undertaken to ensure proper insight into the behavior and management of PTTs.

Methods

Patients <18 years of age with a histological confirmation of PTT diagnosed from 2000 to 2015 were included in this multicenter international retrospective study. Medical records, treatment modalities, and outcomes were analyzed. The patient presentation, tumor management, and clinical course were compared between malignant and benign histotypes. Clinical and surgical variables that might influence event‐free survival were considered.

Results

Among the 78 children identified, PTTs were more likely to be malignant than benign; bronchial carcinoid tumor (n = 31; 40%) was the most common histological subtype, followed by inflammatory myofibroblastic tumor (n = 19; 25%) and mucoepidermoid carcinoma (n = 15; 19%). Regarding symptoms at presentation, wheezing (P = 0.001) and dyspnea (P = 0.03) were more often associated with benign growth, whereas hemoptysis was more frequently associated with malignancy (P = 0.042). Factors that significantly worsened event‐free survival were age at diagnosis earlier than 112 months (P = 0.0035) and duration of symptoms lasting more than 2 months (P = 0.0029).

Conclusion

The results of this international study provide important information regarding the clinical presentation, diagnostic workup, and treatment of PTTs in children, casting new light on the biological behavior of PTTs to ensure appropriate treatments.

Level of Evidence

NA

Laryngoscope, 130:E243–E251, 2020
Potential terrestrial influence on transparent exopolymer particle concentrations in boreal freshwaters
Authors: Attermeyer Katrin , Andersson Sara , Catalán Núria , Einarsdottir Karolina , Groeneveld Marloes , Székely Anna J. , Tranvik Lars J.
Published: May 2019

Transparent exopolymer particles (TEP) are ubiquitous in aquatic ecosystems and contribute, for example, to sedimentation of organic matter in oceans and freshwaters. Earlier studies indicate that the formation of TEP is related to the in situ activity of phytoplankton or bacteria. However, terrestrial sources of TEP and TEP precursors are usually not considered. We investigated TEP concentration and its driving factors in boreal freshwaters, hypothesizing that TEP and TEP precursors can enter freshwaters via terrestrial inputs. In a field survey, we measured TEP concentrations and other environmental factors across 30 aquatic ecosystems in Sweden. In a mesocosm experiment, we further investigated TEP dynamics over time after manipulating terrestrial organic matter input and light conditions. The TEP concentrations in boreal freshwaters ranged from 83 to 4940 μg Gum Xanthan equivalent L−1, which is comparable to other studies in freshwaters. The carbon fraction in TEP in the sampled boreal freshwaters is much higher than the phytoplanktonic carbon, in contrast to previous studies in northern temperate and Mediterranean regions. Boreal TEP concentrations were mostly related to particulate organic carbon, dissolved organic carbon, and optical indices of terrestrial influence but less influenced by bacterial abundance, bacterial production, and chlorophyll a. Hence, our results do not support a major role of the phytoplankton community or aquatic bacteria on TEP concentrations and dynamics. This suggests a strong external control of TEP concentrations in boreal freshwaters, which can in turn affect particle dynamics and sedimentation in the recipient aquatic ecosystem.
Preparation of Hyaluronic‐Acid‐Based Microspherical Particles with Tunable Morphology Using a Spray Method on a Superhydrophobic Surface
Authors: Seong Yun‐Jeong , Kang In‐Gu , Song Eun‐Ho , Kim Hyoun‐Ee , Jeong Seol‐Ha
Published: May 2019

Hyaluronic acid (HA) gel microspheres have advantages in the application of hydrogel injections due to their uniform size and shape. The HA microspheres are typically prepared using oil‐emulsion methods, which often use toxic solvents, or spray methods involving dehydration, which can negatively affect the properties of the hydrogel. In this study, an alternative fabrication method that avoids the use of solvents or dehydration is introduced. A poly‐dimethylsiloxane template is micro‐patterned to mimic the papillae structure of the lotus leaf which has superhydrophobicity. Glycidyl‐methacrylate HA solution is sprayed on the superhydrophobic template followed by photocrosslinking the droplet to produce spherical shapes of HA hydrogel particles. Gel particles with diverse shapes are formed, with the shapes depending on the arrangement of the papillae and surface hydrophobicity. As a result, microspherical particles with aspect ratios greater than 0.8 are produced.
Transparent, Lightweight, and High Strength Polyethylene Films by a Scalable Continuous Extrusion and Solid‐State Drawing Process
Authors: Lin Yunyin , Tu Wei , Verpaalen Rob C. P. , Zhang Han , Bastiaansen Cees W. M. , Peijs Ton
Published: May 2019

The continuous production of transparent high strength ultra‐drawn high‐density polyethylene films or tapes is explored using a cast film extrusion and solid‐state drawing line. Two methodologies are explored to achieve such high strength transparent polyethylene films; i) the use of suitable additives like 2‐(2H‐benzotriazol‐2‐yl)‐4,6‐ditertpentylphenol (BZT) and ii) solid‐state drawing at an optimal temperature of 105 °C (without additives). Both methodologies result in highly oriented films of high transparency (≈91%) in the far field. Maximum attainable modulus (≈33 GPa) and tensile strength (≈900 MPa) of both types of solid‐state drawn films are similar and are an order of magnitude higher than traditional transparent plastics such as polycarbonate (PC) and poly(methyl methacrylate). Special emphasis is devoted to the effect of draw down and pre‐orientation in the as‐extruded films prior to solid‐state drawing. It is shown that pre‐orientation is beneficial in improving mechanical properties of the films at equal draw ratios. However, pre‐orientation lowers the maximum attainable draw ratio and as such the ultimate modulus and tensile strength of the films. Potential applications of these high strength transparent flexible films lie in composite laminates, automotive or aircraft glazing, high impact windows, safety glass, and displays.
Environmentally Benign Polyelectrolyte Complex That Renders Wood Flame Retardant and Mechanically Strengthened
Authors: Kolibaba Thomas J. , Grunlan Jaime C.
Published: May 2019

Home structure fires are responsible for a majority of fire deaths and injuries. Wood is a key component of home construction due to its excellent mechanical properties and renewability, but it is inherently flammable. This study demonstrates the ability of a waterborne polyelectrolyte complex (PEC) to significantly increase wood's time to ignition, while decreasing peak heat release rate and total heat release. The PEC treatment, comprised of polyethylenimine and sodium hexametaphosphate, preserves the visual aesthetic of the wood and adds little additional weight (ca. 6%), while concurrently increasing flexural modulus and flexural strength. Scanning electron microscope images after torch testing provide evidence of a microintumescent flame retardant mechanism. This unique water‐based coating provides an environmentally benign means to render wood construction much safer.
Does cerebrospinal fluid analysis have a meaningful role in the diagnosis of chronic inflammatory demyelinating polyradiculoneuropathy?
Authors: London Zachary N. , Nowacek Dustin G.
Published: May 2019

See article on pages 180–183 in this issue.
“I wish someone had once asked me how I'm doing”: Disadvantages and support needs faced by parents of long‐term childhood cancer survivors
Authors: Christen Salome , Mader Luzius , Baenziger Julia , Roser Katharina , Schindera Christina , Tinner Eva Maria , Michel Gisela
Published: May 2019

Background

Childhood cancer affects the whole family and can have a lasting impact on parents of childhood cancer survivors (CCS). We aimed to (1) describe parents’ perspective of currently experienced disadvantages and of their support needs during treatment, after treatment, and today; (2) identify characteristics associated with disadvantages and support needs; and (3) describe the use of existing support services.

Procedure

In this population‐based study, we identified parents of CCS (diagnosed ≤16 years of age, ≥5 years since diagnosis, aged ≥20 years at study) through the Swiss Childhood Cancer Registry (SCCR). Parents completed a questionnaire on perceived disadvantages (e.g., job‐related, financial, etc.), support needs (e.g., job‐related, financial, etc.), and socio‐demographics. Cancer‐related characteristics were available from the SCCR. We used multivariable multilevel logistic regression to identify characteristics associated with disadvantages and support needs.

Results

An average of 24 years after diagnosis, one‐fifth of parents (n = 59/308; 19.2%) reported disadvantages, and 7.1% reported support needs. Many parents had desired more support during (66.9%) or after (34.4%) their child's cancer treatment. Parents whose child experienced late effects (OR = 26.6; 95% CI, 2.9–241.0) or was dependent on parents (OR = 10.6; 95% CI, 2.1–53.7) reported greater current need for more support. Almost half of parents (43.5%) reported having used existing support services.

Conclusions

Many parents need more support during and after active treatment of their child's cancer, and some experience support needs and disadvantages long into survivorship. Better promotion of existing services for parental and familial support and setting up new services, where needed, may help parents in the long term.