bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinicopathological characteristics and prognosis of pulmonary large cell neuroendocrine carcinoma aged ≥65 years
Authors: Cao Ling , Zhao Ling , Wang Min , Zhang Xu he , Yang Zhu-chun , Liu Yun-peng
Published: May 2019

Objective

The present study was designed to better characterize the clinicopathological features and prognosis in patients aged ≥65 years with pulmonary large cell neuroendocrine carcinoma (LCNEC).

Methods

Eligible patients with pulmonary LCNEC were retrieved from the Surveillance, Epidemiology, and End Results database between January 2004 and December 2013. The primary endpoints included cancer-specific survival (CSS) and overall survival (OS).

Results

Data of 1,619 eligible patients with pulmonary LCNEC were collected. These patients were subsequently categorized into two groups: 890 patients in the older group (age ≥65 years), and 729 in the younger group (age <65 years). More patients were of white ethnicity, stage I, married, and with tumor size <5 cm in the older group in comparison to the younger group. However, there were a significantly lower proportion of patients undergoing surgery, chemotherapy, and radiotherapy in the older group. The 5-year CSS rates of the younger group and older group were 23.94% and 17.94% (P = 0.00031), respectively, and the 5-year OS rates were 20.51% and 13.47% (P < 0.0001), respectively. Multivariate analyses indicated that older age (CSS: HR 1.20, 95% CI [1.07–1.36], P = 0.0024; OS: HR 1.26, 95% CI [1.12–1.41], P < 0.0001) was an independent risk factor for poor prognosis. The mortality risk of the elderly increased in almost every subgroup, especially in OS. Finally, significant predictors for better OS and CSS in patients over age 65 included tumor size <5 cm, lower stage, and receiving surgery, chemotherapy, or radiotherapy.

Conclusion

The prognosis of patients aged ≥65 years with pulmonary LCNEC was worse than that of younger patients. However, active and effective therapy could significantly improve the survival of older patients with pulmonary LCNEC.
Evidence for low prevalence of ranaviruses in Ontario, Canada’s freshwater turtle population
Authors: Carstairs Sue J.
Published: May 2019

Background

Ontario, Canada is home to eight native species of turtles; all eight are federally listed as Species At Risk, due to anthropogenic threats. However, until recently, reports of infectious disease have been lacking. Ranavirus is seen as an emerging threat for ectotherms globally, with mass die-offs most often reported in amphibians. Ranavirus has been detected in Ontario’s amphibian populations, can be transmitted via water, and can be transmitted from amphibians to turtles. However, no studies on the prevalence of this virus in Ontario’s turtles have previously been carried out. With recent reports of two confirmed positive case of ranavirus in turtles in Ontario, a knowledge of the ecology of ranavirus in Ontario’s turtles has become even more important. This study estimates the prevalence of ranavirus in Ontario’s turtles, and investigates the hypothesis that this is a newly emergent disease.

Methods

Sixty-three samples were tested for ranavirus via PCR. These included a variety of turtle species, across their home range in Southern Ontario. Fifty-two of the samples originated from the liver and kidney of turtles who had succumbed to traumatic injuries after being admitted to the Ontario Turtle Conservation Centre; ten of the samples were taken from cloacal swabs, lesion swabs, or tail clips collected from live turtles showing signs of clinical disease. One of the live turtles was later euthanized for humane reasons and PCR was also carried out on the liver/kidney.

Results

None of the 63 samples were found to be positive for ranavirus via PCR. The zero prevalence found in this study translates into a population prevalence estimate of less than 5%, with no change in prevalence from 2014–2018.

Discussion

This is the first report on the prevalence of ranavirus in Ontario’s turtles, and will help build an understanding of the ecology of this virus in Ontario. Ranavirus has historically been underreported in reptiles, but there has been an increase in global reports recently, most likely due to increased awareness. A carrier state is thought to exist in reptiles which makes surveillance in the population via random sampling a viable method of detection of prevalence. The first report of ranavirus in Ontario turtles occurred in 2018. This study suggests a continued low population prevalence for the years 2014–2018, however. Ongoing surveillance is necessary, as well as investigation of the eDNA presence in waterways as compared to the PCR of resident turtles, to further understand the sensitivity of these species to ranavirus infection. The utilization of qPCR would be helpful, to better quantify any positives encountered.
PEMANFAATAN INFORMASI BERDASARKAN PORTER’S FIVE FORCES DALAM BISNIS FABRIKASI BAJA UNTUK MENDAPATKAN KEUNGGULAN BERSAING
Authors: Kusuma Kristiawan Hengki , Budiman Januar
Published: May 2019

Saat ini perusahaan fabrikasi baja telah menyadari pentingnya penggunaan informasi sebagai sebuah tools baru untuk mendapatkan keunggulan bersaing dengan kompetitor. Namun sayangnya penggunaan informasi ini masih diterapkan secara konvensional, yaitu penggunaan informasi yang hanya terbatas pada penggunaan IT, tanpa menyadari sebenarnya penggunaan informasi masih menyimpan banyak potensi besar jika digunakan secara optimal.

Penggunaan Informasi yang “asal pakai” tidak hanya kurang efektif namun juga seringkali menimbulkan permasalahan baru. Hasil penyajian data yang diolah oleh orang IT seringkali tidak sesuai dengan tujuan yang ingin dicapai oleh manajemen perusahaan karena perbedaan penafsiran, adapun hasil pengolahan data seringkali juga dapat menimbulkan kesalahpahaman antar pihak manajemen.

Pada penelitian ini akan dicoba pemanfaatan Informasi dengan menggunakan bantuan Porter’s Five Forces sebagai alat bantu untuk mendapatkan keunggulan bersaing. Akan dijelaskan juga bagaimana cara untuk mengumpulkan informasi apa saja yang ada di dalam business process yang dibutuhkan dalam perusahaan dan bagaimana cara mengolah data ini menjadi keunggulan bersaing bagi perusahaan fabrikasi.

 

Nowadays, steel fabricator has realized the importance of the use of information as a new tools to gain the competitive advantages with competitors. Unfortunely the use odf the information is still applied in an unconventional manner, the use of information are limited only to IT, without realizing actual use information has a lot of great potential if used optimally.

The “reckless” use of information was not only less effective but also often lead to new problems. The result of data processed by IT’s, usually are not in line with the purpose to be achieved by company management due the differences in the interpretation of the concept, and as for the results of data processing can also cause misunderstanding between management.

On this research will try the utilization of information by using Porter’s Five Forces as the tools to gain the competitive advantages. It will be explained also how to collect all information in business process that required in company and how to process this data to be competitive advantages for steel fabrication company.
Quantitative evaluation of breast density using a dual‐energy technique on a digital breast tomosynthesis system
Authors: Lu Kun‐Mu , Yeh Da‐Ming , Cao Bi‐Hui , Lin Chia‐Yi , Liang Chih‐Yu , Zhou Yu‐Bo , Tsai Chia‐Jung
Published: May 2019

Purpose

Although breast density is considered a strong risk factor of breast cancer, its quantitative assessment is difficult. To investigate a quantitative method of measuring breast density using dual‐energy mammographic imaging with central digital breast tomosynthesis in physically uniform and nonuniform phantoms.

Material and methods

The dual‐energy imaging unit used a tungsten anode and silver filter with 30 kVp for high‐energy images and 20 kVp for low‐energy images. Uniform glandular‐equivalent phantoms were used to calibrate a dual‐energy based decomposition algorithm. The first study used uniform breast phantoms which ranged in thicknesses from 20 to 70 mm, in 10‐mm increments, and which provided 30%, 50%, and 70% of breast density. The second study used uniform phantoms ranging from 10% to 90% of breast density. The third study used non‐uniform phantoms (at an average density of 50%) with a thickness which ranged from 20 to 90 mm, in 10‐mm increments.

Results

The root mean square error of breast density measurements was 2.64–3.34% for the uniform, variable thickness phantoms, 4.17% for the uniform, variable density phantoms, and 4.49% for the nonuniform, variable thickness phantoms.

Conclusion

The dual‐energy technique could be used to measure breast density with a margin of error of < 10% using digital breast tomosynthesis.
Effect of Doping and Excitation Wavelength on Charge Carrier Dynamics in Hematite by Time‐Resolved Microwave and Terahertz Photoconductivity
Authors: Kay Asaf , Fiegenbaum‐Raz Mor , Müller Sönke , Eichberger Rainer , Dotan Hen , van de Krol Roel , Abdi Fatwa F. , Rothschild Avner , Friedrich Dennis , Grave Daniel A.
Published: May 2019

The charge carrier dynamics of epitaxial hematite films is studied by time‐resolved microwave (TRMC) and time‐resolved terahertz conductivity (TRTC). After excitation with above bandgap illumination, the TRTC signal decays within 3 ps, consistent with previous reports of charge carrier localization times in hematite. The TRMC measurements probe charge carrier dynamics at longer timescales, exhibiting biexponential decay with characteristic time constants of ≈20–50 ns and 1–2 μs. From the change in photoconductance, the effective carrier mobility is extracted, defined as the product of the charge carrier mobility and photogeneration yield, of differently doped (undoped, Ti, Sn, Zn) hematite films for excitation wavelengths of 355 and 532 nm. It is shown that, unlike in conventional semiconductors, donor doping of hematite dramatically increases the effective mobility of the photogenerated carriers. Furthermore, it is shown that all hematite films possess higher effective mobility for 355 nm excitation than for 532 nm excitation, although the time dependence of the photoconductance decay, or charge carrier lifetime, remains the same. These results provide an explanation for the wavelength dependent photoelectrochemical behavior of hematite photoelectrodes and suggest that an increase in photogeneration yield or charge carrier mobility is responsible for the improved performance at higher excitation energies.
Selective Electroplating for 3D‐Printed Electronics
Authors: Lazarus Nathan , Bedair Sarah S. , Hawasli Sami H. , Kim Myung Jun , Wiley Benjamin J. , Smith Gabriel L.
Published: May 2019

Creating 3D‐printed parts with embedded circuitry is the next frontier in additive manufacturing, but printing of conductors with performance comparable to bulk metals such as copper is a difficult challenge. A hybrid process based on 3D printing followed by electroplating on highly conductive thermoplastic filament is used to manufacture 3D circuit boards and electronic packaging. Dual extruder heads on a standard fused filament fabrication printer are used to selectively define regions for electroplating, allowing distinct traces and multiple materials to be patterned in the same 3D‐printed parts. Using this approach, a 3D‐printed surface‐mount package and a 555 timer oscillator circuit are demonstrated, including soldering of components onto the electroplated copper surface.
Robust clinical and laboratory response to hydroxyurea using pharmacokinetically guided dosing for young children with sickle cell anemia
Authors: McGann Patrick T. , Niss Omar , Dong Min , Marahatta Anu , Howard Thad A. , Mizuno Tomoyuki , Lane Adam , Kalfa Theodosia A. , Malik Punam , Quinn Charles T. , Ware Russell E. , Vinks Alexander A.
Published: May 2019

Hydroxyurea is FDA‐approved and now increasingly used for children with sickle cell anemia (SCA), but dosing strategies, pharmacokinetic (PK) profiles, and treatment responses for individual patients are highly variable. Typical weight‐based dosing with step‐wise escalation to maximum tolerated dose (MTD) leads to predictable laboratory and clinical benefits, but often takes 6 to 12 months to achieve. The Therapeutic Response Evaluation and Adherence Trial (TREAT, NCT02286154) was a single‐center study designed to prospectively validate a novel personalized PK‐guided hydroxyurea dosing strategy with a primary endpoint of time to MTD. Enrolled participants received a single oral 20 mg/kg dose of hydroxyurea, followed by a sparse PK sampling approach with three samples collected over three hours. Analysis of individual PK data into a population PK model generated a starting dose that targets the MTD. The TREAT cohort (n = 50) was young, starting hydroxyurea at a median age of 11 months (IQR 9‐26 months), and PK‐guided starting doses were high (27.7 ± 4.9 mg/kg/d). Time to MTD was 4.8 months (IQR 3.3‐9.3), significantly shorter than comparison studies (p < 0.0001), thus meeting the primary endpoint. More remarkably, the laboratory response for participants starting with a PK‐guided dose was quite robust, achieving higher hemoglobin (10.1 ± 1.3 g/dL) and HbF (33.3 ± 9.1%) levels than traditional dosing. Though higher than traditional dosing, PK‐guided doses were safe without excess hematologic toxicities. Our data suggest early initiation of hydroxyurea, using a personalized dosing strategy for children with SCA, provides laboratory and clinical response beyond what has been seen historically, with traditional weight‐based dosing.
Generalized Darboux Transformations, Rogue Waves, and Modulation Instability for the Coherently Coupled Nonlinear Schrödinger Equations in Nonlinear Optics
Authors: Chen Su‐Su , Tian Bo , Sun Yan , Zhang Chen‐Rong
Published: May 2019

Nonlinear optics plays a central role in the advancement of optical science and laser‐based technologies. The second‐order rogue‐wave solutions and modulation instability for the coherently coupled nonlinear Schrödinger equations with the positive coherent coupling in nonlinear optics are reported in this paper. Generalized Darboux transformations for such coupled equations are derived, with which the second‐order rational solutions for the purpose of modelling the rogue waves are obtained. With respect to the slowly‐varying complex amplitudes of two interacting optical modes, it is observed that 1) number of valleys of the second‐order rogue waves increases and peak value of the second‐order rogue wave decreases first and then increases; 2) single‐hump second‐order rogue wave turns into the double‐hump second‐order rogue wave; 3) single‐hump bright second‐order rogue wave turns into the dark second‐order rogue wave and finally becomes the three‐hump bright second‐order rogue wave. Meanwhile, baseband modulation instability through the linear stability analysis is seen.
Method for Finding the Exact Effective Hamiltonian of Time‐Driven Quantum Systems
Authors: Sandoval‐Santana Juan Carlos , Ibarra‐Sierra Victor Guadalupe , Cardoso José Luis , Kunold Alejandro , Roman‐Taboada Pedro , Naumis Gerardo
Published: May 2019

Time‐driven quantum systems are important in many different fields of physics as cold atoms, solid state, optics, etc. Many of their properties are encoded in the time evolution operator or the effective Hamiltonian. Finding these operators usually requires very complex calculations that often involve some approximations. To perform this task, a systematic scheme that can be cast in the form of a symbolic computational algorithm is presented. It is suitable for periodic and non‐periodic potentials and, for convoluted systems, can also be adapted to yield numerical solutions. The method exploits the structure of the associated Lie group and a decomposition of the evolution operator on each group generator. To illustrate the use of the method, five examples are provided: harmonic oscillator with time‐dependent frequency (Paul trap), modulated optical lattice, time‐driven quantum oscillator, a step‐wise driving of a free particle, and the non‐periodic Caldirola‐Kanai Hamiltonian. To the extent of the authors' knowledge, whereas the exact form of Paul trap's evolution operator is well known, its effective Hamiltonian was until now unknown. The remaining four examples accurately reproduce previous results.
Integrating local ecological knowledge, citizen science and long‐term historical data for endangered species conservation: Additional records of angel sharks (Chondrichthyes: Squatinidae) in the Mediterranean Sea
Authors: Giovos Ioannis , Stoilas Vasilis‐Orestis , Al‐Mabruk Sara AA , Doumpas Nikolaos , Marakis Philippos , Maximiadi Mary , Moutopoulos Dimitrios , Kleitou Periklis , Keramidas Ioannis , Tiralongo Francesco , de Maddalena Alessandro
Published: May 2019

All three species of angel sharks (genus Squatina) inhabiting the Mediterranean Sea are listed as Critically Endangered in the International Union for Conservation of Nature Red List of Threatened Species due to overexploitation.

New records from Cyprus, Greece, Italy and Libya were collected from citizen‐scientists and integrated with local knowledge obtained using structured interviews in the four countries.

Observations and reports, together with an analysis of the reconstructed fisheries data, resulted in the identification of areas of interest, a review of the illegal trade of the species and a debate about the credibility of fisheries data for assessing threatened and/or protected species.

Unconventional sources of information, such as social media, were identified as important tools for monitoring rare and endangered marine wildlife.

This work will contribute to promoting international cooperation for advancing angel shark conservation in line with the Eastern Atlantic and Mediterranean Angel Shark Conservation Strategy.
Inhibition of EZH2 Ameliorates Lupus‐Like Disease in MRL/lpr Mice
Authors: Rohraff Dallas M. , He Ye , Farkash Evan A. , Schonfeld Mark , Tsou Pei‐Suen , Sawalha Amr H.
Published: May 2019

Objective

We previously identified a role for EZH2, a transcriptional regulator in inducing proinflammatory epigenetic changes in lupus CD4+ T cells. This study was undertaken to investigate whether inhibiting EZH2 ameliorates lupus‐like disease in MRL/lpr mice.

Methods

EZH2 expression levels in multiple cell types in lupus patients were evaluated using flow cytometry and messenger RNA expression data. Inhibition of EZH2 in MRL/lpr mice was achieved by intraperitoneal 3′‐deazaneplanocin (DZNep) administration using a preventative and a therapeutic treatment model. Effects of DZNep on animal survival, anti–double‐stranded DNA (anti‐dsDNA) antibody production, proteinuria, renal histopathology, cytokine production, and T and B cell numbers and percentages were assessed.

Results

EZH2 expression levels were increased in whole blood, neutrophils, monocytes, B cells, and CD4+ T cells in lupus patients. In MRL/lpr mice, inhibition of EZH2 by DZNep was confirmed by significant reduction of EZH2 and H3K27me3 in splenocytes. Inhibiting EZH2 with DZNep treatment before or after disease onset improved survival and significantly reduced anti‐dsDNA antibody production. DZNep‐treated mice displayed a significant reduction in renal involvement, splenomegaly, and lymphadenopathy. Lymphoproliferation and numbers of double‐negative T cells were significantly reduced in DZNep‐treated mice. Concentrations of circulating cytokines and chemokines, including tumor necrosis factor, interferon‐γ, CCL2, RANTES/CCL5, interleukin‐10 (IL‐10), keratinocyte‐derived chemokine/CXCL1, IL‐12, IL‐12p40, and CCL4/macrophage inflammatory protein 1β, were decreased in DZNep‐treated mice.

Conclusion

EZH2 is up‐regulated in multiple cell types in lupus patients. Therapeutic inhibition of EZH2 abrogates lupus‐like disease in MRL/lpr mice, suggesting that EZH2 inhibitors may be repurposed as a novel therapeutic option for lupus patients.
A Link Between Plasma Microbial Translocation, Microbiome, and Autoantibody Development in First‐Degree Relatives of Systemic Lupus Erythematosus Patients
Authors: Ogunrinde Elizabeth , Zhou Zejun , Luo Zhenwu , Alekseyenko Alexander , Li Quan‐Zhen , Macedo Danielle , Kamen Diane L. , Oates Jim C. , Gilkeson Gary S. , Jiang Wei
Published: May 2019

Objective

Systemic lupus erythematosus (SLE) is characterized by the production of antibodies against self antigens. However, the events underlying autoantibody formation in SLE remain unclear. This study was undertaken to investigate the role of plasma autoantibody levels, microbial translocation, and the microbiome in SLE.

Methods

Plasma samples from 2 cohorts, one with 18 unrelated healthy controls and 18 first‐degree relatives and the other with 19 healthy controls and 21 SLE patients, were assessed for autoantibody levels by autoantigen microarray analysis, measurement of lipopolysaccharide (LPS) levels by Limulus amebocyte assay, and determination of microbiome composition by microbial 16S ribosomal DNA sequencing.

Results

First‐degree relatives and SLE patients exhibited increased plasma autoantibody levels compared to their control groups. Parents and children of lupus patients exhibited elevated plasma LPS levels compared to controls (P = 0.02). Plasma LPS levels positively correlated with plasma anti–double‐stranded DNA IgG levels in first‐degree relatives (r = 0.51, P = 0.03), but not in SLE patients. Circulating microbiome analysis revealed that first‐degree relatives had significantly reduced microbiome diversity compared to their controls (observed species, P = 0.004; Chao1 index, P = 0.005), but this reduction was not observed in SLE patients. The majority of bacteria that were differentially abundant between unrelated healthy controls and first‐degree relatives were in the Firmicutes phylum, while differences in bacteria from several phyla were identified between healthy controls and SLE patients. Bacteria in the Paenibacillus genus were the only overlapping differentially abundant bacteria in both cohorts, and were reduced in first‐degree relatives (adjusted P [Padj] = 2.13 × 10−12) and SLE patients (Padj = 0.008) but elevated in controls.

Conclusions

These results indicate a possible role of plasma microbial translocation and microbiome composition in influencing autoantibody development in SLE.
The free‐weight matrix approach to event‐driven output H∞ control of networked control systems
Authors: Shen Binbin , Guo Jing , Sun Liankun
Published: May 2019

This paper puts forward a new free‐weight matrix method used to analyse Network control systems (NCSs) with the H∞ performance index level based on event‐driven control. Firstly, design a relative triggering mechanism contain the measured output for a linear system with external disturbances. Secondly, in order to reduce the conservativeness an appropriate Lyapunov‐Krasovskii function is constructed. For the integral term generated after the above functional derivation, the free‐weight matrix inequality is selected for scaling. Finally,the sufficient condition that the closed‐loop system represented by the linear matrix inequality (LMI) satisfies the H∞ performance index and the solution of the controller are obtained.The validity of the scheme is confirmed by a given numerical case.
Vom 3‐D‐Laserscan zum BIM‐Modell
Authors: Mischo Hendrik , Seifried Jörg , Thiele Klaus , Schanzenbach Stephan , Grassl Martin
Published: May 2019

In den kommenden Dekaden erfordern die deutschen Brückenbauwerke eine erhöhte Aufmerksamkeit, da für einen großen Anteil des Bestands die vorgesehene Lebensdauer erreicht ist. Einige dieser Bauwerke haben neben ihrer Bedeutung für die Infrastruktur einen hohen baukulturellen Wert und fordern daher große Sorgfalt seitens der Bauwerkserhaltung.

Für die anstehenden Aufgaben im Bereich bestehender Brückenbauwerke wurde anhand eines Beispiels die Anwendung der Planungsmethodik BIM auf ihre derzeitigen Möglichkeiten untersucht. Im Vordergrund der Untersuchung stehen die Erfassung der Geometrie einer bestehenden Brücke mit einem 3‐D‐Laserscan, die Verarbeitung der resultierenden Punktwolke zu einem virtuellen Bauwerksmodell (BIM‐Modell) und schließlich die Ableitung eines statischen Modells aus dem BIM‐Modell.
Explaining Pathogenicity of Congenital Zika and Guillain–Barré Syndromes: Does Dysregulation of RNA Editing Play a Role?
Authors: Piontkivska Helen , Plonski Noel‐Marie , Miyamoto Michael M. , Wayne Marta L.
Published: May 2019

Previous studies of Zika virus (ZIKV) pathogenesis have focused primarily on virus‐driven pathology and neurotoxicity, as well as host‐related changes in cell proliferation, autophagy, immunity, and uterine function. It is now hypothesized that ZIKV pathogenesis arises instead as an (unintended) consequence of host innate immunity, specifically, as the side effect of an otherwise well‐functioning machine. The hypothesis presented here suggests a new way of thinking about the role of host immune mechanisms in disease pathogenesis, focusing on dysregulation of post‐transcriptional RNA editing as a candidate driver of a broad range of observed neurodevelopmental defects and neurodegenerative clinical symptoms in both infants and adults linked with ZIKV infections. The authors collect and synthesize existing evidence of ZIKV‐mediated changes in the expression of adenosine deaminases acting on RNA (ADARs), known links between abnormal RNA editing and pathogenesis, as well as ideas for future research directions, including potential treatment strategies.
How do counsellors having menopausal symptoms experience their client work: An interpretative phenomenological analysis
Authors: Bodza Carol , Morrey Tara , Hogan Kevin F.
Published: May 2019

Aim

The aim of this study was to discover whether menopausal symptoms have implications for counsellors in their therapeutic work.

Method

Semi‐structured interviews were conducted with three counsellors who have experienced menopausal symptoms. The menopause is a unique experience for the individual. Interpretative phenomenological analysis therefore allowed for a detailed exploration of the participants' experiences.

Findings

Four superordinate themes were identified: transitioning personal and professional identity during menopause; limited dialogue about the menopause; ethical dilemmas of practising as a counsellor when menopausal; and the influence of menopausal symptoms during client work. The findings demonstrated that participants each had very personal and individual experiences of the menopause. A lack of knowledge and understanding of the menopause and limited dialogue within society to discuss symptoms was also reflected in the counselling profession. The capacity to continue working therapeutically presented potential ethical dilemmas which were affected by menopausal symptoms.

Conclusion

Counsellors' experiences of menopausal symptoms may create challenges in their therapeutic work, ranging from a mild distraction, a disconnection with a client, to having to cease engaging with client work. Implications for therapeutic practice are discussed.
Durable complete response in a patient with metastatic left‐sided colon cancer treated with 5‐fluorouracil, folinic acid, and irinotecan (FOLFIRI) and panitumumab: A case report
Authors: Kim Esther , Bay Graham H. , Kim Christina A.
Published: May 2019

There are rare patients with metastatic colon cancer who experience dramatic and durable responses. Primary tumor location is a prognostic and potentially predictive factor and should be taken into consideration when deciding on the optimal first‐line therapy to be used in combination with chemotherapy.
The Origins of the Stereoselectivity and Enantioswitch in the Rare‐Earth‐Catalyzed Michael Addition: A Computational Study
Authors: Miyazaki Aya , Hatanaka Miho
Published: May 2019

The general strategy for forming an opposite enantiomeric product from an asymmetric reaction involves using the opposite enantiomeric catalyst. For the Michael addition of 4‐substituted‐5‐pyrazolones (1) to 1,4‐dicarbonyl but‐2‐enes (2) catalyzed by rare earth with the chiral N,N′‐dioxide derivative ligand (L), the product enantioselectivity was switched only by changing the rare earth from Sc to Y. To understand the mechanism, we investigated the reaction energy profile using the density functional theory combined with the automated reaction path search method. The enantioselectivity on 1 was determined by the coordination structure of the pre‐reaction complex. The pre‐reaction complex of the Sc system was ScL(OTf)1, where only the Si‐face attack of 2 was blocked. Conversely, the pre‐reaction complex of the Y system had one more triflate anion, (YL(OTf)21), which stabilized the different coordination structure, where only the Re‐face attack of 2 was blocked. The origin of the diastereoselectivity was also investigated based on the transition states (TSs) of the C−C bond formation. The orientation of 2 at the TSs was fixed because of the proton transfer, which destabilized the TS affording the minor diastereomer.
Metal Ionic Liquids Produce Metal‐Dispersed Carbon‐Nitrogen Networks for Efficient CO2 Electroreduction
Authors: Cheng Xiuyan , Tan Dongxing , Zeng Shaojuan , Zhang Xiangping , Tan Xiuniang , Shi Jinbiao , Zhang Bingxing , Zheng Lirong , Zhang Fanyu , Feng Jiaqi , Liu Lifei , Wan Qiang , Chen Gang , Han Buxing , Zhang Jing , An Pengfei , Zhang Jianling
Published: May 2019

To develop novel strategies for fabricating metal carbon‐based materials with desirable compositions and structures for catalysis is of great importance. Here we propose for the first time the utilization of metal ionic liquid as a precursor for the synthesis of metal carbon‐based materials through a one‐step pyrolysis route. The method produces the metal dispersed cross‐linked carbon framework with a highly mesoporous structure. Such a Ni/C−N catalyst exhibits outstanding electrocatalytic activity for CO2 reduction reaction, i. e., an excellent CO faradaic efficiency of approximately 94 % at an potential of −0.75 V (versus the reversible hydrogen electrode). The method proposed in this work is simple, convenient, low‐cost, adjustable and versatile for the synthesis of different kinds of M/C−N materials because the structures and properties of metal ionic liquids can be easily designed and tuned by changing the anions and cations.
Models Facilitating the Design of a New Metal‐Organic Framework Catalyst for the Selective Decomposition of Formic Acid into Hydrogen and Carbon Dioxide
Authors: O'Hair Richard A. J. , Mravak Antonija , Krstić Marjan , Bonačić‐Koutecký Vlasta
Published: May 2019

The front cover artwork for Issue 10/2019 is a collaboration between the O'Hair group (University of Melbourne, Australia) and the Bonačić‐Koutecký group (University of Split, Croatia). The image shows how gas‐phase studies of model systems can be used for the design of MOF based catalysts for the selective decomposition of formic acid into hydrogen and carbon dioxide, a reaction of considerable interest for hydrogen storage applications. See the Full Paper itself at https://doi.org/10.1002/cctc.201900346.
New hypothesis for the etiology of SPAST‐based hereditary spastic paraplegia
Authors: Qiang Liang , Piermarini Emanuela , Baas Peter W.
Published: May 2019

Mutations of the SPAST gene are the chief cause of hereditary spastic paraplegia. Controversy exists in the medical community as to whether the etiology of the disease is haploinsufficiency or toxic gain‐of‐function properties of the mutant spastin proteins. In recognition of strong reasons that support each possible mechanism, here we present a novel perspective, based in part on new studies with mouse models and in part on the largest study to date on patients with the disease. We posit that haploinsufficiency does not cause the disease but makes the corticospinal tracts vulnerable to a second hit, which is usually the mutant spastin proteins but could also be proteins generated by mutations of other genes that may or may not cause the disease on their own.
Novel functions of the primary cilium in bone disease and cancer
Authors: Shi Wengui , Ma Zhijian , Zhang Gengyuan , Wang Chen , Jiao Zuoyi
Published: May 2019

The primary cilium, a sensory organelle that emanates from the cell surface of most mammalian cell types during growth arrest, has attracted the attention of many researchers over the past decade. Recently, a large number of new findings have assigned novel functions and roles to the primary cilium in signal transduction and related diseases, which has greatly augmented the importance of the cilium in human health and development. Here, we review emerging evidence supporting the primary cilium as a sensory organelle in signal transduction in microgravity, electromagnetic field sensing, chemosensation and tumorigenesis. We also present an overview of signal transduction crosstalk associated with the primary cilium in bone disease and cancer, including primary cilium‐related Ca2+ signaling, parathyroid hormone signaling, cAMP signaling, BMP/Smad1/5/8 signaling and Wnt signaling. We anticipate that emerging discoveries about the function of the primary cilium will provide novel insight into the molecular mechanisms of stimulus sensation, signal transduction and pathogenesis.
Successful 2.0 management: Focus on the dean, chair, and department
Authors: Chu Don
Published: May 2019

Just about all new campus leaders come to the job with lofty ambitions. They form blue‐ribbon committees charged with developing plans for institutional transformation and then campaigns are launched with great fanfare. Yet as former Secretary of Labor and Professor Robert Reich observes, higher education is stubbornly resistant to change. Why is change slow in higher education? Maybe it isn't consultants who haven't done a good job, or personal motivations or willingness from the top brass to change their organizations. Maybe it isn't the conservatism of faculty wedded to old ways. Maybe there is something in how colleges are managed that creates a gravity that makes it so hard to keep pushing that boulder up the hill and keep it there. Maybe it isn't the engine (i.e., the faculty) or the hands on the steering wheel (i.e., the administration), but maybe it's the link between the two where we should focus if we are to power up higher educational institutions.
Before you click: Publishing accessible websites
Authors: Taylor Zachary W. , LaRonde Susan , Taylor M. Yvonne
Published: May 2019

As technology has advanced in recent years, institutions of higher education have the ability to present digital information in a variety of formats: visual, audio, and interactive. Web accessibility technology has also advanced, allowing students who are deaf, blind, or have other disabilities to access digital content in a variety of formats. For instance, “screen reader” technologies have made it possible for students who are blind to read an entire website, engage with multimedia, and enjoy a web experience that was formerly reserved exclusively for students without disabilities. Technology has increased students with disabilities’ access to and user experience on the internet, yet many institutions of higher education have lagged behind in making their sites fully accessible.
Implementing a Central IRB Model in a Multicenter Research Network
Authors: Burr Jeri S. , Johnson Ann R. , Vasenina Valeriya , Bisping Stephanie , Coleman R. Whitney , Botkin Jeffrey R. , Dean J. Michael
Published: May 2019

Implementing the National Institutes of Health's (NIH's) new single institutional review board (IRB) policy has caused a paradigm shift in IRB review across the country. IRBs and human research protection programs are looking more closely at their processes for ceding review and developing procedures to handle local review when relying on a single IRB. This article describes an NIH‐funded network that proactively instituted a central IRB (CIRB) in 2012, anticipating the NIH future mandate. Lessons learned are described. There was a steep learning curve for IRBs and participating sites. IRB submission workload burden shifted from study teams to the data coordinating center, which created new workflow challenges, especially preparing hundreds of consent documents centrally. Despite difficulties encountered with CIRB review, this network is now fully functioning under a CIRB model. Further review and experience are needed to determine whether this shift in IRB review has eliminated duplicative review or regulatory burden from study teams.
Genomewide identification and analysis of heat‐shock proteins 70/110 to reveal their potential functions in Chinese soft‐shelled turtle Pelodiscus sinensis
Authors: Liu Tengfei , Han Yawen , Liu Ye , Zhao Huiying
Published: May 2019

Heat‐shock proteins 70/110 (Hsp70/110) are vital molecular chaperones and stress proteins whose expression and production are generally induced by extreme temperatures or external stresses. The Hsp70/110 family is largely conserved in diverse animals. Although many reports have studied and elaborated on the characteristics of Hsp70/110 in various species, the systematic identification and analysis of Hsp70/110 are still poor in turtles. In this study, a genomewide search was performed, and 18 candidate PsHSP70/110 family genes were identified in Chinese soft‐shelled turtle, Pelodiscus sinensis. These PsHSP70/110 proteins contained the conserved “heat shock protein 70” domain. Phylogenetic analysis of PsHSP70/110 and their homologs revealed evolutionary conservation of Hsp70/110 across different species. Tissue‐specific expression analysis showed that these PsHSP70/110 genes were differentially expressed in different tissues of P. sinensis. Furthermore, to examine the putative biological functions of PsHSP70/110, the dynamic expression of PsHSP70/110 genes was analyzed in the testis of P. sinensis during seasonal spermatogenesis following germ cell apoptosis. Notably, genes such as PsHSPA1B‐L, PsHSPA2, and PsHSPA8 were significantly upregulated in P. sinensis testes along with a seasonal decrease in apoptosis. Protein interaction prediction revealed that PsHSPA1B‐L, PsHSPA2, and PsHSPA8 may interact with each other and participate in the MAPK signaling pathway. Moreover, immunohistochemical analysis showed that PsHSPA1B‐L, PsHSPA2, and PsHSPA8 protein expression was associated with seasonal temperature variation. The expression profiling and interaction relationships of the PsHSPA1B‐L, PsHSPA2, and PsHSPA8 proteins implied their potential roles in inhibiting the apoptosis of germ cells in P. sinensis. These results provide insights into PsHSP70/110 functions and will serve as a rich resource for further investigation of HSP70/110 family genes in P. sinensis and other turtles.
Performance assessment of a solar tower‐based multigeneration system with thermal energy storage
Authors: Yuksel Yunus E. , Ozturk Murat , Dincer Ibrahim
Published: May 2019

In this study, a thermodynamic analysis of a newly developed solar power tower‐based multigeneration plant is presented. This plant is integrated with thermal energy storage option in order to overcome intermittency of solar radiation. The proposed integrated multigenerational plant consists of the solar tower with thermal energy storage, Rankine cycle, organic Rankine cycle, absorption cooling cycle, hydrogen production and compression unit, hot water production and drying process. The overall energy and exergy efficiencies of integrated plant are determined as 54.15% and 51.28%, respectively. Also, some parametric analyses are carried out to investigate how the system variables affect the performance of the present system.
Developing Triggers for Environmental Effects Monitoring Programs for Trout-Perch in the Lower Athabasca River (Canada)
Authors: Kilgour Bruce W. , Munkittrick Kelly R. , Hamilton Liza , Proulx Catherine L. , Somers Keith M. , Arciszewski Tim , McMaster Mark
Published: May 2019

Baseline variations in trout-perch energy use (growth, gonad size) and energy storage (condition, liver size) were characterized between 2009 and 2015 in 8 reaches of the Athabasca River (AB, Canada), including 2 reaches upstream of the city of Fort McMurray (AB, Canada) and 6 reaches downstream of Fort McMurray among existing oil sands operations. Generalized linear models, used to account for background variation, indicated that fork length, gonad size, and liver size decreased, whereas body weight increased, in relation to river discharge, for both male and female trout-perch. Air temperature was positively correlated with liver size and negatively correlated with gonad size and body weight for females, but only positively correlated with gonad weight for males. These linear models explained approximately 20 to 25% of the variation in adjusted body size, and upward of 80% of the variation in adjusted body weight, liver weight, and gonad weight. Residuals from linear models were used to estimate normal ranges of variation for each of the fish population performance measures. Combined, the models and normal ranges can be used to assess subsequent monitoring data, providing potential triggers for follow-up monitoring activities. Environ Toxicol Chem 2019;38:0–0. Environ Toxicol Chem 2019;38:1890–1901. © 2019 SETAC.
Engaging with Women's Knowledge in Bristol Bay Fisheries through Oral History and Participatory Ethnography
Authors: Lavoie Anna , Lee Jean , Sparks Kim , Hoseth Gayla , Wise Sarah
Published: May 2019

Research on women's contributions to Alaska's salmon fisheries is limited despite their historical engagement in commercial and subsistence fisheries. We interviewed women engaged in salmon fisheries in Bristol Bay, Alaska and illustrate how oral history and participatory ethnography methods contribute to voices being heard, that have been excluded from fisheries research and management. Four broad themes emerged from the interviews: women's knowledge and leadership; social cohesion; environmental change; and identity and place. Women assume major roles by contributing to the preservation of salmon fishing knowledge and cultural values through cross-generational knowledge transfer. Their participation in fisheries, deep knowledge of local resources, and education of youth of the cultural value of fishing and the environment are critical to community socio-cultural and economic wellbeing. We conclude that women's knowledge may be critical in fisheries management decisions, community resilience, and socio-ecological sustainability in a region facing increased threats from climate change.
Water–rock–CO2 interactions and CO2 storage of Honghe tight oil reservoirs: an experimental and simulation study
Authors: He Yingfu , Ji Bingyu , Yang Shu , Liu Xuan , Zhao Shuxia , Zhou Yuanlong
Published: May 2019

CO2 flooding is essential for significantly enhancing oil recoveries and long‐term CO2 storage. We performed CO2 flooding experiments on target tight cores obtained from Honghe oilfield to investigate the water–rock interaction during CO2 flooding. In addition, we investigate the impact of mineralization and CO2 injection patterns on the sweep efficiency and CO2 long‐term storage using numerical simulations. Results show target core samples are composed of calcite, quartz, Na‐feldspar, and K‐feldspar. In particular, the main water–rock interactions during CO2 flooding are calcite and Na‐feldspar dissolution. The impact of water–rock interactions on the reformation of the matrix is not significant. However, such water–rock interactions will decrease the permeability of the natural fracture system near injection wells, which will lead to the enhancement of CO2 flooding efficiency in fractured formations. In addition, results show that water alternating gas injection will enhance oil recovery and CO2 primary storage. After CO2 flooding, mineral‐trapped CO2 is only 0.53wt.% of the total CO2 storage. As the flooding time increases, the mineral‐trapped CO2 increases. Results show that mineral‐trapped CO2 is 31.08% of the total CO2 storage at the simulation time of 500 years. © 2019 Society of Chemical Industry and John Wiley & Sons, Ltd.
Cervical cancer case–control audit: Results from routine evaluation of a nationwide cervical screening program
Authors: Wang Jiangrong , Elfström K. Miriam , Andrae Bengt , Nordqvist Kleppe Sara , Ploner Alexander , Lei Jiayao , Dillner Joakim , Sundström Karin , Sparén Pär
Published: May 2019

Our study used a refined case–control cervical cancer Audit framework to investigate effectiveness of cervical screening, with measures of three screening failures: irregular‐participation, cervical cancer developed after cytological abnormalities and after normal screening results. The register‐based study included 4,254 cervical cancer cases diagnosed in Sweden during 2002–2011, and 30 population‐based controls per case. We used conditional logistic regression models to examine relative risks of cervical cancer in relation to screening participation and screening results in the past two screening rounds from 6 months before cancer diagnosis. We found that women unscreened in past two screening rounds showed four times increased risk of cervical cancer compared to women screened in time (OR = 4.1, 95% CI = 3.8–4.5), and women unscreened in the previous round but screened in the most recent round also showed a statistically significantly elevated risk (OR = 1.6, 95% CI = 1.5–1.8). Women having abnormality in previous two rounds exhibited higher risk of cervical cancer compared to women screened with normal results, while having normal results in the subsequent round after the abnormality also yielded an increased risk (OR = 4.0, 95% CI = 3.2–5.1). Being screened with only normal results was associated with 89% risk reduction for squamous cell cancer, compared to women unscreened, but only 60% reduction for adenocarcinoma. Our findings emphasize the importance of routine participation in cervical screening and suggest that management of abnormalities, as well as sensitivity of the test, warrants improvement especially for preventing cervical adenocarcinoma. The Audit framework serves as routine evaluation model and the findings benchmark for future evaluation of changes in screening practice.
Impact of single‐nucleotide polymorphisms in DNA repair pathway genes on response to chemoradiotherapy in rectal cancer patients: Results from ACCORD‐12/PRODIGE‐2 phase III trial
Authors: Boige Valérie , Mollevi Caroline , Gourgou Sophie , Azria David , Seitz Jean‐François , Vincent Marc , Bigot Ludovic , Juzyna Beata , Miran Isabelle , Gerard Jean‐Pierre , Laurent‐Puig Pierre
Published: May 2019

We examined whether 66 germline single‐nucleotide polymorphisms (SNPs) in 10 candidate genes would predict clinical outcome in 316 patients with resectable locally advanced rectal cancer (LARC) enrolled in the ACCORD‐12 phase III trial who were randomly treated with preoperative radiotherapy plus capecitabine (CAP45; n = 155) or dose‐intensified radiotherapy plus capecitabine and oxaliplatin (CAPOX50; n = 161). The primary endpoint was tumor response according to the Dworak score. Multivariate logistic regression models adjusted on treatment arm and T stage determined the SNPs prognostic and predictive values for tumor response. In univariate analysis, five SNPs in ERCC2, XPA, MTHFR and ERCC1 were associated with the Dworak score in the CAPOX50 arm. In the overall population, interaction with treatment arm was significant for ERCC2 rs1799787 (pinteraction = 0.05) and XPA rs3176683 (pinteraction = 0.008), suggesting a predictive effect for response to oxaliplatin‐based chemoradiotherapy (CRT). All but XPA rs3176683 had a prognostic effect on tumor response. In a multivariate model, interaction remained significant for XPA rs3176683 ([OR 7.33, 95% CI 1.40–38.23], pinteraction = 0.018) and the prognostic effect significant for ERCC2 rs1799787 ([OR 0.55, 95%CI 0.32–0.93], p = 0.027) and ERCC1 rs10412761 ([OR 0.57, 95%CI 0.34–0.98], p = 0.042). Patients with the T/G haplotype of rs1799787 and rs10412761 had a 60% decrease in odds of response (p < 0.001). None of the five SNPs were associated with toxicity, overall and disease‐free survival. These data suggest that genetic variation in DNA repair genes influences response to preoperative CRT in LARC and identify patients who benefit from the addition of oxaliplatin to CRT.