bluuebunny/crossref_metadata_2025 huggingface dataset:
Use of targeted therapies for advanced renal cell carcinoma in the Veterans Health Administration
Authors: Aspinall Sherrie L. , Zhao Xinhua , Geraci Mark C. , Good Chester B. , Cunningham Francesca E. , Heron Bernadette B. , Becker Daniel , Lee Steve , Prasad Vinay ,   for the Targeted Therapies in Veterans with RCC Study Group
Published: September 2019

Background

The objective of this study is to describe the use of targeted therapies for the treatment of advanced renal cell carcinoma (RCC) and overall survival (OS) among patients in clinical practice in the Veterans Health Administration (VHA).

Methods

A retrospective cohort of 286 patients from 24 VHA Medical Centers diagnosed with advanced clear cell RCC between Fiscal Year (FY) 2010 and FY2014 was followed through September 30, 2016. Among patients who received targeted therapy, we described the medications taken, duration of therapy, and overall survival. We also assessed the effect of the first therapy received on overall survival using Cox Proportional Hazards models.

Results

There were 66 patients who did not receive therapy for their advanced RCC. Of the 220 treated patients, the mean (sd) number of medications received was 1.9 (1.1). The medications most commonly used first were sunitinib (61.8%), pazopanib (17.3%), and temsirolimus (10.9%). The median duration of first‐line therapy was 86 days (interquartile range [IQR] 42, 210). Median total duration of therapy was 159 days (IQR 58, 397). 62.3% of patients had ≥ 1 dose of therapy held or reduced, mainly due to an adverse drug event (ADE). Median survival from the start of treatment to death was 1.08 years (IQR 0.80, 1.31). Finally, receipt of temsirolimus vs sunitinib (HR 1.95 [95%CI 1.09,3.47]) as the first targeted therapy was independently associated with an increased hazard of death.

Conclusion

Our analysis of targeted therapies for advanced RCC in VHA suggests duration of treatment is shorter in a real‐world setting than in clinical trials, and dose reductions and ADEs are more common.
Comparative Analyses on the Bioactive Compounds and in Vitro Antioxidant Capacity of Tea Infusions Prepared from Selected Medicinal Fruits
Authors: Zahirul Islam Mohammad , An Hyo‐Geun , Lee Young‐Tack
Published: September 2019

This study was conducted to analyze the bioactive compounds and in vitro antioxidant capacity of tea infusions prepared from whole and ground medicinal fruits, including gardenia, jujube, magnolia, quince, and wolfberries. The dried medicinal fruit samples were ground, and then passed through a 60‐mesh sieve (pore size, 250 μm). Hot water (80 °C) infusions of whole and ground fruits were examined. In average of both whole and ground tea infusions, the maximum bioactive compounds were found in gardenia (β‐carotene, lycopene, and vitamin C), magnolia (total chlorophyll and anthocyanin), quince (flavonoid), and wolfberries (phenolic), and the maximum antioxidant capacity was found in quince (ABTS and DPPH) and wolfberries (NSA). Whole fruit tea infusions showed a higher brightness than the ground fruit tea infusions. The total chlorophyll, anthocyanin, β‐carotene, lycopene, phenolic, flavonoid, and vitamin C contents were found to be significantly (p≤0.001) higher in the ground fruit tea infusions than in the whole fruit tea infusions; additionally, the ground fruit tea infusions had a higher antioxidant capacity especially ABTS, DPPH and NSA. Therefore, the ground fruit tea infusions appeared to be more powerful with regard to the contents of bioactive compounds and antioxidant capacities than the whole fruit tea infusions.
Development of acceptable high‐quality noodles using nonglutinous rice cultivar Akitakomachi flours
Authors: Nagai Takeshi , Takagi Anri , Kai Norihisa , Tanoue Yasuhiro , Suzuki Nobutaka
Published: September 2019

Background and objectives

To elucidate the effects of four different particle sizes of flour from the nonglutinous rice cultivar Akitakomachi on noodle quality and the factors that affect the production of acceptable high‐quality noodles.

Findings

The damaged starch content was lowest in the flour with a particle size range of 53–212 μm, and the water absorption rate increased as the flour particle size ranges decreased. By textural and sensory analyses, noodles made from flour with a particle size range of 53–212 μm showed high breaking strength, cohesiveness, smoothness, gelatinization degree, and acid solubility and low adhesiveness. The expansion rate of noodle strands after cooking, especially noodle width and thickness, was fairly high, and the solubility of proteins and sugars was low in strands made with 0.5% grain vinegar compared to those made without grain vinegar. The total and surface SH group contents in different protein fractions were not different between noodles produced with and without grain vinegar.

Conclusions

Acceptable high‐quality noodles were produced using flour with a particle size range of 53–212 μm and 0.5% grain vinegar. The high‐order structural changes in the rice protein molecules by grain vinegar treatment significantly contributed to noodle quality, particularly their satisfactory firm texture.

Significance and novelty

The use of flour with a particle size range of 53–212 μm and the addition of grain vinegar were important factors for the production of high‐quality noodles with flour from the nonglutinous rice cultivar Akitakomachi. These results provide useful information for rice flour noodle industries.
Redox‐Active Guanidines in Proton‐Coupled Electron‐Transfer Reactions: Real Alternatives to Benzoquinones?
Authors: Wild Ute , Hübner Olaf , Himmel Hans‐Jörg
Published: September 2019

Guanidino‐functionalized aromatics (GFAs) are readily available, stable organic redox‐active compounds. In this work we apply one particular GFA compound, 1,2,4,5‐tetrakis(tetramethylguanidino)benzene, in its oxidized form in a variety of oxidation/oxidative coupling reactions to demonstrate the scope of its proton‐coupled electron transfer (PCET) reactivity. Addition of an excess of acid boosts its oxidation power, enabling the oxidative coupling of substrates with redox potentials of at least +0.77 V vs. Fc+/Fc. The green recyclability by catalytic re‐oxidation with dioxygen is also shown. Finally, a direct comparison indicates that GFAs are real alternatives to toxic halo‐ or cyano‐substituted benzoquinones.
Hydridoorganostannylene Coordination: Group 4 Metallocene Dichloride Reduction in Reaction with Organodihydridostannate Anions
Authors: Maudrich Jakob‐Jonathan , Widemann Max , Diab Fatima , Kern Ralf H. , Sirsch Peter , Sindlinger Christian P. , Schubert Hartmut , Wesemann Lars
Published: September 2019

Organodihydridoelement anions of germanium and tin were reacted with metallocene dichlorides of Group 4 metals Ti, Zr and Hf. The germate anion [Ar*GeH2]−reacts with hafnocene dichloride under formation of the substitution product [Cp2Hf(GeH2Ar*)2]. Reaction of the organodihydridostannate with metallocene dichlorides affords the reduction products [Cp2M(SnHAr*)2] (M=Ti, Zr, Hf). Abstraction of a hydride substituent from the titanium bis(hydridoorganostannylene) complex results in formation of cation [Cp2M(SnAr*)(SnHAr*)]+exhibiting a short Ti–Sn interaction. (Ar*=2,6‐Trip2C6H3, Trip=2,4,6‐triisopropylphenyl).
History and Future of Dative Bonds
Authors: Nandi Ashim , Kozuch Sebastian
Published: September 2019

Dative Bond (IUPAC): “The coordination bond formed upon interaction between molecular species, one of which serves as a donor and the other as an acceptor of the electron pair to be shared in the complex formed… The distinctive feature of dative bonds is that their minimum‐energy rupture in the gas phase or in inert solvent follows the heterolytic bond cleavage path.” This definition encompasses an immense number of molecules such as Lewis adducts, transition‐metal complexes, supposedly hypervalent or hypovalent systems, and many molecules with multifaceted Lewis structures. Still, there is a large reticence to include dative bonds in the regular depiction of molecules, and even a larger unawareness of the dative bond arrow in many chemical circles. Herein we will discuss in simple chemical terms the past, present and future of such bonds. In addition, we will try to provide cleaner options to represent intricate molecules without sacrificing physical accuracy.
Insight into the Formation and Transfer Process of the First Intermediate of CO2 Reduction over Ag‐Decorated Dendritic Cu
Authors: Yang Yang , Ajmal Saira , Feng Yiqing , Li Kejian , Zheng Xiuzhen , Zhang Liwu
Published: September 2019

It is still poorly understood how the first intermediates of CO2 reduction are formed and converted to multi‐carbon products over Cu‐based electrodes. Herein, Ag is used to decorate dendritic Cu and a high Faradaic efficiency (FE) for C2H4 (25 %) is obtained on a CuAg electrode, which is about five times higher than dendritic Cu. The intermediates including *CO2−, OH groups, Cu‐CO, C‐O rotation, and CHx species are investigated by in situ Raman spectroscopy. This work provides spectroscopic evidence that the first intermediate of CO2 reduction on Ag‐decorated Cu is carboxylate anion *CO2− bonded with the catalyst surface through the C and O atom. The formation and evolution process of the *CO2− intermediate over the applied potential are investigated in depth as well. This research contributes to a better understanding of the mechanism of CO2 reduction and multi‐carbon product formation pathways over Ag‐decorated Cu.
Stage I HPV‐positive oropharyngeal cancer: Should all patients receive similar treatments?
Authors: Yoshida Emi J. , Luu Michael , Mallen‐St. Clair Jon , Mita Alain C. , Scher Kevin S. , Lu Diana J. , Nguyen Anthony T. , Shiao Stephen L. , Ho Allen S. , Zumsteg Zachary S.
Published: September 2019

Background

Patients with clinical stage I human papillomavirus (HPV)–positive oropharyngeal squamous cell cancer (OPSCC) according to the American Joint Committee on Cancer (AJCC) eighth edition classification comprise a heterogeneous group formerly classified as stage I to stage IVA according to the seventh edition of the AJCC classification. These patients historically were treated with disparate treatment regimens, particularly with respect to the use of concurrent chemotherapy.

Methods

The National Cancer Data Base was queried for patients with AJCC eighth edition clinical stage I HPV‐positive OPSCC (AJCC seventh edition stage T1‐2N0‐2bM0) who were diagnosed from 2010 to 2014 and underwent definitive radiotherapy. Concurrent chemotherapy with definitive radiotherapy was defined as chemotherapy administered within 7 days of the initiation of radiotherapy.

Results

The current analysis included 4473 patients with HPV‐positive stage I OPSCC with a median follow‐up of 36.3 months. A total of 3127 patients (69.9%) received concurrent chemotherapy. Concurrent chemotherapy was found to be associated with improved overall survival on multivariable analyses (hazard ratio [HR], 0.782; 95% CI, 0.645‐0.948 [P = .012]). The effect of chemotherapy on survival varied based on lymph node involvement (P for interaction = .001). Specifically, chemotherapy was associated with improved survival for patients with lymph node–positive stage I disease (stage III‐IVA according to the AJCC seventh edition: HR, 0.682; 95% CI, 0.557‐0.835 [P < .001]), but not for patients with N0 disease (stage I‐II according to the AJCC seventh edition: HR, 1.646; 95% CI, 1.011‐2.681 [P = .05]). Similar results were noted among propensity score–matched cohorts.

Conclusions

Treatment with concurrent chemotherapy was associated with improved overall survival for patients with lymph node–positive, but not lymph node–negative, AJCC eighth edition stage I HPV‐positive OPSCC undergoing definitive radiotherapy, thereby supporting different treatment paradigms for these patients.
Severity of reduced bone mineral density and risk of fractures in long‐term survivors of childhood leukemia and lymphoma undergoing guideline‐recommended surveillance for bone health
Authors: Bloomhardt Hadley M. , Sint Kyaw , Ross Wilhelmenia L. , Rotatori Jaime , Ness Kathryn , Robinson Cemre , Carpenter Thomas O. , Chow Eric J. , Kadan‐Lottick Nina S.
Published: September 2019

Background

Survivors of childhood leukemia/lymphoma are at increased risk for reduced bone mineral density (BMD). The authors sought to determine the frequency of reduced BMD detected by off‐therapy surveillance, factors associated with reduced BMD, and the association of reduced BMD with fractures.

Methods

This cross‐sectional study included childhood leukemia/lymphoma survivors attending 2 survivorship clinics who received guideline‐recommended BMD surveillance ≥2 years post‐therapy with dual‐energy x‐ray absorptiometry (from January 1, 2004 to August 31, 2016). Lumbar spine BMD z‐scores were height‐for‐age–adjusted. Low and very low BMD were >1 SD and >2 SDs below norms, respectively. Treatment, chronic conditions, and fractures were abstracted from medical records. Logistic regression was used to examine the association of low BMD with patient/treatment factors and fractures.

Results

In total, 542 patients (51.5% female) with a mean age of 15.5 years (range, 4.4‐52.2 years) who were 6 years post‐therapy (range, 2.0‐35.1 years) were evaluated, including 116 who reported post‐therapy fractures. Lumbar spine low BMD was identified in 17.2% of survivors, and very low BMD was identified in 3.5% of survivors, but frequencies varied considerably between subgroups; 10.8% of survivors aged 15 to 19 years at diagnosis had very low BMD. In multivariable analyses, older age at diagnosis, white race, and being underweight were significantly associated with low BMD. Survivors with low BMD had greater odds of nondigit fractures (odds ratio, 2.2; 95% CI, 1.3‐3.7) and specifically long‐bone fractures (odds ratio, 2.7; 95% CI, 1.5‐4.7).

Conclusions

In this study of childhood leukemia/lymphoma survivors undergoing guideline‐recommended dual‐energy x‐ray absorptiometry surveillance, patients who were older at diagnosis, white, and underweight were at the highest risk for lumbar spine low BMD. Low BMD was associated with a greater risk of fractures, emphasizing the clinical importance of surveillance.
Hydrogen‐Bonding‐Driven Ion‐Pair Formation in Protic Ionic Liquid Aqueous Solution
Authors: Zhang Lei , Zhang Zhang , Yuan Wen‐Li , Zhao Nanrong , Zhu Qiu‐Hong , He Ling , Tao Guo‐Hong
Published: September 2019

Protic ionic liquids (PILs) in solution especially in water have attracted more and more attention due to their unique properties. The solvation of PILs in water is important to their properties and applications. To explore the solvation of bio‐based PILs in water, acidity of 49 [AA]X amino acid ionic liquids (AAILs) consisting of 7 different cations and 7 different anions was studied as a favorable probe. The pKa values for [AA]X PILs containing same cations were obtained and discussed. The acidity strength of the [AA]X PILs varies with both cation and anion which does not follow the conventional assumption that the acidity for PILs is independent of anions. The acidic discrepancy of [AA]X PILs aqueous solution is probably mediated by the formation of ion pairs according to a revised solvation model of PILs. Quantum‐chemistry calculation was employed to unpuzzle anion's different effects on the acid balance of cations where cation‐anion hydrogen bonds play an important role. Such difference in acidity allows us to understand the formation of solvated ion pairs. This work provides an insight into the fundamental solvation of PILs from acid perspective and their influence on acidity properties for the first time.
Water Diffusion and Transport in Oil Paints as Studied by Unilateral NMR and 1H High‐Resolution MAS‐NMR Spectroscopy
Authors: Di Tullio Valeria , Zumbulyadis Nicholas , Centeno Silvia A. , Catalano Jaclyn , Wagner Molly , Dybowski Cecil
Published: September 2019

Heavy metal carboxylate degradation severely affects thousands of oil paintings. Relative humidity has been reported to accelerate the rate of the reactions. To evaluate its role further, water diffusion and molecular mobility of protons in linseed oil‐based lead white paints were studied by unilateral NMR and 1H HRMAS spectroscopy. The results indicate that exposure to high %RH for relatively long times affects the dynamics of the oil paint's mobile fraction and that the effect is more pronounced as the thickness of the film increases. It was found that the paint can absorb appreciable amounts of water and has a porosity of approximately 6 % available for the diffusion of water, for which a regime of restricted diffusion was observed. Furthermore, the presence of bound and free‐moving water, due to the possible formation of hydrated ionic‐group clusters, supports the hypothesis of a polymeric/ionomeric network, as well as regions of essentially water free to move as in the bulk. The findings allow a better understanding of the role of water as a factor activating the degradation process in linseed oil‐based lead white paints.
High‐Performance Fuel Cells Based on In2O3–La/Pr‐Doped Ceria Semiconductor–Ionic Conductor Materials Electrolyte
Authors: Xiang Dong , Nie Jingjing , Feng Chu , Liu Kai , He Zili , Shen Liangping , Wang Baoyuan
Published: September 2019

Recent investigations disclose that semiconductor–ionic conductor materials (SIMs) as novel functional materials deliver superior ionic conductivity. However, SIMs are not utilized as electrolyte membranes in traditional fuel cells due to mixed ion–electron conduction. To address this issue, a Schottky fuel cell using In2O3–La/Pr‐doped ceria (LCP) SIMs as the electrolyte membrane is fabricated; such devices take advantage of the superior ionic conductivity of SIMs, combined with the band energy alignment to avoid short circuiting. Through adjusting the weight ratio of In2O3 and LCP, a supreme power density of 730 mW cm−2 is obtained for the Schottky fuel cell operated at 550 °C, which also exhibits decent performance at low temperatures, namely, a power maximum of 370 mW cm−2 even at 500 °C. The rectification curve verifies the existence of Schottky junction in the cell, the corresponding built‐in field prevents the electron from passing through the cell to eliminate short circuiting, and simultaneously promotes the ion across the interface between the electrolyte and anode. The results develop novel In2O3–LCP SIMs with superior conductivity and also demonstrate an efficient cell configuration based on SIMs, which proposes a potential strategy for the application of intermediate/low‐temperature solid oxide fuel cells.
Aligning Utility Regulation to Support the Future Grid
Authors: Aweh Amanda , DeCotis Paul A.
Published: September 2019

Utilities today, for the most part, continue to set rates and revenue, and recover costs the way they have for more than a hundred years. The traditional vertically integrated utility business model has utilities owning and operating large central‐station power plants, moving power over high‐voltage transmission lines to the distribution grid through substations, and delivering one‐way power to residents, businesses, and industry. Whether utilities own generation directly or not, revenue requirements are determined by regulators in a similar manner based on cost of service. Revenue models, and the method for compensating utilities, are straightforward. Utilities receive an agreed‐upon financial return on assets and are allowed full recovery of investments deemed prudent by regulators, with related operating expenses and fuel costs being passed through to customers.
Optimum fluid layer thickness for heat transfer effectiveness using water‐based nanofluids—A numerical estimation
Authors: Krishnan S. Ramesh , Namboothiri V.N. Narayanan , Mathew Abin
Published: September 2019

Nanofluids are considered to be the novel method for heat transfer in heat pipes and heat exchangers. But its application in microlevel cooling systems is still limited because of the paradox that once convection onsets in the base fluid, the effectiveness of nanofluid as a heat transfer medium will be reduced. The onset of convection in the nanofluid occurs only after its onset in the base fluid which is mostly water. Hence, it is vital to estimate the fluid layer thickness of the base fluid at which convection will just onset. The problem is analyzed using the concept of the critical Rayleigh number. The study of velocity and temperature profiles in the fluid gap also gives an indication of convection in the fluid gap.
Lessons from the 2018 International Symposium on Alternatives Assessment: Advances and Reflections on Practice and Ongoing Needs to Build the Field
Authors: Tickner Joel , Simon Rachel , Jacobs Molly , Rudisill Cathy , Tanir Jennifer , Heine Lauren , Spencer Pamela , Fantke Peter , Malloy Tim , Edwards Sally , Zhou Xiaoying
Published: September 2019

Alternatives assessment is gaining traction as a systematic method to support the informed substitution of chemicals of concern. The 2nd International Symposium on Alternatives Assessment, on 1–2 November 2018, convened nearly 150 professionals from government agencies, industry, consultant firms, academia, and advocacy organizations to advance a greater understanding of the evolving methods, practices, and challenges in the use of alternatives assessment. This article reviews highlights and lessons from the symposium, including 1) notable advances in methods, 2) shared insights from practitioners on best practices as well as inherent tensions and challenges, and 3) research and practice needs in the field that can be addressed by organizations such as the newly launched Association for the Advancement of Alternatives Assessment. Being interdisciplinary in nature, the establishment of educational frameworks across disciplines and inclusion of diverse expertise in hazard and exposure assessments, life cycle impacts considerations, design principles, and economic and engineering evaluations will ensure continued growth of the field. Integr Environ Assess Manag 2019;00:1–8. © 2019 SETAC
miR‐200c overexpression inhibits the invasion and tumorigenicity of epithelial ovarian cancer cells by suppressing lncRNA HOTAIR in mice
Authors: Yang Cuiping , Li Huihui , Zhang Tao , Chu Yifan , Chen Dengyu , Zuo Junli
Published: September 2019

Epithelial ovarian cancer (EOC) is a common ovarian cancer in gynecological cancers today. It has been found that microRNAs and long‐chain noncoding RNA (lncRNA) regulate the gene transcriptional expression in cells. However, it is not well understood that the upstream and downstream regulatory molecules of lncRNA HOX antisense intergenic RNA (HOTAIR). The effects of miR‐200c overexpression on the invasion and nude mouse tumorigenicity, as well as lncRNA HOTAIR and snail expression of EOC SKOV3 cells, should be further explored. The expression of miR‐200c and lncRNA HOTAIR was detected by reverse transcription PCR (RT‐PCR) in EOC SKOV3 cells. The whole miR‐200c gene fragment was cloned into a lentiviral plasmid vector. The miR‐200c expression in transducted SKOV3 cells with reconstructed miR‐200c lentivirus was significantly higher than the negative control (P < .01). The lentivirus‐miR‐200c‐SKOV3 cells show that the invasion ability was significantly decreased compared with the negative control (P < .01). The nude mouse tumorigenicity was significantly decreased compared with that of the control group (P < .01). The snail protein expression in lentivirus‐miR‐200c‐SKOV3 xenograft tumor was significantly decreased compared with the negative control lentivirus‐SKOV3 group (P < .05). The miR‐200c overexpression significantly decreased the expressions of lncRNA HOTAIR and snail, but increased E‐cadherin expression in the lentivirus‐miR‐200c transducted SKOV3 cells of xenograft tumor, compared with the negative control (P < .05). The miR‐200c overexpression in SKOV3 cells with transducted lentivirus‐miR‐200c can inhibit lncRNA HOTAIR expression, decrease snail, increase E‐cadherin and significantly reduce the invasion and tumorigenicity of EOC SKOV3 cells. These results suggest that the miR‐200c and lncRNA HOTAIR could be effective therapeutic targets for human epithelial ovarian cancer treatment.
Plateaued functions, partial geometric difference sets, and partial geometric designs
Authors: Xu Bangteng
Published: September 2019

Plateaued functions on finite fields have been studied in many papers in recent years. As a generalization of plateaued functions on finite fields, we introduce the notion of a plateaued function on a finite abelian group. We will give a characterization of a plateaued function in terms of an equation of the matrix associated to the function. Then we establish a one‐to‐one correspondence between the ‐valued plateaued functions and partial geometric difference sets (with specific parameters) in finite abelian groups. We will also discuss two general methods (extension and lifting) for the construction of new partial geometric difference sets from old ones in (abelian or nonabelian) finite groups, and construct many partial geometric difference sets and plateaued functions. A one‐to‐one correspondence between partial geometric difference sets (in arbitrary finite groups) and partial geometric designs will be proved.
Ideological profiles of US adults and their support for youth mentoring
Authors: Hagler Matthew , McQuillin Sam , Rhodes Jean
Published: September 2019

Little is known about the influence of political ideology and religiosity on adults’ support for youth mentoring as a strategy to address social problems. This study used latent class analysis in a large, national sample of US adults to identify underlying ideological profiles associated with support for mentoring programs. Three latent classes emerged. The attitudes of two classes, Classic Conservatives and Progressives, were consistent with traditional political conservatism and liberalism; the latter endorsed higher support for the theory of mentoring and government spending on mentoring programs. Members of the third class, Religious Outsiders, were highly religious, self‐identified as very conservative, and were highly supportive of the theory of mentoring and the use of government funds on mentoring programs. Ad hoc analyses revealed that Religious Outsiders were the most likely to actually participate in mentoring activities. These findings suggest that support for mentoring, while not universal, crosses traditional political lines.
Melatonin attenuates ER stress and mitochondrial damage in septic cardiomyopathy: A new mechanism involving BAP31 upregulation and MAPK‐ERK pathway
Authors: Zhang Jiabing , Wang Leili , Xie Wei , Hu Shunying , Zhou Hao , Zhu Pingjun , Zhu Hang
Published: September 2019

Septic cardiomyopathy is associated with mitochondrial damage and endoplasmic reticulum (ER) dysfunction. However, the upstream mediator of mitochondrial injury and ER stress has not been identified and thus little drug is available to treat septic cardiomyopathy. Here, we explored the role of B‐cell receptor‐associated protein 31 (BAP31) in septic cardiomyopathy and figure out whether melatonin could attenuate sepsis‐mediated myocardial depression via modulating BAP31. Lipopolysaccharide (LPS) was used to establish the septic cardiomyopathy model. Pathway analysis was performed via western blot, quantitative polymerase chain reaction and immunofluorescence. Mitochondrial function and ER stress were detected via enzyme‐linked immunosorbent assay, western blot, and immunofluorescence. After exposure to LPS, cardiac function was reduced due to excessive inflammation response and extensive cardiomyocyte death. Mechanistically, melatonin treatment could dose‐dependently improve cardiomyocyte viability via preserving mitochondrial function and reducing ER stress. Further, we found that BAP31 transcription was repressed by LPS whereas melatonin could restore BAP31 expression; this effect was dependent on the MAPK‐ERK pathway. Inhibition of the ERK pathway and/or knockdown of BAP31 could attenuate the beneficial effects of melatonin on mitochondrial function and ER homeostasis under LPS stress. Altogether, our results indicate that ERK‐BAP31 pathway could be used as a critical mediator for mitochondrial function and ER homeostasis in sepsis‐related myocardial injury. Melatonin could stabilize BAP31 via the ERK pathway and thus contribute to the preservation of cardiac function in septic cardiomyopathy.
Dioscin inhibits the growth of human osteosarcoma by inducing G2/M‐phase arrest, apoptosis, and GSDME‐dependent cell death in vitro and in vivo
Authors: Ding Qiuyue , Zhang Wenda , Cheng Cheng , Mo Fengbo , Chen Lei , Peng Guangfu , Cai Xianyi , Wang Jinglong , Yang Shuhua , Liu Xianzhe
Published: September 2019

Pyroptosis is a form of programmed cell death (PCD) that plays a vital role in immunity and diseases. Although it was recently reported that chemotherapy drugs can induce pyroptosis through caspase‐3‐dependent cleavage of gasdermin E (GSDME), the role of pyroptosis in osteosarcoma (OS) with dioscin is less understood. In this study, we explored the effects of dioscin on OS in vitro and in vivo and further elucidated the underlying molecular mechanisms and found that dioscin‐triggered pyroptosis in GSDME‐dependent cell death and that GSDME‐N was generated by caspase‐3. Furthermore, dioscin inhibited cancer cell growth by inducing G2/M arrest and apoptosis through the JNK/p38 pathway. In vivo, dioscin significantly inhibited OS proliferation. Taken together, our results demonstrate that dioscin can induce apoptosis through the JNK/p38 pathway and GSDME‐dependent pyroptosis in OS, identifying it as a potential therapeutic drug for treatment of this disease.
The long noncoding RNA ZFAS1 promotes the progression of glioma by regulating the miR‐150‐5p/PLP2 axis
Authors: Li Xiaojian , Luo Yidan , Liu Liang , Cui Sitong , Chen Wei , Zeng Ailiang , Shi Yan , Luo Liangsheng
Published: September 2019

Numerous studies have reported that long noncoding RNA (lncRNA) dysregulation is involved in the progression of many malignant tumors, including glioma. The lncRNA ZNFX1 antisense RNA 1 (ZFAS1) plays an oncogenic role in various malignant tumors, such as gastric cancer and hepatocellular carcinoma. However, the underlying molecular mechanism of ZFAS1 in glioma has not been fully clarified. In this study, we found that the expression of ZFAS1 was upregulated in both glioma tissues and cell lines. Functional experiments revealed that ZFAS1 promoted glioma proliferation, migration and invasion, and increased resistance to temozolomide in vitro. By using online databases, RNA pull‐down assays and luciferase reporter assays, ZFAS1 was demonstrated to act as a sponge of miR‐150‐5p. Furthermore, proteolipid protein 2 (PLP2) was shown to be the functional target of miR‐150‐5p. Rescue experiments revealed that ZFAS1 regulated the expression of PLP2 by sponging miR‐150‐5p. Finally, a xenograft tumor assay demonstrated that ZFAS1 promoted glioma growth in vivo. Our results showed that ZFAS1 promoted glioma malignant progression by regulating the miR‐150‐5p/PLP2 axis, which may provide a potential therapeutic target for the treatment of glioma.
Effects of sleep disruption on stress, nigrostriatal markers, and behavior in a chronic/progressive MPTP male mouse model of parkinsonism
Authors: Xu Mo , Bohlen Jerry K. , Moore Cynthia , Nipper Michelle A. , Finn Deborah A. , Jones Carolyn E. , Lim Miranda M. , Meshul Charles K.
Published: September 2019

Sleep complaints are an early clinical symptom of neurodegenerative disorders. Patients with Parkinson's disease (PD) experience sleep disruption (SD). The objective of this study was to determine if preexisting, chronic SD leads to a greater loss of tyrosine hydroxylase (TH) within the striatum and the substantia nigra following chronic/progressive exposure with the neurotoxin, 1‐methyl‐2‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP). Male mice underwent chronic SD for 4 weeks, then injected with vehicle (VEH) or increasing doses of MPTP for 4 weeks. There was a significant decrease in the plasma corticosterone levels in the MPTP group, an increase in the SD group, and a return to the VEH levels in the SD+MPTP group. Protein expression levels for TH in the striatum (terminals) and substantia nigra pars compacta (dopamine [DA] cell counts) revealed up to a 78% and 38% decrease, respectively, in the MPTP and SD+MPTP groups compared to their relevant VEH and SD groups. DA transporter protein expression increased in the striatum in the MPTP versus VEH group and in the SN/midbrain between the SD+MPTP and the VEH group. There was a main effect of MPTP on various gait measures (e.g., braking) relative to the SD or VEH groups. In the SD+MPTP group, there were no differences compared to the VEH group. Thus, SD, prior to administration of MPTP, has effects on serum corticosterone and gait but more importantly does not potentiate greater loss of TH within the nigrostriatal pathway compared to the MPTP group, suggesting that in PD patients with SD, there is no exacerbation of the DA cell loss.
Synchrotron MicroCT Reveals the Potential of the Dual Contrast Technique for Quantitative Assessment of Human Articular Cartilage Composition
Authors: Honkanen Miitu K. M. , Saukko Annina E. A. , Turunen Mikael J. , Shaikh Rubina , Prakash Mithilesh , Lovric Goran , Joukainen Antti , Kröger Heikki , Grinstaff Mark W. , Töyräs Juha
Published: September 2019

Dual contrast micro computed tomography (CT) shows potential for detecting articular cartilage degeneration. However, the performance of conventional CT systems is limited by beam hardening, low image resolution (full‐body CT), and long acquisition times (conventional microCT). Therefore, to reveal the full potential of the dual contrast technique for imaging cartilage composition we employ the technique using synchrotron microCT. We hypothesize that the above‐mentioned limitations are overcome with synchrotron microCT utilizing monochromatic X‐ray beam and fast image acquisition. Human osteochondral samples (n = 41, four cadavers) were immersed in a contrast agent solution containing two agents (cationic CA4+ and non‐ionic gadoteridol) and imaged with synchrotron microCT at an early diffusion time point (2 h) and at diffusion equilibrium (72 h) using two monochromatic X‐ray energies (32 and 34 keV). The dual contrast technique enabled simultaneous determination of CA4+ (i.e., proteoglycan content) and gadoteridol (i.e., water content) partitions within cartilage. Cartilage proteoglycan content and biomechanical properties correlated significantly (0.327 < r < 0.736, p < 0.05) with CA4+ partition in superficial and middle zones at both diffusion time points. Normalization of the CA4+ partition with gadoteridol partition within the cartilage significantly (p < 0.05) improved the detection sensitivity for human osteoarthritic cartilage proteoglycan content, biomechanical properties, and overall condition (Mankin, Osteoarthritis Research Society International, and International Cartilage Repair Society grading systems). The dual energy technique combined with the dual contrast agent enables assessment of human articular cartilage proteoglycan content and biomechanical properties based on CA4+ partition determined using synchrotron microCT. Additionally, the dual contrast technique is not limited by the beam hardening artifact of conventional CT systems. © 2019 The Authors. Journal of Orthopaedic Research® published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society. J Orthop Res 38:563–573, 2020
Numerical and experimental investigation of impacts of nonlinear scattering encapsulated microbubbles on Nakagami distribution
Authors: Wang Diya , Sang Yuchao , Zhang Xinyu , Hu Hong , Lu Shukuan , Zhang Yu , Fu Chaoying , Cloutier Guy , Wan Mingxi
Published: September 2019

Purpose

The Nakagami statistical model and Nakagami shape parameter m have been widely used in linear tissue characterization and preliminarily characterized the envelope distributions of nonlinear encapsulated microbubbles (EMBs). However, the Nakagami distribution of nonlinear scattering EMBs lacked a systematical investigation. Thus, this study aimed to investigate the Nakagami distribution of EMBs and illustrate the impact of EMBs' nonlinearity on the Nakagami model.

Method

A group of simulated EMB phantoms and in vitro EMB dilutions with an increasing concentration distribution under various EMB nonlinearities, as regulated by acoustic parameters, were characterized by using the window‐modulated compounding Greenwood–Durand estimator.

Results

Raw envelope histograms of simulated and in vitro EMBs were well matched with the Nakagami distribution with a high correlation coefficient of 0.965 ± 0.021 (P < 0.005). The mean values and gradients of m parameters of simulated and in vitro EMBs were smaller than those of linear scatterers due to the stronger nonlinearity. These m values exhibited a quasi‐linear improvement with the increase in second harmonic nonlinear‐to‐linear component ratio regulated by pulse lengths and excitation frequencies at low‐ and high‐concentration conditions.

Conclusions

The Nakagami distribution was suitable for the EMBs characterization but the corresponding m parameter was affected by the EMBs' nonlinearity. These validations provided support and nonlinear impact assessment for the EMBs' characterization using the Nakagami statistical model in the future.
Short‐term heat stress impairs testicular functions in the American oyster, Crassostrea virginica: Molecular mechanisms and induction of oxidative stress and apoptosis in spermatogenic cells
Authors: Nash Sarah , Rahman Md Saydur
Published: September 2019

Global temperature is increasing due to anthropogenic activities. Abnormal temperature has devastating effects on growth, reproduction, and development of aquatic organisms. In this study, we examined the effects of short‐term exposure to elevated temperatures (28 and 32°C for 1 week) on testicular functions, heat shock protein‐70 (HSP70), dinitrophenyl protein (DNP, a biomarker of reactive oxygen species [ROS]), and nitrotyrosine protein (NTP, an indicator of reactive nitrogen species [RNS]) expressions, protein carbonyl (PC, a measure of ROS) contents, nitrates/nitrites (NOx, a metabolite of nitric oxide) levels, extrapallial fluid (EPF) conditions, and cellular apoptosis in American oyster (Crassostrea virginica). Higher temperatures significantly decreased (~26%) sperm production in oysters compared with controls (24°C). HSP70, NTP, and DNP expressions were increased after heat exposure, consistent with increased EPF pH, and cellular apoptosis. The enhanced apoptosis in spermatogenic cells is associated with increased caspase 3/7 activity, PC contents, and NOx levels in testicular tissues. Together these results suggest that elevated temperature drastically increases oxidative stress and cellular apoptosis which in turn leads to decreased testicular functions in oysters. To the best of our knowledge, this study reports the first findings on the impacts of elevated temperatures on testicular functions in oysters.
Effect of PPARGC1A on the development and metabolism of early rabbit embryos in vitro
Authors: Zhang Guo‐Min , Guo Yi‐Xuan , Deng Ming‐Tian , Wan Yong‐Jie , Deng Kai‐Ping , Xiao Shen‐Hua , Meng Fan‐Xing , Wang Feng , Lei Zhi‐Hai
Published: September 2019

Peroxisome proliferator‐activated receptor gamma coactivator 1‐alpha (PPARGC1A) is a central regulator of mitochondrial biogenesis and metabolism, and its expression is closely related to embryo development. To gain insights into the possible mechanisms of PPARGC1A during early embryogenesis, the development potential, mitochondrial biogenesis, and the culture medium metabolomics of embryos were evaluated when PPARGC1A overexpressed or suppressed in rabbit zygotes. Results showed that different PPARGC1A levels in rabbit zygotes could affect blastocyst percentage, and the expressions of mitochondrial biogenesis and metabolic‐related genes, as well as the glutathione and adenosine triphosphate levels during early embryo development. In addition, compared with the controls, 12 and 10 different metabolites involved in carbohydrate, amino acid, and fatty acid metabolism were screened in the 5 day's spent culture medium of PPARGC1A overexpressed and suppressed embryos by gas chromatography–mass spectrometer, respectively. Consistent with these metabolite changes, the transcriptions of genes encoding glucose transporters and fatty acid biosynthetic proteins in the embryos from different groups were regulated by PPARGC1A during rabbit embryo development. Taken together, these data provide evidence that PPARGC1A may regulate early rabbit embryo development through mitochondrial biogenesis and metabolism.
Accelerated free‐breathing whole‐heart 3D T2 mapping with high isotropic resolution
Authors: Bustin Aurélien , Milotta Giorgia , Ismail Tevfik F. , Neji Radhouene , Botnar René M. , Prieto Claudia
Published: September 2019

Purpose

To enable free‐breathing whole‐heart 3D T2 mapping with high isotropic resolution in a clinically feasible and predictable scan time. This 3D motion‐corrected undersampled signal matched (MUST) T2 map is achieved by combining an undersampled motion‐compensated T2‐prepared Cartesian acquisition with a high‐order patch‐based reconstruction.

Methods

The 3D MUST‐T2 mapping acquisition consists of an electrocardiogram‐triggered, T2‐prepared, balanced SSFP sequence with nonselective saturation pulses. Three undersampled T2‐weighted volumes are acquired using a 3D Cartesian variable‐density sampling with increasing T2 preparation times. A 2D image‐based navigator is used to correct for respiratory motion of the heart and allow 100% scan efficiency. Multicontrast high‐dimensionality undersampled patch‐based reconstruction is used in concert with dictionary matching to generate 3D T2 maps. The proposed framework was evaluated in simulations, phantom experiments, and in vivo (10 healthy subjects, 2 patients) with 1.5‐mm3 isotropic resolution. Three‐dimensional MUST‐T2 was compared against standard multi‐echo spin‐echo sequence (phantom) and conventional breath‐held single‐shot 2D SSFP T2 mapping (in vivo).

Results

Three‐dimensional MUST‐T2 showed high accuracy in phantom experiments (R2 > 0.99). The precision of T2 values was similar for 3D MUST‐T2 and 2D balanced SSFP T2 mapping in vivo (5 ± 1 ms versus 4 ± 2 ms, P = .52). Slightly longer T2 values were observed with 3D MUST‐T2 in comparison to 2D balanced SSFP T2 mapping (50.7 ± 2 ms versus 48.2 ± 1 ms, P < .05). Preliminary results in patients demonstrated T2 values in agreement with literature values.

Conclusion

The proposed approach enables free‐breathing whole‐heart 3D T2 mapping with high isotropic resolution in about 8 minutes, achieving accurate and precise T2 quantification of myocardial tissue in a clinically feasible scan time.
Nutrition Management in Acute Pancreatitis
Authors: Ramanathan Meera , Aadam Abdul Aziz
Published: September 2019

Acute pancreatitis (AP) is one of the most prevalent gastrointestinal conditions necessitating inpatient care. In the United States, over 275,000 patients are hospitalized for management of AP, with an estimate that over $2.5 billion is spent annually in treatment, with incidence continuing to rise. AP is a highly inflammatory and catabolic state, putting all patients with the condition at risk of malnutrition. Numerous approaches to nutrition support in pancreatitis have been evaluated and remain controversial. In this narrative review, we aim to give an overview of indications for nutrition and approach to management of nutrition in severe and predicted severe AP based on currently available data.
Analysis of the clinical characteristics of pediatric patients who experience ifosfamide‐induced encephalopathy
Authors: Ide Yuichiro , Yanagisawa Ryu , Kubota Noriko , Sakashita Kazuo , Tozuka Minoru , Nakamura Tomohiko , Honda Takayuki
Published: September 2019

Background

Several kinds of pediatric hematological and/or malignant diseases are treated with chemotherapy regimens including ifosfamide (IFO). IFO‐induced encephalopathy (IIE) is one of the serious side effects, but there is not enough evidence regarding the clinical features of IIE in children.

Procedure

We performed a retrospective study on pediatric patients treated with chemotherapy regimens, including IFO, at a single center. We recorded the clinical characteristics of all patients; we compared the clinical characteristics between patients who developed IIE and those who did not.

Results

In total, 88 patients received a chemotherapy regimen including IFO. IIE developed in seven patients (8.0%). The median age of patients at the time of IIE development was 4.3 (range 1.4‐6.5) years in the younger population. Six of seven patients with IIE improved with supportive therapy only; however, one patient died due to heart failure. Overall survival was not different between the two groups. Multivariable analysis revealed that the co‐administration of cisplatin (CDDP) or carboplatin (CBDCA) was a significant risk factor associated with IIE. Although there was no significant difference in laboratory data between the groups before chemotherapy, patients who developed IIE showed exacerbation in several laboratory tests, including those for renal and liver functions.

Conclusions

Renal dysfunction caused by the combination of nephrotoxic agents (IFO and CDDP/CBDCA) seems to be important for the development of pediatric IIE. It was thought to be difficult to predict IIE onset based on laboratory data before the initiation of chemotherapy regimens; however, careful observation of laboratory data during IFO chemotherapy regimens may help predict IIE onset and facilitate early treatment.
Near‐Complete Elimination of Size‐Dependent Efficiency Decrease in GaN Micro‐Light‐Emitting Diodes
Authors: Zhu Jun , Takahashi Tokio , Ohori Daisuke , Endo Kazuhiko , Samukawa Seiji , Shimizu Mitsuaki , Wang Xue-Lun
Published: September 2019

Herein, a successful elimination of the size‐dependent efficiency decrease in GaN micro‐light‐emitting diodes (micro‐LEDs) is achieved using damage‐free neutral beam etching (NBE). The NBE technique, which can obtain ultralow‐damage etching of GaN materials, is used in place of the conventional inductively coupled plasma to form the micro‐LED mesa. It is found that all the fabricated micro‐LEDs with sizes ranging from 40 to 6 μm show external quantum efficiency (EQE) versus current density characteristics similar to those of large‐area GaN LEDs, with a maximum in EQE curves at a current density of as low as about 5 A cm−2. Furthermore, all the fabricated micro‐LEDs, even the 6 μm one, show a similar value of maximum EQE with a variation of less than 10%, clearly indicating a negligible size dependence of emission efficiency of micro‐LEDs fabricated by the NBE technique at least down to the size of 6 μm. These results suggest that the NBE process is a promising method of fabricating high‐efficiency sub‐10 μm GaN micro‐LEDs required for high‐efficiency, high‐brightness, and high‐resolution micro‐LED displays.