bluuebunny/crossref_metadata_2025 huggingface dataset:
Secreted cystatins decrease proliferation and enhance apoptosis of human leukemic cells
Authors: Hunaiti Samar , Wallin Hanna , Eriksson Mia , Järås Marcus , Abrahamson Magnus
Published: August 2020

Cysteine proteases are implicated in proteolysis events favoring cancer cell growth, spread, and death by apoptosis. Herein, we have studied whether the net growth and survival of the leukemic cell lines Jurkat, U937, and HL‐60 are affected by external addition of five proteins acting as natural cysteine protease inhibitors. None of the cystatins examined (A, C, D, and E/M) or chagasin showed consistent effects on Fas‐induced apoptosis when evaluated at 1 µm. In contrast, when the intrinsic apoptosis pathway was activated by hydrogen peroxide, addition of cystatin D augmented caspase‐3‐like activity within all three cell lines. Flow cytometric analysis of U937 cells also showed increased numbers of annexin V‐positive cells when hydrogen peroxide was used to initiate apoptosis and cells were cultured in the presence of cystatin D or C. Moreover, stimulation of hydrogen peroxide‐induced apoptotic U937 cells with either cystatin C or D resulted in a dose‐dependent decrease in the number of cells. Cell viability was also decreased when U937 cells were cultured in the presence of cystatin C or D (1–9 µm) only, demonstrating that these cystatins can reduce cell proliferation by themselves in addition to enhancing apoptosis induced by oxidative stress. These effects on U937 cells were paralleled by internalization of cystatins C and D, indicating these effects are caused by downregulation of intracellular proteolysis. External addition of cystatins C and D to HL‐60 and Jurkat cells demonstrated similar degrees of cystatin D uptake and decreased viability as for U937 cells, indicating that these effects are general for leukemic cells.
Photoluminescence Upconversion Spectroscopy
Authors: Chosrowjan Haik , Taniguchi Seiji
Published: August 2020

The basic physical concepts and main characteristics of transient photoluminescence upconversion spectroscopy, including requirements for nonlinear crystals, acceptance angle, quantum efficiency for upconversion, group velocity mismatch, and photometric calibration, are presented. The main aspects relevant to building an ultrafast upconversion spectrometer are emphasized. Single‐wavelength and broadband implementations of the technique, as well as photoluminescence upconversion microscope, have been presented and discussed. Application examples of the technique in different fields of physics, chemistry, and biology have been presented.
Characterization of an inorganic scintillator for small‐field dosimetry in MR‐guided radiotherapy
Authors: Cusumano Davide , Placidi Lorenzo , D'Agostino Emiliano , Boldrini Luca , Menna Sebastiano , Valentini Vincenzo , De Spirito Marco , Azario Luigi
Published: August 2020

Introduction

Aim of this study is to dosimetrically characterize a new inorganic scintillator designed for magnetic resonance‐guided radiotherapy (MRgRT) in the presence of 0.35 tesla magnetic field (B).

Methods

The detector was characterized in terms of signal to noise ratio (SNR), reproducibility, dose linearity, angular response, and dependence by energy, field size, and B orientation using a 6 MV magnetic resonance (MR)‐Linac and a water tank.

Field size dependence was investigated by measuring the output factor (OF) at 1.5 cm. The results were compared with those measured using other detectors (ion chamber and synthetic diamond) and those calculated using a Monte Carlo (MC) algorithm.

Energy dependence was investigated by acquiring a percentage depth dose (PDD) curve at two field sizes (3.32 × 3.32 and 9.96 × 9.96 cm2) and repeating the OF measurements at 5 and 10 cm depths.

Results

The mean SNR was 116.3 ± 0.6. Detector repeatability was within 1%, angular dependence was <2% and its response variation based on the orientation with respect to the B lines was <1%.

The detector has a temporal resolution of 10 Hz and it showed a linear response (R2 = 1) in the dose range investigated. All the OF values measured at 1.5 cm depth using the scintillator are in accordance within 1% with those measured with other detectors and are calculated using the MC algorithm. PDD values are in accordance with MC algorithm only for 3.32 × 3.32 cm2 field. Numerical models can be applied to compensate for energy dependence in case of larger fields.

Conclusion

The inorganic scintillator in the present form can represent a valuable detector for small‐field dosimetry and periodic quality controls at MR‐Linacs such as dose stability, OFs, and dose linearity.

In particular, the detector can be effectively used for small‐field dosimetry at 1.5 cm depth and for PDD measurements if the field dimension of 3.32 × 3.32 cm2 is not exceeded.
Thermodynamically Metal Atom Trapping in Van der Waals Layers Enabling Multifunctional 3D Carbon Network
Authors: Xu Ming , Li Tianwei , Fei Linfeng , Li Huangxu , Guo Xuyun , Hou Peiyu , Ying Yiran , Zhu Wenlei , Zhou Yang , Lin Yue , Zhang Zhian , Lai Yanqing , Zhu Ye , Zhang Haiyan , Huang Haitao
Published: August 2020

The construction of 3D graphitic structures can lead to many important scientific study and nanotechnology applications, but its widespread use can be limited by the narrow van der Waals gap (vdW; <0.35 nm). Here, this study reports the use of natural adsorbent organisms to engineer the expanded graphitic structure. It shows that, in chitosan, the abundant amino (NH2) and hydroxyl (OH) groups can act as metal ions “pitfalls” for the growth of catalytic transition‐metal crystals under thermally reductive conditions. In situ transmission electron microscopy study reveals the “liquidized” migration process of Ni carbide crystal that catalyzes the graphitization of 3D carbon network and enables the expansion of vdW gaps. A correlation between the thermodynamically trapped metal atoms and the expansion of vdW gaps is established by expanding the study to both Co and Cu. The findings provide insights into new strategy to be explored for engineering 3D carbon‐based materials and show significant potential in energy storage and catalysis technologies.
Recombinant Spider Silk Forms Tough and Elastic Nanomembranes that are Protein‐Permeable and Support Cell Attachment and Growth
Authors: Gustafsson Linnea , Tasiopoulos Christos Panagiotis , Jansson Ronnie , Kvick Mathias , Duursma Thijs , Gasser Thomas Christian , van der Wijngaart Wouter , Hedhammar My
Published: August 2020

Biologically compatible membranes are of high interest for several biological and medical applications. Tissue engineering, for example, would greatly benefit from ultrathin, yet easy‐to‐handle, biodegradable membranes that are permeable to proteins and support cell growth. In this work, nanomembranes are formed by self‐assembly of a recombinant spider silk protein into a nanofibrillar network at the interface of a standing aqueous solution. The membranes are cm‐sized, free‐standing, bioactive and as thin as 250 nm. Despite their nanoscale thickness, the membranes feature an ultimate engineering strain of over 220% and a toughness of 5.2 MPa. Moreover, they are permeable to human blood plasma proteins and promote cell adherence and proliferation. Human keratinocytes seeded on either side of the membrane form a confluent monolayer within three days. The significance of these results lays in the unique combination of nanoscale thickness, elasticity, toughness, biodegradability, protein permeability and support for cell growth, as this may enable new applications in tissue engineering including bi‐layered in vitro tissue models and support for clinical transplantation of coherent cell layers.
Integrated Biomonitoring Sensing with Wearable Asymmetric Supercapacitors Based on Ti3C2 MXene and 1T‐Phase WS2 Nanosheets
Authors: Vaghasiya Jayraj V. , Mayorga‐Martinez Carmen C. , Vyskočil Jan , Sofer Zdeněk , Pumera Martin
Published: August 2020

Research on wearable sensing technologies has been gaining considerable attention in the development of portable bio‐monitoring devices for personal health. However, traditional energy storage systems with defined size and shape have inherent limitations in satisfying the performance requirements for flexible electronics. To overcome this constraint, three different configurations of flexible asymmetric supercapacitor (FASC) are fabricated on polyester/cellulose blend (PCB) cloth substrate using Ti3C2 nanosheet (NS) and 1T WS2 NS as electrodes, and aqueous pluronic gel as an electrolyte. Benefiting from the 2D material electrodes, the interdigitated FASC configuration exhibits excellent performance, flexibility, cyclic stability, wearability and can be configured into multiple units and shapes, which far exceed that exhibited by the textile‐based FASC. Furthermore, the arbitrary (“AFN”) and sandwich (“FLOWER”) configurations Ti3C2 NS/1T WS2 NS FASC can be assembled directly on a PCB cloth substrate, thereby offering good structural integrity coupled with ease of assembly into integrated circuits of different shapes. More specifically, a lightweight, flexible, and wearable bio‐monitoring system is developed by integrating force sensing device with interdigitated FASC, which can be used to monitor the physical status of human body during various activities. A potential application of this system in healthcare is successfully demonstrated and discussed.
Visible‐Light‐Driven Photocatalytic Hydrogen Production on Cd0.5Zn0.5S Nanorods with an Apparent Quantum Efficiency Exceeding 80%
Authors: Khan Khakemin , Tao Xiaoping , Shi Ming , Zeng Bin , Feng Zhaochi , Li Can , Li Rengui
Published: August 2020

1D semiconductor nanomaterials have generated a high interest in heterogeneous photocatalysis. However, most 1D photocatalysts still suffer from poor charge separation and severe charge recombination. Herein, a unique approach via surface doping of phosphorus (P) atoms into 1D Cd0.5Zn0.5S (CZS) nanorods is demonstrated, leading to an imbalanced charge distribution and a localized built‐in electric field, verified by characterizations including photoluminescence and transient absorption spectra. The CZS‐P nanorods exhibit more than two orders of magnitude enhancement in photocatalytic H2 production activity relative to pristine CZS under visible light. Further construction of spatially separated dual‐cocatalysts (Pt and PdS) on the tip and lateral surface of the CZS‐P nanorods enables a significant improvement in the photocatalytic activity, which results in an apparent quantum efficiency exceeding 89% at 420 nm. Such efficient photocatalytic hydrogen production is attributed to the synergistic effect of tuning the intrinsic built‐in electric field for spatial charge separation and simultaneously accelerating the reduction and oxidation reaction rates utilizing photogenerated charges. The idea of integrating spatial charge separation via morphology tailoring, additional built‐in electric field, and spatial separation of dual‐cocatalysts provides a pathway for rationally designing artificial photocatalysts for solar energy conversion.
Remarkable Reduction of Interfacial Thermal Resistance in Nanophononic Heterostructures
Authors: Ren Kai , Liu Xiangjun , Chen Shuai , Cheng Yuan , Tang Wencheng , Zhang Gang
Published: August 2020

This work investigates interfacial thermal transport in phononic‐mismatched heterostructures that consists of pristine black phosphorene and its phononic crystal. It is found that the presence of the sub‐periodic structure results in reduced thermal conductivity in phononic crystals. As opposed to intuitive expectations, a slight temperature jump is observed at the interface of nanophononic heterostructures, which is only about 10% of that at conventional interfaces consisting of dissimilar materials. Consequently, contact thermal conductance in the nanophononic heterostructure is 10−30 times higher than that of mass‐mismatched interfaces in a comparative study. Moreover, in contrast to conventional heterostructures achieved by interfacing dissimilar materials, weak temperature dependence is observed in interfacial thermal conductance, and thermal rectification is sharply suppressed. These phenomena are well explained based on lattice dynamic insights. This work not only enhances the understanding of the fundamental physics of phonons transport across interface, but also facilitates the possible spectrum of application ranges from thermoelectrics, thermal management, to thermal cloak.
Harmonizing the Electronic Structures on BiOI with Active Oxygen Vacancies toward Facet‐Dependent Antibacterial Photodynamic Therapy
Authors: Sun Jingyu , Wen Jinghong , Wu Guizhu , Zhang Ze , Chen Xue , Wang Guichang , Liu Mingyang
Published: August 2020

Due to the unique surface atomic arrangement, exposed facets and defects of nanomaterials play critical roles in their physicochemical properties. Herein, BiOI nanosheets with the same type of defects on different exposed facets such as {001} (BI‐001) and {110} (BI‐110) are engineered to harmonize the electronic structures for antibacterial applications. Results demonstrate that BI‐110 exhibits higher activity in killing Escherichia coli under 808 nm light irradiation than that of BI‐001 due to its superior electronic structures. The density functional theory calculations show that BI‐110 with its excellent geometric effect exhibits stronger adsorption to O2, leading to the formation of highly concentrated single oxygen species, which causes excellent antibacterial performance. This work with the combination of facets engineering and vacancy engineering will inspire future studies on antibacterial photodynamic therapy.
2D TMD Channel Transistors with ZnO Nanowire Gate for Extended Nonvolatile Memory Applications
Authors: Kim Taewook , Kang Donghee , Lee Yangjin , Hong Sungjae , Shin Hyung Gon , Bae Heesun , Yi Yeonjin , Kim Kwanpyo , Im Seongil
Published: August 2020

2D transition metal dichalcogenides (TMDs) have been extensively studied due to their excellent physical properties. Mixed dimensional devices including 2D materials have also been studied, motivated by the possibility of any synergy effect from unique structures. However, only few such studies have been conducted. Here, semiconducting 1D ZnO nanowires are used as thin gate material to support 2D TMD field effect transistors (FETs) and 2D stack‐based interface trap nonvolatile memory. For the trap memory, deep level electron traps formed at the first MoS2/second MoS2 stack interface are exploited, since the first MoS2 is treated in an atomic layer deposition chamber for a short while. On the one hand, a complementary inverter type memory device can also be achieved using a long single ZnO wire as a common gate to simultaneously support both n‐ and p‐channel TMD FETs. In addition, it is found that the semiconducting ZnO nanowire itself operates as an n‐type channel when the TMD materials can become a top‐gate to charge the ZnO channel. It means that 2D (bottom gated) and 1D channel (top gated) FETs are respectively operational in a single device structure. The 1D–2D mixed devices seem deserving broad attention in both aspects of novelty and functionality.
All‐Inorganic CsPbIxBr3−x Perovskite Solar Cells: Crystal Anisotropy Effect
Authors: Zhao Peng , Su Jie , Lin Zhenhua , Wang Jiaping , Zhang Jincheng , Hao Yue , Ouyang Xiaoping , Chang Jingjing
Published: August 2020

Understanding the crystal anisotropy effect of materials on optical and electrical properties is crucial for further comprehension of the device operating mechanism and device performance improvement. In this study, a detailed theoretical analysis is performed to explore the crystal anisotropy effect on the performance of perovskite solar cells by employing state‐of‐the‐art multiscale simulations connecting from the material (first‐principle theory) to the device (drift‐diffusion model). According to the results obtained from first‐principle calculation, the mobility and absorption coefficient of CsPbIBr2 and CsPbI2Br along the [001] orientation are larger than those along the [100] orientation, suggesting that the transport properties and optical properties along the [001] orientation are superior to those along the [100] orientation. According to the results obtained from the drift‐diffusion model, owing to the superior optical and transport characters along the [001] direction, the optimal power conversion efficiencies (PCEs) of CsPbI2Br (18.88%) and CsPbIBr2 (16.42%) solar cells can be obtained. In addition, the two‐terminal CsPbIxBr3‐x/silicon tandem solar cell is also investigated. By utilizing CsPbIBr2/silicon and CsPbI2Br/silicon tandem structures along the [001] orientation, ultrahigh efficiencies are achieved up to 26.32% and 31.39%, respectively. Therefore, the [001] crystal orientation of CsPbIBr2 and CsPbI2Br is more suitable for further applications of optoelectronic devices.
Profit‐maximizing potassium fertilizer recommendations for soybean
Authors: Popp Michael P. , Slaton Nathan A. , Roberts Trenton L.
Published: August 2020

Potassium (K) fertilizer has important yield and cost ramifications in soybean [Glycine max (L.) Merr.] production. Rate recommendations are often based on expected yield response as predicted by a soil test. To that end, soybean response to K application rate studies were analyzed using 86 site‐years from 2004 to 2019. We estimated a generic yield response curve across soybean cultivar and soil texture to allow calculation of profit‐maximizing K rates for producers in the mid‐southern United States that also consider crop value and fertilizer cost. Further, we compared profit‐maximizing fertilizer‐K rates with those currently recommended. Using a spreadsheet‐based decision aid, soybean prices and yields, fertilizer‐K cost, and a range of initial soil‐test K (STK) values, as observed over the last 10 yr, we find that current uniform fertilizer‐K rate recommendations were greater than the predicted profit‐maximizing rates. Profit‐maximizing rates added profit ranging from US$2.32 ha−1 at initial Mehlich‐3 K availability values of 110 mg K kg−1 to US$29.35 ha−1 at 60 mg K kg−1 on average. The corresponding fertilizer‐K rate reductions were 11 and 48 kg K ha−1, respectively, resulting in attendant yield penalties of only 28 and 52 kg ha−1. Furthermore, K fertilization was not economically justifiable beyond STK of 128 mg K kg−1 on average. Hence, performing soil tests and calculating profit‐maximizing fertilizer‐K rates showed promising returns to producers at lesser fertilizer‐K use by sacrificing a minimal amount of yield. Also, variable‐rate applied K fertilizer in comparison to uniform rate application was rarely cost effective within the tested assumptions.
Chromoanasynthesis as a cause of Jacobsen syndrome
Authors: Anzick Sarah , Thurm Audrey , Burkett Sandra , Velez Daniel , Cho Elena , Chlebowski Colby , Virtaneva Kimmo , Bruno Daniel , Martin Clare B. , Lang David M. , Brooks Brian , Martens Craig , McDermott David H. , Murphy Philip M.
Published: August 2020

Jacobsen syndrome (MIM #147791) is a rare multisystem genomic disorder involving craniofacial abnormalities, intellectual disability, other neurodevelopmental defects, and terminal truncation of chromosome 11q, typically deleting ~170 to >340 genes. We describe the first case of Jacobsen syndrome caused by congenital chromoanasynthesis, an extreme form of complex chromosomal rearrangement. Six duplications and five deletions occurred on one copy of chromosome 11q with microhomology signatures in the breakpoint junctions, indicating an all‐at‐once replication‐based rearrangement mechanism in a gametocyte or early post‐zygotic cell. Eighteen genes were deleted from the Jacobsen region, including KIRREL3, which is associated with intellectual disability.
Small vessel disease more than Alzheimer's disease determines diffusion MRI alterations in memory clinic patients
Authors: Finsterwalder Sofia , Vlegels Naomi , Gesierich Benno , Araque Caballero Miguel Á. , Weaver Nick A. , Franzmeier Nicolai , Georgakis Marios K. , Konieczny Marek J. , Koek Huiberdina L. ,   Dominantly Inherited Alzheimer Network (DIAN), Karch Celeste M. , Graff‐Radford Neill R. , Salloway Stephen , Oh Hwamee , Allegri Ricardo F. , Chhatwal Jasmeer P. ,   DELCODE study group, Jessen Frank , Düzel Emrah , Dobisch Laura , Metzger Coraline , Peters Oliver , Incesoy Enise I. , Priller Josef , Spruth Eike J. , Schneider Anja , Fließbach Klaus , Buerger Katharina , Janowitz Daniel , Teipel Stefan J. , Kilimann Ingo , Laske Christoph , Buchmann Martina , Heneka Michael T. , Brosseron Frederic , Spottke Annika , Roy Nina , Ertl‐Wagner Birgit , Scheffler Klaus ,   Alzheimer's Disease Neuroimaging Initiative (ADNI),   Utrecht VCI study group, Seo Sang Won , Kim Yeshin , Na Duk L. , Kim Hee Jin , Jang Hyemin , Ewers Michael , Levin Johannes , Schmidt Reinhold , Pasternak Ofer , Dichgans Martin , Biessels Geert Jan , Duering Marco
Published: August 2020

Introduction

Microstructural alterations as assessed by diffusion tensor imaging (DTI) are key findings in both Alzheimer's disease (AD) and small vessel disease (SVD). We determined the contribution of each of these conditions to diffusion alterations.

Methods

We studied six samples (N = 365 participants) covering the spectrum of AD and SVD, including genetically defined samples. We calculated diffusion measures from DTI and free water imaging. Simple linear, multivariable random forest, and voxel‐based regressions were used to evaluate associations between AD biomarkers (amyloid beta, tau), SVD imaging markers, and diffusion measures.

Results

SVD markers were strongly associated with diffusion measures and showed a higher contribution than AD biomarkers in multivariable analysis across all memory clinic samples. Voxel‐wise analyses between tau and diffusion measures were not significant.

Discussion

In memory clinic patients, the effect of SVD on diffusion alterations largely exceeds the effect of AD, supporting the value of diffusion measures as markers of SVD.
Polyethylenimine‐modified sugarcane bagasse cellulose as an effective adsorbent for removing Cu(II) from aqueous solution
Authors: Jiang Wenyan , Xing Yihao , Zhang Linye , Guo Xiaoming , Lu Yiwen , Yang Mei , Wang Jing , Wei Guangtao
Published: August 2020

Polyethylenimine‐modified sugarcane bagasse cellulose (SBCMP), as a new adsorbent, was synthesized by the reaction of polyethylenimine (PEI) with sugarcane bagasse cellulose and glutaraldehyde. The adsorption of Cu(II) by SBCMP was pH‐dependent, and the higher removal efficiency of Cu(II) appeared in the range of pH 3.0–6.0. The adsorption isothermal data fitted well with the Langmuir model, and the maximum adsorption capacity of SBCMP was up to 107.5 mg/g. The adsorption kinetics was best described by the pseudo‐second‐order kinetic. The adsorption of Cu(II) by SBCMP was unfavorable at high temperatures, and thermodynamic analyses implied that the adsorption of Cu(II) by SBCMP was an exothermic reaction. Fourier transform infrared spectroscopy (FT‐IR) combined with X‐ray photoelectron spectroscopy (XPS) revealed that Cu(II) adsorption on SBCMP mainly controlled by the nitrogen atoms of NH group in PEI. The results of regeneration cycles showed that SBCMP was suitable for reuse in the adsorption of Cu(II) from aqueous solution. These experimental results suggested that SBCMP is expected to be a new biomass adsorbent with high efficiency in removing Cu(II) from wastewater.
Preparation and properties of poly(lactic acid)/lignin‐modified polyvinyl acetate composites
Authors: Shu You , Luo Qionglin , Wang Mingliang , Ouyang Yuejun , Lin Hongwei , Sheng Liping , Su Shengpei
Published: August 2020

Poly(lactic acid)(PLA) has good application in the field of packaging because of its good biodegradability, tensile strength, and film‐forming properties. However, the disadvantages of high brittleness and high cost limit the wider application of PLA. PLA/lignin‐modified polyvinyl acetate (L‐PVAc) composites with excellent toughness were prepared by melt blending PLA with modifier L‐PVAc. The mechanical properties, thermal properties and morphology of the composites were characterized to evaluate the effect of L‐PVAc content on the properties of the composites. The results showed that the introduction of L‐PVAc could increase the impact strength, elongation at break, glass transition temperature, melting temperature and the degree of crystallinity of PLA/L‐PVAc composites. When the L‐PVAc content reached up to 20.0 wt%, the impact strength, elongation at break, glass transition temperature, melting temperature and the degree of crystallinity of the composites were increased by 298.2%, 167.5%, 3.8%, 1.8%, and 78.8%, respectively compared to pure PLA due to the good toughness of PVAc and heterogeneous nucleation of lignin. This research can promote the high‐value utilization of lignin and the application of PLA in the fields of clothing, agriculture, medical and hygiene.
Finite‐time stabilization of maglev system with an output constraint
Authors: Liu Jia‐Nan , Sun Zong‐Yao , Cai Bin , Meng Qinghua
Published: August 2020

This paper considers the problem of finite‐time stabilization for the maglev system with an output constraint whose range depends on the experimental platform. A tan‐type barrier Lyapunov function is introduced to guarantee that the output of the maglev system is restricted in the prescribed region and the state converges to zero in a finite time. The novelty lies in the fact that the design and the analysis for constrained and unconstrained output are unified without changing the structure of the controller. Finally, simulations are given to validate the effectiveness of the theoretical result.
Survival and recurrence after intraperitoneal chemotherapy use: Retrospective review of ovarian cancer hospital registry data
Authors: Adambekov Shalkar , Lopa Samia , Edwards Robert P. , Lemon Lara , Wang Shu , Taylor Sarah E. , Orr Brian , Linkov Faina
Published: August 2020

Background

Intraperitoneal/intravenous chemotherapy (IP/IV) was associated with improved survival for ovarian cancer (OC) patients in several randomized clinical trials. However, the uptake of IP/IV in clinical practice is varied due to conflicting evidence about its impact on survival and recurrence. The aim of this study was to explore the uptake of IP/IV treatment and to evaluate its impact on survival and recurrence in OC patients.

Methods

Demographic and clinical information on OC patients (N = 2916) who underwent treatment for OC between 2000 and 2017 was obtained from the large healthcare system cancer registry. Duplicate records, grade 1, rare (eg, gelatinous carcinoma), and non‐epithelial (eg, granulosa cell carcinoma) tumors were excluded. Kaplan‐Meier survival curves were constructed to compare 5‐ and 10‐year survival based on the chemotherapy type, surgery type, and stage. Multivariable Gray's piecewise constant time‐varying coefficient models were fitted to evaluate the effect of IP/IV on adjusted hazard ratio (AHR) of OC survival and recurrence adjusting for potential confounders.

Results

The final sample consisted of 1846 OC patients, 14% (250/1846) of which received IP/IV chemotherapy. IP/IV was significantly associated with improved 10‐year survival (P < .001). Multivariable Gray's model demonstrated that IP/IV therapy significantly reduced the AHR of death (AHR = 0.39‐1.07, P < .001) with the beneficial effect gradually declining over time. Use of IP/IV chemotherapy had no impact on OC recurrence.

Conclusions

These findings demonstrated that only a small fraction of eligible patients underwent IP/IV chemotherapy. We report a significant 10‐year survival, but not necessarily recurrence benefit is associated with IP/IV chemotherapy compared to IV only, suggesting the need for novel ways of identifying patients who may benefit from IP/IV chemotherapy.
Phase II trial of sorafenib and doxorubicin in patients with advanced hepatocellular carcinoma after disease progression on sorafenib
Authors: El Dika Imane , Capanu Marinela , Chou Joanne F. , Harding James J. , Ly Michele , Hrabovsky Anna D. , Do Richard K.G. , Shia Jinru , Millang Brittanie , Ma Jennifer , O’Reilly Eileen M. , Abou‐Alfa Ghassan K.
Published: August 2020

Background

Patients with advanced hepatocellular carcinoma (HCC) who received second line sorafenib plus doxorubicin following disease progression on sorafenib were shown retrospectively to have improved progression free survival (PFS) and overall survival (OS). Sorafenib plus doxorubicin combination may synergistically promote ASK‐1 mediated apoptosis in cancer cells through RAF‐1 inhibition. Thus, we conducted this phase II study of sorafenib and doxorubicin combination following progression on sorafenib.

Methods

Patients with histologically confirmed advanced HCC, confirmed radiologic progression on sorafenib, Karnofsky performance status (KPS) ≥70%, and Child‐Pugh A liver cirrhosis were eligible. Patients received sorafenib 400 mg twice daily and doxorubicin 60 mg/m2 once every 3‐weeks. The primary endpoint was OS at 6 months (OS6). Secondary endpoints included safety, PFS, OS, response rate (RR) by RECIST 1.1. Additional endpoints included baseline and on‐treatment tumor ASK‐1 and pERK expression levels by immunohistochemistry (IHC) and the correlation with PFS, RR, and OS.

Results

Thirty patients were enrolled in the study, 86% were male, median age was 64 years. OS6 was 76.6% (95%CI: 57.2%‐88.1%). Median OS was 8.6 (95%CI: 7.3‐12) months, and median PFS reached 3.9 (95%CI: 2.4‐4.6) months. Three (11%) partial responses were observed and 17 patients (61%) had stable disease. Pertinent grade 3‐4 adverse events that occurred in more than 10% of patients included neutropenia (16%), febrile neutropenia (10%), anemia (10%), thrombocytopenia (10%), elevated AST (23%) and ALT (10%), hypophosphatemia (10%), and fatigue (10%). No association with the difference in baseline and post‐treatment ASK‐1 and pERK level of expression by IHC and survival outcomes was detected.

Conclusion

Sorafenib plus doxorubicin following progression on sorafenib did not show any improved outcome. We do not recommend further development or use of this combination in HCC.
Cholesterol‐conjugated bovine serum albumin nanoparticles as a tamoxifen tumor‐targeted delivery system
Authors: Gharbavi Mahmoud , Johari Behrooz , Eslami Seyed Sadegh , Mousazadeh Navid , Sharafi Ali
Published: August 2020

In the present study, we introduced cholesterol (CLO)‐conjugated bovine serum albumin nanoparticles (BSA NPs) as a new system for indirect targeting drug delivery. Tamoxifen, as an anticancer drug, was loaded on BSA NPs (BSA‐TAX NPs); CLO was then conjugated to the BSA‐TAX NPs surface for the targeted delivery of NPs system, by 1‐ethyl‐3‐(3‐dimethylaminopropyl) carbodiimide/N‐hydroxy succinimide carbodiimide chemistry (CLO‐BSA‐TAX NPs). The physicochemical properties, toxicity, in vitro, and in vivo biocompatibility of the BSA NPs system were characterized on cancer cell lines (4T1). The results revealed that the BSA NPs system has a regular spherical shape and negative zeta‐potential values. The drug release of BSA NPs system has shown controlled and pH‐dependent drug release behavior. BSA NPs system was biocompatible but it was potentially toxic on the cancer cell line. The CLO‐BSA‐TAX NPs exhibited higher toxicity against cancer cell lines than other NPs formulation (BSA NPs and BSA‐TAX NPs). It can be concluded that the CLO, as an indirect targeting agent, enhances the toxicity and specificity of NPs system on cancer cell lines. It could potentially be suitable approaches to targeting the tumors in clinical cancer therapy.
Combining PARP Inhibition with Platinum, Ruthenium or Gold Complexes for Cancer Therapy
Authors: Yusoh Nur Aininie , Ahmad Haslina , Gill Martin R.
Published: August 2020

Platinum drugs are heavily used first‐line chemotherapeutic agents for many solid tumours and have stimulated substantial interest in the biological activity of DNA‐binding metal complexes. These complexes generate DNA lesions which trigger the activation of DNA damage response (DDR) pathways that are essential to maintain genomic integrity. Cancer cells exploit this intrinsic DNA repair network to counteract many types of chemotherapies. Now, advances in the molecular biology of cancer has paved the way for the combination of DDR inhibitors such as poly (ADP‐ribose) polymerase (PARP) inhibitors (PARPi) and agents that induce high levels of DNA replication stress or single‐strand break damage for synergistic cancer cell killing. In this review, we summarise early‐stage, preclinical and clinical findings exploring platinum and emerging ruthenium anti‐cancer complexes alongside PARPi in combination therapy for cancer and also describe emerging work on the ability of ruthenium and gold complexes to directly inhibit PARP activity.
Activity of Riminophenazines against Mycobacterium tuberculosis: A Review of Studies that Might be Contenders for Use as Antituberculosis Agents
Authors: Bvumbi Mpelegeng Victoria
Published: August 2020

Tuberculosis is one of the leading cause of death in the world, mainly due to the increasing number of multidrug‐resistant TB (MDR‐TB) and extensively drug‐resistant TB (XDR‐TB) strains. Factors such as the HIV pandemic contribute further. Also, the ineffectiveness of the chemotherapy in current use increases the mortality rate. Therefore, new and repurposed antituberculosis drugs are urgently needed for the treatment of MDR‐TB, and riminophenazines are among those drugs that are being reinvestigated for their potential in the treatment of TB. This review delivers a brief historical account of riminophenazines, their general synthesis, mechanisms of action, and their physicochemical properties. The discussion is limited to those studies that investigated the activity of these compounds as antituberculosis agents. Given their unique properties, this review will be of great significance in giving direction towards the design and development of new riminophenazine analogues.
Randomized trial of cognitive behaviour group therapy and a mindfulness‐based intervention for social anxiety disorder: Preliminary findings
Authors: Koszycki Diana , Guérin Eva , DiMillo Julia , Bradwejn Jacques
Published: August 2020

Recent studies have evaluated the possible efficacy of mindfulness‐based interventions (MBIs) for social anxiety disorder (SAD). However, few trials have compared MBIs with a first‐line treatment. This study evaluated the relative efficacy of an MBI adapted for SAD (MBI‐SAD) to cognitive behaviour group therapy (CBGT) for SAD. Participants were randomized to 12 weekly group sessions of the MBI‐SAD (n = 52) or CBGT (n = 45). Results revealed that CBGT fared better than the MBI‐SAD in reducing clinician‐ and self‐rated social anxiety severity. The difference between the MBI‐SAD and CBGT exceeded the prespecified noninferiority margin for our primary outcome the Liebowitz Social Anxiety Scale, but findings are inconclusive as the width of the confidence interval extended in both directions surrounding the noninferiority margin. The MBI‐SAD compared favourably with CBGT in improving other indices of well‐being (depression, self‐esteem, satisfaction with life, social adjustment). Contrary to expectation, the MBI‐SAD did not produce greater changes in mindfulness and self‐compassion than CBGT. Overall, results confirm that CBGT is robust treatment for SAD and should be considered as first‐line treatment.
Cytologic features of blastic plasmacytoid dendritic cell neoplasm involving liver: A case report and literature review
Authors: Ding Yanna , Yang Jack , Lindsey Kathryn
Published: August 2020

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare but clinically aggressive hematologic malignancy, believed to originate from plasmacytoid dendritic cells (PDCs) although it possesses multilineage potentials. Due to the dismal prognosis, accurate and rapid diagnosis is critical for early management. The disease usually initially involves skin and bone marrow. Here we report the cytopathologic findings in a case of BPDCN involving the liver in a patient previously diagnosed with BPDCN from skin and lymph node biopsies. The fine‐needle aspiration specimen from the liver lesion demonstrates a hypercellular smear of atypical epithelioid cells dispersed singly or in loose groups. These cells have enlarged, eccentric, round to irregular nuclei with fine chromatin. The agranular gray‐blue cytoplasm shows delicate wispy cytoplasmic extensions and cytoplasmic microvacuoles. Binucleation is common. The concurrent core biopsy shows that the neoplastic plasmacytoid cells with eccentric nuclei were positive for CD4, CD7, CD43, CD56, and CD68, confirming the diagnosis of BPDCN. Mutations of ASXL1 and TET2, classic for BPDCN, and a complex karyotype were detected in skin, bone marrow, and lymph node specimens. We catalog the heterogeneous pathologic features of this rare disease, emphasizing the clinical and histopathological correlation. The differential diagnoses and review of literature are also included. Awareness of this disease and accurate diagnosis are emphasized to aid early management and potentially produce a better clinical outcome.
Metabolic studies of selective androgen receptor modulators RAD140 and S‐23 in horses
Authors: So Yat‐Ming , Wong Jenny K. Y. , Choi Timmy L. S. , Prabhu Anil , Stewart Brian , Farrington Adrian F. , Robinson Paul , Wan Terence S. M. , Ho Emmie N. M.
Published: August 2020

This paper describes the studies of the in vitro biotransformation of two selective androgen receptor modulators (SARMs), namely, RAD140 and S‐23, and the in vivo metabolism of RAD140 in horses using ultra‐high performance liquid chromatography–high resolution mass spectrometry. in vitro metabolic studies of RAD140 and S‐23 were performed using homogenised horse liver. The more prominent in vitro biotransformation pathways for RAD140 included hydrolysis, hydroxylation, glucuronidation and sulfation. Metabolic pathways for S‐23 were similar to those for other arylpropionamide‐based SARMs. The administration study of RAD140 was carried out using three retired thoroughbred geldings. RAD140 and the majority of the identified in vitro metabolites were detected in post‐administration urine samples. For controlling the misuse of RAD140 in horses, RAD140 and its metabolite in sulfate form gave the longest detection time in hydrolysed urine and could be detected for up to 6 days post‐administration. In plasma, RAD140 itself gave the longest detection time of up to 13 days. Apart from RAD140 glucuronide, the metabolites of RAD140 described herein have never been reported before.
Application of online two‐dimensional high‐performance liquid chromatography as purification procedure to determine the origin of 19‐norandrosterone in urine by gas chromatography–combustion–isotope ratio mass spectrometry
Authors: Wen Chao , Zhu Tianshuo , Wang Jingzhu , Liu Xin , Wang Shan , Zhang Yinong
Published: August 2020

19‐Norandrosterone (19‐NA) is the main metabolite of nandrolone and/or its precursors, which can be found naturally in human urine in trace amount. Gas chromatography–combustion–isotope ratio mass spectrometry (GC–C–IRMS) confirmation procedure can be used to identify a potential exogenous origin of 19‐NA in urine sample. Sample purification for GC–C–IRMS analysis is crucial to the whole confirmation procedure because the concentration of 19‐NA in the urine to be tested is very low. Online two‐dimensional high‐performance liquid chromatography (2D–HPLC) clean‐up procedure with high separation capacity is used to isolate and enrich 19‐NA as a sample pretreatment process. Linearity, lowest detectable concentration, uncertainty, and selectivity of the method are validated according to the World Anti‐doping Agency's (WADA) requirement. Isotope fractionation effect was not observed during the 2D‐HPLC purification process. The validated method provides a high efficient and convenient confirmation procedure to determine the origin of 19‐NA.
Growing‐season warming and winter soil freeze/thaw cycles increase transpiration in a northern hardwood forest
Authors: Harrison Jamie L. , Sanders‐DeMott Rebecca , Reinmann Andrew B. , Sorensen Patrick O. , Phillips Nathan G. , Templer Pamela H.
Published: August 2020

Climate models project higher growing‐season temperatures and a decline in the depth and duration of winter snowpack throughout many north temperate ecosystems over the next century. A smaller snowpack is projected to induce more frequent soil freeze/thaw cycles in winter in northern hardwood forests of the northeastern United States. We measured the combined effects of warmer growing‐season soil temperatures and increased winter freeze/thaw cycles on rates of leaf‐level photosynthesis and transpiration (sap flow) of red maple (Acer rubrum) trees in a northern hardwood forest at the Climate Change Across Seasons Experiment at Hubbard Brook Experimental Forest in New Hampshire. Soil temperatures were warmed 5°C above ambient temperatures during the growing season and soil freeze/thaw cycles were induced in winter to mimic the projected changes in soil temperature over the next century. Relative to reference plots, growing‐season soil warming increased rates of leaf‐level photosynthesis by up to 85.32 ± 4.33%, but these gains were completely offset by soil freeze/thaw cycles in winter, suggesting that increased freeze/thaw cycles in winter over the next 100 yr will reduce the effect of warming on leaf‐level carbon gains. Soil warming in the growing season increased rates of transpiration per kilopascal of vapor pressure deficit (VPD) by up to 727.39 ± 0.28%, even when trees were exposed to increased frequency of soil freeze/thaw cycles in the previous winter, which could influence regional hydrology in the future. Using climate projections downscaled from the Coupled Model Intercomparison Project, we project increased rates of whole‐season transpiration in these forests over the next century by 42–61%. We also project 52–77 additional days when daily air temperatures will be above the long‐term average daily maximum during the growing season at Hubbard Brook. Together, these results show that projected changes in climate across both the growing season and winter are likely to cause greater rates of water uptake and have no effect on rates of leaf‐level carbon uptake by trees, with potential ecosystem consequences for hydrology and carbon cycling in northern hardwood forests.
UV‐aided graphene oxide reduction by TiO2 towards TiO2/reduced graphene oxide composites for dye‐sensitized solar cells
Authors: Madurai Ramakrishnan Venkatraman , N. Muthukumarasamy , Pitchaiya Selvakumar , S. Agilan , Pugazhendhi Arivalagan , Velauthapillai Dhayalan
Published: August 2020

Electron transport layer is one of the important layer in the dye‐sensitized solar cells (DSSCs) which is responsible for the transport of photo‐generated electrons by the dye to the outer circuit. TiO2 has been widely used as electron transport material in DSSCs. However, improving the electrical conductivity of TiO2 without sacrificing the surface area is one of the important strategies to improve the efficiency of the DSSCs. Here graphene oxide (GO) is added as an additive into the TiO2 network towards the preparation of TiO2/reduced graphene oxide (RGO) composites by UV assisted photocatalytic reduction method. The RGO/TiO2 composites with different compositions of RGO were characterized and the performance of DSSCs using the prepared material as photoanode was studied. Furthermore, through the D and G band Raman peaks, the reduction of GO to RGO was confirmed. The optical properties of the prepared material were analyzed using UV‐visible spectroscopy and photoluminescence analysis, respectively. The carrier lifetime of the TiO2 and TiO2/RGO composites was studied using time resolved photoluminescence studies. The high‐resolution transmission electron microscope images of prepared TiO2/RGO composites were found to have sheet‐like structure surrounding the near spherical nanoparticles, which could be attributed to that of RGO and TiO2, respectively. The binding energy states of the prepared material were studied using X‐ray photoelectron spectroscopy (XPS) spectra. The incorporation of RGO in TiO2 was found to improve the Brunauer–Emmett–Teller (BET) surface area of TiO2 and distribution of pores in TiO2 and TiO2/RGO composites was found to be uniform. The DSSCs were fabricated using the prepared TiO2 and TiO2/RGO composites as photoanodes and their power conversion efficiencies were analyzed.
Novel mass‐aggregation‐based calibration of an acoustic method of monitoring bedload flux by infrequent desert flash floods
Authors: Halfi Eran , Paz Dror , Stark Kyle , Yogev Uri , Reid Ian , Dorman Michael , Laronne Jonathan B.
Published: August 2020

The monitoring of bedload flux under flash flood conditions has been successfully achieved since 1992 using slot samplers in the semiarid Nahal Eshtemoa. In the present study, a surrogate bedload monitoring technique ‐ the Japanese plate microphone ‐ has been deployed and calibrated against data from the slot samplers. Since a slot sampler has a sensitivity threshold that becomes especially important when transport rates are low, different averaging periods should be considered for high and low fluxes. In order to overcome the deficiencies of time‐based aggregation used hitherto, we have developed a new method involving mass aggregation and commensurably variable intervals, thereby enabling a more accurate analysis and optimizing the bedload sampler's capabilities. The data derived with this new method has then been utilized to calibrate the Japanese plate microphone. The Eshtemoa is an ephemeral gravel bed channel with a high proportion of fine gravel (< 0.02 m); for these conditions, acoustic sensors have not been calibrated as yet. Two multiple linear regression models incorporating the effect of median bedload grain size on pulse rate have been established to predict bedload flux and cumulative transported bedload mass. The coefficients in these models are statistically significant. Good predictions are obtained for bedload flux (adj. r2 = 0.83) and for cumulative bedload mass (adj. r2 = 0.98) during flood recession. Overall, the multiple linear regression models, used in conjunction with the mass aggregation method of estimating bedload flux, suggest that field calibration of acoustic devices is feasible under these conditions for ca. 90% of the duration of bedload transport. © 2020 John Wiley & Sons, Ltd.