bluuebunny/crossref_metadata_2025 huggingface dataset:
Synergistic Effect of Aligned Graphene Nanosheets in Graphene Foam for High‐Performance Thermally Conductive Composites
Authors: Wu Zhaohong , Xu Chuan , Ma Chaoqun , Liu Zhibo , Cheng Hui‐Ming , Ren Wencai
Published: March 2019

Graphene shows a great potential for high‐performance thermally conductive composite applications because of its extremely high thermal conductivity. However, the graphene‐based polymer composites reported so far only have a limited thermal conductivity, with the highest thermal conductivity enhancement (TCE) per 1 vol% graphene less than 900%. Here, a continuous network of graphene foam (GF), filled with aligned graphene nanosheets (GNs), is shown to be an ideal filler structure for thermally conductive composite materials. Compared to previous reports, a clear thermal percolation is observed at a low graphene loading fraction. The GNs/GF/natural rubber composite shows the highest TCE of 8100% (6.2 vol% graphene loading) ever reported at room temperature, which gives a record‐high TCE per 1 vol% graphene of 1300%. Further analyses reveal a significant synergistic effect between the aligned GNs and 3D interconnected GF, which plays a key role in the formation of a thermal percolation network to remarkably improve the thermal conductivity of the composites. Additionally, the use of this composite for efficient heat dissipation of light‐emitting diode (LED) lamps is demonstrated. These findings provide valuable guidance to design high‐performance graphene‐based thermally conductive materials, and open up the possibility for the use of graphene in high‐power electronic devices.
Key Parameters Requirements for Non‐Fullerene‐Based Organic Solar Cells with Power Conversion Efficiency >20%
Authors: Firdaus Yuliar , Le Corre Vincent M. , Khan Jafar I. , Kan Zhipeng , Laquai Frédéric , Beaujuge Pierre M. , Anthopoulos Thomas D.
Published: March 2019

The reported power conversion efficiencies (PCEs) of nonfullerene acceptor (NFA) based organic photovoltaics (OPVs) now exceed 14% and 17% for single‐junction and two‐terminal tandem cells, respectively. However, increasing the PCE further requires an improved understanding of the factors limiting the device efficiency. Here, the efficiency limits of single‐junction and two‐terminal tandem NFA‐based OPV cells are examined with the aid of a numerical device simulator that takes into account the optical properties of the active material(s), charge recombination effects, and the hole and electron mobilities in the active layer of the device. The simulations reveal that single‐junction NFA OPVs can potentially reach PCE values in excess of 18% with mobility values readily achievable in existing material systems. Furthermore, it is found that balanced electron and hole mobilities of >10−3 cm2 V−1 s−1 in combination with low nongeminate recombination rate constants of 10−12 cm3 s−1 could lead to PCE values in excess of 20% and 25% for single‐junction and two‐terminal tandem OPV cells, respectively. This analysis provides the first tangible description of the practical performance targets and useful design rules for single‐junction and tandem OPVs based on NFA materials, emphasizing the need for developing new material systems that combine these desired characteristics.
AJICAP: Affinity Peptide Mediated Regiodivergent Functionalization of Native Antibodies
Authors: Yamada Kei , Shikida Natsuki , Shimbo Kazutaka , Ito Yuji , Khedri Zahra , Matsuda Yutaka , Mendelsohn Brian A.
Published: March 2019

The need for atom‐precise biomolecule modification, and particularly the irreversible formation of covalent bonds to specific amino acids in proteins, has become an essential issue in the fields of pharmaceuticals and chemical biology. For example, antibody–drug conjugates (ADCs) are increasingly common entries into the clinical oncology pipeline. Herein, we report a new method of affinity peptide mediated regiodivergent functionalization (AJICAP™) that enables the synthesis of ADCs from native IgG antibodies. We succeeded in introducing thiol functional groups onto three lysine residues in IgGs using Fc affinity peptide reagents without antibody engineering. A cytotoxic molecule was then connected to the newly introduced thiol group, and both a surface plasmon resonance binding assay and in vivo xenograft mouse model results showed that the resulting ADC could selectively target and kill HER2‐positive cells. Our strategy provides a new approach for constructing complex antibody‐derived biomolecules.
Tetrodotoxin: Geschichte, Biologie und Synthese
Authors: Makarova Mariia , Rycek Lukas , Hajicek Josef , Baidilov Daler , Hudlicky Tomas
Published: March 2019

Dieser Aufsatz bietet eine umfassende Übersicht über die Geschichte, Biologie und Chemie von Tetrodotoxin (TTX). Er verfolgt den Ursprung dieses bemerkenswerten Moleküls zurück bis zu altertümlichen Aufzeichnungen der chinesischen Medizin. Nach einem kurzen Überblick über die Entdeckung der biologischen Aktivität, die Isolierung und Strukturaufklärung wird die Biologie von TTX diskutiert, hauptsächlich im Zusammenhang mit seiner Wirksamkeit in Natriumkanälen, seiner anästhetischen Wirkung und dem Anwendungspotential in der Krebsbehandlung oder bei Medikamentenabhängigkeit. Der Diskussion der Biosynthese von TTX folgen Ausführungen zur Totalsynthese. Sämtliche Total‐, Formal‐ und Partialsynthesen werden aufgeführt, wobei wir aber diejenigen Totalsynthesen, die bereits in früheren Aufsätzen vorgestellt wurden, nur kurz zusammenfassen. Schließlich werden die Synthesen von natürlichen und nichtnatürlichen Derivaten betrachtet, und es wird eine Zusammenfassung mit Ausblick für dieses sehr umfangreiche Fachgebiet geboten. Nach bestem Wissen haben wir die Literatur bis Dezember 2018 vollständig abgedeckt.
Unveiling the Intrinsic Catalytic Activities of Single‐Gold‐Nanoparticle‐Based Enzyme Mimetics
Authors: Hafez Mahmoud Elsayed , Ma Hui , Ma Wei , Long Yi‐Tao
Published: March 2019

Gold nanoparticles (AuNPs) have been demonstrated to serve as effective nanomaterial‐based enzyme mimetics (nanozymes) for a number of enzymatic reactions under mild conditions. The intrinsic glucose oxidase and peroxidase activities of single AuNPs and Ag–Au nanohybrids, respectively, were investigated by single NP collision electrochemical measurements. A significantly high turnover number of nanozymes was obtained from individual catalytic events compared with the results from the classical, ensemble‐averaged measurements. The unusual enhancement of catalytic activity of single nanozymes is believed to originate from the high accessible surface area of monodispersed NPs and the high activities of carbon‐supported NPs during single‐particle collision at a carbon ultramicroelectrode. This work introduces a new method for the precise characterization of the intrinsic catalytic activities of nanozymes, giving further insights to the design of high‐efficiency nanomaterial catalysts.
Tetrodotoxin: History, Biology, and Synthesis
Authors: Makarova Mariia , Rycek Lukas , Hajicek Josef , Baidilov Daler , Hudlicky Tomas
Published: March 2019

This review provides a comprehensive coverage of the history, biology and chemistry of tetrodotoxin (TTX). It traces the origin of this remarkable molecule all the way back to the ancient Chinese medicine records. The discovery of biological activity, isolation, and a brief overview of structure elucidation are summarized. Next, the biology of TTX is discussed, primarily in the context of its activity in the sodium channels, its anesthetic properties, and its potential use in cancer treatment or drug addiction. Biosynthesis of TTX is covered before the discussion of the total syntheses. All total, formal or partial syntheses are covered but those total syntheses that have been discussed in previous reviews are only briefly summarized. Finally, the synthesis of natural and unnatural derivatives is surveyed, and a conclusion and outlook are provided for this very extensive field of endeavor. To the best of our knowledge the literature coverage is complete up to December 2018.
Organic‐Free Interzeolite Transformation in the Absence of Common Building Units
Authors: Qin Wei , Jain Rishabh , Robles Hernández Francisco C. , Rimer Jeffrey D.
Published: March 2019

Zeolite crystals can be used as seeds or aluminosilicate sources in syntheses to control polymorphs and/or reduce the quantity of organics used as structure‐directing agents. A frequently invoked hypothesis for interzeolite transformations is that zeolites share some underlying similarity in structure, most notably in cases pertaining to organic‐free syntheses. Herein, we show for the first time that ZSM‐5 (MFI) can be directly obtained from USY (FAU) through an interzeolite transformation between parent–daughter structures lacking common building units in the absence of a structure‐directing agent and seeds. We show that interzeolite transformation leads to a crystalline product with fewer defects. Our findings also reveal that ZSM‐5 is a metastable intermediate that undergoes further transformation to mordenite (MOR) and quartz. The MFI‐to‐MOR transition is counter to reported trends for which transformations lead to structures with reduced molar volume. Herein, we propose mechanistic arguments that suggest the driving force for interzeolite transformation is more complex than guidelines posited in the literature.
Emergency percutaneous coronary intervention for left main trunk thrombus following orthotopic heart transplantation
Authors: Tsuji Masaki , Nitta Daisuke , Minatsuki Shun , Maki Hisataka , Hosoya Yumiko , Amiya Eisuke , Hatano Masaru , Takimoto Eiki , Kinoshita Osamu , Nawata Kan , Ono Minoru , Komuro Issei
Published: March 2019

Heart transplantation (HTx) is the gold standard therapy to improve quality and quantity of life in end‐stage heart failure patients. However, recipients are at risk of experiencing allograft rejection and post‐transplant complications, in the acute as well as chronic phase. A 43‐year‐old man with a history of left ventricular non‐compaction underwent orthotopic HTx. On Day 7, transthoracic echocardiography showed a sudden decrease in cardiac function with hypokinesis in a left ventricular anterior wall distribution. Coronary angiography revealed a large thrombus in the left main trunk. With intra‐aortic balloon pump support, emergency percutaneous coronary intervention was performed. Endomyocardial biopsy showed no rejection. A left main trunk thrombus is rare in the early phase after HTx, but it can be a life‐threatening complication. Transthoracic echocardiography is well known to be important in the management of heart transplant recipients, and coronary angiography as well as myocardial biopsy should be considered when left ventricular wall motion is impaired.
A systematic review of clinical prediction rules for the diagnosis of chronic heart failure
Authors: Gallagher Joe , McCormack Darren , Zhou Shuaiwei , Ryan Fiona , Watson Chris , McDonald Kenneth , Ledwidge Mark T.
Published: March 2019

Aims

This study sought to review the literature for clinical prediction models for the diagnosis of patients with chronic heart failure in the community and to validate the models in a novel cohort of patients with a suspected diagnosis of chronic heart failure.

Methods and results

MEDLINE and Embase were searched from 1946 to Q4 2017. Studies were eligible if they contained at least one multivariable model for the diagnosis of chronic heart failure applicable to the primary care setting. The CHARMS checklist was used to evaluate models. We also validated models, where possible, in a novel cohort of patients with a suspected diagnosis of heart failure referred to a rapid access diagnostic clinic.

In total, 5310 articles were identified with nine articles subsequently meeting the eligibility criteria. Three models had undergone internal validation, and four had undergone external validation. No clinical impact studies have been completed to date. Area under the curve (AUC) varied from 0.74 to 0.93 and from 0.60 to 0.65 in the novel cohort for clinical models alone with AUC up to 0.89 in combination with electrocardiogram and B‐type natriuretic peptide (BNP). The AUC for BNP was 0.86 (95% confidence interval 83.3–88.6%).

Conclusions

This review demonstrates that there are a number of clinical prediction rules relevant to the diagnosis of chronic heart failure in the literature. Clinical impact studies are required to compare the use of clinical prediction rules and biomarker strategies in this setting.
Platinum group element geochemistry and whole‐rock systematics of the Vempalle sills, Cuddapah Basin, India: Implications on sulphur saturation history, mantle processes, and tectonic setting
Authors: Singh Th. Dhanakumar , Manikyamba C.
Published: March 2019

The intracratonic Cuddapah Basin of southern peninsular India has multiple phases of magmatism exposed as mafic intrusives and extrusives in the Vempalle and Tadpatri formations. We report platinum group element geochemistry along with whole‐rock systematics of the mafic sills from the Vempalle Formation to understand their sulphur saturation history, source characteristics, and tectonic setting. These sills are medium‐ to fine‐grained dolerites with plagioclase and pyroxenes as essential minerals exhibiting sub‐ophitic to intergranular texture. Geochemically, they are characterized by moderate MgO (6.3–8.5 wt.%), Ni (55–105 ppm), Cr (20–130 ppm), and ∑PGE (22–61 ppb) contents and exhibit transitional to calc‐alkaline in nature. Primitive mantle‐ and chondrite‐normalized trace and rare earth element patterns display relative enrichment of LILE–LREE over HFSE, suggesting plume‐related intraplate magmatism with contributions from subcontinental lithospheric mantle (SCLM), lithosphere–asthenosphere interaction, crustal contamination, and fractional crystallization. Their REE relationship indicates the generation of parent magma from a heterogeneous source marked by 10–25% polybaric partial melting within spinel and garnet lherzolite domain. Platinum group elements (PGE) geochemistry reveals their sulphur‐undersaturated nature, and sulphide fractionation played a key role in the distribution of PGEs, which is evidenced by their enriched character, moderate degrees of partial melting, and crustal contamination. Further, the negative platinum anomalies in these sills indicate its removal during fractional crystallization, and the enrichment of Pd over Pt endorses the decoupling nature of these elements prior to their emplacement. Diagnostic trace element signatures and their relationship corroborate a riftogenic intraplate tectonic regime for the emplacement of the Vempalle sills through an ocean–continent transition zone.
Serpentinisation and magnetite formation in the Angwu ultramafic rocks from the central Bangong–Nujiang suture zone, Tibetan Plateau
Authors: Liu Zhi‐Bo , Li Jing‐Chao , Zhao Tao , Song Yang , Yuan Guo‐Li , Lin Yun , Shao Hua‐Sheng
Published: March 2019

Serpentinised ultramafic rocks are widely distributed in the Bangong–Nujiang suture zone (BNSZ) and show close relationship with the regional mineralisation. Here, we investigate the serpentinised ultramafic rocks from Angwu in the central segment of the BNSZ, where the primary minerals include olivine, clinopyroxene, chromite, lizardite, magnetite, and chlorite. Based on a comprehensive analysis of the results from petrography, back‐scattered electron images (BSE), and energy dispersive spectrographs (EDS), as well as electron probe microanalysis (EPMA), the alteration process of the ultramafic rocks, including serpentinisation, can be divided into three stages: 1, formation of relatively Fe‐rich serpentine (Mg#, 0.82), with no precipitation of magnetite; 2, formation of relatively Mg‐rich serpentine (Mg#, 0.93), with precipitation of magnetite in serpentine veins; and 3, alteration of serpentine into chlorite. We computed the reactions associated with alteration process for the above stages. In addition, thermodynamic modelling in multicomponent mineral equilibrium phase diagrams indicate that during the serpentinisation process, the desilication of pyroxene in caused the enhancement of SiO2 activity and restricted the transformation from olivine to magnetite. The reaction temperature for the serpentinisation of these rocks was relatively high, and within this temperature interval (100–300°C), lizardite was stable, and precipitation of magnetite was not favoured. We also evaluate the factors influencing magnetite precipitation during serpentinisation of ultramafic rocks including the composition of primitive rocks and the activity of SiO2 and temperature. Our study provides insights on the mechanism of magnetite mineralisation associated with the serpentinisation of ultramafic rocks.
Activation‐based association profiles differentiate network roles across cognitive loads
Authors: Zuo Nianming , Salami Alireza , Yang Yihong , Yang Zhengyi , Sui Jing , Jiang Tianzi
Published: March 2019

Working memory (WM) is a complex and pivotal cognitive system underlying the performance of many cognitive behaviors. Although individual differences in WM performance have previously been linked to the blood oxygenation level‐dependent (BOLD) response across several large‐scale brain networks, the unique and shared contributions of each large‐scale brain network to efficient WM processes across different cognitive loads remain elusive. Using a WM paradigm and functional magnetic resonance imaging (fMRI) from the Human Connectome Project, we proposed a framework to assess the association and shared‐association strength between imaging biomarkers and behavioral scales. Association strength is the capability of individual brain regions to modulate WM performance and shared‐association strength measures how different regions share the capability of modulating performance. Under higher cognitive load (2‐back), the frontoparietal executive control network (FPN), dorsal attention network (DAN), and salience network showed significant positive activation and positive associations, whereas the default mode network (DMN) showed the opposite pattern, namely, significant deactivation and negative associations. Comparing the different cognitive loads, the DMN and FPN showed predominant associations and globally shared‐associations. When investigating the differences in association from lower to higher cognitive loads, the DAN demonstrated enhanced association strength and globally shared‐associations, which were significantly greater than those of the other networks. This study characterized how brain regions individually and collaboratively support different cognitive loads.
Pharmacists' perceptions of implementing a pharmacist‐managed area under the concentration time curve‐guided vancomycin dosing program at a large academic medical center
Authors: Claeys Kimberly C. , Hopkins Teri L. , Brown Jessica , Heil Emily L
Published: March 2019

Introduction

A pharmacist‐managed area‐under the concentration time curve/minimum inhibitory concentration (AUC/MIC)‐based vancomycin dosing and monitoring strategy was implemented at the University of Maryland Medical Center (UMMC) in January 2017. Because this was a large change in practice and methodology, we sought to understand pharmacists' perceptions of the practice before and after implementation.

Methods

A mixed methods preimplementation survey was sent to all pharmacists, including residents, completing vancomycin dosing training at UMMC 1 month prior to transition to an AUC‐guided pharmacist‐to‐dose practice. The postimplementation survey was subsequently sent 8 months after program rollout to the same study participants.

Results

A total of 127 responses completed the survey: 78 in the preimplementation and 49 in the postimplementation arm. Clinical specialist pharmacists represented 53.8% vs 49.0%, clinical pharmacists represented 32.1% vs 36.7%, and residents represented 14.3% vs 14.1%, respectively. Prior to implementation, 42.3% responded that AUC/MIC was the ideal pharmacokinetic/pharmacodynamic parameter, compared with 93.9% postimplementation (P < 0.0001). Weight‐based dosing was primarily used preimplementation as opposed to postimplementation (46.2% vs 6.1%; P < 0.0001). The average time spent evaluating a vancomycin dose increased from 8 (interquartile range [IQR] 5‐15) minutes to 15 (IQR 10‐17.5) minutes (P < 0.0001). Respondents strongly agreed that pharmacist‐to‐dose AUC/MIC vancomycin for working at the top of their degree (53.1% preimplementation vs 61.5% postimplementation; P = 0.261). Main concerns regarding changes in vancomycin dosing practices included lack of pharmacist competency, which decreased after rollout (48.7% preimplementation vs 24.5% postimplementation; P = 0.081). Before implementation, respondents felt that practice problems and training sessions (69.2%) and computer decision support (57.7%) would be key to a successful rollout. Satisfaction with the rollout increased postimplementation (26.9% vs 49.0%, respectively P = 0.011).

Conclusion

Pharmacists were in support of pharmacist‐to‐dose AUC vancomycin dosing practices, but there were concerns regarding competency. Training sessions with practice problems and integrated clinical decision support improved the rollout process.
Involvement of GASL1 in postoperative distant recurrence of gastric adenocarcinoma after gastrectomy distal resection and the possible mechanism
Authors: Wang Bing , Chen Huawei , Zhang Yang
Published: March 2019

As a cancer‐related long noncoding RNA, functionality of GASL1 has only been characterized in liver cancer. Our study aimed to investigate the possible involvement of GASL1 in postoperative recurrence of gastric adenocarcinoma. A total of 112 gastric adenocarcinoma patients with a tumor located in the distal third who received gastrectomy distal resection in The Second Hospital of Dalian Medical University from January 2012 to January 2015 were included in this study. Patients were followed up for 3 years. Another 56 healthy people were also included to serve as a control group. Blood was extracted from each subject on the day of discharge, on the day of diagnosis of recurrence or at the end of follow‐up. The GASL1 expression vector was transfected into gastric adenocarcinoma cell lines. It was observed that plasma levels of GASL1 were significantly lower, while plasma levels of transforming growth factor‐β1 (TGF‐β1) were significantly higher in patients than in healthy controls on the day of discharge. Patients with distant recurrence showed significantly lower plasma levels of GASL1 and significantly higher plasma levels of TGF‐β1 compared with patients with local recurrence and patients without recurrence. During follow‐up, plasma levels of GASL1 and TGF‐β1 were negatively correlated in patients with distant recurrence but not in other groups of patients. GASL1 overexpression inhibited, while TGF‐β1 treatment promoted cell migration and invasion. Overexpression of GASL1 led to downregulated and GASL1 knockdown led to upregulated TGF‐β1. However, TGF‐β1 showed no significant effects on GASL1 expression. We conclude that GASL1 may participate in the distant recurrence of gastric adenocarcinoma through the interactions with TGF‐β1.
MicroRNA‐19a‐3p promotes rheumatoid arthritis fibroblast‐like synoviocytes via targeting SOCS3
Authors: Chen Yiyue , Wang Wanchun , Chen You , Tang Qi , Zhu Weihong , Li Ding , Liao Lele
Published: March 2019

Rheumatoid arthritis (RA) is a common chronic autoimmune disease and effective treatment for RA is still lacking. In this study, the regulatory role of miR‐19a‐3p in RA was investigated. Quantitative polymerase chain reaction analysis of human blood samples showed that the level of miR‐19a‐3p was significantly lower in the RA patients compared with that in healthy patients (P < 0.05). In RA fibroblast‐like synoviocytes (RAFLS), miR‐19a‐3p and suppressor of cytokine signaling 3 (SOCS3) were also downregulated and upregulated, respectively, compared with those of normal FLS. Transfection of miR‐19a‐3p mimic in RAFLS inhibited cell proliferation and promoted cell apoptosis. TargetScan identified SOCS3 as a target of miR‐19a‐3p, which was confirmed by dual‐luciferase assay. Western blot indicated that SOCS3 protein level was significantly decreased after miR‐19a‐3p overexpression. Moreover, SOCS3 silencing through siRNA transfection also enhanced cell proliferation, meanwhile inhibiting RAFLS apoptosis. In addition, SOCS3 overexpression abrogated the effects of miR‐19a‐3p overexpression on cell proliferation and apoptosis, corroborating that SOCS3 acts as a downstream effector in the miR‐19a‐3p‐mediated function of RAFLS. These findings suggest that miR‐19a‐3p plays an important role in RA, and the miR‐19a‐3p/SOCS3 axis may become a potential therapeutic target for RA.
Rhoifolin ameliorates titanium particle‐stimulated osteolysis and attenuates osteoclastogenesis via RANKL‐induced NF‐κB and MAPK pathways
Authors: Liao Shijie , Song Fangmin , Feng Wenyu , Ding Xiaofei , Yao Jun , Song Huijie , Liu Yun , Ma Shiting , Wang Ziyi , Lin Xixi , Xu Jiake , Zhao Jinmin , Liu Qian
Published: March 2019

Prosthesis loosening is a highly troublesome clinical problem following total joint arthroplasty. Wear‐particle‐induced osteoclastogenesis has been shown to be the primary cause of periprosthetic osteolysis that eventually leads to aseptic prosthesis loosening. Therefore, inhibiting osteoclastogenesis is a promising strategy to control periprosthetic osteolysis. The possible mechanism of action of rhoifolin on osteoclastogenesis and titanium particle‐induced calvarial osteolysis was examined in this study. The in vitro study showed that rhoifolin could strongly suppress the receptor activators of nuclear factor‐κB (NF‐κB) ligand‐stimulated osteoclastogenesis, hydroxyapatite resorption, F‐actin formation, and the gene expression of osteoclast‐related genes. Western blot analysis illustrated that rhoifolin could attenuate the NF‐κB and mitogen‐activated protein kinase pathways, and the expression of transcriptional factors nuclear factor of activated T cells 1 (NFATc1) and c‐Fos. Further studies indicated that rhoifolin inhibited p65 translocation to the nucleus and the activity of NFATc1 and NF‐κB rhoifolin could decrease the number of tartrate‐resistant acid phosphate‐positive osteoclasts and titanium particle‐induced C57 mouse calvarial bone loss in vivo. In conclusion, our results suggest that rhoifolin can ameliorate the osteoclasts‐stimulated osteolysis, and may be a potential agent for the treatment of prosthesis loosening.
Quercetin attenuates oxidative stress‐induced apoptosis via SIRT1/AMPK‐mediated inhibition of ER stress in rat chondrocytes and prevents the progression of osteoarthritis in a rat model
Authors: Feng Kai , Chen Zhaoxun , Pengcheng Liu , Zhang Shuhong , Wang Xiaoqing
Published: March 2019

Apoptosis of chondrocytes are the main initiator of osteoarthritis (OA) and can be explained by oxidative stress and endoplasmic reticulum (ER) stress, thus the pharmacological interventions aimed at inhibiting of these pathways may be a promising approach for the management of OA. Quercetin is a member of the flavonoid family and has antioxidant and anti‐inflammatory properties in degenerative diseases. However, its effects and potential mechanisms on the pathological process of OA are not very clear. The present study aimed to investigate the protective effects of quercetin on OA and the underlying mechanisms. The tert‐butyl hydroperoxide (TBHP)‐stimulated rat chondrocytes and destabilization of the medial meniscus OA rat model was used to explore the protective effects of quercetin. Our results showed that quercetin treatment can attenuate oxidative stress, ER stress, and associated apoptosis. Moreover, quercetin inhibited ER stress through activating the sirtuin1/adenosine monophosphate‐activated protein kinase (SIRT1/AMPK) signaling pathway. The protective effects of quercetin were also observed in OA rat model which is evidenced by abolished cartilage degeneration and decreased chondrocytes apoptosis in the knee joints. Our results suggested that quercetin is a promising treatment for OA.
Novel trastuzumab‐DM1 conjugate: Synthesis and bio‐evaluation
Authors: Abedi Mehri , Cohan Reza Ahangari , Mahboudi Fereidoun , Faramarzi Mohammad Ali , Fazel Ramin , Damavandi Narges , Ardestani Mehdi Shafiee , Davami Fatemeh
Published: March 2019

Antibody‐drug conjugates are now of considerable interest and are recommended for the treatment of cancers. Linkers are having a crucial role in potency and efficacy of these drugs. Herein, for the first time, we have used a water‐soluble poly‐ethylene glycol based linker (succinimidyl‐[(N‐maleimido propionamido)‐diethyleneglycol] [SM(PEG)2]) for lysine amide coupling of DM1 drug to trastuzumab considering evaluation of the effect of using a hydrophilic linker on physicochemical and biological properties of the resulting conjugate in comparison to the conjugate containing succinimidyl 4‐(N‐maleimidomethyl) cyclohexane‐1‐carboxylate (SMCC) linker, which has a relative hydrophobic nature. The physicochemical properties of synthesized conjugates were investigated in terms of drug to antibody ratio, size variants and free drug quantities. In vitro biological activity of trastuzumab‐DM1 conjugates was assessed on breast cancer cell lines expressing different levels of HER2 using binding affinity, antiproliferative, apoptosis, and antibody‐dependent cell‐mediated cytotoxicity (ADCC) assays. Synthesized conjugate containing hydrophilic linker, showed higher drug to antibody ratio, no aggregated form and higher cellular toxicity in comparison to SMCC bearing conjugate. Binding affinity and ADCC potential of conjugates was not affected upon the usage of hydrophilic linker. In conclusion, application of SM(PEG)2 for coupling of DM1 to trastuzumab enhance desirable characteristics of the resulting conjugate.
Pancreas deformation in the presence of tumors using feature tracking from free‐breathing XD‐GRASP MRI
Authors: Chitiboi Teodora , Muckley Matthew , Dane Bari , Huang Chenchan , Feng Li , Chandarana Hersh
Published: March 2019

Background

Quantifying the biomechanical properties of pancreatic tumors could potentially help with assessment of tumor aggressiveness, prognosis, and prediction of therapy response.

Purpose

To quantify respiratory‐induced deformation in the pancreas and pancreatic lesions using XD‐GRASP (eXtra‐Dimensional Golden‐angle RAdial Sparse Parallel), MRI.

Study Type

Retrospective study where patients undergoing clinically indicated abdominal MRI which included free‐breathing radial T1‐weighted (T1W) imaging were studied.

Subjects

Thirty‐two patients (12 male and 20 female) including nine with pancreatic lesions constituted our study cohort.

Field Strength/Sequence

3.0 T with T1WI contrast‐enhanced gradient echo radial free‐breathing acquisition.

Assessment

Using the XD‐GRASP imaging technique, the acquired free‐breathing radial data were sorted and binned into 10 consecutive respiratory motion states that were jointly reconstructed. 3D deformation fields along the respiratory dimension were computed using an optical flow method and were analyzed in the pancreas.

Statistical Tests

The Wilcoxon signed‐rank test was used to assess the difference in average displacement across pancreatic regions, while the Wilcoxon rank‐sum test was used for displacement differences between patients with and without tumors. The interclass correlation coefficient (ICC) was computed to assess consistency between observers for each image quality measure.

Results

There was a significantly larger displacement in the pancreatic tail compared with the head (8.2 ± 3.7 mm > 5.8 ± 2.4 mm; P < 0.001) and body regions (8.2 ± 3.7 mm > 6.6 ± 2.9 mm; P < 0.001). Furthermore, there was reduced normalized average displacement in patients with pancreatic lesions compared with subjects without lesions (0.33 ± 0.1 < 0.69 ± 0.26, P < 0.001 for the head; 0.30 ± 0.1 < 0.84 ± 0.31, P < 0.001 for the body; and 0.44 ± 0.31 < 1.08 ± 0.53, P < 0.001 for the tail, respectively).

Data Conclusion

Free‐breathing respiratory motion‐sorted XD‐GRASP MRI has the potential to noninvasively characterize the biomechanical properties of the pancreas by quantifying breathing‐induced mechanical displacement.

Level of Evidence: 4

Technical Efficacy: Stage 2

J. Magn. Reson. Imaging 2019;50:1633–1640.
Diurnal variability in alkaline phosphatase activity and the potential role of zooplankton
Authors: Davis C. , Lohan M. C. , Tuerena R. , Cerdan‐Garcia E. , Woodward E. M. S. , Tagliabue A. , Mahaffey C.
Published: March 2019

Daily light–dark cycles drive the circadian rhythm of many ocean processes including photosynthesis, gene expression, and zooplankton diel vertical migration (DVM). In phosphate deplete surface ocean regions, microbes produce metalloenzymes, such as alkaline phosphatases (AP), to access dissolved organic phosphorus. Here, we provide novel evidence of diurnal variation in AP activity (APA) in the subtropical North Atlantic using two independent datasets, with APA being two‐ to three‐fold higher at night. We demonstrate that zooplankton are a source of AP and postulate that zooplankton DVM is a source of enhanced AP in the surface waters at night, with reduction or degradation of AP during the day. Our results challenge the current assumption that APA is linear over a 24‐h period. While future ocean scenarios predict intensification and expansion of oceanic phosphate limitation, our findings indicate a role for zooplankton in regenerating phosphate that is currently missing in conceptual and numerical models.
Exact analysis of (R, s, S) inventory control systems with lost sales and zero lead time
Authors: Esmaili Nazanin , Norman Bryan A. , Rajgopal Jayant
Published: March 2019

We study an (R, s, S) inventory control policy with stochastic demand, lost sales, zero lead‐time and a target service level to be satisfied. The system is modeled as a discrete time Markov chain for which we present a novel approach to derive exact closed‐form solutions for the limiting distribution of the on‐hand inventory level at the end of a review period, given the reorder level (s) and order‐up‐to level (S). We then establish a relationship between the limiting distributions for adjacent values of the reorder point that is used in an efficient recursive algorithm to determine the optimal parameter values of the (R, s, S) replenishment policy. The algorithm is easy to implement and entails less effort than solving the steady‐state equations for the corresponding Markov model. Point‐of‐use hospital inventory systems share the essential characteristics of the inventory system we model, and a case study using real data from such a system shows that with our approach, optimal policies with significant savings in inventory management effort are easily obtained for a large family of items.
Developing a culturally tailored multigenerational intervention to prevent and manage type 2 diabetes in American Indian families living in rural settings: Findings from a focus group study
Authors: Scarton Lisa , Velazquez Ilse , O'Neal LaToya J. , Iyerm Samvit , Cannady Tamela , Choate Annette , Mitchell Cayla , Wilkie Diana J.
Published: March 2019

The study purpose was to understand the characteristics of interventions that would be most relevant and beneficial to address the diabetes‐related needs and challenges of rural American Indians/Alaska Natives (AIAN) with type 2 diabetes (T2D) and their families. In an exploratory study design, we held a total of seven focus groups in Florida and rural Oklahoma. Groups included 3–13 individuals (62 total, 77% were female, mean age 55.3 [11.4] years and mean duration of diabetes 10.4 [SD 9.1] years) who were referred by staff from HealthStreet, Consent2Share mechanism, and by tribal educators. All groups were moderated by the same American Indian research team member using a discussion guide with open‐ended questions, followed by probes. Findings revealed themes centered on optimal intervention components, barriers to type 2 diabetes—prevention and management (T2D‐PM), personal experiences with T2D, and impact of family behaviors on T2D‐PM. Findings indicate that the participants desire diabetes programs that include family members and a hands‐on, culturally meaningful approach. Creating an intervention based on the AIAN community's insights that include the entire family may improve T2D‐PM outcomes for this population.
Effects of a primary palliative care intervention on quality of life and mental health in cystic fibrosis
Authors: Friedman Deborah , Linnemann Rachel W. , Altstein Lily L. , Georgiopoulos Anna M. , Islam Suhayla , Bach Kieu‐Tram , St. John Anita , Fracchia M. Shannon , Neuringer Isabel , Lapey Allen , Sicilian Leonard , Moskowitz Samuel M. , Yonker Lael M.
Published: March 2019

Background

Despite the significant impact of chronic symptoms on quality of life with cystic fibrosis (CF), the role of palliative care in management of this disease is not well defined. The coping, goal assessment, and relief from evolving CF symptoms (CF‐CARES) model is a primary palliative care intervention designed to provide chronic symptom management at all stages of the disease. The goal of this pilot study was to estimate the effectiveness of the CF‐CARES intervention on improving chronic symptoms and quality of life for people living with CF.

Methods

A structured assessment was used to guide referral to supportive services intended to address burdensome symptoms. Follow‐up assessments were performed approximately 3 and 6 months later. Longitudinal regression analyses of changes in symptoms and quality of life were performed for all participants regardless of utilization of supportive services. Subgroup analyses were performed for subjects participating in mental health and alternative health services.

Results

Forty‐one subjects completed assessment and referral processes. The mean number of CF‐associated symptoms decreased over time, as did respiratory symptom‐related distress and depressive symptoms. Subjects utilizing alternative health services reported less psychological distress at follow‐up. Among subjects with severe disease, mental health, and quality of life improved, especially for those using mental health services.

Conclusions

The CF‐CARES model resulted in significant mental health and quality‐of‐life benefits, suggesting the value of integrating symptom management interventions into routine CF care. Moreover, mental health services can play a key role in CF‐specific primary palliative care, especially for those with advanced disease.
Endothall behavior in Myriophyllum spicatum and Hydrilla verticillata
Authors: Ortiz Mirella F , Nissen Scott J , Gray Cody J
Published: March 2019

BACKGROUND

Endothall has been used to control submersed aquatic plants since 1960, providing broad‐spectrum control of aquatic weeds. Although endothall is considered a contact herbicide, many field observations suggest that it might have systemic activity. The goals of this research were to determine endothall's (i) absorption characteristics, (ii) translocation from shoots to roots, and (iii) potential for desorption in Eurasian watermilfoil (EWM), monoecious and dioecious hydrilla.

RESULTS

Endothall absorption was linear in dioecious hydrilla up to 192 HAT, while in EWM and monoecious hydrilla absorption data best fit an asymptotic rise function. Endothall absorption in EWM, monoecious and dioecious hydrilla was 3.3, 6.6, and 11.0 times the external herbicide concentration determined by the plant concentration factor. Translocation to EWM roots reached 7.9% of total absorbed radioactivity by 192 HAT, while translocation to monoecious and dioecious hydrilla roots reached 17.8% and 16.4% by 192 HAT, respectively. For all three species, no more than 30% of absorbed endothall moved from the plant to clean water 96 HAT.

CONCLUSION

Endothall is a very water soluble compound and yet it accumulated in these three important aquatic weeds at concentrations significantly higher than the external herbicide concentration. These data provide evidence that endothall could have systemic activity in these aquatic species. Following 14C‐endothall applications, more 14C translocated from shoots to roots compared to the translocation of 14C for other systemic aquatic herbicides. The final confirmation of endothall's systemic behavior requires that the radioactivity found in the root system of these aquatic plants is 14C endothall. © 2019 Society of Chemical Industry
MEBoost: Variable selection in the presence of measurement error
Authors: Brown Ben , Weaver Timothy , Wolfson Julian
Published: March 2019

We present a novel method for variable selection in regression models when covariates are measured with error. The iterative algorithm we propose, Measurement Error Boosting (MEBoost), follows a path defined by estimating equations that correct for covariate measurement error. We illustrate the use of MEBoost in practice by analyzing data from the Box Lunch Study, a clinical trial in nutrition where several variables are based on self‐report and, hence, measured with error, where we are interested in performing model selection from a large data set to select variables that are related to the number of times a subject binge ate in the last 28 days. Furthermore, we evaluated our method and compared its performance to the recently proposed Convex Conditioned Lasso and to the “naive” Lasso, which does not correct for measurement error through a simulation study. Increasing the degree of measurement error increased prediction error and decreased the probability of accurate covariate selection, but this loss of accuracy occurred to a lesser degree when using MEBoost. Through simulations, we also make a case for the consistency of the model selected.
Self-esteem and cyberchondria: The mediation effects of health anxiety and obsessive–compulsive symptoms in a community sample
Authors: Bajcar Beata , Babiak Jolanta
Published: March 2019

Cyberchondria refers to the excessive and repeated searching for medical information on the Internet and may be considered as health-related problematic Internet use. Previous findings indicated that cyberchondria is positively associated with health anxiety and obsessive–compulsive symptoms. Also, research suggests that excessive or problematic Internet use as well as health worries and compulsive behaviors are present among individuals with low self-esteem. This study sought to examine: (1) the association between self-esteem and cyberchondria, and (2) the mediating role of health anxiety and obsessive–compulsive symptoms in the relationship between self-esteem and cyberchondria. Participants (N = 207) from a community sample completed self-report measures assessing global self-esteem, health anxiety, obsessive–compulsive symptoms, and cyberchondria. We found that self-esteem directly predicted cyberchondria and that health anxiety and obsessive–compulsive symptoms parallelly mediated the relationship between self-esteem and cyberchondria. These findings suggest that low self-esteem, health anxiety and obsessive–compulsive symptoms can be considered vulnerability factors for cyberchondria. In addition, the reverse mediation model indicated that cyberchondria potentially predicts self-esteem both directly and through health anxiety and obsessive–compulsive symptoms. The bidirectional relationship among the analyzed variables are discussed in the context of potential psychological predictors and consequences of cyberchondria and possible mechanisms explaining cyberchondria. The current study provides further insight into the conceptualization of cyberchondria and the feasibility of specific treatment directions.
Assessment of Groundwater Pollution Vulnerability Using GIS Based Modified DRASTIC Model in Raipur City, Chhattisgarh
Authors: Khan Rubia , Jhariya D. C.
Published: March 2019

In the present study DRASTIC model was used to assess the groundwater vulnerable zone for Raipur city. In this study DRASTIC model is modified into four ways i.e. DRASTIC, Modified DRASTIC-Lu, DRASTIC AHP and Modified DRASTIC-Lu AHP. To modify the DRASTIC model, LULC parameter was added in the real DRASTIC model and also AHP technique applied to determine the rating and weight. In this study, it is observed that 2.83%, 7.57%, 32.03%, 47.78% and 9.8% areas are respectively falling under very low, low, moderate, high and very high vulnerable DRASTIC index, 2.56%, 10.96%, 30.10%, 47.47% and 8.9% areas are respectively falling under very low, low, moderate, high and very high vulnerable modified DRASTIC-Lu index, 3.27%, 16.63%, 47.14%, 74.44% and 9.96% area are respectively falling under very low, low, moderate, high and very high vulnerable DRASTIC-AHP index classes and 2.74%, 12.27%, 38.16%, 41.5% and 5.3% area are respectively falling under very low, low, moderate, high and very high vulnerable modified DRASTIC-Lu AHP index. To determine the accuracy of the DRASTIC models, total 50 groundwater samples of nitrate concentration were used for pre-monsoon and post-monsoon seasons and it was observed that Modified DRASTIC-Lu AHP model is most accurate and suitable for present study area.
Linking Racial Classification, Racial Inequality, and Racial Formation: The Contributions ofPulled Over
Authors: Gordon Daanika , Shakeshaft Emma
Published: March 2019

Pulled Over: How Police Stops Define Race and Citizenship, by Charles R. Epp, Steven Maynard-Mood, and Donald Haider-Markel, is an important piece of law and society scholarship that isolates investigatory police stops as an institutional practice with profound consequences for racial inequality. Pulled Over also speaks to scholarship on race and ethnicity by addressing an ongoing tension between a focus on the socially constructed nature of racial categories and their stratifying significance. Pulled Over offers an important model for future studies by incorporating social constructionist insights into how race is measured, empirically documenting institutionally produced racial inequalities, and linking these inequalities to the evolving meaning of race itself.
Comparing the serum TAG response to high-dose supplementation of either DHA or EPA among individuals with increased cardiovascular risk: the ComparED study
Authors: Allaire Janie , Vors Cécile , Harris William S. , Jackson Kristina Harris , Tchernof André , Couture Patrick , Lamarche Benoît
Published: March 2019

Studies have shown that the reduction in serum TAG concentrations with long-chain n-3 fatty acid supplementation is highly variable among individuals. The objectives of the present study were to compare the proportions of individuals whose TAG concentrations lowered after high-dose DHA and EPA, and to identify the predictors of response to both modalities. In a double-blind, controlled, crossover study, 154 men and women were randomised to three supplemented phases of 10 weeks each: (1) 2·7 g/d of DHA, (2) 2·7 g/d of EPA and (3) 3 g/d of maize oil, separated by 9-week washouts. As secondary analyses, the mean intra-individual variation in TAG was calculated using the standard deviation from the mean of four off-treatment samples. The response remained within the intra-individual variation (±0·25 mmol/l) in 47 and 57 % of participants after DHA and EPA, respectively. Although there was a greater proportion of participants with a reduction >0·25 mmol/l after DHA than after EPA (45 υ. 32 %; P < 0·001), the mean TAG reduction was comparable between groups (–0·59 (sem 0·04) υ. –0·57 (sem 0·05) mmol/l). Participants with a reduction >0·25 mmol/l after both DHA and EPA had higher non-HDL-cholesterol, TAG and insulin concentrations compared with other responders at baseline (all P < 0·05). In conclusion, supplementation with 2·7 g/d DHA or EPA had no meaningful effect on TAG concentrations in a large proportion of individuals with normal mean TAG concentrations at baseline. Although DHA lowered TAG in a greater proportion of individuals compared with EPA, the magnitude of TAG lowering among them was similar.