bluuebunny/crossref_metadata_2025 huggingface dataset:
Transparent, Anisotropic Biofilm with Aligned Bacterial Cellulose Nanofibers
Authors: Wang Sha , Li Tian , Chen Chaoji , Kong Weiqing , Zhu Shuze , Dai Jiaqi , Diaz Alfredo J. , Hitz Emily , Solares Santiago D. , Li Teng , Hu Liangbing
Published: February 2018

Cellulose nanofibrils are attractive as building blocks for advanced photonic, optoelectronic, microfluidic, and bio‐based devices ranging from transistors and solar cells to fluidic and biocompatible injectable devices. For the first time, an ultrastrong and ultratough cellulose film, which is composed of densely packed bacterial cellulose (BC) nanofibrils with hierarchical fibril alignments, is successfully demonstrated. The molecular level alignment stems from the intrinsic parallel orientation of crystalline cellulose molecules produced by Acetobacter xylinum. These aligned long‐chain cellulose molecules form subfibrils with a diameter of 2–4 nm, which are further aligned to form nanofibril bundles. The BC film yields a record‐high tensile strength (≈1.0 GPa) and toughness (≈25 MJ m−3). Being ultrastrong and ultratough, yet the BC film is also highly flexible and can be folded into desirable shapes. The BC film exhibits a controllable manner of alignment and is highly transparent with modulated optical properties, paving the way to enabling new functionalities in mechanical, electrical, fluidic, photonics, and biocompatible applications.
Oxide Thin‐Film Electronics using All‐MXene Electrical Contacts
Authors: Wang Zhenwei , Kim Hyunho , Alshareef Husam N.
Published: February 2018

2D MXenes have shown great promise in electrochemical and electromagnetic shielding applications. However, their potential use in electronic devices is significantly less explored. The unique combination of metallic conductivity and hydrophilic surface suggests that MXenes can also be promising in electronics and sensing applications. Here, it is shown that metallic Ti3C2 MXene with work function of 4.60 eV can make good electrical contact with both zinc oxide (ZnO) and tin monoxide (SnO) semiconductors, with negligible band offsets. Consequently, both n‐type ZnO and p‐type SnO thin‐film transistors (TFTs) have been fabricated entirely using large‐area MXene (Ti3C2) electrical contacts, including gate, source, and drain. The n‐ and p‐type TFTs show balanced performance, including field‐effect mobilities of 2.61 and 2.01 cm2 V−1 s−1 and switching ratios of 3.6 × 106 and 1.1 × 103, respectively. Further, complementary metal oxide semiconductor (CMOS) inverters are demonstrated. The CMOS inverters show large voltage gain of 80 and excellent noise margin of 3.54 V, which is 70.8% of the ideal value. Moreover, the operation of CMOS inverters is shown to be very stable under a 100 Hz square waveform input. The current results suggest that MXene (Ti3C2) can play an important role as contact material in nanoelectronics.
How the catalyst circulates and works in organocatalyzed atom transfer radical polymerization
Authors: Guo Jun‐Kang , Luo Zheng‐Hong
Published: February 2018

The catalyst plays a vital role in organocatalyzed atom transfer radical polymerization (O‐ATRP). Catalysts in the ground‐state, excited‐state, and oxidized‐state are in competitive equilibrium and mutually transforming status. However, the catalyst circulation process remains unclear in some respects. In this work, for the first time, a novel kinetic model is successfully developed to illustrate the exact circulation process and working mechanism of catalyst. For a broad range of conditions, the reported model presents excellent descriptions of kinetic behaviors of O‐ATRP. In the polymerization process, the photolysis effect contributes to a small proportion of radical generation. Sufficient deactivation effect is crucial for controlled polymerization at the early stage of polymerization. And increased light intensity, halide ion concentration, catalyst loading and initiator concentration accelerate the establishment of catalyst dynamic equilibrium. Additionally, the excited‐state catalyst quenches with an extremely high rate, leading to an immediate dormant period in “on–off” light switching regulation. The formulated results shed light on the catalyst circulation process and provide insights into the polymerization kinetics. © 2018 American Institute of Chemical Engineers AIChE J, 64: 2581–2591, 2018
Bendamustine‐based conditioning prior to autologous stem cell transplantation (ASCT): Results of a French multicenter study of 474 patients from LYmphoma Study Association (LYSA) centers
Authors: Chantepie Sylvain P. , Garciaz Sylvain , Tchernonog Emmanuelle , Peyrade Frederic , Larcher Marie‐Virginie , Diouf Momar , Fornecker Luc‐Mathieu , Houot Roch , Gastinne Thomas , Soussain Carole , Malak Sandra , Lemal Richard , Delette Caroline , Ibrahim Ahmad , Gac Anne‐Claire , Reboursière Emilie , Vilque Jean‐Pierre , Bekadja Mohamed‐Amine , Casasnovas Rene‐Olivier , Gressin Remy , Guidez Stéphanie , Coso Diane , Herbaux Charles , Yakoub‐Agha Ibrahim , Bouabdallah Krimo , Durot Eric , Damaj Gandhi
Published: February 2018

Carmustine shortage has led to an increase use of alternative conditioning regimens prior to autologous stem cell transplantation for the treatment of lymphoma, including Bendamustine‐based (BeEAM). The aim of this study was to evaluate the safety of the BeEAM regimen in a large cohort of patients. A total of 474 patients with a median age of 56 years were analyzed. The majority of patients had diffuse large B‐cell lymphoma (43.5%). Bendamustine was administered at a median dose of 197 mg/m2/day (50‐250) on days‐7 and −6. The observed grade 1‐4 toxicities included mucositis (83.5%), gastroenteritis (53%), skin toxicity (34%), colitis (29%), liver toxicity (19%), pneumonitis (5%), and cardiac rhythm disorders (4%). Nonrelapse mortality (NRM) was reported in 3.3% of patients. Acute renal failure (ARF) was reported in 132 cases (27.9%) (G ≥2; 12.3%). Organ toxicities and death were more frequent in patients with post conditioning renal failure. In a multivariate analysis, pretransplant chronic renal failure, bendamustine dose >160 mg/m2 and age were independent prognostic factors for ARF. Pretransplant chronic renal failure, hyperhydration volume, duration of hyperhydration, and etoposide dose were predictive factors of NRM. A simple, four‐point scoring system can stratify patients by levels of risk for ARF and may allow for a reduction in the bendamustine dose to avoid toxicity. Drugs shortage may have dangerous consequences. Prospective, comparative studies are needed to confirm the toxicity/efficacy extents from this conditioning regimen compared to other types of high dose therapy.
Quantifying linear enamel hypoplasia in Virunga Mountain gorillas and other great apes
Authors: McGrath Kate , El‐Zaatari Sireen , Guatelli‐Steinberg Debbie , Stanton Margaret A. , Reid Donald J. , Stoinski Tara S. , Cranfield Michael R. , Mudakikwa Antoine , McFarlin Shannon C.
Published: February 2018

Objective

Linear enamel hypoplasia (LEH) is a condition marked by localized reductions in enamel thickness, resulting from growth disruptions during dental development. We use quantitative criteria to characterize the depth of LEH defects and “normal” perikymata in great apes. We test the hypothesis that mountain gorillas have shallow defects compared to other taxa, which may have led to their underestimation in previous studies.

Materials and Methods

Previous attempts to characterize LEH morphology quantitatively have been limited in sample size and scope. We generated digital elevation models using optical profilometry (Sensofar PLu Neox) and extracted 2D coordinates using ImageJ to quantify depths in canines from three great ape genera (N = 75 perikymata; 255 defects).

Results

All defect depths fall outside the distribution of perikymata depths. Mountain gorilla defects are significantly shallower than those of other great ape taxa examined, including western lowland gorillas. Females have significantly deeper defects than males in all taxa. The deepest defect belongs to a wild‐captured zoo gorilla. Virunga mountain gorilla specimens collected by Dian Fossey exhibit deeper defects than those collected recently.

Discussion

Shallow defect morphology in mountain gorillas may have led to an underestimation of LEH prevalence in past studies. Defect depth is used as a proxy for insult severity, but depth might be influenced by inter‐ and intra‐specific variation in enamel growth. Future studies should test whether severe insults are associated with deeper defects, as might be the case with Haloko, a wild‐captured gorilla. Ongoing histologic studies incorporating associated behavioral records will test possible factors that underlie differences in defect morphology.
Dorsal root ganglia volume differentiates schwannomatosis and neurofibromatosis 2
Authors: Godel Tim , Mautner Victor‐Felix , Farschtschi Said , Pham Mirko , Schwarz Daniel , Kronlage Moritz , Gugel Isabel , Heiland Sabine , Bendszus Martin , Bäumer Philipp
Published: February 2018

Schwannomatosis and neurofibromatosis type 2 are hereditary tumor syndromes, and peripheral neuropathy has been reported in both. We prospectively applied in vivo morphometric measurement of dorsal root ganglia volume in 16 schwannomatosis patients, 14 neurofibromatosis type 2 patients, and 26 healthy controls by magnetic resonance neurography. Compared to healthy controls, dorsal root ganglia hypertrophy was a consistent finding in neurofibromatosis type 2 (L3, + 267%; L4, + 235%; L5, + 241%; S1, + 300%; S2, + 242%; Bonferroni‐adjusted p < 0.001) but not in schwannomatosis. Dorsal root ganglia may be a vulnerable site in origination of areflexia and sensory loss and a useful diagnostic marker in neurofibromatosis type 2. Ann Neurol 2018;83:854–857
Temperature and frequency‐dependent creep and recovery studies on PVDF‐HFP/organo‐modified layered double hydroxides nanocomposites
Authors: Shojaei Leila , Goodarzi Vahabodin , Otadi Maryam , Khonakdar Hossein Ali , Jafari Seyed Hassan , Asghari Gholam hossein , Reuter Uta
Published: February 2018

A series of poly(vinylidene fluoride‐co‐hexafluoropropylene) (PVDF‐HFP) loaded with various contents of layered double hydroxides (LDHs) nanoparticles were prepared via a melt mixing method. Detailed investigations on LDH dispersion state in the polymeric matrix conducted by TEM revealed intercalated/exfoliated, and agglomerated structures at low (1 wt %) and high (>3 wt %) loadings of LDH contents, respectively. Wide angle X‐ray scattering and DSC results showed that incorporation of LDH into PVDF‐HFP matrix reduced its overall crystallinity and helped to form polar crystallites, while the crystal size at 020 crystallographic directions was found to be most affected by presence and dispersion state of LDH in the matrix. TGA results showed LDH improved thermal stability of matrix however, unlike many other nanomaterials it significantly reduced the residual mass which highlights catalytic role of LDH in degradation of residual carbon char. Detailed analysis on creep and recovery data over wide range of selected temperatures revealed that the creep compliance of nanocomposites are basically controlled by crystallinity and presence of LDH at low and high temperatures, respectively. Based on obtained storage modulus and creep compliance master curves it was also found that the influence of LDH on decreasing the creep compliance and improving viscoelastic properties of PVDF‐HFP over long time period and over high frequency ranges becomes more pronounced. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018, 135, 46352.
Controllable design of nanostructure in block copolymer reinforced epoxy composites
Authors: Heng Zhengguang , Zhang Haoruo , Chen Yang , Zou Huawei , Liang Mei
Published: February 2018

The modification of epoxy composites through the construction of nanostructures via the self‐organization of block copolymers in epoxy has become a hot topic. In this research, polystyrene‐b‐poly(ɛ‐caprolactone)‐b‐polydimethylsiloxane‐b‐poly(ɛ‐caprolactone)‐b‐polystyrene (PS‐PCL‐PDMS‐PCL‐PS) block copolymers with different lengths of PS subchains were synthesized and incorporated into epoxy thermoset. Due to the difference in the length of PS subchains, two different sizes of core‐shell nanostructures were obtained. When these two block copolymers were incorporated into epoxy, the tensile strength, elongation at break, damping temperature in range (tan δ > 0.2), and storage modulus of the epoxy thermoset below 105 °C were simultaneously improved. Meanwhile, the effects of the lengths of PS subchains on the size of nanostructures and the relationship between microstructure and macroscopic properties of epoxy composites were systematically investigated. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018, 135, 46362.
Brief Report: Attenuated Effectiveness of Tumor Necrosis Factor Inhibitors for Anti–Human T Lymphotropic Virus Type I Antibody–Positive Rheumatoid Arthritis
Authors: Suzuki Takahisa , Fukui Shoichi , Umekita Kunihiko , Miyamoto Junya , Umeda Masataka , Nishino Ayako , Okada Akitomo , Koga Tomohiro , Kawashiri Shin‐ya , Iwamoto Naoki , Ichinose Kunihiro , Tamai Mami , Fujikawa Keita , Aramaki Toshiyuki , Mizokami Akinari , Matsuoka Naoki , Ueki Yukitaka , Eguchi Katsumi , Sato Shuntaro , Hidaka Toshihiko , Origuchi Tomoki , Okayama Akihiko , Kawakami Atsushi , Nakamura Hideki
Published: February 2018

Objective

To evaluate the effectiveness of tumor necrosis factor (TNF) inhibitors for the treatment of human T lymphotropic virus type I (HTLV‐I)–positive patients with rheumatoid arthritis (RA) in an area endemic for HTLV‐I infection.

Methods

We conducted an observational study of 585 RA patients in whom TNF inhibitors were newly introduced as a first biologic disease‐modifying antirheumatic drug in an area in southwestern Japan that is endemic for HTLV‐I infection.

Results

Fifty patients (8.5%) were anti–HTLV‐I antibody–positive. The ages of the patients in this group were significantly higher at entry compared with the ages of patients who were anti–HTLV‐I antibody–negative (n = 535). The median Disease Activity Score in 28 joints using the erythrocyte sedimentation rate (DAS28‐ESR) was 5.21. Among the total group of patients, 82% were anti–citrullinated protein antibody (ACPA)–positive. The persistence rate of TNF inhibitors at 24 weeks was 89%. The median DAS28‐ESR was significantly decreased at 24 weeks in each group. The European League Against Rheumatism (EULAR) response rate was significantly better in the anti–HTLV‐I antibody–negative patients (P = 0.0277). Multiple regression analysis demonstrated that anti–HTLV‐I antibody status was significantly associated with the EULAR response rate and change in the DAS28‐ESR and was prominent especially in the ACPA‐negative subjects. No patients developed adult T cell leukemia/lymphoma (ATL) or HTLV‐I–associated myelopathy (HAM) during the 24‐week treatment period.

Conclusion

The efficacy of TNF inhibitors may be attenuated in anti–HTLV‐I antibody–positive patients with RA. ATL and HAM did not develop when TNF inhibitors were used for 24 weeks, but the long‐term risk is not known.
An intrinsic information content‐based semantic similarity measure considering the disjoint common subsumers of concepts of an ontology
Authors: Adhikari Abhijit , Dutta Biswanath , Dutta Animesh , Mondal Deepjyoti , Singh Shivang
Published: February 2018

Finding similarity between concepts based on semantics has become a new trend in many applications (e.g., biomedical informatics, natural language processing). Measuring the Semantic Similarity (SS) with higher accuracy is a challenging task. In this context, the Information Content (IC)‐based SS measure has gained popularity over the others. The notion of IC evolves from the science of information theory. Information theory has very high potential to characterize the semantics of concepts. Designing an IC‐based SS framework comprises (i) an IC calculator, and (ii) an SS calculator. In this article, we propose a generic intrinsic IC‐based SS calculator. We also introduce here a new structural aspect of an ontology called DCS (Disjoint Common Subsumers) that plays a significant role in deciding the similarity between two concepts. We evaluated our proposed similarity calculator with the existing intrinsic IC‐based similarity calculators, as well as corpora‐dependent similarity calculators using several benchmark data sets. The experimental results show that the proposed similarity calculator produces a high correlation with human evaluation over the existing state‐of‐the‐art IC‐based similarity calculators.
Differences in nonclinical pharmacokinetics between species and prediction of human pharmacokinetics of TAK‐272 (SCO‐272), a novel orally active renin inhibitor
Authors: Ebihara Takuya , Nishihara Mitsuhiro , Takahashi Junzo , Jinno Fumihiro , Tagawa Yoshihiko
Published: February 2018

In the search for orally available drugs, the prediction of human pharmacokinetics (PK) is essential for successfully selecting compounds that will be clinically useful. This report describes the selection of TAK‐272 (SCO‐272), a novel orally active renin inhibitor, as a clinical candidate via the detailed investigation of nonclinical PK data and human PK prediction. The bioavailability (BA) of TAK‐272 after oral administration to rats and monkeys was low, especially in fasted monkeys, and the systemic exposure of TAK‐272 was highly variable in monkeys. The results of mass balance studies in animals suggested that the absorbed TAK‐272 was largely eliminated by metabolism. In vitro studies revealed that TAK‐272 was mainly metabolized by CYP3A4/5 in humans, and it was a P‐glycoprotein substrate. PK analysis suggested that the factors responsible for the low BA were different in rats and monkeys. First‐pass hepatic extraction was high in rats, while the fraction absorbed from the gastrointestinal tract (Fa * Fg) was low in monkeys. It was predicted that humans would have a higher BA and a longer half‐life in the plasma compared with the animals by a simple calculation using intrinsic hepatic clearance in monkeys, which correlates well with human values for CYP3A4 substrates, and Fa * Fg in rats, which correlates relatively well with human values. TAK‐272 was finally selected as a clinical candidate based on the result of human PK prediction. The actual human PK after oral administration of TAK‐272 was comparable to the predicted profile and was preferable for clinical usage.
Income tax and the motivation to work
Authors: Rick Scott , Paolacci Gabriele , Burson Katherine
Published: February 2018

Does income tax influence the motivation to work? We propose that the degree of effort exertion in the presence of income tax depends on people's attitudes toward two key components of taxation: redistribution and government intervention. For people favorable toward both, working while taxed is aligned with personal identity and may actually enhance motivation. All others, however, may find taxes demotivating. In two incentive‐compatible labor experiments, framing wages as subject to an income tax significantly increased productivity among people chronically favorable toward both redistribution and government intervention. For everyone else, taxes did not reliably influence productivity. An objectively equivalent intervention that did not redistribute a portion of participants' wages (framed as a wage “match” rather than a “tax”) did not motivate anyone to work harder. Our findings suggest that the net effect of income tax on productivity partly depends on the distribution of attitudes toward redistribution and government intervention.
Embryo‐fetal development studies with the dietary supplement vinpocetine in the rat and rabbit
Authors: Catlin Natasha , Waidyanatha Suramya , Mylchreest Eve , Miller‐Pinsler Lutfiya , Cunny Helen , Foster Paul , Sutherland Vicki , McIntyre Barry
Published: February 2018

Dietary supplement and natural product use is increasing within the United States, resulting in growing concern for exposure in vulnerable populations, including young adults and women of child‐bearing potential. Vinpocetine is a semisynthetic derivative of the Vinca minor extract, vincamine. Human exposure to vinpocetine occurs through its use as a dietary supplement for its purported nootropic and neuroprotective effects. To investigate the effects of vinpocetine on embryo‐fetal development, groups of 25 pregnant Sprague‐Dawley rats and 8 pregnant New Zealand White rabbits were orally administered 0, 5, 20, or 60 mg vinpocetine/kg and 0, 25, 75, 150, or 300 mg/kg daily from gestational day (GD) 6‐20 and GD 7‐28, respectively. Pregnant rats dosed with vinpocetine demonstrated dose‐dependent increases in postimplantation loss, higher frequency of early and total resorptions, lower fetal body weights, and fewer live fetuses following administration of 60 mg/kg, in the absence of maternal toxicity. Additionally, the rat fetuses displayed dose‐dependent increases in the incidences of ventricular septum defects and full supernumerary thoracolumbar ribs. Similarly, albeit at higher doses than the rats, pregnant rabbits administered vinpocetine displayed an increase in postimplantation loss and fewer live fetuses (300 mg/kg), in addition to significantly lower fetal body weights (≥75 mg/kg). In conclusion, vinpocetine exposure resulted in similar effects on embryo‐fetal development in the rat and rabbit. The species differences in sensitivity and magnitude of response is likely attributable to a species difference in metabolism. Taken together, these data suggest a potential hazard for pregnant women who may be taking vinpocetine.
PROTACs: An Emerging Targeting Technique for Protein Degradation in Drug Discovery
Authors: Gu Shanshan , Cui Danrui , Chen Xiaoyu , Xiong Xiufang , Zhao Yongchao
Published: February 2018

Proteolysis‐targeting chimeric molecules (PROTACs) represent an emerging technique that is receiving much attention for therapeutic intervention. The mechanism is based on the inhibition of protein function by hijacking a ubiquitin E3 ligase for protein degradation. The hetero‐bifunctional PROTACs contain a ligand for recruiting an E3 ligase, a linker, and another ligand to bind with the protein targeted for degradation. Thus, PROTACs have profound potential to eliminate “undruggable” protein targets, such as transcription factors and non‐enzymatic proteins, which are not limited to physiological substrates of the ubiquitin‐proteasome system. These findings indicate great prospects for PROTACs in the development of therapeutics. However, there are several limitations related to poor stability, biodistribution, and penetrability in vivo. This review provides an overview of the main PROTAC‐based approaches that have been developed and discusses the promising opportunities and considerations for the application of this technology in therapies and drug discovery.
Electrosynthesized Molecularly Imprinted Polymer for Laccase Using the Inactivated Enzyme as the Target
Authors: Yarman Aysu
Published: February 2018

The first molecularly imprinted polymer (MIP) for the recognition of the copper‐enzyme laccase was successfully prepared by electropolymerizing scopoletin in the presence of alkaline‐inactivated enzyme. Laccase‐MIP and the control polymer without laccase (nonimprinted polymer, NIP) were characterized by voltammetry using the redox marker ferricyanide. After electropolymerization, the signals for ferricyanide for both the MIP and the NIP were almost completely suppressed and increased after removal of the target from the polymer layer. Rebinding of both inactivated and active laccase decreased the ferricyanide peak currents to almost equal extent. The relative decrease of signal suppression approached saturation above 10 nM. Furthermore, the surface activity of rebound laccase toward the oxidation of catechol was investigated. The surface activity approached saturation above 10 nM, a value close to the value of the measurements with ferricyanide. Interaction of NIP with laccase brought about a six times smaller signal of catechol oxidation.
Determination of metoserpate, buquinolate, and diclofenac in pork, eggs, and milk using liquid chromatography–tandem mass spectrometry
Authors: Park Jin‐A , Abd El‐Aty A. M. , Zheng Weijia , Kim Seong‐Kwan , Choi Jeong‐min , Hacımüftüoğlu Ahmet , Shim Jae‐Han , Shin Ho‐Chul
Published: February 2018

In this work, a method was developed for the simultaneous determination of residual metoserpate, buquinolate and diclofenac in pork, milk, and eggs. Samples were extracted with 0.1% formic acid in acetonitrile, defatted with n‐hexane, and filtered prior to analysis using liquid chromatography–tandem mass spectrometry. The analytes were separated on a C18 column using 0.1% acetic acid and methanol as the mobile phase. The matrix‐matched calibration curves showed good linearity over a concentration range of 5–50 ng/g with coefficients of determination (R2) ≥0.991. The intra‐ and inter‐day accuracies (expressed as recovery percentage values) calculated using three spiking levels (5, 10, and 20 μg/kg) were 80–108.65 and 74.06–107.15%, respectively, and the precisions (expressed as relative standard deviation) were 2.86–13.67 and 0.05–11.74%, respectively, for the tested drugs determined in various matrices. The limits of quantification (1 and 2 μg/kg) were below the uniform residual level (0.01 mg/kg) set for compounds that have no specific maximum residue limit (MRL). The developed method was tested using market samples and none of the target analytes was detected in any of the samples. The validated method proved to be practicable for detection of the tested analytes in pork, milk, and eggs.
The MRCI with juvenile detainees: optimizing performance or emphasizing ecological validity?
Authors: Rogers Richard , Sharf Allyson J. , Carter Rachel M. , Winningham Darby B. , Sternad Rose N.
Published: February 2018

The Miranda Rights Comprehension Instruments (MRCI) are intended to be administered to legally involved youths in a setting free from distractions and stressors with the explicit goal of assessing the examinee's best understanding. However, marked disparities have been observed between juveniles' MRCI performance and their unassisted recall of a representative Miranda warning. We hypothesized that youths' very strong MRCI performance might be partially due to prompts and clarifications used whenever incomplete or ambiguous answers are provided. In this archival study, we systematically re‐scored three MRCI instruments from 231 legally involved youths to evaluate their original responses (i.e., non‐queried scoring). This approach is viewed as more ecologically valid because actual Miranda warnings are typically provided in a routine manner without assistance following each Miranda component. For the large majority of legally involved juveniles, only small differences were noted between standard and non‐queried scoring. However, some dramatic decrements were observed, especially on the Comprehension of Miranda Rights‐II (CMR‐II). More specifically, 15.7% of CMR‐II percentiles dropped precipitously by 60% or more, when using the non‐queried scores. The results are discussed within the context of optimized performances versus ecological validity as applied to Miranda evaluations.
Recent NLRB developments signal key shift for unionization rights on campus
Authors: Starich Megan
Published: February 2018

On the surface, the Dec. 1, 2017, memorandum issued by the National Labor Relations Board's newly confirmed general counsel appears relatively brief and concise. But upon careful review, the GC memo indicates a coming sea change in the agency's enforcement stance and a rollback of some of the most significant and aggressive changes put into place under the previous administration. More specifically, the GC memo addresses how the NLRB general counsel's office will approach the rights of faculty and students at higher education institutions going forward, and rescinds entirely a previous memo on this issue.
The current state and future perspectives of cannabinoids in cancer biology
Authors: Śledziński Paweł , Zeyland Joanna , Słomski Ryszard , Nowak Agnieszka
Published: February 2018

To date, cannabinoids have been allowed in the palliative medicine due to their analgesic and antiemetic effects, but increasing number of preclinical studies indicates their anticancer properties. Cannabinoids exhibit their action by a modulation of the signaling pathways crucial in the control of cell proliferation and survival. Many in vitro and in vivo experiments have shown that cannabinoids inhibit proliferation of cancer cells, stimulate autophagy and apoptosis, and have also a potential to inhibit angiogenesis and metastasis. In this review, we present an actual state of knowledge regarding molecular mechanisms of cannabinoids’ anticancer action, but we discuss also aspects that are still not fully understood such as the role of the endocannabinoid system in a carcinogenesis, the impact of cannabinoids on the immune system in the context of cancer development, or the cases of a stimulation of cancer cells’ proliferation by cannabinoids. The review includes also a summary of currently ongoing clinical trials evaluating the safety and efficacy of cannabinoids as anticancer agents.
Clofarabine exerts antileukemic activity against cytarabine‐resistant B‐cell precursor acute lymphoblastic leukemia with low deoxycytidine kinase expression
Authors: Huang Meixian , Inukai Takeshi , Miyake Kunio , Tanaka Yoichi , Kagami Keiko , Abe Masako , Goto Hiroaki , Minegishi Masayoshi , Iwamoto Shotaro , Sugihara Eiji , Watanabe Atsushi , Somazu Shinpei , Shinohara Tamao , Oshiro Hiroko , Akahane Koshi , Goi Kumiko , Sugita Kanji
Published: February 2018

Cytosine arabinoside (Ara‐C) is one of the key drugs for the treatment of acute myeloid leukemia. It is also used for consolidation therapy of acute lymphoblastic leukemia (ALL). Ara‐C is a deoxyadenosine analog and is phosphorylated to form cytosine arabinoside triphosphate (Ara‐CTP) as an active form. In the first step of the metabolic pathway, Ara‐C is phosphorylated to Ara‐CMP by deoxycytidine kinase (DCK). However, the current cumulative evidence in the association of the Ara‐C sensitivity in ALL appears inconclusive. We analyzed various cell lines for the possible involvement of DCK in the sensitivities of B‐cell precursor ALL (BCP‐ALL) to Ara‐C. Higher DCK expression was associated with higher Ara‐C sensitivity. DCK knockout by genome editing with a CRISPR‐Cas9 system in an Ara‐C‐sensitive‐ALL cell line induced marked resistance to Ara‐C, but not to vincristine and daunorubicin, indicating the involvement of DCK expression in the Ara‐C sensitivity of BCP‐ALL. DCK gene silencing due to the hypermethylation of a CpG island and reduced DCK activity due to a nonsynonymous variant allele were not associated with Ara‐C sensitivity. Clofarabine is a second‐generation deoxyadenosine analog rationally synthesized to improve stability and reduce toxicity. The IC50 of clofarabine in 79 BCP‐ALL cell lines was approximately 20 times lower than that of Ara‐C. In contrast to Ara‐C, although the knockout of DCK induced marked resistance to clofarabine, sensitivity to clofarabine was only marginally associated with DCK gene expression level, suggesting a possible efficacy of clofarabine for BCP‐ALL that shows relative Ara‐C resistance due to low DCK expression.
A nomogram incorporating six easily obtained parameters to discriminate intrahepatic cholangiocarcinoma and hepatocellular carcinoma
Authors: Wang Mengmeng , Gao Yuzhen , Feng Huijuan , Warner Elisa , An Mingrui , Jia Jian'an , Chen Shipeng , Fang Meng , Ji Jun , Gu Xing , Gao Chunfang
Published: February 2018

Intrahepatic cholangiocarcinoma (ICC) and hepatocellular carcinoma (HCC) are the most prevalent histologic types of primary liver cancer (PLC). Although ICC and HCC share similar risk factors and clinical manifestations, ICC usually bears poorer prognosis than HCC. Confidently discriminating ICC and HCC before surgery is beneficial to both treatment and prognosis. Given the lack of effective differential diagnosis biomarkers and methods, construction of models based on available clinicopathological characteristics is in need. Nomograms present a simple and efficient way to make a discrimination. A total of 2894 patients who underwent surgery for PLC were collected. Of these, 1614 patients formed the training cohort for nomogram construction, and thereafter, 1280 patients formed the validation cohort to confirm the model's performance. Histopathologically confirmed ICC was diagnosed in 401 (24.8%) and 296 (23.1%) patients in these two cohorts, respectively. A nomogram integrating six easily obtained variables (Gender, Hepatitis B surface antigen, Aspartate aminotransferase, Alpha‐fetoprotein, Carcinoembryonic antigen, Carbohydrate antigen 19‐9) is proposed in accordance with Akaike's Information Criterion (AIC). A score of 15 was determined as the cut‐off value, and the corresponding discrimination efficacy was sufficient. Additionally, patients who scored higher than 15 suffered poorer prognosis than those with lower scores, regardless of the subtype of PLC. A nomogram for clinical discrimination of ICC and HCC has been established, where a higher score indicates ICC and poor prognosis. Further application of this nomogram in multicenter investigations may confirm the practicality of this tool for future clinical use.
Chromosomal abnormality variation detected by G‐banding is associated with prognosis of diffuse large B‐cell lymphoma treated by R‐CHOP‐based therapy
Authors: Mizuno Yoshimi , Tsukamoto Taku , Kawata Eri , Uoshima Nobuhiko , Uchiyama Hitoji , Yokota Isao , Maegawa Saori , Takimoto Tomoko , Tanba Kazuna , Matsumura‐Kimoto Yayoi , Kuwahara‐Ota Saeko , Fujibayashi Yuto , Yamamoto‐Sugitani Mio , Chinen Yoshiaki , Shimura Yuji , Horiike Shigeo , Taniwaki Masafumi , Kobayashi Tsutomu , Kuroda Junya
Published: February 2018

Diffuse large B‐cell lymphoma (DLBCL), which is the most prevalent disease subtype of non‐Hodgkin lymphoma, is highly heterogeneous in terms of cytogenetic and molecular features. This study retrospectively investigated the clinical impact of G‐banding‐defined chromosomal abnormality on treatment outcomes of DLBCL in the era of rituximab‐containing immunochemotherapy. Of 181 patients who were diagnosed with DLBCL and treated with R‐CHOP or an R‐CHOP‐like regimen between January 2006 and April 2014, metaphase spreads were evaluable for G‐banding in 120. In these 120 patients, 40 were found to harbor a single chromosomal aberration type; 63 showed chromosomal abnormality variations (CAVs), which are defined by the presence of different types of chromosomal abnormalities in G‐banding, including 19 with two CAVs and 44 with ≥3 CAVs; and 17 had normal karyotypes. No specific chromosomal break point or numerical abnormality was associated with overall survival (OS) or progression‐free survival (PFS), but the presence of ≥3 CAVs was significantly associated with inferior OS rates (hazard ratio (HR): 2.222, 95% confidence interval (CI): 1.056–4.677, P = 0.031) and tended to be associated with shorter PFS (HR: 1.796, 95% CI: 0.965–3.344, P = 0.061). In addition, ≥3 CAVs more frequently accumulated in high‐risk patients, as defined by several conventional prognostic indices, such as the revised International Prognostic Index. In conclusion, our results suggest that the emergence of more CAVs, especially ≥3, based on chromosomal instability underlies the development of high‐risk disease features and a poor prognosis in DLBCL.
Treatment‐related mortality in newly diagnosed pediatric cancer: a population‐based analysis
Authors: Gibson Paul , Pole Jason D. , Lazor Tanya , Johnston Donna , Portwine Carol , Silva Mariana , Alexander Sarah , Sung Lillian ,   the International Pediatric Oncology Mortality Classification (IPOMC) Group
Published: February 2018

Using a previously developed reliable and valid treatment‐related mortality (TRM) definition, our objective was to describe the proportion of children newly diagnosed with cancer experiencing TRM and to identify risk factors for TRM in a population‐based cohort. We included children with cancer <19 years diagnosed and treated in Ontario who were diagnosed between 2003 and 2012. Children with cancer were identified using data in a provincial registry. Cumulative incidence of TRM was calculated where progressive disease death was considered a competing event. Among the 5179 children included, 179 had TRM, 478 died of progressive disease, and 4522 were still alive. At 5 years, the cumulative incidence of TRM among the entire cohort was 3.9% (95% confidence interval (CI) 3.3–4.5%). When compared to brain tumor patients, leukemia and lymphoma patients had a significantly higher risk of TRM (hazard ratio (HR) 2.5, 95% CI: 1.6–4.0; P < 0.0001). Infants were at significantly higher risk of TRM across diagnostic groups. Other factors associated with higher risks of TRM were metastatic disease (P < 0.0001), diagnosis prior to 1 January 2008 (P = 0.001), hematopoietic stem cell transplantation (HSCT) (P < 0.0001), and relapse (P < 0.0001). The 5‐year cumulative incidence of TRM was 3.9% among newly diagnosed children with cancer. Infants were at higher risk of TRM across diagnostic groups. Other risk factors for TRM were leukemia or lymphoma, metastatic disease, earlier diagnosis year, HSCT, and relapse. Future work should further refine prognostic factors by specific cancer diagnosis to best understand when and how to intervene to improve outcomes.
Risk factors and survival outcomes in patients with breast cancer and lung metastasis: a population‐based study
Authors: Xiao Weikai , Zheng Shaoquan , Liu Peng , Zou Yutian , Xie Xinhua , Yu Ping , Tang Hailin , Xie Xiaoming
Published: February 2018

The risk factors for morbidity and mortality in breast cancer lung metastases (BCLM) patients still remain poorly identified. The aim of this study was to assess the incidence and survival of BCLM and associated risk factors. Patients with BCLM were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Multivariate logistic regression analysis was used to determine the risk factors for BCLM. Predictors of factors associated with death were analyzed in Cox regression and Fine and Gray's test. Of the 11568 patients with stage IV breast cancer, 4213 (36.4%) had BCLM and 1214 (10.5%) had metastases confined to lungs. The median survival time for patients with BCLM was 21 months, and 15.5% of the patients were alive more than 3 years. The tumor subtype distribution was 45.3% HR−/HER2−, 12.2% HR+/HER2+, 7.8% HR−/HER2+, and 15.0% triple‐negative subtype. Compared with patients without BCLM, those with BCLM were more likely to be aged, female, black, higher tumor grade, HR−/HER2+, HR+/HER2+, and triple‐negative subtypes at diagnosis. Survival analysis showed that the aged, black race, HR−/HER2+, triple‐negative subtype, higher grade were the independent risk factor for BCLM patients’ survival, while HR+/HER2+ subtype, insured status, and married status suggested better prognosis. In conclusion, the incidence and prognosis of BCLM varied by tumor subtypes, age, and race. Elderly patients with HER2‐positive or triple‐negative tumors were more likely to have BCLM.
Employment benefits and job retention: evidence among patients with colorectal cancer
Authors: Veenstra Christine M. , Abrahamse Paul , Wagner Todd H. , Hawley Sarah T. , Banerjee Mousumi , Morris Arden M.
Published: February 2018

A “health shock,” that is, a large, unanticipated adverse health event, can have long‐term financial implications for patients and their families. Colorectal cancer is the third most commonly diagnosed cancer among men and women and is an example of a specific health shock. We examined whether specific benefits (employer‐based health insurance, paid sick leave, extended sick leave, unpaid time off, disability benefits) are associated with job retention after diagnosis and treatment of colorectal cancer. In 2011–14, we surveyed patients with Stage III colorectal cancer from two representative SEER registries. The final sample was 1301 patients (68% survey response rate). For this study, we excluded 735 respondents who were not employed and 20 with unknown employment status. The final analytic sample included 546 respondents. Job retention in the year following diagnosis was assessed, and multivariable logistic regression was used to evaluate associations between job retention and access to specific employment benefits. Employer‐based health insurance (OR = 2.97; 95% CI = 1.56–6.01; P = 0.003) and paid sick leave (OR = 2.93; 95% CI = 1.23–6.98; P = 0.015) were significantly associated with job retention, after adjusting for sociodemographic, clinical, geographic, and job characteristics.
Adopt a trauma‐informed response to sexual assault investigations
Authors: Hope Joan
Published: February 2018

When you're investigating a sexual assault allegation, understanding how trauma impacts victims can help you conduct a comprehensive and fair investigation. Josh Bronson, director of training for the International Association of Campus Law Enforcement Administrators, formerly the lead sexual assault investigator at the University of Maryland, developed training on trauma‐informed investigations for IACLEA.
Tragedies call for re‐evaluating approach to event safety, security
Authors: O'Brien Timothy
Published: February 2018

The horrific and tragic shooting at the concert in Las Vegas and the use of trucks as deadly weapons in large crowds in France and New York have once again thrust the issues of event‐related safety, security, and liability into the spotlight.
Understand how to comply with NCAA's Academic‐Based Revenue Distribution program
Authors: Shukie John
Published: February 2018

The National Collegiate Athletic Association made an unprecedented announcement in October 2016. For the first time in its history, the NCAA was going to distribute revenue earned from its men's basketball TV contract based on the academic performance of student‐athletes.
Optimizing Water Exchange Rates and Rotational Mobility for High‐Relaxivity of a Novel Gd‐DO3A Derivative Complex Conjugated to Inulin as Macromolecular Contrast Agents for MRI
Authors: Granato Luigi , Vander Elst Luce , Henoumont Celine , Muller Robert N. , Laurent Sophie
Published: February 2018

Thanks to the understanding of the relationships between the residence lifetime τM of the coordinated water molecules to macrocyclic Gd‐complexes and the rotational mobility τR of these structures, and according to the theory for paramagnetic relaxation, it is now possible to design macromolecular contrast agents with enhanced relaxivities by optimizing these two parameters through ligand structural modification. We succeeded in accelerating the water exchange rate by inducing steric compression around the water binding site, and by removing the amide function from the DOTA‐AA ligand [1,4,7,10‐tetraazacyclododecane‐1,4,7,10‐tetraacetic acid mono(p‐aminoanilide)] (L) previously designed. This new ligand 10[2(1‐oxo‐1‐p‐propylthioureidophenylpropyl]‐1,4,7,10‐tetraazacyclodecane‐1,4,7‐tetraacetic acid (L1) was then covalently conjugated to API [O‐(aminopropyl)inulin] to get the complex API‐(GdL1)x with intent to slow down the rotational correlation time (τR) of the macromolecular complex. The evaluation of the longitudinal relaxivity at different magnetic fields and the study of the 17O‐NMR at variable temperature of the low‐molecular‐weight compound (GdL1) showed a slight decrease of the τM value ( = 331 ns vs.  = 450 ns for the GdL complex). Consequently to the increase of the size of the API‐(GdL1)x complex, the rotational correlation time becomes about 360 times longer compared to the monomeric GdL1 complex (τR = 33,700 ps), which results in an enhanced proton relaxivity.
Cyanine Photocages Enable Spatial Control of Inducible Cre‐Mediated Recombination
Authors: Gorka Alexander P. , Yamamoto Tsuyoshi , Zhu Jianjian , Schnermann Martin J.
Published: February 2018

Optical control over protein expression could provide a means to interrogate a range of biological processes. One approach has employed caged ligands of the estrogen receptor (ER) in combination with broadly used ligand‐dependent Cre recombinase proteins. Existing approaches use UV or blue wavelengths, which hinders their application in tissue settings. Additionally, issues of payload diffusion can impede fine spatial control over the recombination process. Here, we detail the chemical optimization of a near‐infrared (NIR) light‐activated variant of the ER antagonist cyclofen. These studies resulted in modification of both the caging group and payload with lipophilic n‐butyl esters. The appendage of esters to the cyanine cage improved cellular uptake and retention. The installation of a 4‐piperidyl ester enabled high spatial resolution of the light‐initiated Cre‐mediated recombination event. These studies described chemical modifications with potential general utility for improving spatial control of intracellular caging strategies. Additionally, these efforts will enable future applications to use these molecules in complex physiological settings.
Understanding the importance of process alarms based on the analysis of deep recurrent neural networks trained for fault isolation
Authors: Dorgo Gyula , Pigler Peter , Abonyi Janos
Published: February 2018

The identification of process faults is a complex and challenging task due to the high amount of alarms and warnings of control systems. To extract information about the relationships between these discrete events, we utilise multitemporal sequences of alarm and warning signals as inputs of a recurrent neural network–based classifier and visualise the network by principal component analysis. The similarity of the events and their applicability in fault isolation can be evaluated based on the linear embedding layer of the network, which maps the input signals into a continuous‐valued vector space. The method is demonstrated in a simulated vinyl acetate production technology. The results illustrate that with the application of recurrent neural network–based sequence learning not only accurate fault classification solutions can be developed, but the visualisation of the model can give useful hints for hazard analysis.
Elucidating the Nature of the Excited State of a Heteroleptic Copper Photosensitizer by using Time‐Resolved X‐ray Absorption Spectroscopy
Authors: Moonshiram Dooshaye , Garrido‐Barros Pablo , Gimbert‐Suriñach Carolina , Picón Antonio , Liu Cunming , Zhang Xiaoyi , Karnahl Michael , Llobet Antoni
Published: February 2018

We report the light‐induced electronic and geometric changes taking place within a heteroleptic CuI photosensitizer, namely [(xant)Cu(Me2phenPh2)]PF6 (xant=xantphos, Me2phenPh2=bathocuproine), by time‐resolved X‐ray absorption spectroscopy in the ps–μs time regime. Time‐resolved X‐ray absorption near edge structure (XANES) and extended X‐ray absorption fine structure (EXAFS) analysis enabled the elucidation of the electronic and structural configuration of the copper center in the excited state as well as its decay dynamics in different solvent conditions with and without triethylamine acting as a sacrificial electron donor. A three‐fold decrease in the decay lifetime of the excited state is observed in the presence of triethylamine, showing the feasibility of the reductive quenching pathway in the latter case. A prominent pre‐edge feature is observed in the XANES spectrum of the excited state upon metal to charge ligand transfer transition, showing an increased hybridization of the 3d states with the ligand p orbitals in the tetrahedron around the Cu center. EXAFS and density functional theory illustrate a significant shortening of the Cu−N and an elongation of the Cu−P bonds together with a decrease in the torsional angle between the xantphos and bathocuproine ligand. This study provides mechanistic time‐resolved understanding for the development of improved heteroleptic CuI photosensitizers, which can be used for the light‐driven production of hydrogen from water.