bluuebunny/crossref_metadata_2025 huggingface dataset:
Bio‐ethylene from sugarcane as a competitiveness strategy for the Brazilian chemical industry
Authors: Oliveira Camilla C.N. , Rochedo Pedro R.R. , Bhardwaj Rajat , Worrell Ernst , Szklo Alexandre
Published: December 2019

The urgency with which the world economy needs to be decarbonized could lead to the emergence of regions with the capacity to produce renewable feedstock such as biomass. The competitiveness of these regions could result from their ability to produce high value‐added chemicals at the lowest cost. The biomass embodied in a chemical product could reduce carbon emissions, leading to net CO2 removal. The aim of this study was to test the hypothesis that bio‐ethylene could make the Brazilian chemical industry more competitive. This would be achieved by applying the revenues from carbon credits associated with using ethanol and sugarcane bagasse as feedstocks for bio‐ethylene production. Three production routes were compared according to their estimated cost of production in Brazil under a simplified life‐cycle analysis: sugar‐cane‐derived ethanol to ethylene (with and without CO2 capture and storage – BECCS); bio‐methanol to olefin; and conventional steam cracking of naphtha. When associated with the production of long‐lasting materials, the ethanol‐to‐ethylene with BECCS route achieved the lower CO2 break‐even price (US$75/t CO2), followed by ethanol to ethylene without BECCS (US$82/t CO2) and bio‐methanol to ethylene (US$106/t CO2). Our findings highlight the advantage for the Brazilian chemical industry of implementing a national or, even better, a global carbon‐pricing instrument. © 2019 Society of Chemical Industry and John Wiley & Sons, Ltd
A two‐level study of predictors of private tutoring attendance at the beginning of secondary schooling in Germany: The role of individual learning support in the classroom
Authors: Guill Karin , Lüdtke Oliver , Schwanenberg Jasmin
Published: December 2019

More and more students attend private supplementary tutoring to improve their academic achievement. Private tutoring might be understood as a reaction to insufficient instructional quality in school, especially regarding individual support. However, it might also be possible that parents generally see insufficient grades as an indicator of lacking support and engage a tutor in hopes of improvement or to enhance a competitive edge for their children. So far, the relationship between tutoring attendance and perceived individual learning support during classroom lessons has not been tested. We used multilevel analyses based on N = 2,842 students in 102 Grade 5 classrooms at German academic track schools to test for a relationship between private tutoring in several subjects and students’ shared perception of the instructional quality in these subjects. On the individual level, we controlled for typical predictors of private tutoring such as academic achievement and family income, as well as for additional variables such as working behaviour and parental homework assistance. In classrooms with more individual support, students were less likely to start private tutoring in English. However, we did not find comparable relationships for tutoring in mathematics and German. Therefore, school principals and educational policy‐makers should monitor the incidence of private tutoring and consider within‐school structured tutoring programmes as an effective measure to improve academic achievement and to meet parents’ desire for individualised instruction.
Evaluation of Lateral Resolution for Confocal Raman Microscopy Using Gold Nano‐Lines Made by Electron Beam Lithography
Authors: Park Jaesung , Kim Jeongyong , Kwon Hyuksang
Published: December 2019

Assessing the instrumental resolution of confocal Raman microscopy is a key aspect in 2D or 3D imaging in various applications. An important issue in this regard is the experimental measurement of a lateral resolution for the Raman microscope system. Several methods have been proposed for the resolution measurement in fluorescence microscopy; however, these methods have rather limited applications. In this paper, we demonstrate an experimental approach for evaluating the lateral resolution with well‐defined nano‐patterns in confocal Raman microscopy and discuss the factors that can improve estimation of instrumental resolution. This study contributes to the further understanding of the assessment of instrumental resolution in confocal scanning Raman microscopy.
Pharmacokinetics of doxorubicin following concomitant intravenous administration of olaratumab (IMC‐3G3) to patients with advanced soft tissue sarcoma
Authors: Villalobos Victor M. , Mo Gary , Agulnik Mark , Pollack Seth M. , Rushing Daniel A. , Singh Arun , Van Tine Brian A. , McNaughton Rhian , Decker Rodney L. , Zhang Wei , Shahir Ashwin , Cronier Damien M.
Published: December 2019

Background

Olaratumab, a fully human monoclonal antibody, selectively binds to human platelet‐derived growth factor receptor alpha and blocks ligand binding. This study assessed the effect of olaratumab on the pharmacokinetics (PK) of doxorubicin and the safety of olaratumab alone and in combination with doxorubicin.

Methods

This open‐label randomized phase 1 trial enrolled 49 patients ages 27 to 83 with metastatic or locally advanced soft tissue sarcoma (STS). Patients participated in 21‐day treatment cycles (up to 8) until they met discontinuation criteria. In cycles 1 and 2, patients received olaratumab (15 mg/kg in Part A, 20 mg/kg in Part B) and doxorubicin (75 mg/m2). In cycles 3 through 8, patients continued combination treatment (15 mg/kg olaratumab + doxorubicin). Effect of olaratumab on PK of doxorubicin was determined in patients who received all doses in cycles 1 and 2.

Results

PK properties of doxorubicin administered alone or in combination with olaratumab (15 or 20 mg/kg) were similar for AUC(0‐tlast), AUC(0‐∞), and Cmax. PK properties of olaratumab (15 or 20 mg/kg) were also similar when administered alone or in combination with doxorubicin. Three patients died (2 of disease progression and 1 of neutropenic enterocolitis). Fatigue and nausea (>75% of patients) were the most common treatment‐emergent adverse events (TEAEs). Other common TEAEs included musculoskeletal pain, mucositis, constipation, and diarrhea.

Conclusions

Olaratumab at 15 or 20 mg/kg before doxorubicin infusion had no clinically relevant effect on systemic exposure to doxorubicin compared with doxorubicin alone in patients with metastatic or locally advanced STS.
Autoimmune diseases and immunosuppressive therapy in relation to the risk of glioma
Authors: Haedenkamp Tareq M. , Leitzmann Michael F. , Linker Ralf A. , Meier Christoph , Becker Claudia , Jick Susan , Sahm Katharina , Platten Michael , Hau Peter , Seliger Corinna
Published: December 2019

Effectors from the immune system can modulate the course and possibly the early development of gliomas. We, therefore, hypothesized that autoimmune diseases associated with increased immune‐surveillance may also modulate the risk of human glioma. To test this hypothesis, we used data from the well‐validated Clinical Practice Research Datalink (CPRD) GOLD from the UK to analyze the association of immune‐related disorders or use of immunosuppressive drugs and the risk of glioma. We identified 3112 incident glioma cases diagnosed between 1995 and 2017. We randomly selected up to 10 controls, matching them to glioma cases on age, sex, index date, general practice, and number of years of active history in the database prior to the index date. We performed conditional logistic regression analyses to estimate Odds Ratios (ORs) of glioma among those exposed to allergies, autoimmune diseases, and immunosuppressive drugs. Overall, we found no materially altered association between a history of any autoimmune disease (OR 0.98, 95% CI 0.86‐1.11), allergy (OR 0.97, 95% CI 0.89‐1.05), or use of immunosuppressive drugs and the risk of glioma. However, subgroup analyses among younger patients found a statistically significant increased risk of glioma in patients with a history of inflammatory bowel disease (IBD) (OR 2.59, 95% CI 1.31‐5.12). There was also an inverse association between asthma and risk of glioma in patients with longer survival (OR 0.73, 95% CI 0.58‐0.91) and between long‐term duration diabetes and risk of glioma (OR 0.71, 95% CI 0.53‐0.96).
Calcium Regulates S100A12 Zinc Sequestration by Limiting Structural Variations
Authors: Wang Qian , Aleshintsev Aleksey , Jose Aneesha N. , Aramini James M. , Gupta Rupal
Published: December 2019

Antimicrobial proteins such as S100A12 and S100A8/A9 are highly expressed and secreted by neutrophils during infection and participate in human immune response by sequestering transition metals. At neutral pH, S100A12 sequesters Zn2+ with nanomolar affinity, which is further enhanced upon calcium binding. We investigated the pH dependence of human S100A12 zinc sequestration by using Co2+ as a surrogate. Apo‐S100A12 exhibits strong Co2+ binding between pH 7.0 and 10.0 that progressively diminishes as the pH is decreased to 5.3. Ca2+‐S100A12 can retain nanomolar Co2+ binding up to pH 5.7. NMR spectroscopic measurements revealed that calcium binding does not alter the side‐chain protonation of the Co2+/Zn2+ binding histidine residues. Instead, the calcium‐mediated modulation is achieved by restraining pH‐dependent conformational changes to EF loop 1, which contains Co2+/Zn2+ binding Asp25. This calcium‐induced enhancement of Co2+/Zn2+ binding might assist in the promotion of antimicrobial activities in humans by S100 proteins during neutrophil activation under subneutral pH conditions.
A rare entity: Sympathetic ophthalmia presumably after blunt trauma to the phthisical eye and optical coherence tomography angiography metrics to monitor response to treatment
Authors: Khatri Anadi , Timalsena Satish , Khatri Bal Kumar , Kharel Muna , Gautam Sudhir , Gurung Jeena , Kafle Santosh
Published: December 2019

A blunt trauma to a phthisical eye may elicit sympathetic ophthalmia. Non invasive imaging such as use of optical coherence tomography and angiography metrics of the retinal and choroidal vasculature can help monitor response to the treatment.
Iron‐porphyrin Catalyzed Carbene Transfer Reactions – an Evolution from Biomimetic Catalysis towards Chemistry‐inspired Non‐natural Reactivities of Enzymes
Authors: Weissenborn Martin J. , Koenigs Rene M.
Published: December 2019

Bioinspired, synthetic porphyrin complexes are important catalysts in organic synthesis and play a pivotal role in efficient carbene transfer reactions. The advances in this research area stimulated recent, “chemo‐inspired” developments in biocatalysis. Today, both synthetic iron complexes and enzymes play an important role to conduct carbene transfer reactions. The advances and potential developments in both research areas are discussed in this concept article.
Recent Advances in Electrochemical Oxidative Cross‐Coupling of Alkenes with H2 Evolution
Authors: Wang Pan , Gao Xinlong , Huang Pengfei , Lei Aiwen
Published: December 2019

Alkenes are a kind of valuable building blocks which have been found in natural products, pharmaceuticals and industrial materials. Direct functionalization of olefins has been extensively studied over the past years. The replacement of conventional approach by more atom‐economic and greener electrochemical method is an attractive technique with huge synthetic potential as well as inherent safety. Electrochemical oxidative cross coupling of alkenes, which conforms to green synthesis and atom economy has been developed in recent years. This review summarizes the recent development of electrochemical dehydrogenative functionalization of alkenes in different transformations.
Novel LIBS method for micro‐spatial chemical analysis of inorganic gunshot residues
Authors: Menking‐Hoggatt Korina , Arroyo Luis , Curran James , Trejos Tatiana
Published: December 2019

This study developed a reliable laser‐induced breakdown spectroscopy (LIBS) screening approach capable of detecting GSR in just a few minutes with minimal damage to the sample, high specificity, and sensitivity. Moreover, a novel micro‐sampling method was developed to gather three‐dimensional data of the simultaneous occurrence of IGSR markers from a discrete space. The method is capable of micro‐spatial chemical analysis from just two laser shots fired at an area of 100‐μm diameter. The performance of the micro‐spot method is compared with our previously published bulk‐line method. Superior accuracy, spatial information of IGSR distribution in the sample, and a less invasive sampling are some of the advantages of the newly proposed method. A benefit afforded by this approach is the use of the universal hand's collection method currently used by practitioners, while leaving over 99% of the stub left unaltered for further analysis.

Machine learning algorithms were used for the classification of samples derived from shooters' hands versus nonshooters hands, based on their LIBS spectrochemical data. Four different approaches—critical threshold, logistic regression, naïve Bayes, and neural networks—were applied to examine the performance and accuracy of two different ablation patterns (micro‐spot and bulk‐line mode). A validation set of 326 samples originated from 51 nonshooters and 56 known shooters resulted in an overall accuracy between 87% and 100%, depending on the ablation pattern and the type of prediction model applied. The incorporation of this rapid screening and statistical decision‐making approach could offer more efficient case management in firearm‐related investigations.
Molecular Engineering Approaches Towards All‐Organic White Light Emitting Materials
Authors: Kundu Subhankar , Sk Bahadur , Pallavi Pragyan , Giri Arkaprabha , Patra Abhijit
Published: December 2019

White light emitting (WLE) materials are of increasing interest owing to their promising applications in artificial lighting, display devices, molecular sensors, and switches. In this context, organic WLE materials cater to the interest of the scientific community owing to their promising features like color purity, long‐term stability, solution processability, cost‐effectiveness, and low toxicity. The typical method for the generation of white light is to combine three primary (red, green, and blue) or the two complementary (e.g., yellow and blue or red and cyan) emissive units covering the whole visible spectral window (400–800 nm). The judicious choice of molecular building blocks and connecting them through either strong covalent bonds or assembling through weak noncovalent interactions are the key to achieve enhanced emission spanning the entire visible region. In the present review article, molecular engineering approaches for the development of all‐organic WLE materials are analyzed in view of different photophysical processes like fluorescence resonance energy transfer (FRET), excited‐state intramolecular proton transfer (ESIPT), charge transfer (CT), monomer‐excimer emission, triplet‐state harvesting, etc. The key aspect of tuning the molecular fluorescence under the influence of pH, heat, and host–guest interactions is also discussed. The white light emission obtained from small organic molecules to supramolecular assemblies is presented, including polymers, micelles, and also employing covalent organic frameworks. The state‐of‐the‐art knowledge in the field of organic WLE materials, challenges, and future scope are delineated.
Different formins restrict localization of distinct tropomyosins on dorsal stress fibers in osteosarcoma cells
Authors: Zhao Shuangshuang , Cai Jinping , Zhang Xin , Cui Jie , Jiu Yaming
Published: December 2019

Formins and tropomyosins (Tpms) are two central components of the microfilaments. Formins are involved in the nucleation and polymerization of actin filaments, and Tpms form along the actin stress fibers to regulate their dynamics. However, the correlation between formins and Tpms remains unclear. Here, we elucidated the function of distinct formins and their specific regulation to the subcellular‐localization of Tpm isoforms on dorsal stress fibers in human osteosarcoma cells. Knockdown of individual formin isoform led to varied defects in actin stress fiber network, but did not affect the expression level of other formin isoforms and Tpms. Further investigation showed that different formins regulated distinct Tpm isoforms in decorating dorsal stress fibers. Specifically, DAAM1 and FHOD1 restricted the distal end expression of Tpm3.1; INF2 controlled the approximate localization of Tpm4.2; and Dia1 partially modulated the dorsal localization of Tpm1.6. Taken together, these data provide microscopy experimental evidence that different formins restrict the localization of distinct Tpm isoforms on dorsal actin stress fibers.
Communication during childhood cancer: Systematic review of patient perspectives
Authors: Lin Beryl , Gutman Talia , Hanson Camilla S. , Ju Angela , Manera Karine , Butow Phyllis , Cohn Richard J. , Dalla‐Pozza Luciano , Greenzang Katie A. , Mack Jennifer , Wakefield Claire E. , Craig Jonathan C. , Tong Allison
Published: December 2019

Effective communication is challenging in childhood cancer, where decisions carry unpredictable and life‐threatening implications. We aimed to describe patients' experiences of communicating with clinicians during treatment of childhood cancer. A systematic review of qualitative studies to April 2019 was performed. Eligible studies included patients diagnosed with cancer at age ≤ 18 years and reported their perspectives of communicating with clinicians during treatment of childhood cancer. Data were extracted from primary studies for thematic synthesis. From 101 articles across 25 countries involving 1870 participants who were diagnosed with cancer between ages 3 to 18 years, we identified 6 themes: 1) rendered invisible and powerless (displaced and undermined by adult authority; betrayed and distrustful; feeling neglected; helpless and intimidated; disempowered by lack of information); 2) fear and worry for the future (paralyzed by devastating news; uncertainty, anticipation, and dread; broaching intimate and private topics); 3) burdened with responsibility (pressured and unprepared; balancing external expectations; protecting hope); 4) therapeutic patient-provider relationships (emotional support and encouragement; validated personhood and companionship); 5) safety in trust (truthfulness and transparency; prepared by awareness and understanding; reassured by reliable expertise; depending on adults for protection and difficult decisions; security in expressing opinions and needs); and 6) empowerment and assertive agency (right to individual knowledge and choice; control over own life; partnership and respect; enhancing capacity for self‐management). During treatment of childhood cancer, patients gain a sense of respect, safety, and control when they feel clinicians address their information and developmental needs. However, communication that is perceived to be parent‐centered can be disempowering. Promoting child agency and partnership may improve care and outcomes for children with cancer.
Integrated cancer networks improve compliance with national guidelines and outcomes for resectable gastric cancer
Authors: Thiels Cornelius A. , Hanson Kristine T. , Habermann Elizabeth B. , Boughey Judy C. , Grotz Travis E.
Published: December 2019

Background

National Comprehensive Cancer Network (NCCN) guidelines recommend accurate clinical staging, perioperative therapy, and complete lymphadenectomy for patients with stage II to III gastric cancer. However, national compliance remains low. It was hypothesized that integrated cancer networks might improve compliance and outcomes within the community.

Methods

Patients with stage II to III gastric adenocarcinoma undergoing curative‐intent resection (National Cancer Data Base, 2006‐2015) were examined. Guideline compliance was defined as any perioperative adjunctive therapy, complete lymphadenectomy, complete clinical staging, and complete compliance (all measures). Univariate comparisons and multivariable regression were used to assess factors associated with compliance, and Kaplan‐Meier analysis was used to assess survival.

Results

There were 27,210 patients identified: 7235 (26.6%) underwent surgery alone, whereas 19,975 (73.4%) received additional therapy. Half (53.1%) had complete lymphadenectomies, whereas complete clinical staging was available for 65.5%. Overall compliance with all 3 measures was 30.1%. Compliance improved by approximately 20% for each measure across the 10‐year study period. Although patients treated at academic programs were most likely to receive concordant care in an adjusted analysis, those treated at integrated care networks were more likely to receive guideline‐concordant care (odds ratio [OR], 0.69) than those treated at comprehensive community programs (OR, 0.48) or community programs (OR, 0.45; all P values <.001). The median overall survival was 45.5 months for patients who received guideline‐concordant care and 32.0 months for those who did not (P < .001, reference for all ORs: academic programs).

Conclusions

Compliance with guidelines was associated with improved outcomes. Although the rate of compliance with NCCN guidelines is improving, integrated care networks may be an important way of improving the quality of gastric cancer care within the community.
PD‐L1 and thyroid cytology: A possible diagnostic and prognostic marker
Authors: Dell’Aquila Marco , Granitto Alessia , Martini Maurizio , Capodimonti Sara , Cocomazzi Alessandra , Musarra Teresa , Fiorentino Vincenzo , Pontecorvi Alfredo , Lombardi Celestino Pio , Fadda Guido , Pantanowitz Liron , Larocca Luigi Maria , Rossi Esther Diana
Published: December 2019

Background

Programmed death‐ligand 1 (PD‐L1) expression is emerging as an important predictive biomarker in anti–PD‐L1 cancer immunotherapy. Its role has been clearly defined in various human cancers and is linked to a poor prognosis and resistance to anticancer therapies. The role of PD‐L1 in thyroid cancers has not been well defined in fine‐needle aspiration cytology (FNAC). The authors examined the performance of PD‐L1 immunostaining in liquid‐based cytology (LBC) to determine whether it could be a biomarker of malignancy or aggressive disease.

Methods

From January 2018 to March 2019, 236 thyroid lesions, which had been diagnosed by FNAC as indeterminate lesions, suspicious for malignancy (SFM), and malignant, were enrolled. PD‐L1 immunostaining was performed on both LBC and corresponding histology samples.

Results

The FNAC cohort included 50 benign negative controls, 42 samples of atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS), 33 samples of follicular neoplasm/suspicious for follicular neoplasm (FN/SFN), 53 samples that were suspicious for malignancy (SFM), and 58 malignant samples. AUS/FLUS samples included 3 goiters, 32 follicular adenomas (FAs), 1 noninvasive follicular thyroid neoplasm with papillary‐like nuclear features (NIFTP), 5 invasive follicular variants of papillary thyroid carcinoma (I‐FVPTCs), and 1 follicular carcinoma; whereas FN/SFN samples included 24 FAs and 9 malignancies (4 I‐FVPTCs, 1 NIFTP, 3 papillary thyroid carcinomas [PTCs], and 1 oncocytic follicular carcinoma). The 53 SFM samples were diagnosed on histopathology as 2 FAs, 5 NIFTPs, 15 I‐FVPTCs, and 31 PTCs; whereas the 58 malignant specimens included 5 NIFTPs, 5 I‐FVPTCs, and 48 PTCs. Increased plasma membrane and cytoplasmic PD‐L1 expression was found in 79 cases (38.5%), including 61 PTCs (conventional and variants). Negative PD‐L1 expression was found in NIFTPs and FAs. A BRAF V600E mutation was identified in 15% of PD‐L1–positive malignancies.

Conclusions

The current data suggest that PD‐L1 expression in the thyroid gland might represent a marker of malignancy that correlates with PTC, but not with NIFTP. Thyroid neoplasms with PD‐L1 expression also ae enriched with BRAF V600E mutations, suggesting that they are associated with more aggressive behavior.
Microstructural analysis of skeletal muscle force generation during aging
Authors: Zhang Yantao , Chen Jiun‐Shyan , He Qizhi , He Xiaolong , Basava Ramya R. , Hodgson John , Sinha Usha , Sinha Shantanu
Published: December 2019

Human aging results in a progressive decline in the active force generation capability of skeletal muscle. While many factors related to the changes of morphological and structural properties in muscle fibers and the extracellular matrix (ECM) have been considered as possible reasons for causing age‐related force reduction, it is still not fully understood why the decrease in force generation under eccentric contraction (lengthening) is much less than that under concentric contraction (shortening). Biomechanically, it was observed that connective tissues (endomysium) stiffen as ages, and the volume ratio of connective tissues exhibits an age‐related increase. However, limited skeletal muscle models take into account the microstructural characteristics as well as the volume fraction of tissue material. This study aims to provide a numerical investigation in which the muscle fibers and the ECM are explicitly represented to allow quantitative assessment of the age‐related force reduction mechanism. To this end, a fiber‐level honeycomb‐like microstructure is constructed and modeled by a pixel‐based Reproducing Kernel Particle Method (RKPM), which allows modeling of smooth transition in biomaterial properties across material interfaces. The numerical investigation reveals that the increased stiffness of the passive materials of muscle tissue reduces the force generation capability under concentric contraction while maintains the force generation capability under eccentric contraction. The proposed RKPM microscopic model provides effective means for the cellular‐scale numerical investigation of skeletal muscle physiology.

Novelty Statement

A cellular‐scale honeycomb‐like microstructural muscle model constructed from a histological cross‐sectional image of muscle is employed to study the causal relations between age‐associated microstructural changes and age‐related force loss using Reproducing Kernel Particle Method (RKPM).

The employed RKPM offers an effective means for modeling biological materials based on pixel points in the medical images and allow modeling of smooth transition in the material properties across interfaces.

The proposed microstructure‐informed muscle model enables quantitative evaluation on how cellular‐scale compositions contribute to muscle functionality and explain differences in age‐related force changes during concentric, isometric and eccentric contractions.
Evaluation of Clinical Cardiac Safety of Itacitinib, a JAK1 Inhibitor, in Healthy Participants
Authors: Gong Xiaohua , Darpo Borje , Xue Hongqi , Punwani Naresh , He Kevin , Barbour April M. , Epstein Noam , Landman Robert , Chen Xuejun , Yeleswaram Swamy
Published: December 2019

Itacitinib is a JAK1‐selective inhibitor in phase 3 development in graft‐versus‐host disease. A post hoc electrocardiogram (ECG) analysis and a plasma concentration‐QTc (C‐QTc) analysis were performed to assess cardiac safety using data from the first‐in‐human itacitinib study. The study included 2 cohorts of 12 healthy participants each in an interleaving dosing design with single doses of 10‐300 mg or placebo; 500 and 1000 mg doses were subsequently added with 12 participants randomized to itacitinib or placebo. Continuous Holter recordings were collected from 1 hour predose to 8 hours postdose on each dosing day, and ECG intervals were blindly extracted to match timed pharmacokinetic samples. Data showed no hysteresis, and a prespecified linear mixed‐effects C‐QTc model was used with change‐from‐baseline QTcF (QT interval corrected for heart rate by Fridericia's method) as the dependent variable, plasma itacitinib concentrations and centered baseline QTcF as continuous covariates, treatment and time as categorical factors, and a random intercept per participant. The estimated slope of the C‐QTc relationship was not significantly different from zero: 0.0002 milliseconds per nM (90%CI, ‐0.00019 to 0.00054 milliseconds). No clinically meaningful effects on cardiac conduction (PR and QRS intervals) or any categorical PR or QRS outliers were observed. A QTc effect exceeding the threshold of concern (10 milliseconds) can be excluded for itacitinib plasma concentrations up to ∼13 000 nM (∼7200 ng/mL), which is well above the maximum concentration expected with the highest proposed therapeutic dose of itacitinib either with concomitant use of cytochrome P450 3A4 inhibitors or in patients with impaired hepatic function.
Performance enhancement for iterative data computing with in‐memory concurrent processing
Authors: Wen Yean‐Fu , Chen Yu‐Fang , Chiu Tse Kai , Chen Yen‐Chou
Published: December 2019

The big data era has resulted in the development of several data analysis tools. Spark is a type of in‐memory processing fitted iteration and interactive data mining tool. This tool possesses higher data‐processing performance than MapReduce, which is an offline storage mechanism. However, some disadvantages of in‐memory processing, such as massive in‐memory data requirements, cause cross‐node data transfer that result in a long computation time. The performance of the process can be improved if the in‐memory process is executed with fewer shuffle instructions. Therefore, this study aims to enhance the performance of iterative application through instruction replacement. Three empirical research cases with diverse datasets and iterations are used to modify the program. We adopt a strategy of downloading a small resilient distributed dataset and replacing the shuffle‐included instructions to shorten the processing time with an automated code replacement by using exhaustively code matching. The experimental results reveal an improvement of up to 39% in the execution time compared with the existing in‐memory processing programs with various dataset sizes.
Novel Photoactive Spirooxazine Based Switch@MOF Composite Materials
Authors: Schwartz Heidi A. , Werker Melanie , Tobeck Christian , Christoffels Ronja , Schaniel Dominik , Olthof Selina , Meerholz Klaus , Kopacka Holger , Huppertz Hubert , Ruschewitz Uwe
Published: December 2019

Molecules, which reversibly transform between two structural configurations upon excitation with electromagnetic radiation, are attractive candidates for the design of smart materials e. g. memory devices. A possible approach for the development of such smart materials is the construction of hybrid systems that contain these photochromic molecules as well as a porous host matrix, which enables their switching process in the solid state. We herein present the first light‐responsive materials consisting of the photoswitchable spirooxazine 1,3,3‐trimethyl indolinonaphthospirooxazine (SP−O) and crystalline porous MOF (metal–organic framework) hosts, namely MOF‐5, MIL‐68(In), MIL‐68(Ga), and MIL‐53(Al), which were combined to form hybrid SP−O@MOF composites. These systems show a reversible photochromic response and host‐dependent absorption maxima of the incorporated guest molecules. Most remarkably, SP−O is extremely photostable upon repetitive and prolonged UV light exposure especially inside MOF‐5, making these composite materials attractive candidates for potential applications in data storage devices.
Surgery for the diabetic foot: A key component of care
Authors: Frykberg Robert G. , Wukich Dane K. , Kavarthapu Venu , Zgonis Thomas , Dalla Paola Luca ,   Board of the Association of Diabetic Foot Surgeons
Published: December 2019

Surgery for acute and chronic diabetic foot problems has long been an integral component of care. While partial foot amputations remain as important diabetic limb‐salvaging operations, foot‐sparing reconstructive procedures have become equally important strategies to preserve the functional anatomy of the foot while addressing infection, chronic deformities, and ulcerations. A classification of types of diabetic foot surgery is discussed in accordance with the soft tissue status and acuity of the presenting foot problem. This brief overview from the Association for Diabetic Foot Surgeons describes common conditions best treated by surgical interventions, as well as specific indications. While techniques and indications continue to evolve, effective surgical management of the diabetic foot remains an integral component of care as well as for the prevention of recurrent ulceration.
Shipping alters the movement and behavior of Arctic cod (Boreogadus saida), a keystone fish in Arctic marine ecosystems
Authors: Ivanova Silviya V. , Kessel Steven T. , Espinoza Mario , McLean Montana F. , O'Neill Caitlin , Landry Justin , Hussey Nigel E. , Williams Rob , Vagle Svein , Fisk Aaron T.
Published: December 2019

Anthropogenic noise associated with shipping has emerged as a major disruptor of aquatic animal behavior worldwide. The Arctic marine realm has historically experienced little noise‐generating human activity; however, the continual loss of sea ice has facilitated a dramatic increase in shipping activity. Here, we use a combination of acoustic telemetry and modeling of ship noise to examine the temporospatial habitat use of key Arctic forage fish, Arctic cod (Boreogadus saida) in the presence and absence of vessels in Resolute Bay, Nunavut, Canada. The presence and movement of vessels induced a horizontal shift in the home ranges of Arctic cod with low core overlap when compared to periods without vessel activity. Home range displacement occurred near the vessel. Individuals also altered their swimming behaviors in response to vessel presence with searching decreasing and travelling increasing in proportion. Results indicate that Arctic cod perceive vessel noise and presence as a threat and react by moving away and decreasing exploratory activities. These changes in fish behavior also coincide with the critical open water feeding period suggesting an interruption in exploitation of important and seasonally abundant food resources, and carry broader implications for dependent seabirds and marine mammals, and indirectly for all Arctic indigenous peoples’ subsistence and long‐term cultural traditions. Our study implies that strategic management is required for aquatic acoustic disturbance as an environmental stressor in the Arctic marine ecosystem, and highlights ecologically and socially important impacts that require timely conservation action.
Dialectical behavior therapy self‐help for binge‐eating disorder: A randomized controlled study
Authors: Carter Jacqueline C. , Kenny Therese E. , Singleton Christopher , Van Wijk Megan , Heath Olga
Published: December 2019

Objective

The objective of this study was to compare the relative effectiveness of dialectical behavior therapy guided self‐help (DBT‐GSH) and DBT unguided self‐help (DBT‐USH) with an unguided self‐help control condition in the treatment of binge‐eating disorder (BED).

Method

Seventy‐one participants who met diagnostic criteria for BED based on Eating Disorder Examination (EDE) interview were randomly assigned to DBT‐GSH, DBT‐USH or active control USH for 12 weeks. Assessments took place at baseline, 12 weeks and 3‐month follow‐up. Outcome measures included the EDE to assess binge frequency, the EDE‐Questionnaire (EDE‐Q), the Brief Symptom Inventory, and the Short Form 6D.

Results

The overall completion rate was 65% at post‐treatment and 63% at 3‐month follow‐up. Intention to treat analyses showed that participants in all three conditions reported significant reductions in binge frequency with large effect sizes. A similar pattern emerged for secondary outcome variables including eating disorder psychopathology, general psychological distress, and health‐related quality of life.

Discussion

Self‐help may be an effective way to disseminate DBT for BED. However, future research should evaluate DBT self‐help using a larger sample size, possibly in a multisite design.
The fiddler crab, Minuca pugnax, follows Bergmann's rule
Authors: Johnson David Samuel , Crowley Cynthia , Longmire Katherine , Nelson James , Williams Bethany , Wittyngham Serina
Published: December 2019

Bergmann's rule predicts that organisms at higher latitudes are larger than ones at lower latitudes. Here, we examine the body size pattern of the Atlantic marsh fiddler crab, Minuca pugnax (formerly Uca pugnax), from salt marshes on the east coast of the United States across 12 degrees of latitude. We found that M. pugnax followed Bergmann's rule and that, on average, crab carapace width increased by 0.5 mm per degree of latitude. Minuca pugnax body size also followed the temperature–size rule with body size inversely related to mean water temperature. Because an organism's size influences its impact on an ecosystem, and M. pugnax is an ecosystem engineer that affects marsh functioning, the larger crabs at higher latitudes may have greater per‐capita impacts on salt marshes than the smaller crabs at lower latitudes.
Trait‐based diatom functional diversity as an appropriate tool for understanding the effects of environmental changes in soda pans
Authors: Stenger‐Kovács Csilla , Lengyel Edina , Buczkó Krisztina , Padisák Judit , Korponai János
Published: December 2019

Saline lakes, among the most seriously endangered ecosystems, are threatened due to climate change and human activities. One valuable feature of these environments is that they constitute areas of high biodiversity. Ecologists are, therefore, under great pressure to improve their understanding of the effects of natural and anthropogenic disturbances on the biodiversity of saline lakes. In this study, a total of 257 samples from 32 soda pans in Central Europe between 2006 and 2015 were examined. The effects of environmental variables and of geographical and limnoecological factors on functional diversity were analyzed. Furthermore, the explanatory power of the trait‐based approach was assessed, and the applicability of the indices for biomonitoring purposes was determined. It was found that low habitat heterogeneity and harsh environments lead to the selection of a small number of suitable traits, and consequently, to a naturally low level of functional diversity. Anthropogenic activities enhance diversity at functional level due to the shift toward freshwater characteristics. On the regional scale, the effects of the region and status (natural, degraded, reconstructed) on diatom functional diversity were significant and more pronounced than that of the environmental and other limnoecological factors. The degree of variance found in functional diversity ascribed to environmental variables is five times greater in the case of the application of a trait‐based approach, than when a taxonomic one is employed in the literature. Each of the tested functional diversity indices was sensitive to the most important environmental variables. Furthermore, these were type‐specific and proved to be more complex indicators than taxonomic metrics. It is possible to suggest four functional diversity indices (FGR, FRic, FDis, and FDiv) which emphasize their independence from substrate and seasonal variations for ecological status assessment and conservation planning.
Development of a model ensemble to predict Peary caribou populations in the Canadian Arctic Archipelago
Authors: Kaluskar Samarth , Blukacz‐Richards E. Agnes , Johnson Cheryl Ann , He Yuhong , Langlois Alexandre , Kim Dong‐Kyun , Arhonditsis George
Published: December 2019

In the field of biological conservation, mathematical modeling has been an indispensable tool to advance our understanding of population dynamics. Modeling rare and endangered species with complex ecophysiological tools can be challenging due to the constraints imposed by data availability. One strategy to overcome the mismatch between what we are trying to learn from a modeling exercise and the available empirical knowledge is to develop statistical models that tend to be more parsimonious. In the present study, we introduce a spatially explicit modeling framework to examine the strength and nature of the relationships of snow density and vegetation abundance with Peary caribou (Rangifer tarandus pearyi) populations. Peary caribou are vital to the livelihood and culture of High Arctic Inuit communities, but changing climatic conditions and anthropogenic disturbances may affect the integrity of this endemic species population. Owing to an estimated decline of over 35% during the last three generations, a recent assessment by the Committee on the Status of Endangered Wildlife in Canada assigned a Threatened status to Peary caribou in 2015. Recognizing the uncertainty typically associated with the selection of the best subset of explanatory variables and their optimal functional relationship with the response variable, we examined four models across six island complexes (Banks, Axel Heiberg, Melville, Bathurst, Mackenzie King, and Boothia) of the Arctic Archipelago and formulated two ensembles to synthesize their predictions into averaged Peary caribou population distributions. Our analysis showed that an ensemble strategy with region‐specific weights displayed the highest performance and most balanced error across the six island complexes. The causal linkages between snow, vegetation abundance, and Peary caribou did manifest themselves with the models examined, but the noise‐to‐signal ratios of the corresponding regression coefficients were generally high and there were instances where they were not discernible from zero. We also present a sensitivity analysis exercise that elucidates the influence of the observation/imputation errors on the model‐training phase, thereby highlighting the importance of assigning realistic error estimates that will not hamper the identification of important cause–effect relationships. Our study identifies critical augmentations of the available scientific knowledge that necessitate to design the optimal management actions of Peary caribou populations across the Canadian Arctic Archipelago.
Baseline features of the VICTORIA (Vericiguat Global Study in Subjects with Heart Failure with Reduced Ejection Fraction) trial
Authors: Pieske Burkert , Patel Mahesh J. , Westerhout Cynthia M. , Anstrom Kevin J. , Butler Javed , Ezekowitz Justin , Hernandez Adrian F. , Koglin Joerg , Lam Carolyn S.P. , Ponikowski Piotr , Roessig Lothar , Voors Adriaan A. , O'Connor Christopher M. , Armstrong Paul W. ,   on behalf of the VICTORIA Study Group
Published: December 2019

Aim

Describe the distinguishing features of heart failure (HF) patients with reduced ejection fraction (HFrEF) in the VICTORIA (Vericiguat Global Study in Patients with Heart Failure with Reduced Ejection Fraction) trial.

Methods and results

Key background characteristics were evaluated in 5050 patients randomized in VICTORIA and categorized into three cohorts reflecting their index worsening HF event. Differences within the VICTORIA population were assessed and compared with PARADIGM‐HF (Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) and COMMANDER HF (A Study to Assess the Effectiveness and Safety of Rivaroxaban in Reducing the Risk of Death, Myocardial Infarction, or Stroke in Participants with Heart Failure and Coronary Artery Disease Following an Episode of Decompensated Heart Failure). VICTORIA patients had increased risk of mortality and rehospitalization: New York Heart Association class (40% class III), atrial fibrillation (45%), diabetes (47%), hypertension (79%) and mean estimated glomerular filtration rate of 61.5 mL/min/1.73 m2. Baseline standard of HF care was very good: 60% received triple therapy. Their N‐terminal pro‐B‐type natriuretic peptide was 3377 pg/mL [interquartile range (IQR) 1992–6380]. Natriuretic peptides were 30% higher level in the 67% patients with HF hospitalization <3 months, compared to those within 3–6 months of HF hospitalization and those randomized after recent outpatient intravenous diuretic therapy. Overall the median MAGGIC (Meta‐Analysis Global Group in Chronic Heart Failure) risk score in VICTORIA was 23 (IQR 18–27) as compared to the MAGGIC risk score in PARADIGM‐HF of 20 (IQR 16–24).

Conclusions

VICTORIA comprises a broadly generalizable high‐risk population of three unique clinical strata of worsening chronic HFrEF despite very good HF therapy. VICTORIA will establish the role of vericiguat, a soluble guanylate cyclase stimulator, in HFrEF.
Coexistence of Metal Phthalocyanine and Fullerene C60 Anions in Mixed {cryptand[2.2.2](Na+)}x(MPc)–x‐1·(C60) – Salts (M = CoI, VIVO, x = 2 and 1.5)
Authors: Konarev Dmitri V. , Andronov Mikhail G. , Kuzmin Alexey V. , Khasanov Salavat S. , Lyubovskaya Rimma N.
Published: December 2019

Salts containing metal phthalocyanine and fullerene anions: {cryptand[2.2.2](Na+)}1.5{CoI(Pc2–)}–0.5(C60·–)·2C6H4Cl2 (1) and {cryptand[2.2.2](Na+)}2{VIVO(Pc·3–)}–(C60–)·C6H4Cl2 (2) were obtained. The {CoI(Pc2–)}–anions are formed by metal centered reduction whereas the Pc2– macrocycles are reduced at the formation of {VIVO(Pc·3–)}–. Fullerenes form zigzag chains in 1 in which they are positionally disordered showing different degree of dimerization [loose packed or π‐stacked pairs from the monomers and singly bonded (C60–)2 dimers]. Singly bonded (C60–)2 dimers in 2 also coexist with pairs of π‐stacked C60·–monomers. The (MPc)– anions are isolated in the salts alternating with the {cryptand(Na+)} cations. Magnetic measurements by EPR technique show the presence of spins in 1 both on C60·–(S = 1/2) and the CoI atoms having S = 1 spin state. These spins are weakly antiferromagnetically coupled in the fullerene chains (Θ = –6 K) but show nearly paramagnetic behaviour for isolated {CoI(Pc2–)}– anions. Both S = 1/2 spins in 2 are mainly localized on VIV and delocalized over Pc·3– since only about 10 % of C60·– from total amount of fullerene is preserved. Spins in 2 show only weak antiferromagnetic coupling with Θ = –2 K within one {VIVO(Pc·3–)}– unit.
An efficient certificateless public key encryption with equality test toward Internet of Vehicles
Authors: Zhao Yanan , Hou Yingzhe , Chen Yanan , Kumar Sachin , Deng Fuhu
Published: December 2019

With the rapid development of the Internet of Vehicles, a great amount of vehicles are connected to Internet of Vehicles environment. These vehicles can exchange data to each other and upload the data to a cloud server for backup. Since the data contains some sensitive information, it is necessary to encrypt the data before uploading to the cloud server. However, this method severely hampers the utilization of data because of the tremendous difficulty in the search for encrypted data. For addressing the above issue, we propose a novel certificateless public key encryption supporting the equality test on ciphertexts that are performed by the cloud server while revealing nothing about the corresponding plaintexts. Our scheme has proved to be secure in bilinear Diffie‐Hellman assumption under the model of random oracle. At the same time, both theoretical analysis and experimental evaluation indicate the security, efficiency, as well as effectiveness of the proposed scheme.