bluuebunny/crossref_metadata_2025 huggingface dataset:
How Do Actinyls Interact with Hyperphosphorylated Yolk Protein Phosvitin?
Authors: Kumar Sumit , Creff Gaëlle , Hennig Christoph , Rossberg André , Steudtner Robin , Raff Johannes , Vidaud Claude , Oberhaensli François R. , Bottein Marie‐Yasmine Dechraoui , Den Auwer Christophe
Published: June 2019

The development of the nuclear industry has raised multiple questions about its impact on the biotope and humans. Proteins are key biomolecules in cell machinery and essential in deciphering toxicological processes. Phosvitin was chosen as a relevant model for phosphorylated proteins because of its important role as an iron, calcium, and magnesium storage protein in egg yolk. A multitechnique spectroscopic investigation was performed to reveal the coordination geometry of two oxocations of the actinide family (actinyl UVI, NpV) in speciation with phosvitin. IR spectroscopy revealed phosphoryl groups as the main functional groups interacting with UVI. This was confirmed through laser luminescence spectroscopy (U) and UV/Vis absorption spectroscopy (Np). For UVI, X‐ray absorption spectroscopy at the LIII edge revealed a small contribution of bidentate binding present, along with predominantly monodentate binding of phosphoryl groups; for NpV, uniquely bidentate binding was revealed. As a perspective to this work, X‐ray absorption spectroscopy speciation of UVI and NpV in the extracted yolk of living eggs of the dogfish Scyliorhinus canicula was determined; this corroborated the binding of phosphorous together with a reduction of the actinyl moiety. Such data are essential to pinpoint the mechanisms of heavy metals (actinyls) accumulation and toxicity in oviparous organisms, and therefore, contribute to a shift from descriptive approaches to predictive toxicology.
Intramolecular Catalyst Transfer on a Variety of Functional Groups between Benzene Rings in a Suzuki–Miyaura Coupling Reaction
Authors: Yokozawa Tsutomu , Harada Natsumi , Sugita Hajime , Ohta Yoshihiro
Published: June 2019

Suzuki–Miyaura coupling reaction of BrC6H4‐X‐C6H4Br 1 (X=CH2, CO, N‐Bu, O, S, SO, and SO2) with arylboronic acid 2 was investigated in the presence of tBu3PPd precatalyst and CsF/[18]crown‐6 as a base to establish whether or not the Pd catalyst can undergo catalyst transfer on these functional groups. In the reaction of 1 (X=CH2, CO, N‐Bu, O, and SO2) with 2, aryl‐disubstituted product 3 (Ar‐C6H4‐X‐C6H4‐Ar) was exclusively obtained, indicating that the Pd catalyst undergoes catalyst transfer on these functional groups. On the other hand, the reaction of 1 e (X=S) and 1 f (X=SO) with 2 afforded only aryl‐monosubstituted product 4 (Ar‐C6H4‐X‐C6H4‐Br) and a mixture of 3 and 4, respectively, indicating that S and SO interfere with intramolecular catalyst transfer. Furthermore, we found that Suzuki–Miyaura polycondensation of 1 (X=CH2, CO, N‐Bu, O, and SO2) and phenylenediboronic acid 5 in the presence of tBu3PPd precatalyst afforded high‐molecular‐weight polymer even when excess 1 was used. The polymers obtained from 1 (X=CH2, N‐Bu, and O) and 5 turned out to be cyclic.
Photoluminescent Lanthanide(III) Single‐Molecule Magnets in Three‐Dimensional Polycyanidocuprate(I)‐Based Frameworks
Authors: Zakrzewski Jakub J. , Chorazy Szymon , Nakabayashi Koji , Ohkoshi Shin‐ichi , Sieklucka Barbara
Published: June 2019

Three‐dimensional bimetallic cyanido‐bridged frameworks, [LnIII(2,2′‐bipyridine N,N′‐dioxide)2(H2O)][CuI2(CN)5]⋅5 H2O (Ln=Dy, 1; Yb, 2), are reported. They exhibit the effect of slow relaxation of magnetization, leading to a magnetic hysteresis loop, and sensitized visible‐to‐near‐infrared photoluminescence. Both physical properties are related to the eight‐coordinated lanthanide(III) complexes embedded in the unprecedented coordination skeleton composed of symmetry‐breaking polycyanidocuprate linkers. The three‐dimensional d–f cyanido‐bridged network was shown to serve as an efficient coordination scaffold to achieve emissive lanthanide single‐molecule magnets.
Back Cover: Lewis Acid‐Catalyzed Intramolecular [3 + 2] Cross‐Cycloaddition of Donor‐ Acceptor Epoxides with Alkenes for Construction of Oxa‐[n.2.1] Skeletons (Chin. J. Chem. 7/2019)
Authors: Chen Lu , Tian Jun , Zhan Yizhou , Ren Jun , Wang Zhong‐Wen
Published: June 2019

The back cover picture shows the first LA‐catalyzed [3+2]IMCC of GDA‐epoxides with carbon‐carbon double bonds. This provides an efficient and general strategy for construction of bridged oxa‐[n.2.1] skeletons. A novel SN‐like mechanism through a carbon‐carbon bond cleavage of epoxide ring has been proposed. The colorful fireworks in the picture imply the generation of skeletal diversity from the epoxide‐diene, and express a dedication to the 100th Anniversary of Nankai University as well. More details are discussed in the article by Wang et al. on page 695–699.

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Development, implementation, and effects of a cancer center's exercise‐oncology program
Authors: Santa Mina Daniel , Au Darren , Auger Leslie E. , Alibhai Shabbir M. H. , Matthew Andrew G. , Sabiston Catherine M. , Oh Paul , Ritvo Paul G. , Chang Eugene B. , Jones Jennifer M.
Published: June 2019

Background

National and international bodies acknowledge the benefit of exercise for people with cancer, yet limited accessibility to related programing remains. Given their involvement in managing the disease, cancer centers can play a central role in delivering exercise‐oncology services. The authors developed and implemented a clinically integrated exercise‐oncology program at a major cancer center and evaluated its effectiveness and participant experience.

Methods

A hospital‐based program with prescribed at‐home exercise was developed and accepted referrals over a 42‐month period (3.5 years). Implementation was conducted in 2 phases: a pilot phase for women with breast cancer and men with genitourinary cancer and a roll‐out phase for all patients with cancer. Enrolled patients were assessed and received an exercise prescription as well as a program manual, resistance bands, and a stability ball from a kinesiologist. Program participation and effectiveness were evaluated up to 48 weeks after the baseline assessment using intention‐to‐treat analyses. Participants in the roll‐out phase were asked to complete a program experience questionnaire at the completion of the 48‐week follow‐up.

Results

In total, 112 participants enrolled in the pilot, and 150 enrolled in the roll‐out phase. Program attrition to 48 weeks was 48% and 65% in the pilot and roll‐out phases, respectively. In participants who consented to research evaluation of their performance, objective and patient‐reported measures of functional capacity improved significantly from baseline in both phases. Participants were highly satisfied with the program.

Conclusions

Despite significant drop‐out to program endpoints, our cancer‐exercise program demonstrated clinically relevant improvement in functional outcomes and was highly appreciated by participants.
Risk of breast cancer by prior screening results among women participating in BreastScreen Norway
Authors: Lilleborge Marie , Falk Ragnhild S. , Russnes Hege , Sauer Torill , Ursin Giske , Hofvind Solveig
Published: June 2019

Background

A premalignant lesion in the breast is associated with an increased risk of breast cancer. The aim of this article was to identify women with an increased risk of breast cancer based on prior screening results (PSRs).

Methods

This registry‐based cohort study followed women who participated in the organized breast cancer screening program in Norway, BreastScreen Norway, in 1995‐2016. Incidence rates and incidence rate ratios were used to estimate absolute and relative risks of breast cancer associated with PSRs. Histopathological characteristics of subsequent breast cancers were presented by PSRs.

Results

This study included 762,643 women with up to 21 years of follow‐up. In comparison with negatively screened women, increased incidence rate ratios of 1.8, 2.0, 2.9, and 3.8 were observed after negative additional imaging, for benign biopsy, for hyperplasia with atypia, and for carcinoma in situ, respectively. Subsequent breast cancers did not differ in tumor diameter or histological grade, whereas the proportion of lymph node–positive breast cancers decreased as the presumed malignancy potential of PSRs increased.

Conclusions

The risk of subsequent breast cancer increased with the presumed malignancy potential of PSRs, whereas the tumor characteristics of subsequent cancers did not differ except for the lymph node status. Women with screen‐detected benign lesions or hyperplasia with atypia might benefit from more frequent screening.
Genetic testing for breast cancer in the Hispanic community
Authors: Narod Steven A.
Published: June 2019

Approximately 1 in 10 Hispanic women with breast cancer carry a mutation in a cancer susceptibility gene; approximately one half of these mutations are in genes other than BRCA1 and BRCA2. Genetic testing for Hispanic patients with breast cancer should be extended to include PALB2.
Augmented resistive immersed surfaces valve model for the simulation of cardiac hemodynamics with isovolumetric phases
Authors: This Alexandre , Boilevin‐Kayl Ludovic , Fernández Miguel A. , Gerbeau Jean‐Frédéric
Published: June 2019

In order to reduce the complexity of heart hemodynamics simulations, uncoupling approaches are often considered for the modeling of the immersed valves as an alternative to complex fluid‐structure interaction (FSI) models. A possible shortcoming of these simplified approaches is the difficulty to correctly capture the pressure dynamics during the isovolumetric phases. In this work, we propose an enhanced resistive immersed surfaces (RIS) model of cardiac valves, which overcomes this issue. The benefits of the model are investigated and tested in blood flow simulations of the left heart where the physiological behavior of the intracavity pressure during the isovolumetric phases is recovered without using fully coupled fluid‐structure models and without important alteration of the associated velocity field.
Bioequivalence of Ertugliflozin/Metformin Fixed‐Dose Combination Tablets and Coadministration of Respective Strengths of Individual Components
Authors: Dawra Vikas Kumar , Liang Yali , Wei Hua , Pelletier Kathleen , Shi Haihong , Hickman Anne , Bass Almasa , Terra Steven G. , Zhou Susan , Krishna Rajesh , Sahasrabudhe Vaishali
Published: June 2019

A fixed‐dose combination (FDC) of ertugliflozin, a selective sodium‐glucose cotransporter 2 inhibitor, and immediate‐release metformin is approved for the treatment of type 2 diabetes mellitus in the United States and European Union. Four open‐label, randomized, 2‐period, single‐dose, crossover studies were conducted under fasted conditions in healthy subjects to demonstrate bioequivalence of the ertugliflozin/metformin FDC tablets and coadministration of the individual components at respective strengths. In each study, 32 or 34 subjects received an ertugliflozin/metformin FDC tablet (2.5 mg/500 mg, 7.5 mg/850 mg, or 7.5 mg/1000 mg) and the respective doses of individual components (ertugliflozin with US‐ or EU‐sourced metformin [Glucophage]). Plasma samples for ertugliflozin and metformin concentrations were collected for 72 hours in each period. For both ertugliflozin and metformin, the 90% confidence intervals for the adjusted geometric mean ratio (FDC : coadministration) for area under the plasma concentration–time profile from time zero extrapolated to infinity and maximum observed plasma concentration were within acceptance criteria for bioequivalence. The majority of adverse events were mild in intensity. The studies demonstrated that each strength of FDC tablet is bioequivalent to respective doses of coadministered individual components, supporting that safety and efficacy can be bridged to the individual components used in phase 3 studies evaluating ertugliflozin in combination with metformin.
Digital Learning to Improve Safe and Effective Prescribing: A Systematic Review
Authors: Bakkum Michiel J. , Tichelaar Jelle , Wellink Anne , Richir Milan C. , van Agtmael Michiel A.
Published: June 2019

With the aim to modernize and harmonize prescribing education, the European Association for Clinical Pharmacology and Therapeutics (EACPT) Working Group on education recommended the extensive use and distribution of digital learning resources (DLRs). However, it is unclear whether the complex task of prescribing medicine can be taught digitally. Therefore, the aim of this review was to investigate the effect of diverse DLRs in clinical pharmacology and therapeutics education. Databases PubMed, EMBASE, CINAHL, ERIC, and CENTRAL were systematically searched. Sixty‐five articles were included in the analyses. Direct effects on patients were studied, but not detected, in six articles. Skills and behavior were studied in 11 articles, 8 of which reported positive effects. Knowledge acquisition was investigated in 19 articles, all with positive effects. Qualitative analyses yielded 10 recommendations for the future development of DLRs. Digital learning is effective in teaching knowledge, attitudes, and skills associated with safe and effective prescribing.
Calling Star Alleles With Stargazer in 28 Pharmacogenes With Whole Genome Sequences
Authors: Lee Seung‐been , Wheeler Marsha M. , Thummel Kenneth E. , Nickerson Deborah A.
Published: June 2019

Variation in the enzymatic activity of pharmacogenes is defined by star alleles (haplotypes) comprised of single‐nucleotide variants, small insertion‐deletions, and large structural variants. We recently developed Stargazer, a next‐generation sequencing‐based tool to call star alleles for the clinically important CYP2D6 gene. Here, we present the utility of extending Stargazer to call star alleles for 28 pharmacogenes using whole genome sequencing (WGS) data. We applied Stargazer to WGS data from 70 ethnically diverse samples from the Genetic Testing Reference Materials Coordination Program (GeT‐RM). These reference samples were extensively characterized by GeT‐RM using multiple pharmacogenetic testing assays. In all 28 genes, Stargazer recalled 100% of star alleles (N = 92) present in GeT‐RM's consensus genotypes (N = 1,559). Stargazer also detected star alleles not previously reported by GeT‐RM, including complex structural variants. Our results demonstrate that combining WGS data and Stargazer enables automated, accurate, and comprehensive genotyping of pharmacogenes in the human genome.
Estrogen‐Containing Oral Contraceptives Are Associated With Polycystic Liver Disease Severity in Premenopausal Patients
Authors: van Aerts René M.M. , Bernts Lucas H.P. , Gevers Tom J.G. , Kievit Wietske , Koopmans Lisanne , Nieboer Theodoor E. , Nevens Frederik , Drenth Joost P.H.
Published: June 2019

The association between estrogen‐containing oral contraceptives and history of pregnancies with disease severity in women with polycystic liver disease (PLD) is unclear. We performed a cross‐sectional cohort study to assess this association by selecting female patients with PLD of which imaging was available prior to any liver volume‐reducing therapy. Patients received a questionnaire to collect detailed information on estrogen use and pregnancies. Preplanned subgroup analyses were performed on premenopausal and postmenopausal patients. The questionnaire was returned by 287 of 360 selected patients (80%). There was no significant association between estrogen‐containing oral contraceptives and height‐adjusted total liver volume (hTLV) in the total group (P = 0.06) and postmenopausal subgroup (P = 0.7). By contrast, each year of exposure corresponds with a 1.45% higher hTLV (P = 0.02) in the premenopausal subgroup, equivalent to a 15.5% higher hTLV for every 10 years of use. Pregnancy duration was not associated with hTLV. In conclusion, patients with PLD should avoid exogenous estrogens.
Competition in technology and innovation, motivation crowding, and environmental policy
Authors: Graafland Johan
Published: June 2019

This paper investigates the theoretical and empirical relevance of motivation crowding theory for owner–managers' motivation towards sustainable development. Motivation crowding theory has argued that external pressures enforce (crowd in) moral motivation if these pressures are perceived as supportive. On the basis of this theory, we conjecture that a competitive environment that is characterized by a high intensity of competition on innovation will crowd in moral motivation towards sustainable development if owner–managers believe that environmental policy practices increase the innovative capability of their company. Test results on survey data filled out by 650 owner–managers support this hypothesis. These results imply that policy makers, who aim at stimulating innovation as well as sustainable development, should inform managers about the innovation‐enhancing effects of environmental policy practices.
A pairing‐free identity‐based handover AKE protocol with anonymity in the heterogeneous wireless networks
Authors: Lei Liting , Zhang Wenfang , Wang Yu , Wang Xiaomin
Published: June 2019

Nowadays, seamless roaming service in heterogeneous wireless networks attracts more and more attention. When a mobile user roams into a foreign domain, the process of secure handover authentication and key exchange (AKE) plays an important role to verify the authenticity and establish a secure communication between the user and the access point. Meanwhile, to prevent the user's current location and moving history information from being tracked, privacy preservation should be also considered. However, existing handover AKE schemes have more or less defects in security aspects or efficiency. In this paper, a secure pairing‐free identity‐based handover AKE protocol with privacy preservation is proposed. In our scheme, users' temporary identities will be used to conceal their real identities during the handover process, and the foreign server can verify the legitimacy of the user with the home server's assistance. Besides, to resist ephemeral private key leakage attack, the session key is generated from the static private keys and the ephemeral private keys together. Security analysis shows that our protocol is provably secure in extended Canetti‐Krawczyk (eCK) model under the computational Diffie‐Hellman (CDH) assumption and can capture desirable security properties including key‐compromise impersonation resistance, ephemeral secrets reveal resistance, strong anonymity, etc. Furthermore, the efficiency of our identity‐based protocol is improved by removing pairings, which not only simplifies the complex management of public key infrastructure (PKI) but also reduces the computation overhead of ID‐based cryptosystem with pairings. It is shown that our proposed handover AKE protocol provides better security assurance and higher computational efficiency for roaming authentication in heterogeneous wireless networks.
An effective back‐off selection technique for reliable beacon reception in VANETs
Authors: Shah Syed Adeel Ali , Ahmed Ejaz , Ahsan Qureshi Muhammad , Jan Sadeeq , MD Noor Rafidah
Published: June 2019

In safety‐critical scenarios, reliable reception of beacons transmitted by a subject vehicle is critical to avoid vehicle collision. According to the employed contention window sizes in IEEE 802.11p, beacons are transmitted with a small contention window size. As a result, multiple vehicles contend for the shared channel access by selecting the same back‐off slot. This is a perfect recipe for synchronous collisions wherein reliable beacon delivery cannot be guaranteed for any vehicle. We consider the problem of selecting the back‐off slots from the current contention window to provide reliable delivery of beacons transmitted by a subject vehicle to its neighbors. Given a safety scenario, we propose a Pseudo‐Random Number Generator (PRNG)‐inspired back‐off selection (PBS) technique. The proposed technique works on the hypothesis that synchronous collisions of beacons transmitted by a subject vehicle can be reduced if all its neighbors select different back‐off slots (ie, not the back‐off slot selected by the subject vehicle). The discrete‐event simulations demonstrate that PBS can increase the overall message reception from a subject vehicle, in comparison with the uniform random probability back‐off selection in IEEE 802.11p.
Prognostic impact of Framingham heart failure criteria in heart failure with preserved ejection fraction
Authors: Löfström Ulrika , Hage Camilla , Savarese Gianluigi , Donal Erwan , Daubert Jean‐Claude , Lund Lars H. , Linde Cecilia
Published: June 2019

Aims

This study aims to assess prognostic impact of Framingham criteria for heart failure (FC‐HF) in patients with stable heart failure (HF) with preserved ejection fraction (HFpEF).

Methods and results

In the prospective Karolinska‐Rennes (KaRen) study, we assessed stable HFpEF patients after an acute HF episode. We evaluated associations between the four descriptive models of HFpEF and the composite endpoint of all‐cause mortality and HF hospitalization. The descriptive models were FC‐HF alone, FC‐HF + natriuretic peptides (NPs) according to the PARAGON trial, FC‐HF + NPs + echocardiographic HFpEF criteria according to European Society of Cardiology HF guidelines, and FC‐HF + NPs + echocardiographic criteria according to the PARAGON trial. Out of the 539 patients enrolled in KaRen, 438 returned for the stable state revisit after 4–8 weeks, 13 (2.4%) patients died before the planned follow‐up, and 88 patients (16%) declined or were unable to return. Three hundred ninety‐nine patients have FC registered at follow‐up, and among these, the four descriptive models were met in 107 (27%), 82 (22%), 61 (21%), and 69 (22%) patients, and not met in 292 (73%). The 107 patients that had FC‐HF at stable state (descriptive model 1) could also be part of the other models because all patients in models 1–4 had to fulfil the FC‐HF. The patients in model 0 did not fulfil the criteria for FC‐HF but could have single FC. Of single FC, only pleural effusion predicted the endpoint [hazard ratio (HR) 3.38, 95% confidence interval (CI) 1.47–7.76, P = 0.004]. Patients without FC‐HF had better prognosis than patients meeting FC‐HF. The unadjusted associations between the four HFpEF descriptive models and the endpoint were HR 1.54, 95% CI 1.14–2.09, P = 0.005; HR 1.71, 95% CI 1.24–2.36, P = 0.002; HR 1.95, 95% CI 1.36–2.81, P = 0.001; and HR 2.05, 95% CI 1.45–2.91, P < 0.001, for descriptive models 1–4, respectively. No descriptive model independently predicted the endpoint.

Conclusions

In ambulatory HFpEF patients, a quarter met FC‐HF, while most met NP and echocardiography criteria for HF. Residual FC‐HF tended to be associated with increased risk for mortality and HF hospitalization, further strengthened by NPs and echocardiographic criteria, highlighting its role in clinical risk assessment.
Design and optimization of a fused‐silica microfluidic device for separation of trivalent lanthanides by isotachophoresis
Authors: Bottenus Danny , Branch Shirmir , Lackey Hope , Ivory Cornelius , Katalenich Jeff , Clark Sue , Lines Amanda
Published: June 2019

Elemental analysis of rare earth elements is essential in a variety of fields including environmental monitoring and nuclear safeguards; however, current techniques are often labor intensive, time consuming, and/or costly to perform. The difficulty arises in preparing samples, which requires separating the chemically and physically similar lanthanides. However, by transitioning these separations to the microscale, the speed, cost, and simplicity of sample preparation can be drastically improved. Here, all fourteen non‐radioactive lanthanides (lanthanum through lutetium minus promethium) are separated by ITP for the first time in a serpentine fused‐silica microchannel (70 µm wide × 70 µm tall × 33 cm long) in <10 min at voltages ≤8 kV with limits of detection on the order of picomoles. This time includes the 2 min electrokinetic injection time at 2 kV to load sample into the microchannel. The final leading electrolyte consisted of 10 mM ammonium acetate, 7 mM α‐hydroxyisobutyric acid, 1% polyvinylpyrrolidone, and the final terminating electrolyte consisted of 10 mM acetic acid, 7 mM α‐hydroxyisobutyric acid, and 1% polyvinylpyrrolidone. Electrophoretic electrodes are embedded in the microchip reservoirs so that voltages can be quickly applied and switched during operation. The limits of detection are quantified using a commercial capacitively coupled contactless conductivity detector (C4D) to calculate ITP zone lengths in combination with ITP theory. Optimization of experimental procedures and reproducibility based on statistical analysis of subsequent experimental results are addressed. Percent error values in band length and conductivity are ≤8.1 and 0.37%, respectively.
Mathematical model to reduce loop mediated isothermal amplification (LAMP) false‐positive diagnosis
Authors: Schneider Lindsay , Blakely Hannah , Tripathi Anubhav
Published: June 2019

Loop mediated isothermal amplification (LAMP) is a nucleic acid amplification technique performed under isothermal conditions. The output of this amplification technique includes multiple different sizes of deoxyribonucleic acid (DNA) structures which are identified by a banding pattern on gel electrophoresis plots. Although this is a specific amplification technique, the complexity of the primer design and amplification still lead to the issue of obtaining false‐positive results, especially when a positive reading is determined solely by whether there is any banding pattern in the gel electrophoresis plot. Here, we first performed extensive LAMP experiments and evaluated the DNA structures using microchip electrophoresis. We then developed a mathematical model derived from the various components that make up an entire LAMP structure to predict the full LAMP structure size in base pairs. This model can be implemented by users to make predictions for specific, DNA size dependent, banding patterns on their gel electrophoresis plots. Each prediction is specific to the target sequence and primers used and therefore reduces incorrect diagnosis errors through identifying true‐positive and false‐positive results. This model was accurately tested with multiple primer sets in house and was also translatable to different DNA and RNA types in previously published literature. The mathematical model can ultimately be used to reduce false‐positive LAMP diagnosis errors for applications ranging from tuberculosis diagnostics to E. coli to numerous other infectious diseases.
Stripe‐based fragility analysis of multispan concrete bridge classes using machine learning techniques
Authors: Mangalathu Sujith , Jeon Jong‐Su
Published: June 2019

A framework for the generation of bridge‐specific fragility curves utilizing the capabilities of machine learning and stripe‐based approach is presented in this paper. The proposed methodology using random forests helps to generate or update fragility curves for a new set of input parameters with less computational effort and expensive resimulation. The methodology does not place any assumptions on the demand model of various components and helps to identify the relative importance of each uncertain variable in their seismic demand model. The methodology is demonstrated through the case study of a multispan concrete bridge class in California. Geometric, material, and structural uncertainties are accounted for in the generation of bridge numerical models and their fragility curves. It is also noted that the traditional lognormality assumption on the demand model leads to unrealistic fragility estimates. Fragility results obtained by the proposed methodology can be deployed in a risk assessment platform such as HAZUS for regional loss estimation.
Smart modeling by using artificial intelligent techniques on thermal performance of flat‐plate solar collector using nanofluid
Authors: Sadeghzadeh Milad , Ahmadi Mohammad Hossein , Kahani Mostafa , Sakhaeinia Hossein , Chaji Hossein , Chen Lingen
Published: June 2019

In the current study, Multilayer Perceptron Artificial Neural Network (MLP‐ANN) mode, Radial Basis Function Artificial Neural Network (RBF‐ANN), and Elman Back Propagation Neural Network (Elamn BP‐ANN) are developed to predict the thermal efficiency of a flat‐plate solar collector. TiO2 (20 nm)/water nanofluids are prepared using two‐step method and used in the designed solar system. All experiments are done in Mashhad city, Iran (Longitude/Latitude: 36.2605°N, 59.6168°E), according to EUROPEAN STANDARD EN 12975‐2 as a quasi‐dynamic test (QDT) method, and the solar collector is exposed to the south with the tilt angle of 55°. Three levels of inlet temperature (ambient air temperature, 52 and 74°C), 3 levels of volumetric flow rate (36, 72, and 108 L/(m2.h)), and 4 levels of nanofluid concentrations (0, 0.1, 0.2, and 0.3 wt.%) are considered as the input data, and the thermal efficiency of the solar system is calculated. According to the output results of developed models, the best prediction of thermal performance is obtained by MLP‐ANN model, although other generated models are also able to predict the efficiency of the solar collector with appropriated accuracy.
A constrained framework for context‐aware remote E‐healthcare (CARE) services
Authors: Sharma Ashutosh , Kumar Rajiv
Published: June 2019

Recently, due to the health awareness among the current generations, it leads us to give special attention to the remote E‐healthcare services. The remote E‐healthcare services have been categorized mainly into three categories: primary care, secondary care, and emergency care. Due to the categorized remote healthcare services, the resources must have to be utilized efficiently. Therefore, context‐aware modelling for the remote E‐healthcare (CARE) services has been used to save the resource wastage. The CARE services have been divided into three categories primary context‐aware remote E‐healthcare, secondary context‐aware remote E‐healthcare, and emergency context‐aware remote E‐healthcare (E‐CARE). Three different algorithms have been proposed for the performance analysis. The result shows that the proposed algorithms for the primary context‐aware remote E‐healthcare and secondary context‐aware remote E‐healthcare do not make more difference in the routing. However, the selection of the path for the E‐CARE shows that the hop count of the path has been increased. The increase in the hop count leads to an increase in energy efficiency and the life of the services. Additionally, observation made from our assigned algorithm E‐CARE shows that it performs extremely well for the E‐healthcare services without incrementing the time complexity. Furthermore, major characteristics of the algorithm has been explored and analyzed for the E‐healthcare services.
Using social media mining technology to improve stock price forecast accuracy
Authors: Huang Jia‐Yen , Liu Jin‐Hao
Published: June 2019

Many stock investors make investment decisions based on stock‐price‐related chip indicators. However, in addition to quantified data, financial news often has a nonnegligible impact on stock price. Nowadays, as new reviews are posted daily on social media, there may be value in using web opinions to improve the performance of stock price prediction. To this end, we use logistic regression to screen the chip indicators and establish a basic stock price prediction model. Then, we employ text mining technology to quantify the unstructured data of social media opinions on stock‐related news into sentiment scores, which are found to correlate significantly with the change extent of the stock price. Based on the findings that the higher the sentiment scores, the lower the prediction accuracy of the logistic regression model, we propose an improved prediction approach that integrates sentiment scores into the logistic regression model. Our results show that the proposed model can improve the prediction accuracy for stock prices, and can thus provide a new reference for investment strategies for stock investors.
Combined fractional anisotropy and subcortical volumetric abnormalities in healthy immigrants to high altitude: A longitudinal study
Authors: Chen Xiaoming , Li Hong , Zhang Qian , Wang Jiye , Zhang Wenbin , Liu Jian , Li Baojuan , Xin Zhenlong , Liu Jie , Yin Hong , Chen Jingyuan , Kong Yazhuo , Luo Wenjing
Published: June 2019

The study of individuals at high‐altitude (HA) exposure provides an important opportunity for unraveling physiological and psychological mechanism of brain underlying hypoxia condition. However, this has rarely been assessed longitudinally. We aim to explore the cognitive and cerebral microstructural alterations after chronic HA exposure. We recruited 49 college freshmen who immigrated to Tibet and followed up for 2 years. Control group consisted of 49 gender and age‐matched subjects from sea level. Neuropsychological tests were also conducted to determine whether the subjects' cognitive function had changed in response to chronic HA exposure. Surface‐based cortical and subcortical volumes were calculated from structural magnetic resonance imaging data, and tract‐based spatial statistics (TBSS) analysis of white matter (WM) fractional anisotropy (FA) based on diffusion weighted images were performed. Compared to healthy controls, the high‐altitude exposed individuals showed significantly lower accuracy and longer reaction times in memory tests. Significantly decreased gray matter volume in the caudate region and significant FA changes in multiple WM tracts were observed for HA immigrants. Furthermore, differences in subcortical volume and WM integration were found to be significantly correlated with the cognitive changes after 2 years' HA exposure. Cognitive functions such as working memory and psychomotor function were found to be impaired during chronic HA. Differences of brain subcortical volumes and WM integration between HA and sea‐level participants indicated potential impairments in the brain structural modifications and microstructural integrity of WM tracts after HA exposure.
Direct and Indirect Effects of Fibroblast Growth Factor (FGF) 15 and FGF19 on Liver Fibrosis Development
Authors: Schumacher Justin D. , Kong Bo , Wu Jason , Rizzolo Daniel , Armstrong Laura E. , Chow Monica D. , Goedken Michael , Lee Yi‐Horng , Guo Grace L.
Published: June 2019

Farnesoid X receptor (FXR) induces fibroblast growth factor 15 (FGF15; human ortholog FGF19) in the gut to potently inhibit bile acid (BA) synthesis in the liver. FXR activation in hepatic stellate cells (HSCs) reduces liver fibrosis (LF). Fgf15
–/– mice develop attenuated LF, but the underlying mechanisms for this protection are unclear. We hypothesized that FGF15/19 functions as a profibrotic mediator or mitogen to HSCs and increased BAs in Fgf15
–/– mice leads to enhanced FXR activation in HSCs, subsequently reducing fibrogenesis. In this study, complimentary in vivo and in vitro approaches were used: (1) CCl4‐induced LF model in wild type (WT), Fgf15
–/–, and Fgf15 transgenic (TG) mice with BA levels modulated by feeding cholestyramine‐ or cholic acid–containing diets; (2) analysis of primary HSCs isolated from WT and Fgf15–/–
mice; and (3) treatment of a human HSC line, LX‐2, with FXR activators and/or recombinant FGF19 protein. The results showed that Fgf15–/–
mice had lower basal collagen expression, which was increased by BA sequestration. CCl4 induced fibrosis with similar severity in all genotypes; however, cholestyramine increased fibrosis severity only in Fgf15
–/– mice. HSCs from Fgf15–/–
mice showed increased FXR activity and reduced expression of profibrotic mediators. In LX‐2 cells, FXR activation increased peroxisome proliferator‐activated receptor gamma activity and reduced proliferation. FGF19 activated both signal transducer and activator of transcription 3 and c‐Jun N‐terminal kinase pathways and reduced nuclear factor kappa‐light‐chain‐enhancer of activated B cells signaling without increasing fibrogenic gene expression or cell proliferation. Conclusion: FGF15/19 does not act as a direct profibrotic mediator or mitogen to HSCs in our models, and the protection against fibrosis by FGF15 deficiency may be mediated through increased BA activation of FXR in HSCs.
Vessels Encapsulating Tumor Clusters (VETC) Is a Powerful Predictor of Aggressive Hepatocellular Carcinoma
Authors: Renne Salvatore Lorenzo , Woo Ha Young , Allegra Sarah , Rudini Noemi , Yano Hirohisa , Donadon Matteo , Viganò Luca , Akiba Jun , Lee Hye Sun , Rhee Hyungjin , Park Young Nyun , Roncalli Massimo , Di Tommaso Luca
Published: June 2019

We investigated the clinical significance of a vascular growth pattern of hepatocellular carcinoma (HCC), the vessels that encapsulate tumor clusters (VETC), previously linked to HCC metastatic dissemination. VETC was assessed in a large multi‐institutional cohort of 541 resected HCCs from Italy, Korea and Japan, and matched against a full spectrum of clinical and pathological variables. The VETC phenotype (defined as ≥ 55% tumor area by CD34 immunostaining) was easily reproducible and reliably detectable in whole sections and small‐sized tissues of tissue microarray. VETC HCCs represented 18.9% of the whole series, the lowest proportion occurring in the cohort with smallest tumors (8.7%, Japanese series). VETC was significantly associated with several clinical and pathological features such as high alfa‐fetoprotein (AFP) level, tumor size greater than 5 cm, poor differentiation, macrotrabecular pattern, less compact pattern, less inflammatory infiltrates, and frequent microvascular invasion. VETC was associated with early recurrence (hazard ratio [HR]: 1.52 [1.06‐2.19], P = 0.023), disease‐free survival (HR: 1.66 [1.21‐2.27], P = 0.002), and overall survival (HR: 2.26 [1.37‐3.72], P = 0.001) at multivariable analysis. VETC affected the survival in HCC patients stratified for etiology (hepatitis C virus/hepatitis B virus), vascular invasion, and specific molecular phenotypes (β‐catenin/GS+). This distinct vascular pattern was enriched in the recently reported macrotrabecular massive HCC subtype, which was seen in 7.8% (42 of 541) of patients and associated with high AFP levels and poor differentiation. Conclusion: The VETC pattern was found to be easily detectable in a consistent fraction of HCC and a powerful pathological finding affecting survival. This study suggests that the heterogeneous pattern of angiogenesis is involved in HCC behavior.
Randomized feasibility study of suction‐tube uterine tamponade for postpartum hemorrhage
Authors: Hofmeyr G. Justus , Middleton Katrin , Singata‐Madliki Mandisa
Published: June 2019

Objective

To identify an inexpensive catheter suitable for uterine suction tamponade (UST) for postpartum hemorrhage and assess its functionality.

Methods

Randomized, single‐center, double‐blind feasibility study in East London, South Africa, among 45 women undergoing cesarean delivery between October and November 2018. A search of medical supply websites for catheters with predefined characteristics (inexpensive, flexible, wide‐bore, circumferentially‐arranged side apertures, rounded tip) identified the FG36 Levin stomach tube. During cesarean, the tube was placed in the uterus and connected transvaginally to a suction unit. Participants were randomized via a computer‐generated random sequence to early (after uterine closure; n=24) or delayed (after skin closure; n=21) UST.

Results

The tube functioned well with respect to stability in the uterus and aspirating blood from the uterine cavity without blockage. Blood loss was similar between the groups (mean difference, 7.3 mL; 95% confidence interval, −61 to 75; P=0.433), as were secondary outcomes. There were no complications. Absolute effectiveness was not tested because there was no non‐suction group.

Conclusion

The FG36 Levin tube was found to be a suitable device for “suction‐tube uterine tamponade”. There was no difference in functionality between early and late UST. Future trials should assess the effectiveness of this approach for postpartum hemorrhage.

Clinical trial registration: Registered in the Pan African Clinical Trial Registry as PACTR201809584199573.
Rare case of Richter syndrome with testicular involvement successfully obtained good prognosis with rapid operation and immunochemotherapy
Authors: Kawase Kengo , Naiki Taku , Naiki‐Ito Aya , Yanada Masamitsu , Ikegami Yosuke , Ota Yuya , Hattori Tatsuya , Matsuyama Nayuka , Hamakawa Takashi , Maruyama Tetsuji , Yasui Takahiro
Published: June 2019

Introduction

Richter syndrome refers to the transformation from chronic lymphocytic leukemia to assaultive lymphoma, often a diffuse large B‐cell lymphoma, and has a greatly poor prognosis. Richter syndrome is characterized by rapidly growing lymphadenopathy but rarely presents with extra‐nodal involvement, common sites being the digestive tract, lungs, kidneys, and central nervous system. However, Richter syndrome with testicular involvement is extremely rare.

Case presentation

Herein we report a very scare case of a male at the age of 72 with Richter syndrome and testicular involvement, diagnosed by the investigation of bilateral scrotal swellings. The patient had attained disease‐free survival for over a year with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone, and the intrathecal administration of chemotherapeutic agents after diagnosis by immediate orchiectomy.

Conclusion

An early pathological diagnosis by immediate orchiectomy and the early initiation of induction immunochemotherapy may be good prognostic factors in Richter syndrome involving the testes.
An evolving tale of two interacting RNAs—themes and variations of the T‐box riboswitch mechanism
Authors: Suddala Krishna C. , Zhang Jinwei
Published: June 2019

T‐box riboswitches are a widespread class of structured noncoding RNAs in Gram‐positive bacteria that regulate the expression of amino acid‐related genes. They form negative feedback loops to maintain steady supplies of aminoacyl‐transfer RNAs (tRNAs) to the translating ribosomes. T‐box riboswitches are located in the 5′ leader regions of mRNAs that they regulate and directly bind to their cognate tRNA ligands. T‐boxes further sense the aminoacylation state of the bound tRNAs and, based on this readout, regulate gene expression at the level of transcription or translation. T‐box riboswitches consist of two conserved domains—a 5′ Stem I domain that is involved in specific tRNA recognition and a 3′ antiterminator/antisequestrator (or discriminator) domain that senses the amino acid on the 3′ end of the bound tRNA. Interaction of the 3′ end of an uncharged but not charged tRNA with a thermodynamically weak discriminator domain stabilizes it to promote transcription readthrough or translation initiation. Recent biochemical, biophysical, and structural studies have provided high‐resolution insights into the mechanism of tRNA recognition by Stem I, several structural models of full‐length T‐box‐tRNA complexes, mechanism of amino acid sensing by the antiterminator domain, as well as kinetic details of tRNA binding to the T‐box riboswitches. In addition, translation‐regulating T‐box riboswitches have been recently characterized, which presented key differences from the canonical transcriptional T‐boxes. Here, we review the recent developments in understanding the T‐box riboswitch mechanism that have employed various complementary approaches. Further, the regulation of multiple essential genes by T‐boxes makes them very attractive drug targets to combat drug resistance. The recent progress in understanding the biochemical, structural, and dynamic aspects of the T‐box riboswitch mechanism will enable more precise and effective targeting with small molecules. © 2019 IUBMB Life, 2019 © 2019 IUBMB Life, 71(8):1167–1180, 2019
Effects of dual plasma molecular adsorption system on liver function, electrolytes, inflammation, and immunity in patients with chronic severe hepatitis
Authors: Chen Gao , Wu Mengzheng , Wu Bibo , Liu Feifei , Liu Jianying , Liu Li
Published: June 2019

Background

To investigate the effects of dual plasma molecular adsorption system (DPMAS) on the liver function, electrolytes, inflammation, and immunity in patients with chronic severe hepatitis (CSH).

Methods

Total of 162 patients with CSH treated in our hospital from March 2016 to December 2018 were enrolled and equally randomly divided into control group (n = 81) and observation group (n = 81). The patients in control group were treated with plasma exchange, while those in observation group were additionally treated with DPMAS based on the treatment in control group. The liver function, electrolytes, inflammation, and immunity were evaluated and compared between the two groups.

Results

After treatment, the liver function indexes in observation group were significantly favorable compared with those in control group, with the reduction in TBIL, DBIL, ALT, and rise of CHE levels (P < 0.05). The levels of K+, Na+, Cl−, and Ca2+ in both groups were significantly improved after treatment (P < 0.05), although there were no significant differences between the two groups (P > 0.05). The levels of C‐reactive protein (CRP), interleukin‐6 (IL‐6), and tumor necrosis factor‐α (TNF‐α) in both groups declined after treatment compared with those before treatment, and those levels in observation group were higher than that in control group (P < 0.05). After treatment, the levels of cluster of differentiation 3+ (CD3+), CD4+, and CD4+/CD8+ were higher in observation group than those in control group, with decreasing level of CD8+ (P < 0.05).

Conclusion

Dual plasma molecular adsorption system can effectively improve the liver function, effectively correct the electrolyte disorders, reduce the inflammatory response, and adjust the immunity in patients with CSH.
Control of specific growth rate for the enhanced production of human interferon α2b in glycoengineered Pichia pastoris: process analytical technology guided approach
Authors: Katla Srikanth , Mohan Naresh , Pavan Satya S , Pal Uttariya , Sivaprakasam Senthilkumar
Published: June 2019

BACKGROUND

Process variability in bioprocess systems involving genetically engineered strains is a common bottleneck and a real‐time insight of the on‐going process is crucial to achieve the desired product and its quality. In this study, a process analytical technology (PAT) platform was developed for the monitoring and control of specific growth rate during methanol induction phase (μmet) of glycoengineered Pichia pastoris fermentation for human interferon alpha 2b (huIFNα2b) production.

RESULTS

The PAT guided approach involves real‐time monitoring of capacitance (ΔC) facilitating online estimation of specific growth rate (μest), which serves as a process input during controller application. Fed‐batch experiments using pulsed‐feeding of methanol at different dosage (20 g and 30 g) did not significantly influence μmet. Exponential methanol feeding was achieved using a modified proportional, integral and derivative (PID) controller for different predefined specific growth rate set point (μsp) values, namely 0.015, 0.03, 0.04 and 0.06 h−1. Exponential feeding strategy during the induction phase resulted in two crucial outcomes: (i) controlled methanol feeding rate (regulated by the developed PID controller) balanced the methanol consumption rate (qs, met) of the P. pastoris; (ii) significant improvement in huIFNα2b titer (1483 mg L−1) and specific productivity(>0.4 mg g−1. h) was achieved by the robust control of μmet at optimal (0.04 h−1) value. The purified huIFNα2b was found to exhibit antiproliferative effect against human breast cancer cell lines.

CONCLUSIONS

Efficient control of μmet at a very low narrow range was achieved with a long‐term controller stability (>10 h) and the highest titer reported to date for huIFNα2b (at optimal μmet) in the yeast expression platform. © 2019 Society of Chemical Industry