bluuebunny/crossref_metadata_2025 huggingface dataset:
Diabetes Is Associated With Increased Risk of Hepatocellular Carcinoma in Patients With Cirrhosis From Nonalcoholic Fatty Liver Disease
Authors: Yang Ju Dong , Ahmed Fowsiyo , Mara Kristin C. , Addissie Benyam D. , Allen Alina M. , Gores Gregory J. , Roberts Lewis R.
Published: July 2019

Diabetes increases the risk of liver disease progression and cirrhosis development in patients with nonalcoholic steatohepatitis (NASH). The association between diabetes and the risk of hepatocellular carcinoma (HCC) in NASH patients with cirrhosis is not well quantified. All patients with the diagnosis of NASH cirrhosis seen at Mayo Clinic Rochester between January 2006 and December 2015 were identified. All adult liver transplant registrants with NASH between 2004 and 2017 were identified using the United Network for Organ Sharing (UNOS)/Organ Procurement and Transplantation registry for external validation. Cox proportional hazard analysis was performed to investigate the association between diabetes and HCC risk. Among 354 Mayo Clinic patients with NASH cirrhosis, 253 (71%) had diabetes and 145 (41%) were male. Mean age at cirrhosis evaluation was 62. During a median follow‐up of 47 months, 30 patients developed HCC. Diabetes was associated with an increased risk of developing HCC in univariate (hazard ratio [HR] = 3.6; 95% confidence interval [CI] = 1.1‐11.9; P = 0.04) and multivariable analysis (HR = 4.2; 95% CI = 1.2‐14.2; P = 0.02). In addition, age (per decade, HR = 1.8; 95% CI = 1.2‐2.6; P < 0.01) and low serum albumin (HR = 2.1; 95% CI = 1.5‐2.9; P < 0.01) were significantly associated with an increased risk of developing HCC in multivariable analysis. Other metabolic risk factors, including body mass index, hyperlipidemia, and hypertension, were not associated with HCC risk. Among UNOS NASH registrants (N = 6,630), 58% had diabetes. Diabetes was associated with an increased risk of developing HCC in univariate (HR = 1.4; 95% CI = 1.1‐1.8; P < 0.01) and multivariable (HR = 1.3; 95% CI = 1.0‐1.7; P = 0.03) analysis. Conclusion: Diabetes is associated with an increased risk of HCC in patients with NASH cirrhosis.
A review of the incidence and determinants of catastrophic health expenditure in Nigeria: Implications for universal health coverage
Authors: Okedo‐Alex Ijeoma Nkem , Akamike Ifeyinwa Chizoba , Ezeanosike Obumneme Benaiah , Uneke Chigozie Jesse
Published: July 2019

Background

In the Nigerian context, preconditions for financial catastrophe are operational as there is high out‐of‐pocket spending (OOPS) on health with low capacity to pay, presence of user fees, and poor prepayment insurance coverage. We reviewed the incidence and determinants of catastrophic health expenditure (CHE) in Nigeria.

Methods

Databases including PubMed, OVID, EMBASE, CINAHL, and Web of Science were searched for primary research studies on the incidence and determinants of CHE in Nigeria published between 2003 and 2018. Search terms used include household, out‐of‐pocket expenditure, catastrophic health expenditure, and Nigeria.

Results

Twenty studies that met the inclusion criteria were included in the review. At 10% of total household and nonfood expenditure, the incidence of CHE was 8.2% to 50%, while 3.2% to 100% households incurred CHE at 40% of nonfood expenditure. The incidence of CHE was higher among inpatients and studies with lower threshold definitions. Outpatient CHE was highest for type 2 diabetes and tuberculosis while human immunodeficiency virus (HIV) care incurred the most CHE among inpatients. Determinants of CHE include wealth status, age, gender, place of residence/geographical location, household size/composition, educational status, health insurance status, illness, and health provider types.

Conclusion

There is a high incidence of CHE across various common health conditions in Nigeria. CHE was more among the poor, elderly, rural dwellers, private facility utilization, female gender, and noninsured among others. We recommend expansion of the National Health Insurance Scheme via informal social and financing networks platforms. Increased budgetary allocation to health and intersectoral collaboration will also play a significant role in CHE reduction.
Analysis of activation energy and thermal radiation on convective flow of a power‐law fluid under convective heating and chemical reaction
Authors: RamReddy Ch. , Naveen P.
Published: July 2019

The purpose of the present article is to explore the influence of activation energy in the mixed convective flow of a power‐law fluid over a permeable inclined plate. The energy expression is incorporated with thermal radiation effect. Additionally, the suction/injection effect and convective thermal conditions are considered at the surface of the inclined plate. The convection along with a nonlinear Boussinesq approximation (i.e., quadratic or nonlinear convection) and usual boundary‐layer assumptions are used in the mathematical formulation. A combined local non‐similarity and successive linearization techniques are used to evaluate the highly complicated governing equations. The effect of pertinent parameters on the fluid flow characteristics and its solutions are conferred using this study with the help of graphs. This kind of investigation is useful in the mechanism of combustion, aerosol technology, high‐temperature polymeric mixtures, and solar collectors, which operate at moderate to very high temperatures.
Factors explaining community contrast of Trichoptera assemblages at insular Western Carpathian spring fens to the adjacent headwaters
Authors: Petruželová Jana , Bojková Jindřiška , Hubáčková Lenka , Šorfová Vanda , Syrovátka Vít , Horsák Michal
Published: July 2019

The specific biota of isolated habitats is determined by habitat properties (e.g., age, size, environmental conditions), their spatial isolation and the characteristics of the surrounding landscape matrix. In this study, we examine the contrast in Trichoptera assemblages between isolated island‐like Western Carpathian spring fens and nearby headwater streams. We evaluate the potential of streams and their mesohabitats to serve as stepping‐stone habitats for fen species, and identify factors determining the dissimilarity of the Trichoptera between the fens and streams. Of 24 studied fen‐stream pairs, 80 Trichoptera taxa, mainly species, were identified. Out of these, 17 and 34 species were exclusive for fens and streams, respectively. Although the remaining 29 species were in common, a clear preference of each species to one of these two habitat types was observed, which resulted in highly contrasting assemblages in terms of species composition. A clear difference was found also at the level of species traits, as cold‐adapted crenobiont and crenophilous species of small body size, limited dispersal ability, and long larval development prevailed at the fens. The fen‐stream dissimilarity of Trichoptera was not associated either with fen habitat properties (age, size and environmental conditions) or with the distance between the habitats. Only stream characteristics reducing the fen‐stream environmental contrast were important. Abundance of fen species at streams was negatively related with substrate roughness and stream size, suggesting that small streams with a fine substrate can serve preferably as stepping‐stone habitats for the fen species. Our results show the high conservation value of spring‐fen Trichoptera assemblages due to the prevalence of habitat specialists as well as cold stenothermic and pollution‐sensitive species. It also seems that the isolation of fens surrounded only by unsuitable streams is additionally increased by a lack of stepping‐stone habitats in the surrounding matrix.
Macroeconomic forecast accuracy in a data‐rich environment
Authors: Kotchoni Rachidi , Leroux Maxime , Stevanovic Dalibor
Published: July 2019

The performance of six classes of models in forecasting different types of economic series is evaluated in an extensive pseudo out‐of‐sample exercise. One of these forecasting models, regularized data‐rich model averaging (RDRMA), is new in the literature. The findings can be summarized in four points. First, RDRMA is difficult to beat in general and generates the best forecasts for real variables. This performance is attributed to the combination of regularization and model averaging, and it confirms that a smart handling of large data sets can lead to substantial improvements over univariate approaches. Second, the ARMA(1,1) model emerges as the best to forecast inflation changes in the short run, while RDRMA dominates at longer horizons. Third, the returns on the S&P 500 index are predictable by RDRMA at short horizons. Finally, the forecast accuracy and the optimal structure of the forecasting equations are quite unstable over time.
Post-fracture Risk Assessment: Target the Centrally Sited Fractures First! A Substudy of NoFRACT
Authors: Borgen Tove T , Bjørnerem åshild , Solberg Lene B , Andreasen Camilla , Brunborg Cathrine , Stenbro May-Britt , Hübschle Lars M , Froholdt Anne , Figved Wender , Apalset Ellen M , Gjertsen Jan-Erik , Basso Trude , Lund Ida , Hansen Ann K , Stutzer Jens-Meinhard , Omsland Tone K , Nordsletten Lars , Frihagen Frede , Eriksen Erik F
Published: July 2019

The location of osteoporotic fragility fractures adds crucial information to post-fracture risk estimation. Triaging patients according to fracture site for secondary fracture prevention can therefore be of interest to prioritize patients considering the high imminent fracture risk. The objectives of this cross-sectional study were therefore to explore potential differences between central (vertebral, hip, proximal humerus, pelvis) and peripheral (forearm, ankle, other) fractures. This substudy of the Norwegian Capture the Fracture Initiative (NoFRACT) included 495 women and 119 men ≥50 years with fragility fractures. They had bone mineral density (BMD) of the femoral neck, total hip, and lumbar spine assessed using dual-energy X-ray absorptiometry (DXA), trabecular bone score (TBS) calculated, concomitantly vertebral fracture assessment (VFA) with semiquantitative grading of vertebral fractures (SQ1–SQ3), and a questionnaire concerning risk factors for fractures was answered. Patients with central fractures exhibited lower BMD of the femoral neck (765 versus 827 mg/cm2), total hip (800 versus 876 mg/cm2), and lumbar spine (1024 versus 1062 mg/cm2); lower mean TBS (1.24 versus 1.28); and a higher proportion of SQ1-SQ3 fractures (52.0% versus 27.7%), SQ2–SQ3 fractures (36.8% versus 13.4%), and SQ3 fractures (21.5% versus 2.2%) than patients with peripheral fractures (all p < 0.05). All analyses were adjusted for sex, age, and body mass index (BMI); and the analyses of TBS and SQ1–SQ3 fracture prevalence was additionally adjusted for BMD). In conclusion, patients with central fragility fractures revealed lower femoral neck BMD, lower TBS, and higher prevalence of vertebral fractures on VFA than the patients with peripheral fractures. This suggests that patients with central fragility fractures exhibit more severe deterioration of bone structure, translating into a higher risk of subsequent fragility fractures and therefore they should get the highest priority in secondary fracture prevention, although attention to peripheral fractures should still not be diminished. © 2019 American Society for Bone and Mineral Research. © 2019 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.

Abstract

Fractures at central sites are associated with lower BMD at the femoral neck, total hip, and the site with lowest T-score, lower TBS, and higher prevalence of vertebral fractures. BMD = bone mineral density; TBS = trabecular bone score.
Pamidronate Administration During Pregnancy and Lactation Induces Temporal Preservation of Maternal Bone Mass in a Mouse Model of Osteogenesis Imperfecta
Authors: Olvera Diana , Stolzenfeld Rachel , Fisher Emily , Nolan Bonnie , Caird Michelle S , Kozloff Kenneth M
Published: July 2019

During pregnancy and lactation, the maternal skeleton undergoes significant bone loss through increased resorption to provide the necessary calcium supply to the developing fetus and suckling neonate. This period of skeletal vulnerability has not been clearly associated with increased maternal fracture risk, but these physiological conditions can exacerbate an underlying metabolic bone condition like osteogenesis imperfecta. Although bisphosphonates (BPs) are commonly used in postmenopausal women, there are cases where premenopausal women taking BPs become pregnant. Given BPs’ long half-life, there is a need to establish how BPs affect the maternal skeleton during periods of demanding metabolic bone changes that are critical for the skeletal development of their offspring. In the present study, pamidronate- (PAM-) amplified pregnancy-induced bone mass gains and lactation-induced bone loss were prevented. This preservation of bone mass was less robust when PAM was administered at late stages of lactation compared with early pregnancy and first day of lactation. Pregnancy-induced osteocyte osteolysis was also observed and was unaffected with PAM treatment. No negative skeletal effects were observed in offspring from PAM-treated dams despite lactation-induced bone loss prevention. These findings provide important insight into (1) a treatment window for when PAM is most effective in preserving maternal bone mass, and (2) the maternal changes in bone metabolism that maintain calcium homeostasis crucial for fetal and neonatal bone development. © 2019 American Society for Bone and Mineral Research
Fe2O3/Mn2O3 nanoparticles: Preparations and applications in the photocatalytic degradation of phenol and parathion in water
Authors: Mai Nguyen Vu Ngoc , Lim Duong Thi , Bac Nguyen Quang , Chi Nguyen Thi Ha , Dung Doan Trung , Pham Ngo Nghia , Nhiem Dao Ngoc
Published: July 2019

In this study, nanoparticles of Fe2O3/Mn2O3 mixture were obtained using the sol–gel method. The synthesis uses the combination of polyvinyl alcohol (PVA) and tartaric acid (TA). Synthesized catalysts prove superior compared to those afforded from previous reports. To be specific, desired catalysts can be received at lower calcination temperature. Furthermore, their structures display higher uniformity in term of particle sizes. Finally, they show better performance for the photocatalytic degradation of model‐persistent organic compounds.
A recurrent missense mutation in the EDAR gene causes severe autosomal recessive hypohidrotic ectodermal dysplasia in two consanguineous Kashmiri families
Authors: Sadia  , Foo Jia Nee , Khor Chiea Chuen , Jelani Musharraf , Ali Ghazanfar
Published: July 2019

Background

Hypohidrotic ectodermal dysplasia (HED) is a rare congenital disorder arising from the abnormal development of ectoderm derived structures, including skin, hair, nails, teeth and glands. These patients have sparse hair on the whole body, including the scalp, as well as hypoplastic teeth. They have no resistance to heat as a result of abnormal sweat glands. In total, four genes, namely ectodysplasin A (EDA), ectodysplasin A receptor (EDAR), EDAR‐associated death domain protein (EDARADD) and Wnt family member 10A (WNT10A), are known to be involved in the etiology of HED.

Methods

In the present study, we investigated two consanguineous Kashmiri families (A &B) with an autosomal recessive form of HED. Using whole exome sequencing and different bioinformatics tools, we detected a recurrent mutation causing severe HED.

Results

We identified an already known rare homozygous missense (NM_022336 c.1300 T>C; p.W434R; minor allele frequency 0.00007) variant in exon 12 of the EDAR gene. This variant segregated with a homozygous form in all patients and their obligate carriers were heterozygous. A panel of > 100 unrelated ethnically matched controls was screened, and the mutation was not identified outside the families. Furthermore, the candidate variant is predicted to be damaging by in silico software giving a CADD (Combined Annotation Dependent Depletion) score of 25.5, which indicates that the variant is among the top 1% of the deleterious variants in the human genome.

Conclusions

The identification of the same homozygous mutation segregating with disease in two different families supports the important role of the gene in the development of the disorder and this may contribute to novel approaches, prenatal diagnosis and genetic counseling of families with EDAR related disorders.
Thermal Behavior Analysis of Two Synthesized Flavor Precursors of N‐alkylpyrrole Derivatives
Authors: Ai Lvye , Liu Mengzhen , Ji Xiaoming , Lai Miao , Zhao Mingqin , Ren Tianbao
Published: July 2019

To expand the library of pyrrole‐containing flavor precursors, two new flavor precursors—methyl N‐benzyl‐2‐methyl‐5‐formylpyrrole‐3‐carboxylate (NBMF) and methyl N‐butyl‐2‐methyl‐5‐formylpyrrole‐3‐carboxylate (NUMF)—were synthesized by cyclization, oxidation, and alkylation reactions. Thermogravimetry (TG), differential scanning calorimeter, and pyrolysis–gas chromatography/mass spectrometry were utilized to analyze the thermal degradation behavior and thermal degradation products of NBMF and NUMF. The TG‐DTG curve indicated that the maximum mass loss rates of NBMF and NUMF appear at 310 and 268°C, respectively. The largest peaks of NBMF and NUMF showed by the differential scanning calorimeter curve were 315 and 274°C, respectively. Pyrolysis–gas chromatography/mass spectrometry detected small molecule fragrance compounds appeared during thermal degradation, such as 2‐methylpyrrole, 1‐methylpyrrole‐2‐carboxylic acid methyl ester, limonene, and methyl formate. Finally, the thermal degradation mechanism of NBMF and NUMF was discussed, which provided a theoretical basis for their application in tobacco flavoring additives.
Investigation of geometrical and doping parameter variations on GaSb/Si‐based double gate tunnel FETs: A qualitative and quantitative approach for RF performance enhancement
Authors: Shanmuganathan Poorvasha , Balasubramanian Lakshmi
Published: July 2019

This paper compares the radio frequency (RF) performance enhancement of GaSb/Si‐based double gate (DG) tunnel field‐effect transistors (TFETs) and DG TFETs with gate‐drain overlap devices using technology computer‐aided design (TCAD) simulations. The geometrical parameters taken under consideration are gate length (Lg), gate oxide thickness (tox), channel thickness (tch), and doping parameters are channel doping (Nch), drain doping (Nd), and source doping (Ns). These parameters are varied to extract the RF parameters, cut‐off frequency (ft), maximum oscillation frequency (fmax), intrinsic gain, and admittance (Y) parameters. DG TFET with gate‐drain overlap offers highest fmax values of 977 GHz for drain doping of 1e20 cm−3. Higher values of output resistance (Ro) results in high intrinsic gain values for DG TFET with gate‐drain overlap. In terms of Y parameters, DG TFET with gate‐drain overlap shows better Y11 and Y22 values compared with DG TFET. A quantitative model as a function of geometrical and doping parameters is modelled for all the RF parameters that validate the simulated values and predicted values.
Acclimation of a rocky shore algal reef builder Neogoniolithon sp. to changing illuminations
Authors: Gefen‐Treves Shany , Kedem Isaac , Weiss Gad , Wagner Dirk , Tchernov Dan , Kaplan Aaron
Published: July 2019

Vermetid reefs and rocky shores are hot spots of biodiversity, often referred to as the subtropical equivalent of coral reefs. The development of the ecosystem depends on the activity of several reef builders, including red crustose coralline algae (CCA) such as Neogoniolithon brassica‐florida. Despite its importance, little is known about Neogoniolithon sp. acclimation to rapid changes in light intensity and corresponding photosynthetic activity. To overcome the large spatial variability in the light field (due to location and the porous nature of the rocks) we grew Neogoniolithon sp. on glass slides and characterized its photosynthetic performance in response to various light intensities by following O2 exchange and fluorescence parameters. This was also performed on rock‐inhabiting thalli collected from the east Mediterranean basin. Generally, maximal photosynthetic rate was reached when Neogoniolithon sp. thalli grown under low illumination (such as in protected niches where the light intensity can be as low as 1% of surface illumination) were examined. When exposed to light intensities higher than those experienced during growth, Neogoniolithon sp. activates adaptive/protective mechanisms such as state transition and nonphotochemical fluorescence quenching and increases the dark respiration thereafter. We find that the Fv/Fm parameter (variable/maximal fluorescence) is not suitable to assess photosynthetic performance in Neogoniolithon sp. and propose using instead an alternative parameter recently developed. Our findings help to clarify why Neogoniolithon sp. is usually observed in shaded niches along the reef surfaces.
Polymeric Micelles Loading Proteins through Concurrent Ion Complexation and pH‐Cleavable Covalent Bonding for In Vivo Delivery
Authors: Tao Anqi , Huang George Lo , Igarashi Kazunori , Hong Taehun , Liao Suiyang , Stellacci Francesco , Matsumoto Yu , Yamasoba Tatsuya , Kataoka Kazunori , Cabral Horacio
Published: July 2019

Protein drugs have great potential as targeted therapies, yet their application suffers from several drawbacks, such as instability, short half‐life, and adverse immune responses. Thus, protein delivery approaches based on stimuli‐responsive nanocarriers can provide effective strategies for selectively enhancing the availability and activation of proteins in targeted tissues. Herein, polymeric micelles with the ability of encapsulating proteins are developed via concurrent ion complexation and pH‐cleavable covalent bonding between proteins and block copolymers directed to pH‐triggered release of the protein payload. Carboxydimethylmaleic anhydride (CDM) is selected as the pH‐sensitive moiety, since the CDMamide bond is stable at physiological pH (pH 7.4), while it cleaves at pH 6.5, that is, the pathophysiological pH of tumors and inflammatory tissues. By using poly(ethylene glycol)‐poly(l‐lysine) block copolymers having 45% CDM addition, different proteins with various sizes and isoelectric points are loaded successfully. By using myoglobin‐loaded micelles (myo/m) as a model, the stability of the micelles in physiological conditions and the dissociation and release of functional myoglobin at pH 6.5 are successfully confirmed. Moreover, myo/m shows extended half‐life in blood compared to free myoglobin and micelles assembled solely by polyion complex, indicating the potential of this system for in vivo delivery of proteins.
Quantification of Tafel coefficients according to passive/active state of steel carbonation‐induced corrosion in concrete
Authors: Duprat Frédéric , de Larrard Thomas , Vu Ngoc Tru
Published: July 2019

Statistical quantification of Tafel coefficients is investigated in this study for isolated steel rebar embedded in concrete. The survey is supported by a wide experimental campaign carried out earlier to characterize the passive and active states of carbonation‐induced corrosion of steel. Electrochemical measurements (polarization resistance, corrosion potential, Tafel coefficients) and gravimetric estimations of iron loss were regularly conducted over 417 days on 108 concrete specimens. The statistical analysis reveals that the mean value of Tafel coefficients, both cathodic and anodic, is higher under active corrosion, which seems to contradict the general tendency found for chloride‐induced corrosion, while their coefficient of variation is smaller. The statistical inference was based on the first step of distributions fitting the experimental data and then on the second step of goodness‐of‐fit tests. The most suitable of the distributions proposed were the Burr, Rayleigh, and Gamma distributions. A similar analysis was made for the corrosion potential and polarization resistance. The findings of the study will be valuable for probabilistic approaches to corrosion where probabilistic distributions are required.
Performance of Quebracho extract as eco‐friendly corrosion inhibitor for SAE 1010 steel in the oil field environment
Authors: Bacca Katryanne R. G. , Lopes Natália F. , Marcolino Juliane B. , dos Santos Grasel Fábio , da Costa Eleani M.
Published: July 2019

The inhibitive behavior of Quebracho tannin extract on SAE 1010 steel corrosion in the acidic media is investigated. Potentiodynamic polarization, electrochemical impedance spectroscopy (EIS), and scanning electron microscopy (SEM) are first used to determine the inhibition efficiency of Quebracho in 0.1 M HCl solution to identify the best extract concentration to subsequently evaluate the inhibitor activity in CO2‐rich aqueous solution at high pressure (15 MPa) and high temperature (70°C). Polarization curves revealed that Quebracho extract acted as cathodic inhibitor and that the inhibition efficiency is dependent on the extract concentration. The EIS measurements and SEM analysis showed that the inhibitor had been adsorbed on the steel surface. The inhibition efficiency of Quebracho in CO2 medium was similar to the 0.1 M HCl, reducing expressively the corrosion rate. The SEM images and X‐ray diffraction analysis showed that iron carbonate was the main corrosion product formed on the metal surface in CO2‐rich environment in the presence of Quebracho. Besides, the corrosion scale was thinner and more compact in the presence of inhibitor.
Early limbic microstructural alterations in apathy and depression in de novo Parkinson's disease
Authors: Prange Stéphane , Metereau Elise , Maillet Audrey , Lhommée Eugénie , Klinger Hélène , Pelissier Pierre , Ibarrola Danielle , Heckemann Rolf A. , Castrioto Anna , Tremblay Léon , Sgambato Véronique , Broussolle Emmanuel , Krack Paul , Thobois Stéphane
Published: July 2019

Background

Whether structural alterations underpin apathy and depression in de novo parkinsonian patients is unknown. The objectives of this study were to investigate whether apathy and depression in de novo parkinsonian patients are related to structural alterations and how structural abnormalities relate to serotonergic or dopaminergic dysfunction.

Methods

We compared the morphological and microstructural architecture in gray matter using voxel‐based morphometry and diffusion tensor imaging coupled with white matter tract‐based spatial statistics in a multimodal imaging case‐control study enrolling 14 apathetic and 13 nonapathetic patients with de novo Parkinson's disease and 15 age‐matched healthy controls, paired with PET imaging of the presynaptic dopaminergic and serotonergic systems.

Results

De novo parkinsonian patients with apathy had bilateral microstructural alterations in the medial corticostriatal limbic system, exhibiting decreased fractional anisotropy and increased mean diffusivity in the anterior striatum and pregenual anterior cingulate cortex in conjunction with serotonergic dysfunction. Furthermore, microstructural alterations extended to the medial frontal cortex, the subgenual anterior cingulate cortex and subcallosal gyrus, the medial thalamus, and the caudal midbrain, suggesting disruption of long‐range nondopaminergic projections originating in the brainstem, in addition to microstructural alterations in callosal interhemispheric connections and frontostriatal association tracts early in the disease course. In addition, microstructural abnormalities related to depressive symptoms in apathetic and nonapathetic patients revealed a distinct, mainly right‐sided limbic subnetwork involving limbic and frontal association tracts.

Conclusions

Early limbic microstructural alterations specifically related to apathy and depression emphasize the role of early disruption of ascending nondopaminergic projections and related corticocortical and corticosubcortical networks which underpin the variable expression of nonmotor and neuropsychiatric symptoms in Parkinson's disease. © 2019 International Parkinson and Movement Disorder Society
Asymptotic analysis of a boundary optimal control problem on a general branched structure
Authors: Aiyappan S. , Nandakumaran A. K. , Sufian Abu
Published: July 2019

We consider an optimal control problem posed on a domain with a highly oscillating smooth boundary where the controls are applied on the oscillating part of the boundary. There are many results on domains with oscillating boundaries where the oscillations are pillar‐type (non‐smooth) while the literature on smooth oscillating boundary is very few. In this article, we use appropriate scaling on the controls acting on the oscillating boundary leading to different limit control problems, namely, boundary optimal control and interior optimal control problem. In the last part of the article, we visualize the domains as a branched structure, and we introduce unfolding operators to get contributions from each level at every branch.
MultiRBE: Treatment planning for protons with selective radiobiological effectiveness
Authors: Sánchez‐Parcerisa Daniel , López‐Aguirre Miguel , Dolcet Llerena Ana , Udías José Manuel
Published: July 2019

Purpose

Clinical treatment planning protocols for protons recommend a uniform value radiobiological effectiveness (RBE) of protons of 1.1 throughout the treatment field, despite evidence from in‐vitro and animal studies that proton RBE increases with linear energy transfer (LET), causing tissues placed distally to the target location to receive a presumably higher biological dose than estimated. While several voices in the medical physics community have advocated for variable RBE‐based optimization, the uncertainties in RBE models have prevented its implementation in clinical practice, since an overestimation of RBE could cause significant target underdosage.

Methods

We propose a mixed RBE model (MultiRBE), where a uniform RBE is used in the target contours to ensure an adequate tumor coverage in terms of physical dose, but a variable RBE is used elsewhere. Our model was implemented in the open‐source treatment planning system matRad and three example cases were planned: a homogeneous phantom, a prostate tumor and a head‐and‐neck case. MultiRBE was used for plan optimization, and the produced plans were subsequently evaluated in terms of physical dose coverage (V95%) and variable RBE‐weighted dose in organs at risk and normal tissue complication probabilities (NTCP), where prediction models were available.

Results

The planning algorithm showed potential for reducing the biological dose in organs surrounding the planning target and thus decreasing the probability for complications in normal tissue (by up to 62% in the prostate case and 37% in the head‐and‐neck patient). This was achieved without compromising the target coverage or homogeneity in terms of physical dose, as a result of a smarter redistribution of dose among the surrounding tissues with regard to the optimization constraints.

Conclusions

The results prove the ability of the MultiRBE model to reduce biological dose at healthy tissues without compromising the dose coverage of the tumor, with independence of the variable RBE models used.
Is the endorsement of the Attention Deficit Hyperactivity Disorder symptom criteria ratings influenced by informant assessment, gender, age, and co‐occurring disorders? A measurement invariance study
Authors: Vitoratou Silia , Garcia‐Rosales Alexandra , Banaschewski Tobias , Sonuga‐Barke Edmund , Buitelaar Jan , Oades Robert D. , Rothenberger Aribert , Steinhausen Hans‐Christoph , Taylor Eric , Faraone Stephen V. , Chen Wai
Published: July 2019

Objectives

This study aims to ascertain whether the differences of prevalence and severity of attention deficit hyperactivity disorder (ADHD) are true or whether children are perceived and rated differently by parent and teacher informant assessments (INFAs) according to gender, age, and co‐occurring disorders, even at equal levels of latent ADHD traits.

Methods

Use of latent trait models (for binary responses) to evaluate measurement invariance in children with ADHD and their siblings from the International Multicenter ADHD Gene data.

Results

Substantial measurement noninvariance between parent and teacher INFAs was detected for seven out of nine inattention (IA) and six out of nine hyperactivity/impulsivity (HI) items; the correlations between parent and teacher INFAs for six IA and four HI items were not significantly different from zero, which suggests that parent and teacher INFAs are essentially rating different kinds of behaviours expressed in different settings, instead of measurement bias. However, age and gender did not affect substantially the endorsement probability of either IA or HI symptom criteria, regardless of INFA. For co‐occurring disorders, teacher INFA ratings were largely unaffected by co‐morbidity; conversely, parental endorsement of HI symptoms is substantially influenced by co‐occurring oppositional defiant disorder.

Conclusions

Our findings suggest general robustness of Diagnostic and Statistical Manual of Mental Disorders ADHD diagnostic items in relation to age and gender. Further research on classroom presentations is needed.
Quantized CP approximation and sparse tensor interpolation of function‐generated data
Authors: Khoromskij Boris N. , Kishore Kumar N. , Schneider Jan
Published: July 2019

In this article, we consider the iterative schemes to compute the canonical polyadic (CP) approximation of quantized data generated by a function discretized on a large uniform grid in an interval on the real line. This paper continues the research on the quantics‐tensor train (QTT) method (“O(d log N)‐quantics approximation of N‐d tensors in high‐dimensional numerical modeling” in Constructive Approximation, 2011) developed for the tensor train (TT) approximation of the quantized images of function related data. In the QTT approach, the target vector of length 2L is reshaped to a Lth‐order tensor with two entries in each mode (quantized representation) and then approximated by the QTT tensor including 2r2L parameters, where r is the maximal TT rank. In what follows, we consider the alternating least squares (ALS) iterative scheme to compute the rank‐r CP approximation of the quantized vectors, which requires only 2rL≪2L parameters for storage. In the earlier papers (“Tensors‐structured numerical methods in scientific computing: survey on recent advances” in Chemom Intell Lab Syst, 2012), such a representation was called QCan format, whereas in this paper, we abbreviate it as the QCP (quantized canonical polyadic) representation. We test the ALS algorithm to calculate the QCP approximation on various functions, and in all cases, we observed the exponential error decay in the QCP rank. The main idea for recovering a discretized function in the rank‐r QCP format using the reduced number of the functional samples, calculated only at O(2rL) grid points, is presented. The special version of the ALS scheme for solving the arising minimization problem is described. This approach can be viewed as the sparse QCP‐interpolation method that allows to recover all 2rL representation parameters of the rank‐r QCP tensor. Numerical examples show the efficiency of the QCP‐ALS‐type iteration and indicate the exponential convergence rate in r.
Mentors’ perspectives on the successes and challenges of mentoring in the COG Young Investigator mentorship program: A report from the Children's Oncology Group
Authors: Esbenshade Adam J. , Kahalley Lisa S. , Baertschiger Reto , Dasgupta Roshni , Goldsmith Kelly C. , Nathan Paul C. , Harker‐Murray Paul , Kitko Carrie L. , Kolb Edward Anders , Murphy Erin S. , Muscal Jodi A. , Pierson Christopher R. , Reed Damon , Schore Reuven , Unguru Yoram , Venkatramani Rajkumar , Wistinghausen Birte , Dhall Girish
Published: July 2019

Background

Identification and development of young investigators (YI) is critical to the long‐term success of research organizations. In 2004, the Children's Oncology Group (COG) created a mentorship program to foster the career development of YIs (faculty <10 years from initial appointment). This study sought to assess mentors’ long‐term assessment of this program.

Procedure

In 2018, 101 past or current mentors in the COG YI mentorship program completed an online survey. Statistical comparisons were made with the Kruskal‐Walis test.

Results

The response rate was 74.2%. As some mentors had multiple mentees, we report on 138 total mentee‐mentor pairs. Mentors were 57.4% male, and mentees were 39.1% male. Mentors rated being mentored as a YI as important with a median rating of 90 on a scale of 1‐100, interquartile range (IQR) 80‐100. Most mentors reported that being mentored themselves helped their own success within COG (78.2%) and with their overall career development (92.1%). Most mentors enjoyed serving in the program (72.3%) and the median success rating (on a scale of 1‐100) across the mentor‐mentee pairings was 75, IQR 39‐90. Success ratings did not differ by mentor/mentee gender, but improved with increased frequency of mentor‐mentee interactions (P < .001). Mentor‐mentee pairs who set initial goals reported higher success ratings than those who did not (P < .001). Tangible successes included current mentee COG committee involvement (45.7%), ongoing mentor‐mentee collaboration (53.6%), and co‐authored manuscript publication (38.4%).

Conclusion

These data indicate that mentorship is important for successful professional development. Long‐term mentoring success improves when mentors and mentees set goals upfront and meet frequently.
Gas‐emission craters of the Yamal and Gydan peninsulas: A proposed mechanism for lake genesis and development of permafrost landscapes
Authors: Dvornikov Yury A. , Leibman Marina O. , Khomutov Artem V. , Kizyakov Alexander I. , Semenov Petr , Bussmann Ingeborg , Babkin Evgeny M. , Heim Birgit , Portnov Alexey , Babkina Elena A. , Streletskaya Irina D. , Chetverova Antonina A. , Kozachek Anna , Meyer Hanno
Published: July 2019

This paper describes two gas‐emission craters (GECs) in permafrost regions of the Yamal and Gydan peninsulas. We show that in three consecutive years after GEC formation (2014–2017), both morphometry and hydrochemistry of the inner crater lakes can become indistinguishable from other lakes. Craters GEC‐1 and AntGEC, with initial depths of 50–70 and 15–19 m respectively, have transformed into lakes 3–5 m deep. Crater‐like depressions were mapped in the bottom of 13 out of 22 Yamal lakes. However, we found no evidence that these depressions could have been formed as a result of gas emission. Dissolved methane (dCH4) concentration measured in the water collected from these depressions was at a background level (45 ppm on average). Yet, the concentration of dCH4 from the near‐bottom layer of lake GEC‐1 was significantly higher (824–968 ppm) during initial stages. We established that hydrochemical parameters (dissolved organic carbon, major ions, isotopes) measured in GEC lakes approached values measured in other lakes over time. Therefore, these parameters could not be used to search for Western Siberian lakes that potentially resulted from gas emission. Temperature profiles measured in GEC lakes show that the water column temperatures in GEC‐1 are lower than in Yamal lakes and in AntGEC – close to values of Gydan lakes. Given the initial GEC depth > 50 m, we suggest that at least in GEC‐1 possible re‐freezing of sediments from below might take place. However, with the present data we cannot establish the modern thickness of the closed talik under newly formed GEC lakes.
Structural basis for the ORC1‐Cyclin A association
Authors: Wang Boxiao , Song Jikui
Published: July 2019

Progression of cell cycle is regulated by sequential expression of cyclins, which associate with distinct cyclin kinases to drive the transition between different cell cycle phases. The complex of Cyclin A with cyclin‐dependent kinase 2 (CDK2) controls the DNA replication activity through phosphorylation of a set of chromatin factors, which critically influences the S phase transition. It has been shown that the direct interaction between the Cyclin A‐CDK2 complex and origin recognition complex subunit 1 (ORC1) mediates the localization of ORC1 to centrosomes, where ORC1 inhibits cyclin E‐mediated centrosome reduplication. However, the molecular basis underlying the specific recognition between ORC1 and cyclins remains elusive. Here we report the crystal structure of Cyclin A‐CDK2 complex bound to a peptide derived from ORC1 at 2.54 å resolution. The structure revealed that the ORC1 peptide interacts with a hydrophobic groove, termed cyclin binding groove (CBG), of Cyclin A via a KXL motif. Distinct from other identified CBG‐binding sequences, an arginine residue flanking the KXL motif of ORC1 inserts into a neighboring acidic pocket, contributing to the strong ORC1‐Cyclin A association. Furthermore, structural and sequence analysis of cyclins reveals divergence on the ORC1‐binding sites, which may underpin their differential ORC1‐binding activities. This study provides a structural basis of the specific ORC1‐cyclins recognition, with implication in development of novel inhibitors against the cyclin/CDK complexes.
The aspartimide problem persists: Fluorenylmethyloxycarbonyl‐solid‐phase peptide synthesis (Fmoc‐SPPS) chain termination due to formation of N‐terminal piperazine‐2,5‐diones
Authors: Samson Daniel , Rentsch Daniel , Minuth Marco , Meier Thomas , Loidl Günther
Published: July 2019

Aspartimide (Asi) formation is a notorious side reaction in peptide synthesis that is well characterized and described in literature. In this context, we observed significant amounts of chain termination in Fmoc‐SPPS while synthesizing the N‐terminal Xaa‐Asp‐Yaa motif. This termination was caused by the formation of piperazine‐2,5‐diones. We investigated this side reaction using a linear model peptide and independently synthesizing its piperazine‐2,5‐dione derivative. Nuclear magnetic resonance (NMR) data of the side product present in the crude linear peptide proves that exclusively the six‐membered ring is formed whereas the theoretically conceivable seven‐membered 1,4‐diazepine‐2,5‐dione is not found. We propose a mechanism where nucleophilic attack of the N‐terminal amino function takes place at the α‐carbon of the carbonyl group of the corresponding Asi intermediate.

In addition, we systematically investigated the impact of (a) different adjacent amino acid residues, (b) backbone protection, and (c) side chain protection of flanking amino acids. The side reaction is directly related to the Asi intermediate. Hence, hindering or avoiding Asi formation reduces or completely suppresses this side reaction.
Templated chemistry for bioorganic synthesis and chemical biology
Authors: Seitz Oliver
Published: July 2019

In light of the 2018 Max Bergmann Medal, this review discusses advancements on chemical biology–driven templated chemistry developed in the author's laboratories. The focused review introduces the template categories applied to orient functional units such as functional groups, chromophores, biomolecules, or ligands in space. Unimolecular templates applied in protein synthesis facilitate fragment coupling of unprotected peptides. Templating via bimolecular assemblies provides control over proximity relationships between functional units of two molecules. As an instructive example, the coiled coil peptide–templated labelling of receptor proteins on live cells will be shown. Termolecular assemblies provide the opportunity to put the proximity of functional units on two (bio)molecules under the control of a third party molecule. This allows the design of conditional bimolecular reactions. A notable example is DNA/RNA–triggered peptide synthesis. The last section shows how termolecular and multimolecular assemblies can be used to better characterize and understand multivalent protein‐ligand interactions.
A randomized, triple‐blind, placebo‐controlled clinical trial, evaluating the sesamin supplement effects on proteolytic enzymes, inflammatory markers, and clinical indices in women with rheumatoid arthritis
Authors: Helli Bizhan , Shahi Majid Mohammad , Mowla Karim , Jalali Mohammad Taha , Haghighian Hossein Khadem
Published: July 2019

Inflammation is one of the main characteristics of rheumatoid arthritis. Based on the antiinflammatory properties of sesame, this study was conducted to evaluate the sesamin supplement effects on serum levels of some proteolytic enzymes, inflammatory biomarkers, and clinical indices in women with rheumatoid arthritis. In this randomized, triple‐blind, placebo‐controlled clinical trial, 44 patients were randomly divided in intervention and control groups. Patients received 200‐mg/day sesamin supplement or placebo in the intervention and control group for 6 weeks. Serum levels of proteolytic enzymes (hyaluronidase, aggrecanase, and matrix metalloproteinases‐3) and inflammatory biomarkers (hs‐CRP, IL‐1β, IL‐6, TNF‐α, and cyclooxygenase‐2) were measured with enzyme‐linked immunosorbent assay method at the beginning and end of the study. After intervention, serum levels of hyaluronidase and matrix metalloproteinases‐3 decreased significantly in sesamin group. Also, serum levels of hs‐CRP, TNF‐α, and cyclooxygenase‐2 in intervention group were significantly decreased in intervention group compared with placebo group. Sesamin supplementation also caused a significant reduction in the number of tender joints and severity of pain in these patients. According to the results, it seems that the sesamin by reducing inflammatory mediators can relieve clinical symptoms and pathological changes that caused by inflammatory impairment in patients with rheumatoid arthritis.
Verification of numerical creep and shrinkage models in an arch bridge analysis
Authors: Kolínský Vojtěch , Vítek Jan L.
Published: July 2019

The highway arch bridge at Oparno in the Czech Republic is composed of the two independent almost identical structures; each of them carries one direction of the traffic. Each structure has a fixed end arch with the span of 135 m. The rise of the arch is 30 m. The bridge deck has a double T cross section and it is longitudinally prestressed. The arch was cast by cantilever method using temporary pylons with temporary stays. The arch is made of reinforced concrete and it is subjected preferably to compression. Therefore, it represents a suitable structure for comparison of strains and deflections obtained by measurements on the site and those obtained by a numerical analysis using different prediction models which may be applied in design calculations. The arch was equipped by vibrating wire strain gauges and the strains were recorded during the construction process and later during the early service life of the bridge. Additionally, the deflections of cantilevers during construction were also recorded. The measured values were used for adjustment of the form traveler and finally for evaluation of the prediction models. The bridge was built in the period 2008–2010. It was open to traffic significantly later (at the end of 2016) because the highway could not be finished earlier due to different nontechnical reasons.
Effects of hybrid steel fiber reinforced composites on structural performance of segmental linings subjected to TBM jacks
Authors: Jamshidi Avanaki Mohammad
Published: July 2019

In recent years, incorporating fibers as the main reinforcement in segmental lined tunnels has gained significant interest. Damage to segmental linings due to the thrust force of TBM jacks is one of the main problems that arises in the assembly phase, reducing serviceability and durability of tunnels. The aim of this paper is to experimentally and numerically investigate the effects of fiber size, content, and hybridization on the performance of steel fiber reinforced concrete (SFRC) tunnel segments under TBM jack forces compared to conventionally reinforced concrete (RC) segments. In this regard, different scenarios of segment support conditions and eccentricity of the applied TBM jack loads are investigated in a particular real tunnel. The results showed that under various configurations of segment support and load eccentricity, SFRC composites show better performance over RC in both SLS and ULS conditions under TBM jack loads in terms of cracking strength and damage propagation.