bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterizing the function of domain linkers in regulating the dynamics of multi‐domain fusion proteins by microsecond molecular dynamics simulations and artificial intelligence
Authors: Wang Bo , Su Zhaoqian , Wu Yinghao
Published: February 2021

Multi‐domain proteins are not only formed through natural evolution but can also be generated by recombinant DNA technology. Because many fusion proteins can enhance the selectivity of cell targeting, these artificially produced molecules, called multi‐specific biologics, are promising drug candidates, especially for immunotherapy. Moreover, the rational design of domain linkers in fusion proteins is becoming an essential step toward a quantitative understanding of the dynamics in these biopharmaceutics. We developed a computational framework to characterize the impacts of peptide linkers on the dynamics of multi‐specific biologics. Specifically, we first constructed a benchmark containing six types of linkers that represent various lengths and degrees of flexibility and used them to connect two natural proteins as a test system. We then projected the microsecond dynamics of these proteins generated from Anton onto a coarse‐grained conformational space. We further analyzed the similarity of dynamics among different proteins in this low‐dimensional space by a neural‐network‐based classification model. Finally, we applied hierarchical clustering to place linkers into different subgroups based on the classification results. The clustering results suggest that the length of linkers, which is used to spatially separate different functional modules, plays the most important role in regulating the dynamics of this fusion protein. Given the same number of amino acids, linker flexibility functions as a regulator of protein dynamics. In summary, we illustrated that a new computational strategy can be used to study the dynamics of multi‐domain fusion proteins by a combination of long timescale molecular dynamics simulation, coarse‐grained feature extraction, and artificial intelligence.
A large‐scale survey of pairwise epistasis reveals a mechanism for evolutionary expansion and specialization of PDZ domains
Authors: Nedrud David , Coyote‐Maestas Willow , Schmidt Daniel
Published: February 2021

Deep mutational scanning (DMS) facilitates data‐driven models of protein structure and function. Here, we adapted Saturated Programmable Insertion Engineering (SPINE) as a programmable DMS technique. We validate SPINE with a reference single mutant dataset in the PSD95 PDZ3 domain and then characterize most pairwise double mutants to study epistasis. We observe wide‐spread proximal negative epistasis, which we attribute to mutations affecting thermodynamic stability, and strong long‐range positive epistasis, which is enriched in an evolutionarily conserved and function‐defining network of “sector” and clade‐specifying residues. Conditional neutrality of mutations in clade‐specifying residues compensates for deleterious mutations in sector positions. This suggests that epistatic interactions between these position pairs facilitated the evolutionary expansion and specialization of PDZ domains. We propose that SPINE provides easy experimental access to reveal epistasis signatures in proteins that will improve our understanding of the structural basis for protein function and adaptation.
Farmers' behavior in reading and using risk information displayed on pesticide labels: a test with the theory of planned behavior
Authors: Bagheri Asghar , Emami Naier , Damalas Christos A
Published: February 2021

BACKGROUND

Labels are the first source of information for the safe use of pesticides, but farmers rarely read labels before pesticide use. Using data from a sample of 300 orchard farmers in Meshginshar County, Iran, this study examined farmers' intention and behavior in reading and using risk information displayed on pesticide labels, using the theory of planned behavior (TPB).

RESULTS

Only 26% of the respondents mentioned that they read pesticide labels. Most farmers showed a low tendency towards reading pesticide labels due to low education, advanced age, and label‐related problems, i.e., use of too technical language and unclear texts with small and illegible fonts. From the three basic variables of the TPB, subjective norms and perceived behavioral control (PBC) showed a significant impact on intention, while attitudes showed no significant impact. The three main variables of the TPB explained 90.2% of the variance in farmers' intention to read and use the labels. Furthermore, PBC and intention significantly affected farmers' actual behavior in reading and using the labels, explaining 78.5% of the variance in farmers' actual behavior. Age, experience in farming, and experience in spraying were negatively correlated with all variables of the TPB.

CONCLUSION

Findings provide new insights into farmers' behavior in reading pesticide labels by using for the first time the TPB. Pesticide manufacturers should consider the special conditions of subsistence farmers (low education and advanced age) when preparing pesticide labels and the extension services could use those findings to improve farmers' training in the use of pesticide labels.

© 2021 Society of Chemical Industry.
Epigenetic targeting of cancer stem cells by polyphenols (cancer stem cells targeting)
Authors: Ghasemi Sorayya , Xu Suowen , Nabavi Seyed Mohammad , Amirkhani Mohammad Amir , Sureda Antoni , Tejada Silvia , Lorigooini Zahra
Published: February 2021

Epigenetic alterations are one of the main factors that disrupt the expression of genes and consequently, they have an important role in the carcinogenicity and the progression of different cancers. Cancer stem cells (CSCs) are accountable for the recurrence, metastasis, and therapeutic failure of cancer. The noticeable and specific pathways in CSCs can be organized by epigenetic mechanisms such as DNA methylation, chromatin remodeling, regulatory RNAs, among others. Since epigenetics modifications can be changed and reversed, it is a possible tool for cancer control and treatment. Epigenetic therapies against CSCs are emerging as a very new strategy with a good future expectation to treat cancer patients. Phenolic compounds are a vast group of substances with anticarcinogenic functions, antiinflammatory, and antioxidative activities. It seems these characteristics are related to neutralizing CSCs development, their microenvironment, and metabolism through epigenetic mechanisms. In the current work, the types of epigenetic changes known in these cells are introduced. In addition, some studies about the use of polyphenols acting through a variety of epigenetic mechanisms to counteract these cells will be reviewed. The reported results seem to indicate that the use of these phenolic compounds may be useful for CSCs defeat.
Interplay of Magnetic Properties and Doping in Epitaxial Films of h‐REFeO3 Multiferroic Oxides
Authors: Baghizadeh Ali , Vaghefi Pegah Mirzadeh , Huang Xing , Borme Jerome , Almeida Bernardo , Salak Andrei N. , Willinger Marc‐Georg , Amaral Vitor B. , Vieira Joaquim M.
Published: February 2021

Multiferroic materials demonstrating coexistence of magnetic and ferroelectric orders are promising candidates for magnetoelectric devices. While understanding the underlying mechanism of interplaying of ferroic properties is important, tailoring their properties to make them potential candidates for magnetoelectric devices is challenging. Here, the antiferromagnetic Neel ordering temperature above 200 K is realized in successfully stabilized epitaxial films of (Lu,Sc)FeO3 multiferroic oxide. The first‐principles calculations show the shrinkage of in‐plane lattice constants of the unit cells of the films on different substrates which corroborates well the enhancement of the Neel ordering temperature (TN). The profound effect of lattice strain/stress at the interface due to differences of in‐plane lattice constants on out of plane magnetic properties and on spin reorientation temperature in the antiferromagnetic region is further elucidated in the epitaxial films with and without buffer layer of Mn‐doped LuFeO3. Writing and reading ferroelectric domains reveal the ferroelectric response of the films at room temperature. Detailed electron microscopy shows the presence of lattice defects in atomic scale. First‐principles calculations show that orbital rehybridization of rare‐earth ions and oxygen is one of the main driving force of ferroelectricity along c‐axis in thin films of hexagonal ferrites.
All‐Inorganic Lead‐Free Perovskite(‐Like) Single Crystals: Synthesis, Properties, and Applications
Authors: Zhao Shuangyi , Cai Wensi , Wang Huaxin , Zang Zhigang , Chen Jiangzhao
Published: February 2021

Due to their nontoxicity, stability, and unique optoelectronic properties, all‐inorganic lead‐free halide semiconductors with perovskite and perovskite‐like structures have successfully emerged as promising optoelectronic materials for various applications, such as solar cells, light‐emitting diodes (LEDs), photodetectors, and X‐ray detectors. To further explore their practical potentials, researchers have paid more attention in all‐inorganic lead‐free perovskite (‐like) (ILFP) single crystals. For these single crystals, the advantages of large sizes, uniform surface morphology, and few defects can facilitate their excellent performances and practical applications. Besides, compared with the low dimensional and polycrystalline ILFP materials, the ILFP single crystals feature enhanced performances, including a longer carrier diffusion length and a larger light absorption coefficient, which attract a great deal of attention. Therefore, focus is on the researching progress of ILFP single crystals and the development of their preparation methods, as well as the novel properties of ILFP single crystals. In addition, the reported applications of ILFP single crystals are proposed to highlight their practical importance. With the perspective of the evolution and challenges, the current limitations of the materials and devices are discussed, followed by an inspirational outlook on their future development directions.
Numerical Analysis of Fluid Flow and Heat Transfer by Means of a Unified Model in a Direct Current Electric Arc Furnace
Authors: Yao Cong-Lin , Zhu Hong-Chun , Jiang Zhou-Hua , Pan Tao
Published: February 2021

Herein, a unified 2D axially symmetric model coupling the plasma arc and molten bath in a direct current electric arc furnace is established, with the physical phenomena at the plasma arc/molten bath interface to be confronted by the “local thermodynamic equilibrium diffusion approximation” method. After ensuring model validation and grid independence test, the fluid flow and heat transfer processes are analyzed. The numerical investigation reveals that in terms of the relative importance of driving forces in the molten bath, an anticlockwise eddy is formed at the molten bath center driven by electromagnetic force, whereas a clockwise eddy is formed near the lateral part of the molten bath driven by buoyancy force. Regarding the distribution of heat ﬂux, the convection–conduction and radiation heat govern the rate of heat transfer from the plasma arc to the molten bath. In addition, for larger arc current, higher arc power in the plasma arc region and higher heating rates in the molten bath are obtained when the arc length is held constant; for shorter arc length, lower arc power in the plasma arc region but higher heat transfer efficiency in the molten bath is attained when the arc current is held constant.
Suppression of food restriction‐evoked hyperactivity in activity‐based anorexia animal model through glutamate transporters GLT‐1 at excitatory synapses in the hippocampus
Authors: Bilash Olesia M. , Actor‐Engel Hannah S. , Sherpa Ang D. , Chen Yi‐Wen , Aoki Chiye
Published: February 2021

Severe voluntary food restriction is the defining symptom of anorexia nervosa (AN), but anxiety and excessive exercise are maladaptive symptoms that contribute significantly to the severity of AN and which individuals with AN have difficulty suppressing. We hypothesized that the excitability of hippocampal pyramidal neurons, known to contribute to anxiety, leads to the maladaptive behavior of excessive exercise. Conversely, since glutamate transporter GLT‐1 dampens the excitability of hippocampal pyramidal neurons through the uptake of ambient glutamate and suppression of the GluN2B‐subunit containing NMDA receptors (GluN2B‐NMDARs), GLT‐1 may contribute toward dampening excessive exercise. This hypothesis was tested using the mouse model of AN, called activity‐based anorexia (ABA), whereby food restriction evokes the maladaptive behavior of excessive wheel running (food restriction‐evoked running, FRER). We tested whether individual differences in ABA vulnerability of mice, quantified based on FRER, correlated with individual differences in the levels of GLT‐1 at excitatory synapses of the hippocampus. Electron microscopic immunocytochemistry (EM‐ICC) was used to quantify GLT‐1 levels at the excitatory synapses of the hippocampus. The FRER seen in individual mice varied more than 10‐fold, and Pearson correlation analyses revealed a strong negative correlation (p = .02) between FRER and GLT‐1 levels at the axon terminals of excitatory synapses and at the surrounding astrocytic plasma membranes. Moreover, synaptic levels of GluN2B‐NMDARs correlated strongly with GLT‐1 levels at perisynaptic astrocytic plasma membranes. There is at present no accepted pharmacotherapy for AN, and little is known about the etiology of this deadly illness. Current findings suggest that drugs increasing GLT‐1 expression may reduce AN severity through the reduction of GluN2B‐NMDAR activity.
Reconstruction of Partially Occluded Facial Image for Classification
Authors: Zou Min , You Mengbo , Akashi Takuya
Published: February 2021

The recent literature indicates that face recognition and facial expression classification has achieved a high accuracy on benchmark datasets with a large number of face images in the wild. On the other hand, unlike the purpose of recognizing as many people as possible, real applications for families or companies usually aim to recognize a small group of people as accurate as possible. In case of the face is partially occluded, convolutional solutions always simply put images with occlusions into the training dataset and hope the convolution neural network learn a model robust to partial occlusion. These processes not only increase the burden of learning, but also affect the model to identify normal images without occlusions. In this paper, we investigate the research problem of facial image reconstruction to discard the influence of partial occlusion. Based on the phenomenon that human faces are roughly symmetrical, we propose to reconstruct the facial information of occluded areas with the intact half face. Specifically, occlusion on the left‐half face is reconstructed with a linear combination of features on the right‐half face and vice versa. The process is modeled by keeping row sparsity for the coefficient matrix with l2,1‐norm regularization while minimizing the reconstruction error. An alternative iterative algorithm is proposed to solve the optimization problem. To validate the effectiveness of the reconstruction, we fine‐tune a pretrained model, AlexNet, training on normal face images and test with various occluded images. Extensive experimental results show that our method has improved the classification performance effectively. © 2021 Institute of Electrical Engineers of Japan. Published by Wiley Periodicals LLC.
Routine third‐trimester ultrasound for the detection of small‐for‐gestational age in low‐risk pregnancies (ROTTUS study): randomized controlled trial
Authors: Wanyonyi S. Z. , Orwa J. , Ozelle H. , Martinez J. , Atsali E. , Vinayak S. , Temmerman M. , Figueras F.
Published: February 2021

Objective

To compare the proportion of small‐for‐gestational‐age (SGA) infants detected by routine third‐trimester ultrasound vs those detected by selective ultrasound based on serial symphysis–fundus height (SFH) measurements (standard care) in low‐risk pregnancy.

Methods

This was an open‐label randomized controlled trial conducted at a hospital in Kenya between May 2018 and February 2020. Low‐risk pregnant women were randomly allocated (ratio of 1:1) to routine ultrasound for fetal growth assessment between 36 + 0 and 37 + 6 weeks' gestation (intervention group) or to standard care, which involved a selective growth scan on clinical suspicion of fetal growth abnormality based on serial SFH measurements (control group). During ultrasound examination, fetal growth was assessed by measurement of the abdominal circumference (AC), and AC < 10th centile was used to diagnose a SGA fetus. The main prespecified outcomes were the detection of neonatal SGA, defined as birth weight < 10th centile, and of severe neonatal SGA, defined as birth weight < 3rd centile. The predictive performance of routine third‐trimester ultrasound and selective ultrasound based on serial SFH measurements was determined using receiver‐operating‐characteristics (ROC)‐curve analysis.

Results

Of 566 women assessed for eligibility, 508 (89.8%) were randomized, of whom 253 were allocated to the intervention group and 255 to the control group. Thirty‐six babies in the intervention group and 26 in the control group had a birth weight < 10th centile. The detection rate of SGA infants by routine third‐trimester ultrasound vs that by standard care was 52.8% (19/36) vs 7.7% (2/26) (P < 0.001) and the specificity was 95.5% (191/200) and 97.9% (191/195), respectively (P = 0.08). The detection rate of severe SGA was 66.7% (12/18) by routine ultrasound vs 8.3% (1/12) by selective ultrasound based on SFH measurements (P < 0.001), with specificities of 91.7% (200/218) and 98.1% (205/209), respectively (P = 0.006). The area under the ROC curve of routine third‐trimester ultrasound in prediction of SGA was significantly greater than that of selective ultrasound based on SFH measurements (0.92 (95% CI, 0.87–0.96) vs 0.68 (95% CI, 0.58–0.77); P < 0.001).

Conclusions

In low‐risk pregnancy, routine ultrasound performed between 36 + 0 and 37 + 6 weeks is superior to selective ultrasound based on serial SFH measurements for the detection of true SGA, with high specificity. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.
Two‐dimensional and doppler echocardiographic evaluation in twenty‐one healthy Python regius
Authors: Bagardi Mara , Bardi Edoardo , Manfredi Martina , Segala Arianna , Belfatto Antonella , Cusaro Stefano , Romussi Stefano , Brambilla Paola Giuseppina
Published: February 2021

Echocardiographic evaluation is a diagnostic tool for the in vivo diagnosis of heart diseases. Specific and unique anatomical characteristics of the ophidian heart such as the single ventricular cavity, a tubular sinus venosus opening into the right atrium, the presence of three arterial trunks and extreme mobility in the coelomic cavity during the cardiac cycle directly affect echocardiographic examination. Twenty‐one awake, healthy ball pythons (Python regius) were analysed based on guidelines for performing echocardiographic examinations. Imaging in the sagittal plane demonstrated the caudal vena cava, sinus venosus valve (SVV) and right atrium and the various portions of the ventricle, horizontal septum, left aortic arch and pulmonary artery. Transverse imaging depicted the spatial relationship of the left and right aortic arches, the pulmonary artery and the horizontal septum. Basic knowledge of cardiac blood flow in reptiles is necessary to understand the echocardiographic anatomy. The flow of the arterial trunks and SVV was analysed using pulsed‐wave Doppler based on the approach used for humans and companion mammals. The walls and diameters of the cavum arteriosum, cavum venosum and cavum pulmonale were also evaluated. This study should improve the veterinarian's knowledge of ophidian heart basal physiology and contribute to the development of cardiology in reptiles.
A comprehensive study on the semileptonic decay of heavy flavor mesons
Authors: Zhang Lu , Kang Xian-Wei , Guo Xin-Heng , Dai Ling-Yun , Luo Tao , Wang Chao
Published: February 2021

Abstract

The semileptonic decay of heavy flavor mesons offers a clean environment for extraction of the Cabibbo-Kobayashi-Maskawa (CKM) matrix elements, which describes the CP-violating and flavor changing process in the Standard Model. The involved form factors where the dynamical information is encoded play an essential role in achieving any conclusive statement. That is, the knowledge of the form factors should be under good control, requiring one to examine more observables in addition to the branching fraction. In this paper, we provide the mean value and the q2-dependent shape for further observables [differential decay distribution (dΓ/dq2), forward-backward asymmetry $$ \left({\mathcal{A}}_{FB}^{ls}\right) $$

A
FB
ls

, longitudinal $$ \left({P}_L^l\right) $$

P
L
l

and transverse $$ \left({P}_T^l\right) $$

P
T
l

polarization of a charged lepton, longitudinal polarization of a vector meson in the final state $$ \left({F}_L^l(V)\right) $$

F
L
l

V

, leptonic convexity parameter $$ \left({C}_F^l\right) $$

C
F
l

, and trigonometric moments $$ \left({W}_i^l\right) $$

W
i
l

in the decay of D(s) and B(s) to P/Vl+νl (l = e, μ or τ)], based on the predictions of the relevant form factors from the covariant light-front quark model. P and V denote the pseudoscalar and vector meson, respectively. As a comparison, we find a good agreement with the results from the covariant confining quark model and the relativistic quark model in the literature. As it has been observed that the $$ {P}_L^l $$

P
L
l

and $$ {F}_L^l(V) $$

F
L
l

V

are crucial quantities to discriminate various New Physics models, the reexamination of these observables from a different method is also essential and necessary.
Vacuum fermionic currents in braneworld models on AdS bulk with a cosmic string
Authors: Bellucci S. , dos Santos W. Oliveira , de Mello E.R. Bezerra , Saharian A.A.
Published: February 2021

Abstract

We investigate the effects of a brane and magnetic-flux-carrying cosmic string on the vacuum expectation value (VEV) of the current density for a charged fermionic field in the background geometry of (4+1)-dimensional anti-de Sitter (AdS) spacetime. The brane is parallel to the AdS boundary and the cosmic string is orthogonal to the brane. Two types of boundary conditions are considered on the brane that include the MIT bag boundary condition and the boundary conditions in Z2-symmetric braneworld models. The brane divides the space into two regions with different properties of the vacuum state. The only nonzero component of the current density is along the azimuthal direction and in both the regions the corresponding VEV is decomposed into the brane- free and brane-induced contributions. The latter vanishes on the string and near the string the total current is dominated by the brane-free part. At large distances from the string and in the region between the brane and AdS horizon the decay of the brane-induced current density, as a function of the proper distance, is power-law for both massless and massive fields. For a massive field this behavior is essentially different from that in the Minkowski bulk. In the region between the brane and AdS boundary the large-distance decay of the current density is exponential. Depending on the boundary condition on the brane, the brane-induced contribution is dominant or subdominant in the total current density at large distances from the string. By using the results for fields realizing two inequivalent irreducible representations of the Clifford algebra, the vacuum current density is investigated in C - and P -symmetric fermionic models. Applications are given for a cosmic string in the Randall-Sundrum-type braneworld model with a single brane.
Failure analysis and recommendations for treatment of posttraumatic non-unions of the distal humerus during childhood
Authors: Sommerfeldt Dirk Walther , Schmittenbecher Peter Paul
Published: February 2021

Purpose

Non-unions of the distal humerus are rare complications of common children’s fractures such as radial condyle fractures and supracondylar fractures. The aim of this paper was to update the knowledge about etiology, reasons, management, and results of these troublesome, and sometimes debilitating entities.

Methods

The sparse literature concerning nonunions following condylar or supracondylar fractures was analyzed together with the presentation of some typical clinical cases.

Results

In most of the cases, non-unions were induced by neglect, unstable fixation, too early implant removal, too much revision surgery, and an inconsequent transfer of follow-up algorithms, or combinations of the above. Treatment of non-union should start as early as possible because the effort of required surgery increases with time that the nonunion has been neglected. Often a combination of stable fixation of the pseudarthrosis and correction of the elbow axis are necessary to achieve a satisfying outcome.

Conclusion

In pediatric traumatology, qualified and consequent care for children’s fractures of the distal humerus can prevent rare complications such as non-unions in almost any situation. If such a disturbance of healing is noticed, immediate and adequate, i.e. children specific surgical consequences achieve best results.
Tranexamsäure zur Blutungsprophylaxe bei Trauma und orthopädischen Eingriffen – Standard oder individualisierte Anwendung?
Authors: Pekrul Isabell , Schachtner Thomas , Zwißler Bernhard , Möhnle Patrick
Published: February 2021

Tranexamsäure hat einen etablierten Stellenwert in der Behandlung von Blutungen, v. a. bei Hyperfibrinolyse. Zunehmend wird TXA auch prophylaktisch bei Trauma und orthopädischen Eingriffen eingesetzt, wobei sich Fragen nach Risiken sowie einem möglichen Off-Label-Einsatz ergeben. Auf Basis der verfügbaren Literatur lässt sich schließen, dass ein prophylaktischer Einsatz des Präparates in diesen Indikationsbereichen vertretbar ist. Jedoch sollte bei Patienten mit erhöhtem Risiko für thrombembolische Ereignisse weiterhin eine individuelle Abwägung von Nutzen und Risiken durchgeführt und dokumentiert werden. Obwohl die Indikationsgebiete des prophylaktischen Einsatzes bei Trauma und orthopädischen Eingriffen nicht spezifisch in der Fachinformation aufgeführt sind, ist die Anwendung unseres Erachtens nicht als Off Label Use zu bewerten.
Universal Qudit Hamiltonians
Authors: Piddock Stephen , Montanaro Ashley
Published: February 2021

A family of quantum Hamiltonians is said to be universal if any other finite-dimensional Hamiltonian can be approximately encoded within the low-energy space of a Hamiltonian from that family. If the encoding is efficient, universal families of Hamiltonians can be used as universal analogue quantum simulators and universal quantum computers, and the problem of approximately determining the ground-state energy of a Hamiltonian from a universal family is QMA-complete. One natural way to categorise Hamiltonians into families is in terms of the interactions they are built from. Here we prove universality of some important classes of interactions on qudits (d-level systems):

We completely characterise the k-qudit interactions which are universal, if augmented with arbitrary Hermitian 1-local terms.

We find that, for all $$k \geqslant 2$$

k
⩾
2

and all local dimensions $$d \geqslant 2$$

d
⩾
2

, almost all such interactions are universal aside from a simple stoquastic class.

We prove universality of generalisations of the Heisenberg model that are ubiquitous in condensed-matter physics, even if free 1-local terms are not provided. We show that the SU(d) and SU(2) Heisenberg interactions are universal for all local dimensions $$d \geqslant 2$$

d
⩾
2

(spin $$\geqslant 1/2$$

⩾
1
/
2

), implying that a quantum variant of the Max-d-Cut problem is QMA-complete. We also show that for $$d=3$$

d
=
3

all bilinear-biquadratic Heisenberg interactions are universal. One example is the general AKLT model.

We prove universality of any interaction proportional to the projector onto a pure entangled state.
Regularity of the free boundary for the two-phase Bernoulli problem
Authors: De Philippis Guido , Spolaor Luca , Velichkov Bozhidar
Published: February 2021

We prove a regularity theorem for the free boundary of minimizers of the two-phase Bernoulli problem, completing the analysis started by Alt, Caffarelli and Friedman in the 80s. As a consequence, we also show regularity of minimizers of the multiphase spectral optimization problem for the principal eigenvalue of the Dirichlet Laplacian.
A randomized, double-blind study of iodine supplementation during pregnancy in Sweden: pilot evaluation of maternal iodine status and thyroid function
Authors: Manousou Sofia , Eggertsen Robert , Hulthén Lena , Filipsson Nyström Helena
Published: February 2021

Purpose

Pregnant women in Sweden are mildly iodine deficient. We investigated the effect of daily iodine supplementation on the iodine and thyroid status of pregnant women.

Methods

In this pilot, randomized, double-blind trial, 200 thyroid-healthy pregnant women were recruited at mean (standard deviation) pregnancy week 8.85 (1.62) and assigned (1:1) to daily intake of a multivitamin tablet with or without 150 μg of iodine. Urine and serum samples were collected at baseline and once during the second and third trimesters. Urinary iodine concentration (UIC), serum thyroglobulin (Tg), thyroid-stimulating hormone (TSH), free thyroxine (FT4), and thyroid peroxidase antibodies (TPOabs) were analyzed. Neonatal TSH data were collected. UIC and Tg were also analyzed in a group of 89 thyroid-healthy non-pregnant women of reproductive age (WRA).

Results

At baseline, the intervention and the control groups had similar median UIC (interquartile range (IQR)): 110 μg/L (74–119) and 111 μg/L (66–168), respectively. The intervention group reached iodine sufficiency with median UIC (IQR) 139 μg/L (89–234) and 136 μg/L (91–211) in the second and third trimester, respectively, without significant difference from the lower limit of the recommended range, i.e. 150–250 μg/L (p = 0.42 and p = 0.87, respectively). The intervention group had higher median UIC and lower median Tg compared to the control group during the second (p < 0.001 and p = 0.019, respectively) and third trimester (p < 0.001 and p = 0.003, respectively), whereas thyroid hormones, serum TPOabs, and neonatal TSH were similar. The WRA group presented median UIC (IQR) 65 μg/L (30–98) and median Tg (IQR) 18 μg/L (13–27).

Conclusion

A daily supplement containing 150 μg of iodine to a group of pregnant women with mild iodine deficiency improved the iodine status from mild ID to iodine sufficiency. This improvement seems to have had a positive impact on maternal thyroglobulin. This study is now under extension to investigate the children’s neuropsychological development.

Trial registration

ClinicalTrials.gov Identifier NCT02378246, May 3, 2015, retrospectively registered.
Serendipita indica changes host sugar and defense status in Arabidopsis thaliana: cooperation or exploitation?
Authors: Opitz Michael W. , Daneshkhah Roshanak , Lorenz Cindy , Ludwig Roland , Steinkellner Siegrid , Wieczorek Krzysztof
Published: February 2021

Main conclusion

Manipulation of sugar metabolism upon S. indica root colonization triggers changes in sugar pools and defense responses in A. thaliana.

Serendipita indica is an endophytic fungus that establishes mutualistic relationships with many different plants including important crops as well as the model plant A. thaliana. Successful root colonization typically results in growth promotion and enhanced tolerance against various biotic and abiotic stresses. The fungus delivers phosphorus to the host and receives in exchange carbohydrates. There are hints that S. indica prefers hexoses, glucose, and fructose, products of saccharose cleavage driven by invertases (INVs) and sucrose synthases (SUSs). Carbohydrate metabolism in this interaction, however, remains still widely unexplored. Therefore, in this work, the sugar pools as well as the expression of SUSs and cytosolic INVs in plants colonized by S. indica were analyzed. Using sus1/2/3/4 and cinv1/2 mutants the importance of these genes for the induction of growth promotion and proper root colonization was demonstrated. Furthermore, the expression of several defense-related marker genes in both multiple mutants in comparison to the wild-type plants was determined. Our results show that in colonized A. thaliana plants S. indica manipulates the sugar metabolism by altering the expression of host’s INV and SUS and modulates both the sugar pools and plant defense in its favor. We conclude that the interaction A. thaliana–S. indica is a balancing act between cooperation and exploitation, in which sugar metabolism plays a crucial role. Small changes in this mechanism can lead to severe disruption resulting in the lack of growth promotion or altered colonization rate.
Evidence-based clinical practice guidelines for peptic ulcer disease 2020
Authors: Kamada Tomoari , Satoh Kiichi , Itoh Toshiyuki , Ito Masanori , Iwamoto Junichi , Okimoto Tadayoshi , Kanno Takeshi , Sugimoto Mitsushige , Chiba Toshimi , Nomura Sachiyo , Mieda Mitsuyo , Hiraishi Hideyuki , Yoshino Junji , Takagi Atsushi , Watanabe Sumio , Koike Kazuhiko
Published: February 2021

The Japanese Society of Gastroenterology (JSGE) revised the third edition of evidence-based clinical practice guidelines for peptic ulcer disease in 2020 and created an English version. The revised guidelines consist of nine items: epidemiology, hemorrhagic gastric and duodenal ulcers, Helicobacter pylori (H. pylori) eradication therapy, non-eradication therapy, drug-induced ulcers, non-H. pylori, and nonsteroidal anti-inflammatory drug (NSAID) ulcers, remnant gastric ulcers, surgical treatment, and conservative therapy for perforation and stenosis. Therapeutic algorithms for the treatment of peptic ulcers differ based on ulcer complications. In patients with NSAID-induced ulcers, NSAIDs are discontinued and anti-ulcer therapy is administered. If NSAIDs cannot be discontinued, the ulcer is treated with proton pump inhibitors (PPIs). Vonoprazan (VPZ) with antibiotics is recommended as the first-line treatment for H. pylori eradication, and PPIs or VPZ with antibiotics is recommended as a second-line therapy. Patients who do not use NSAIDs and are H. pylori negative are considered to have idiopathic peptic ulcers. Algorithms for the prevention of NSAID- and low-dose aspirin (LDA)-related ulcers are presented in this guideline. These algorithms differ based on the concomitant use of LDA or NSAIDs and ulcer history or hemorrhagic ulcer history. In patients with a history of ulcers receiving NSAID therapy, PPIs with or without celecoxib are recommended and the administration of VPZ is suggested for the prevention of ulcer recurrence. In patients with a history of ulcers receiving LDA therapy, PPIs or VPZ are recommended and the administration of a histamine 2-receptor antagonist is suggested for the prevention of ulcer recurrence.
Techno-economic assessment of microalgae cultivation in a tubular photobioreactor for food in a humid continental climate
Authors: Schade S. , Meier T.
Published: February 2021

Fish as the primary source for the essential n − 3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) cannot cover the global demand for these important nutrients resulting in a supply gap of currently 1.1 million tons of EPA + DHA annually. A further exploitation of natural fish stocks is linked to great damage to ecosystems. Oleaginous microalgae are a natural source for EPA and DHA and could possibly contribute to closing this gap. The cultivation in photobioreactors (PBR) in a ‘cold-weather’ climate showed that microalgae compare favorably to aquaculture fish. The present study assesses the economic potential of microalgae for food in such system model. Techno-economic assessment was conducted on the basis of a dynamic system model for the cultivation of Nannochloropsis sp. in industrial scale in Central Germany over a time span of 30 years. The net present value (NPV) and return-on-investment (ROI) were obtained for a number of scenarios in which technic and economic parameters were altered. Taking the size of the PBR considered into account, the cultivation of Nannochloropsis sp. yielded a positive NPV of EUR 4.5 million after 30 years which translates to an annualized ROI of 1.87%. The sensitivity analysis overall resulted in annualized ROIs between 1.12 and 2.47%. Major expenditures comprised the PBR infrastructure, maintenance and labor cost. An extended cultivation season by four weeks was responsible for an NPV surplus of almost one third (32%). An increase in the selling price by 15% was responsible for a 47% higher NPV. In comparison with Atlantic salmon (Salmo salar) raised in aquaculture, EPA from Nannochloropsis sp. resulted in about halved cultivation costs (− 44 to − 60%). In this study we could show that microalgae from photoautotrophic cultivation not only have the potential to supply humans with essential nutrients, but they are also a lucrative investment, even in a ‘cold-weather’ climate where cultivation cannot take place year round.

Graphic abstract
The Radiology Virtual Reading Room: During and Beyond the COVID-19 Pandemic
Authors: Yacoub Joseph H. , Swanson Carl E. , Jay Ann K. , Cooper Cirrelda , Spies James , Krishnan Pranay
Published: February 2021

The COVID-19 pandemic has disrupted the radiology reading room with a potentially lasting impact. This disruption could introduce the risk of obviating the need for the reading room, which would be detrimental to many of the roles of radiology that occur in and around the reading room. This disruption could also create the opportunity for accelerated evolution of the reading room to meet the strategic needs of radiology and health care through thoughtful re-design of the virtual reading room. In this article, we overview the impact of the COVID-19 pandemic on radiology in our institution and across the country, specifically on the dynamics of the radiology reading room. We introduce the concept of the virtual reading room, which is a redesigned alternative to the physical reading room that can serve the diverse needs of radiology and healthcare during and beyond the pandemic.
Reconstruction of full thickness wounds using glyaderm in a single-staged procedure
Authors: de Henau Melissa , Kruit Anne Sophie , Ulrich Dietmar J. O.
Published: February 2021

Introduction

In large full-thickness skin defects, donor site morbidity limits the available thickness and surface of skin autografts and therefore only split-thickness skin grafts are possible for reconstruction. Dermal equivalents can be added to these split-thickness grafts to acquire an anatomically better skin reconstruction. Glyaderm is a human derived, acellular dermis and up until now has only been used in a two-staged procedure. This report describes results of a case series using Glyaderm and split-thickness skin grafts in a single-staged procedure.

Methods

Glyaderm was introduced in 2017 in Radboudumc (Nijmegen, The Netherlands). Glyaderm and autologous split-skin grafts were simultaneously applied to the wounds. In cases with large wound surfaces or wounds covering highly mobile areas, negative pressure wound therapy was additionally applied. The first ten cases were followed with regular intervals post-operatively, assessing graft take, scar appearance, post-operative wound problems and re-interventions.

Results

Patients were aged 3 weeks to 76 years-old. Treated skin surface varied from 1–16% total body surface. Wounds resulted from trauma (n = 4), burns (n = 4) or soft tissue infections (n = 2). Follow-up varied from 4 months to 1.5 years. No complications occurred after surgery. Average take rate was 98%. Two patients had a later re-intervention to further improve the aesthetic appearance of the scarred area.

Conclusion

Our first results with the application of Glyaderm in a single-staged procedure provided good healing, graft take and scar appearance. Glyaderm was found a suitable dermal substitute in the treatment of full thickness wounds.
Automated patch assessment for program repair at scale
Authors: Ye He , Martinez Matias , Monperrus Martin
Published: February 2021

In this paper, we do automatic correctness assessment for patches generated by program repair systems. We consider the human-written patch as ground truth oracle and randomly generate tests based on it, a technique proposed by Shamshiri et al., called Random testing with Ground Truth (RGT) in this paper. We build a curated dataset of 638 patches for Defects4J generated by 14 state-of-the-art repair systems, we evaluate automated patch assessment on this dataset. The results of this study are novel and significant: First, we improve the state of the art performance of automatic patch assessment with RGT by 190% by improving the oracle; Second, we show that RGT is reliable enough to help scientists to do overfitting analysis when they evaluate program repair systems; Third, we improve the external validity of the program repair knowledge with the largest study ever.
Optimal patient protocols in regional acute stroke care
Authors: Garcia B. L. , Bekker R. , van der Mei R. D. , Chavannes N. H. , Kruyt N. D.
Published: February 2021

In acute stroke care two proven reperfusion treatments exist: (1) a blood thinner and (2) an interventional procedure. The interventional procedure can only be given in a stroke centre with specialized facilities. Rapid initiation of either is key to improving the functional outcome (often emphasized by the common phrase in acute stroke care “time=brain”). Delays between the moment the ambulance is called and the initiation of one or both reperfusion treatment(s) should therefore be as short as possible. The speed of the process strongly depends on five factors: patient location, regional patient allocation by emergency medical services (EMS), travel times of EMS, treatment locations, and in-hospital delays. Regional patient allocation by EMS and treatment locations are sub-optimally configured in daily practice. Our aim is to construct a mathematical model for the joint decision of treatment locations and allocation of acute stroke patients in a region, such that the time until treatment is minimized. We describe acute stroke care as a multi-flow two-level hierarchical facility location problem and the model is formulated as a mixed integer linear program. The objective of the model is the minimization of the total time until treatment in a region and it incorporates volume-dependent in-hospital delays. The resulting model is used to gain insight in the performance of practically oriented patient allocation protocols, used by EMS. We observe that the protocol of directly driving to the nearest stroke centre with special facilities (i.e., the mothership protocol) performs closest to optimal, with an average total time delay that is 3.9% above optimal. Driving to the nearest regional stroke centre (i.e., the drip-and-ship protocol) is on average 8.6% worse than optimal. However, drip-and-ship performs better than the mothership protocol in rural areas and when a small fraction of the population (at most 30%) requires the second procedure, assuming sufficient patient volumes per stroke centre. In the experiments, the time until treatment using the optimal model is reduced by at most 18.9 minutes per treated patient. In economical terms, assuming 150 interventional procedures per year, the value of medical intervention in acute stroke can be improved upon up to € 1,800,000 per year.
Enhanced Magneto-Optical Kerr Effect of GaAs-Based P-N Junctions in the Terahertz Range
Authors: Miyagawa Keita , Nagai Masaya , Ashida Masaaki , Kim Changsu , Akiyama Hidefumi
Published: February 2021

We demonstrate that the magneto-optical Kerr effect at normal incidence in the terahertz (THz) frequency range is useful for evaluating carrier transport properties of particular layers of a p-n junction. Since a single p-type thin film only exhibits a small magneto-optical Kerr effect, magneto-optical Kerr spectroscopy cannot be used to determine the carrier densities of such a film with high sensitivity. However, because the electric field is enhanced at the p-layer in a p-n junction due to the interference between the THz waves that are reflected at the highly doped substrate and the p-layer at the surface, it is possible to conduct magneto-optical Kerr spectroscopy with a higher sensitivity. We numerically calculate and experimentally determine the spectra of the ellipticity and polarization rotation angles for single n- and p-GaAs epitaxial layers and GaAs-based photovoltaic devices with a p-i-n structure and evaluate the carrier densities of the n- and p-layers. At normal incidence, this method has a high spatial resolution, which is beneficial for imaging of large-area devices.
Computer Says I Don’t Know: An Empirical Approach to Capture Moral Uncertainty in Artificial Intelligence
Authors: Martinho Andreia , Kroesen Maarten , Chorus Caspar
Published: February 2021

As AI Systems become increasingly autonomous, they are expected to engage in decision-making processes that have moral implications. In this research we integrate theoretical and empirical lines of thought to address the matters of moral reasoning and moral uncertainty in AI Systems. We reconceptualize the metanormative framework for decision-making under moral uncertainty and we operationalize it through a latent class choice model. The core idea being that moral heterogeneity in society can be codified in terms of a small number of classes with distinct moral preferences and that this codification can be used to express moral uncertainty of an AI. Choice analysis allows for the identification of classes and their moral preferences based on observed choice data. Our reformulation of the metanormative framework is theory-rooted and practical in the sense that it avoids runtime issues in real time applications. To illustrate our approach we conceptualize a society in which AI Systems are in charge of making policy choices. While one of the systems uses a baseline morally certain model, the other uses a morally uncertain model. We highlight cases in which the AI Systems disagree about the policy to be chosen, thus illustrating the need to capture moral uncertainty in AI systems.
Echoes of Eriugena in the Old English Boethius
Authors: Ponirakis Eleni
Published: February 2021

This article identifies a passage from Eriugena’sPeriphyseonas a source for an interpolation in theOld English Boethius. The interpolation introduces an unambiguous reference to the Neoplatonic idea ofreditus, the return of all created creatures to God. This is not the first such evidence of Neoplatonic ideas in Old English texts and the article explores the significance of this new identification as further evidence for the presence of eastern mystical traditions in early English monastic and courtly circles, challenging the idea that English mysticism began in the Middle English period.
“At Least I Tried”: Swedish Police Officers’ Experiences of Meeting with Women Who Were Raped
Authors: Rudolfsson Lisa
Published: February 2021

Interactions with police officers are of great importance as to how the reporting raped woman continues to process what has happened. The focus of this study was on police officers’ experiences regarding contact with women who report rape. Sixteen officers participated in focus groups, and the data were subjected to inductive thematic analysis. Participants stressed their wish to be supportive and empathic, but also their lack of support and prerequisites, e.g., lack of amenities in interrogation rooms. They felt frustrated and described their work as “trying” rather than succeeding. If unaddressed, such shortcomings risk negatively affecting both police officers and victims.