bluuebunny/crossref_metadata_2025 huggingface dataset:
Functional Comparison of Interferon‐α Subtypes Reveals Potent Hepatitis B Virus Suppression by a Concerted Action of Interferon‐α and Interferon‐γ Signaling
Authors: Chen Jieliang , Li Yaming , Lai Fritz , Wang Yang , Sutter Kathrin , Dittmer Ulf , Ye Jianyu , Zai Wenjing , Liu Min , Shen Fang , Wu Min , Hu Kongying , Li Baocun , Lu Mengji , Zhang Xiaonan , Zhang Jiming , Li Jianhua , Chen Qingfeng , Yuan Zhenghong
Published: April 2020

Background and Aims

Interferon (IFN)‐α, composed of numerous subtypes, plays a crucial role in immune defense. As the most studied subtype, IFN‐α2 has been used for treating chronic hepatitis B virus (HBV) infection, with advantages of finite treatment duration and sustained virologic response, but its efficacy remains relatively low. This study aimed to screen for IFN‐α subtypes with the highest anti‐HBV potency and to characterize mechanisms of IFN‐α–mediated HBV restriction.

Approach and Results

Using cell culture–based HBV infection systems and a human‐liver chimeric mouse model, IFN‐α subtype–mediated antiviral response and signaling activation were comprehensively analyzed. IFN‐α14 was identified as the most effective subtype in suppression of HBV covalently closed circular DNA transcription and HBV e antigen/HBV surface antigen production, with median inhibitory concentration values approximately 100‐fold lower than those of the conventional IFN‐α2. IFN‐α14 alone elicited IFN‐α and IFN‐γ signaling crosstalk in a manner similar to the combined use of IFN‐α2 and IFN‐γ, inducing multiple potent antiviral effectors, which synergistically restricted HBV replication. Guanylate binding protein 5, one of the most differentially expressed genes between IFN‐α14–treated and IFN‐α2–treated liver cells, was identified as an HBV restriction factor. A strong IFN‐α–IFN‐α receptor subunit 1 interaction determines the anti‐HBV activity of IFN‐α. The in vivo anti‐HBV activity of IFN‐α14 and treatment‐related transcriptional patterns were further confirmed, and few adverse effects were observed.

Conclusions

A concerted IFN‐α and IFN‐γ response in liver, which could be efficiently elicited by IFN‐α subtype 14, is associated with potent HBV suppression. These data deepen the understanding of the divergent activities of IFN‐α subtypes and the mechanism underlying the synergism between IFN‐α and IFN‐γ signaling, with implications for improved IFN therapy and HBV curative strategies.
Towards a global consensus on GDM diagnosis: Light at the end of the tunnel?
Authors: Kapur Anil , McIntyre H. David , Divakar Hema , Di Renzo Gian Carlo , Kihara Anne Beatrice , McAuliffe Fionnuala , Hanson Mark , Ma Ronald C. , Hod Moshe ,   FIGO Working Group on Hyperglycemia in Pregnancy
Published: April 2020

The diagnostic criteria for GDM continue to be debated. The arguments presented here may help to dissipate confusion and help build global consensus.
Front Cover: Photoacoustic imaging of the human placental vasculature (J. Biophotonics 4/2020)
Authors: Maneas Efthymios , Aughwane Rosalind , Huynh Nam , Xia Wenfeng , Ansari Rehman , Kuniyil Ajith Singh Mithun , Hutchinson J. Ciaran , Sebire Neil J. , Arthurs Owen J. , Deprest Jan , Ourselin Sebastien , Beard Paul C. , Melbourne Andrew , Vercauteren Tom , David Anna L. , Desjardins Adrien E.
Published: April 2020

Successful therapy of twin‐to‐twin transfusion syndrome requires accurate imaging to guide laser photocoagulation of the anastomosing placental vessels. Photoacoustic (PA) imaging is an alternative imaging method that provides contrast for hemoglobin, and in this study, it was used to visualize chorionic superficial and subsurface vasculature in human placentas. The strong potential of PA imaging to guide minimally invasive fetal therapies was demonstrated.

Further details can be found in the article by Efthymios Maneas, Rosalind Aughwane, Nam Huynh, et al. (e201900167).

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Fetal adrenal gland: Total gland volume and fetal zone to total gland ratio as markers of small for gestational age
Authors: Sennaiyan Usha N. , Melov Sarah J. , Arcus Charles , Kirby Adrienne , Alahakoon Thushari I.
Published: April 2020

Purpose

Fetal adrenal gland changes have previously been investigated as novel markers of preterm labor and small for gestational age (SGA) fetuses. We aimed to compare the fetal adrenal gland parameters in SGA and appropriate for gestational age (AGA) fetuses.

Methods

A prospective cohort study was conducted on SGA fetuses with estimated fetal weight (EFW) ≤10th centile and AGA (EFW >10th centile) at 17 to 34 weeks gestation. Fetal adrenal total gland volume (TGV), TGV corrected for EFW (cTGV), fetal zone volume (FZV), FZV corrected for EFW (cFZV), and FZV:TGV ratio were compared and correlated with gestational age and EFW. Receiver operator curves assessed FZV:TGV ratio, cTGV, and cFZV in detecting SGA.

Results

Ultrasound examinations from 103 AGA and 50 SGA fetuses showed that (a) SGA fetuses had higher TGV (P = .002), FZV (P = .001), and FZV:TGV (P = .036) compared to AGA fetuses; (b) fetal adrenal TGV, FZV, cFZV, and FZV:TGV increase with advancing gestational age and EFW while cTGV does not; (c) Fetal adrenal changes in cTGV, cFZV, and FZV:TGV have ability to differentiate SGA; (d) FZV:TGV ratio 10 and 25 may be used to identify or exclude SGA in antenatally suspected SGA.

Conclusions

We investigated the concept that SGA fetuses have measurable changes to the adrenal gland. We have shown that fetal TGV, TGV, and FZV:TGV ratio show differences between AGA and SGA with TGV remaining significant after accounting for GA at scan. These findings may be useful as potential biomarkers for diagnosing or excluding SGA.
PTPN22 gene polymorphism and susceptibility to rheumatoid arthritis (RA): Updated systematic review and meta‐analysis
Authors: Abbasifard Mitra , Imani Danyal , Bagheri‐Hosseinabadi Zahra
Published: April 2020

Background

Several genome‐wide association studies have revealed a genetic background with respect to susceptibility to rheumatoid arthritis (RA). Although several individual case–control studies have evaluated the role of protein tyrosine phosphatase non‐receptor 22 (PTPN22) gene rs2476601 single nucleotide polymorphism (SNP) in conferring a risk for RA, the results have been conflicting. Hence, this meta‐analysis was aimed to provide a solution for this issue.

Methods

To search for studies assessing the association between the PTPN22 gene rs2476601 SNP and the risk of RA, a systematic search was conducted in the main databases, including PubMed, Scopus and Web of Science, prior to December 2019. The odds ratio (OR) and corresponding 95% confidence interval (CI) was calculated to assess the possibility of association risk.

Results

The literature search identified 52 case–control studies. The pooled analysis detected significant positive association of rs2476601 in all genetic models, including dominant model (OR = 1.69, 95% CI = 1.55–1.84, P < 0.001), recessive model (OR = 2.50, 95% CI = 2.06–3.05, P < 0.001), allelic model (OR = 1.80, 95% CI = 1.60–2.2, P < 0.001), TT versus CC model (OR = 2.79, 95% CI = 2.28–3.41, P < 0.001) and CT versus CC model (OR = 1.59, 95% CI = 1.50–1.67, P < 0.001). Analyses based on population stratification indicated that rs2476601 SNP strongly increased the risk of RA in Caucasians and Africans under all genotype models.

Conclusions

This meta‐analysis reports that the PTPN22 gene rs2476601 SNP increases RA risk, especially in Caucasians and Africans.
Synthesis of antimicrobial agents of tetra‐substituted thiophenes from ethyl 5‐(2‐bromoacetyl)‐4‐phenyl‐2‐(phenylamino)thiophene‐3‐carboxylate
Authors: Alsayari Abdulrahman , Muhsinah Abdullatif Bin , Asiri Yahya I. , Alfaifi Mohammad Y. , Elbehairi Serag Eldin I. , Alatibi Fatima , El‐Sayed Nahed Nasser E. , Mabkhot Yahia N.
Published: April 2020

5‐(2‐Bromoacetyl)‐2,3,4‐trisubstituted‐thiophene was used as a synthetic intermediate to prepare a series of thiophene derivatives and thiophene incorporating oxazole, imidazole, thiazole, pyrrole, and pyridine rings via substitution and cyclo‐condensation reactions. The data were extracted from the spectra of the resulting products confirmed their suggested structures. The newly synthesized compounds were screened to evaluate their in vitro antimicrobial activity vs several positive and negative gram bacteria and fungi. The screening data revealed that the thiophene derivative 7a, incorporating a thiazole ring, displayed strong activity against all tested microorganisms when compared with the antibiotics used.
How case law impacts risk management
Authors: Groszkruger Dan
Published: April 2020

Published decisions by federal and state appellate courts impact health care risk management in a number of ways, including overruling precedents, explaining and clarifying new laws and regulations, describing new and novel rules, describing new performance standards, and describing new civil rights.
Enhanced immunovirological response in women compared to men after antiretroviral therapy initiation during acute and early HIV‐1 infection: results from a longitudinal study in the French ANRS Primo cohort
Authors: Novelli Sophie , Delobel Pierre , Bouchaud Olivier , Avettand‐Fenoel Véronique , Fialaire Pascale , Cabié André , Souala Faouzi , Raffi François , Catalan Pilartxo , Weiss Laurence , Meyer Laurence , Goujard Cécile
Published: April 2020

Introduction

Previous studies have reported better immunovirological characteristics in women compared with men after HIV seroconversion. We investigated whether differences persisted under long‐term antiretroviral therapy (ART) in individuals treated since acute and early HIV‐1 infection (AHI).

Methods

Data were obtained for 262 women and 1783 men enrolled between 1996 and 2017 in the French multicentre ANRS PRIMO cohort. We modelled the viral response, long‐term immune recovery and HIV DNA decay in the 143 women and 1126 men who initiated ART within the first three months of infection.

Results

The participants were mostly white. The mean age was 37 years at AHI diagnosis. Pre‐ART viral loads were lower in women than men, 5.2 and 5.6 log10 copies/mL (p = 0.001). After ART initiation, women more rapidly achieved viral suppression than men (adjusted hazard ratio: 1.33, 95% confidence interval 1.09 to 1.69). They also experienced a faster increase in CD4+ T‐cell count and CD4:CD8 ratio during the first months of treatment. Sex‐related differences in CD4+ T‐cell counts were more pronounced with increasing age. This led to a sustained mean difference of 99 to 168 CD4+ T‐cells/µL depending on age between women and men at 150 months of ART. Moreover, CD4:CD8 ratio of women was higher than that of men by 0.31, at 150 months of ART. There was no statistically significant difference between sexes for the levels of HIV DNA over time (mean estimate at the last modelling point: 1.9 log10 copies/106 PBMCs after 70 months of ART for both sexes).

Conclusions

The high level of immune recovery and decrease in total HIV DNA levels achieved after ART initiation during AHI reinforce the importance of early diagnosis of HIV infection and immediate ART initiation. The immunological benefit of being female increased throughout prolonged ART duration, which may give women additional protection from adverse clinical events and premature ageing.
Structural white matter alterations as compensatory mechanisms in Parkinson's disease: A systematic review of diffusion tensor imaging studies
Authors: Sanjari Moghaddam Hossein , Dolatshahi Mahsa , Mohebi Farnam , Aarabi Mohammad Hadi
Published: April 2020

Compensation is described as normal or near to normal performance in Parkinson's disease (PD), despite the ongoing neural loss. Functional compensation typically proceeds in an inverse U‐shaped manner: compensation initiates in the prodromal phase, followed by an increasing episode until plateauing and diminishes in the advanced stages of the disease. The first evidence of the structural compensation was reported by functional magnetic resonance imaging studies. Recent studies, which have used diffusion tensor imaging (DTI) as the basis for their investigation, have shown improved white matter diffusional properties both in motor‐ and non‐motor‐related structures in association with improved clinical scores in patients with PD. The majority of DTI studies have demonstrated microstructural compensation in the prodromal/early stages of PD at the regional scale. However, there have been reports of compensation in later stages of the disease and the whole‐brain/network scale that are probably due to the heterogeneous nature of PD. Although serving as a promising beginning to characterize compensation, lots remain to be clarified in understanding the underlying mechanisms of compensation and its structural pattern in PD. The existing knowledge gap necessitates studies that their main research questions are focused on structural compensation. This requirement becomes more apparent because structural compensation evidence has mostly emerged from the post hoc analysis of data and incidental findings of studies. Thus, future studies are required to investigate compensatory microstructural changes in PD to clarify the exact underlying mechanisms. These studies would also provide a basis to develop clinical improvements in the early diagnosis and management of PD.
Sex/gender differences in brain function and structure in alcohol use: A narrative review of neuroimaging findings over the last 10 years
Authors: Verplaetse Terril L. , Cosgrove Kelly P. , Tanabe Jody , McKee Sherry A.
Published: April 2020

Over the last 10 years, rates of alcohol use disorder (AUD) have increased in women by 84% relative to a 35% increase in men. Rates of alcohol use and high‐risk drinking have also increased in women by 16% and 58% relative to a 7% and 16% increase in men, respectively, over the last decade. This robust increase in drinking among women highlights the critical need to identify the underlying neural mechanisms that may contribute to problematic alcohol consumption across sex/gender (SG), especially given that many neuroimaging studies are underpowered to detect main or interactive effects of SG on imaging outcomes. This narrative review aims to explore the recent neuroimaging literature on SG differences in brain function and structure as it pertains to alcohol across positron emission tomography, magnetic resonance imaging, and functional magnetic resonance imaging modalities in humans. Additional work using magnetic resonance spectroscopy, diffusion tensor imaging, and event‐related potentials to examine SG differences in AUD will be covered. Overall, current research on the neuroimaging of AUD, alcohol consumption, or risk of AUD is limited, and findings are mixed regarding the effect of SG on neurochemical, structural, and functional mechanisms associated with AUD. We address SG disparities in the neuroimaging of AUD and propose a call to action to include women in brain imaging research. Future studies are crucial to our understanding of the neurobiological underpinnings of AUD across neural systems and the vulnerability for AUD among women and men.
Human capital resource emergence and leadership
Authors: Eckardt Rory , Tsai Chou‐Yu , Dionne Shelley D. , Dunne Danielle , Spain Seth M. , Park Jin Won , Cheong Minyoung , Kim Jayoung , Guo Jie , Hao Chanyu , Kim Eung Il
Published: April 2020

Drawing on multilevel theory of human capital resource emergence (HCRE), this paper reviews existing empirical research to better understand the effect of leadership on this emergence process. Specifically, we summarize the current literature pertaining to how leaders may impact the process through which individual‐level human capital—the knowledge, skills, and abilities of individuals—emerges into a valuable unit‐level human capital resource. We review 132 empirical articles and examine how leadership research on task‐ and relational‐oriented factors at different levels of analysis affects the important task and social environment enabling factors of HCRE. Our paper makes important progress towards integrating leadership research with extant theorizing on HCRE and identifies areas in both literatures where additional research is needed.
Identification by NMR of key compounds present in beer distillates and residual phases after dealcoholization by vacuum distillation
Authors: Labrado David , Ferrero Sergio , Caballero Isabel , Alvarez Celedonio M , Villafañe Fernando , Blanco Carlos A
Published: April 2020

BACKGROUND

Nowadays, low alcohol and non‐alcohol beer intake has increased due to expanding concerns about healthy diets. However, there are still appreciable differences between non‐alcoholic beer and conventional beer, particularly regarding flavor. Vacuum distillation is commonly used to remove ethanol from the beer in industrial processes and it is used here.

RESULTS

The presence of n‐propanol, isobutanol, 3‐methylbutanol, 2‐methylbutanol, 2‐phenylethanol, ethyl acetate, isoamyl acetate, and acetaldehyde, which are key compounds responsible for aroma and flavor of beer, have been analyzed using nuclear magnetic resonance (NMR) spectroscopy in commercial beers and also in the corresponding distillates and residual phases after dealcoholization.

CONCLUSION

The compounds present in each phase were identified by monodimensional and bidimensional NMR spectra. The compounds that are completely removed or that remain in the residue of the conventional beers studied are described in detail. The presence of these compounds in dealcoholized beer would be beneficial in keeping the aroma and flavor in dealcoholized beer. © 2020 Society of Chemical Industry
Adamantinomatous tumors: Long‐term follow‐up study of 20 patients treated at a single institution
Authors: Schwarzkopf Eugenia , Tavarez Yoely , Healey John H. , Hameed Meera , Prince Daniel E.
Published: April 2020

Background and Objectives

Adamantinomas are primary, low‐grade malignant tumors of the bone that have metastatic potential to the lungs, lymph nodes, and other regions. The rarity of this disease and its nonspecific symptoms complicate diagnosis.

Materials and Methods

Records for 20 patients who underwent treatment for adamantinoma from 1975 to 2018 were reviewed for demographic, clinical, and pathological data, treatment details, postoperative complications, and outcomes.

Results

Patients presented at a median age of 22 years (1‐79 years): 14 patients had a localized primary tumor, three presented with local recurrence, and three with metastatic disease. Median tumor size was 5.7 cm (0.5‐15.5 cm). Wide excision was performed primarily in 15 cases; the remaining five patients underwent intralesional curettage. At a median follow‐up of 7.3 years, 14 patients had no evidence of disease; two patients were alive with disease, and four patients died from the disease. Local recurrence and distant metastasis occurred at a median of 11.4 years (6 month‐19 years) and 15.8 years (4 month‐23 years) after diagnosis.

Conclusions

Adequate histopathological diagnosis is crucial to avoid misdiagnosis of this rare tumor. Local and distant recuAbs_Para_meprrence can occur more than 20 years after the initial diagnosis. Life‐long follow‐up with clinical examination and imaging is required.
Measuring the neutral zone of spinal motion segments: Comparison of multiple analysis methods to quantify spinal instability
Authors: Di Pauli von Treuheim Theodor , Torre Olivia M. , Mosley Grace E. , Nasser Philip , Iatridis James C.
Published: April 2020

Purpose

Neutral zone (NZ) parameters in spinal biomechanics studies are sensitive to spinal instability, disc degeneration, and repair. Multiple methods in the literature quantify NZ, yet no consensus exists on applicability and comparability of methods. This study compares five different NZ quantification methods using two different load‐deflection profiles.

Methods

Rat caudal and lumbar motion segments were tested in axial rotation to generate load‐deflection curves with profiles exhibiting prominent distinction between elastic and NZ regions (ie, triphasic) and profiles that did not (ie, viscoelastic). NZ was quantified using five methods: trilinear, double sigmoid (DS), zero load, stiffness threshold (ST), and extrapolated elastic zone. Absolute agreement and consistency of NZ parameters were assessed using intraclass correlation (ICC), Bland‐Altman analyses, and analysis of variance.

Results

For triphasic profiles, NZ magnitude exhibited high consistency (methods correlate but differ in absolute values), and only some methods exhibited agreement. For viscoelastic profiles, NZ magnitude showed limited consistency and no absolute agreement. NZ stiffness had high agreement and consistency across most methods and profiles. For triphasic profiles, the linear NZ regions for all methods were not well‐described by a linear fit yet for viscoelastic profiles all methods characterized a linear NZ region.

Conclusion

This NZ comparison study showed surprisingly limited agreement and consistency among NZ parameters with approximately 5% to 100% difference depending on the method and load‐deflection profile. Nevertheless, the DS and ST methods appeared to be most comparable. We conclude that most NZ quantification methods cannot be applied interchangeably, highlighting a need to clearly state NZ calculation methods. Future studies are required to identify which methods are most sensitive to disc degeneration and repair in order to identify a “best” method.
Distinguishing a Trichilemmal Cyst From a Pilomatricoma With Ultrasound
Authors: He Ping , Chen Wen , Zhang Qian , Cui Li‐Gang , Zhang Qian
Published: April 2020

Objectives

To determine whether ultrasound (US) could distinguish a trichilemmal cyst from a pilomatricoma preoperatively.

Methods

Ultrasound images of 61 pathologically proven trichilemmal cysts and 90 pathologically proven pilomatricomas were analyzed retrospectively. Two radiologists evaluated several US features. The sensitivity, specificity, Youden index, and predictive values of statistically significant US features were assessed. Parallel combined tests, serial combined tests, or both were performed to identify US features with high statistical significance.

Results

Results from individual US features were not satisfactory; however, serial combined tests that included absence of complete internal echogenic foci, absence of a hypoechoic rim, absence of peritumoral hyperechogenicity, and absence of vascularity showed higher diagnostic utility. The sensitivity, specificity, Youden index, positive predictive value, and negative predictive value for correctly identifying a trichilemmal cyst were 74%, 88%, 0.62, 80%, and 83%, respectively. If 1 of these 4 US features was not a match for a trichilemmal cyst, pilomatricoma was considered.

Conclusions

It may be possible to distinguish trichilemmal cysts from pilomatricomas preoperatively using US. A combined test is superior to using any individual US feature.
Handheld Ultrasound
Authors: Acuña Josie , Sorenson Jacob , Gades Anthony , Wyatt Ryan , Stea Nicholas , Drachman Maili , Adhikari Srikar
Published: April 2020

Objectives

The purpose of this study was to evaluate the performance of a handheld ultrasound device for difficult peripheral intravenous (PIV) access performed by nurses and paramedics in the emergency department (ED).

Methods

This was a retrospective review at an academic medical center. Participants were ED nurses and paramedics with competence in ultrasound‐guided PIV placement. Participants were asked to log their use of the handheld device when used on patients deemed to have “difficult” access and complete a questionnaire, which consisted of items related to the effectiveness and ease of use of the device. Data were collected over the course of 1 year. An electronic medical record review was performed to track the success rates and the occurrence of any associated complications throughout the hospital stay.

Results

Nurses and paramedics logged a total of 483 cases in which PIV access was attempted with the handheld ultrasound device. Ninety‐two percent (95% confidence interval [CI], 89%–94%) of the ultrasound‐guided PIV lines attempted were placed successfully. Eighty‐four percent (95% CI, 80%–87%) of the lines were placed successfully on the first attempt. In most cases (396 of 483 [82%]), no complications associated with the PIV occurred. A total of 429 questionnaires were completed over the study period. Most of the operators (84%; 95% CI, 80%–87%) stated that the handheld device was adequate to perform ultrasound‐guided PIV access.

Conclusions

The handheld ultrasound device performed well in terms of usability and reliability for PIV access.
Application of infrared spectroscopy for the prediction of nutritional content and quality assessment of faba bean (Vicia faba L.)
Authors: Johnson Joel B. , Walsh Kerry , Naiker Mani
Published: April 2020

With growing consumer interest and demand for health‐benefiting functional foods such as faba beans, particularly evident in developed countries, commercial production of this crop is increasing. In concert with increased production levels comes an equally great need for the inexpensive rapid measurement of nutritional parameters for quality determining purposes. As an analytical tool, near‐infrared spectroscopy has been well explored for the quantification of proximate nutritional composition, such as protein, starch and oil contents in faba bean and faba bean‐derived products. Near‐infrared spectroscopy has also been demonstrated to have potential for the noninvasive prediction of low‐level micronutrients such as the total polyphenol content in faba bean and faba bean‐derived products, although further exploration in this area is required to provide a more acceptable model. In some instances, the authors may be inadvertently measuring micronutrient concentrations through a secondary correlation with certain macronutrients. It is particularly difficult to determine if this is the case if exacerbated by the lack of an independent validation test set in the paper in question. The associated technique of mid‐infrared spectroscopy shows particular promise for the rapid, noninvasive characterisation of structural components of faba bean, such as carbohydrates and proteins. Complementary applications of these two technologies are likely to yield a wealth of potential applications.
Parallel Generative Topographic Mapping: An Efficient Approach for Big Data Handling
Authors: Lin Arkadii , Baskin Igor I. , Marcou Gilles , Horvath Dragos , Beck Bernd , Varnek Alexandre
Published: April 2020

Generative Topographic Mapping (GTM) can be efficiently used to visualize, analyze and model large chemical data. The GTM manifold needs to span the chemical space deemed relevant for a given problem. Therefore, the Frame set (FS) of compounds used for the manifold construction must well cover a given chemical space. Intuitively, the FS size must raise with the size and diversity of the target library. At the same time, the GTM training can be very slow or even becomes technically impossible at FS sizes of the order of 105 compounds – which is a very small number compared to today's commercially accessible compounds, and, especially, to the theoretically feasible molecules. In order to solve this problem, we propose a Parallel GTM algorithm based on the merging of “intermediate” manifolds constructed in parallel for different subsets of molecules. An ensemble of these subsets forms a FS for the “final” manifold. In order to assess the efficiency of the new algorithm, 80 GTMs were built on the FSs of different sizes ranging from 10 to 1.8 M compounds selected from the ChEMBL database. Each GTM was challenged to build classification models for up to 712 biological activities (depending on the FS size). With the novel parallel GTM procedure, we could thus cover the entire spectrum of possible FS sizes, whereas previous studies were forced to rely on the working hypothesis that FS sizes of few thousands of compounds are sufficient to describe the ChEMBL chemical space. In fact, this study formally proves this to be true: a FS containing only 5000 randomly picked compounds is sufficient to represent the entire ChEMBL collection (1.8 M molecules), in the sense that a further increase of FS compound numbers has no benefice impact on the predictive propensity of the above‐mentioned 712 activity classification models. Parallel GTM may, however, be required to generate maps based on very large FS, that might improve chemical space cartography of big commercial and virtual libraries, approaching billions of compounds
A comprehensive probabilistic analysis of approximate SIR‐type epidemiological models via full randomized discrete‐time Markov chain formulation with applications
Authors: Cortés J.‐C. , El‐Labany S.K. , Navarro‐Quiles A. , Selim Mustafa M. , Slama H.
Published: April 2020

This paper provides a comprehensive probabilistic analysis of a full randomization of approximate SIR‐type epidemiological models based on discrete‐time Markov chain formulation. The randomization is performed by assuming that all input data (initial conditions, the contagion, and recovering rates involved in the transition matrix) are random variables instead of deterministic constants. In the first part of the paper, we determine explicit expressions for the so called first probability density function of each subpopulation identified as the corresponding states of the Markov chain (susceptible, infected, and recovered) in terms of the probability density function of each input random variable. Afterwards, we obtain the probability density functions of the times until a given proportion of the population remains susceptible, infected, and recovered, respectively. The theoretical analysis is completed by computing explicit expressions of important randomized epidemiological quantities, namely, the basic reproduction number, the effective reproduction number, and the herd immunity threshold. The study is conducted under very general assumptions and taking extensive advantage of the random variable transformation technique. The second part of the paper is devoted to apply our theoretical findings to describe the dynamics of the pandemic influenza in Egypt using simulated data excerpted from the literature. The simulations are complemented with valuable information, which is seldom displayed in epidemiological models. In spite of the nonlinear mathematical nature of SIR epidemiological model, our results show a strong agreement with the approximation via an appropriate randomized Markov chain. A justification in this regard is discussed.
Modulating electromagnetic properties in three‐dimensional diamond‐structured photonic crystals with double planar defects
Authors: Chen Shibin , Zhao Xin , Yao Yunshi , Gao Yongchang , Shi Xingtai
Published: April 2020

Three‐dimensional (3D) diamond structure photonic crystals (PhCs) with planar defects were fabricated with alumina using 3D printing combining gel casting, sintering process, and vacuum freezing‐dry technique. In this article, the influences of twinned planar defect and the positions of planar defect in a single lattice period on the transmission properties of the electromagnetic wave (EM) in the PhCs is studied. The normalized resonant intensities are 0.5 for twinned planar defected photonic crystals (PhCs). When the planar defect position lies in the nonkey positions (key position is n*(a/4)), the band gap becomes narrow and the resonant peak disappears. When the twinned planar defected with different interval periods is integer, obvious resonant peaks can be found in the EM band gap of the planar defects PhCs with 2 and 3 symmetrical periods. When a PhC with two planar defects is constructed, its band gap width increases and the resonant peaks intensities decrease.
A compact multiband dielectric resonator antenna for wireless communications
Authors: Guo Qianqian , Zhang Jingwei , Zhu Jiajia , Yan Dandan
Published: April 2020

A compact multiband rectangular dielectric resonator antenna (RDRA) is proposed in this study for worldwide interoperability for microwave access, wireless local area network, and fifth‐generation applications. The dielectric resonator antenna is fed by a 2‐slot etched coplanar waveguide with a conformal strip feed, a dielectric resonator with a dielectric constant of 37 is used and embedded into the substrate, and a foam substrate is used as a holder. The RDRA exhibits multiband and omnidirectional radiation patterns by generating a monopole mode as well as the typical and modes, which provides impedance bandwidths (|S11| < −10 dB) of 29.0% at the first band, 15.1% at the second band, and 6.2% at the third band. Additionally, the RDRA achieves a maximum total efficiency of 94.4% at 4.8 GHz and an overall total efficiency of 70% at the desired frequency bands.
Dose image prediction for range and width verifications from carbon ion‐induced secondary electron bremsstrahlung x‐rays using deep learning workflow
Authors: Yamaguchi Mitsutaka , Liu Chih‐Chieh , Huang Hsuan‐Ming , Yabe Takuya , Akagi Takashi , Kawachi Naoki , Yamamoto Seiichi
Published: April 2020

Purpose

Imaging of the secondary electron bremsstrahlung (SEB) x rays emitted during particle‐ion irradiation is a promising method for beam range estimation. However, the SEB x‐ray images are not directly correlated to the dose images. In addition, limited spatial resolution of the x‐ray camera and low‐count situation may impede correctly estimating the beam range and width in SEB x‐ray images. To overcome these limitations of the SEB x‐ray images measured by the x‐ray camera, a deep learning (DL) approach was proposed in this work to predict the dose images for estimating the range and width of the carbon ion beam on the measured SEB x‐ray images.

Methods

To prepare enough data for the DL training efficiently, 10,000 simulated SEB x‐ray and dose image pairs were generated by our in‐house developed model function for different carbon ion beam energies and doses. The proposed DL neural network consists of two U‐nets for SEB x ray to dose image conversion and super resolution. After the network being trained with these simulated x‐ray and dose image pairs, the dose images were predicted from simulated and measured SEB x‐ray testing images for performance evaluation.

Results

For the 500 simulated testing images, the average mean squared error (MSE) was 2.5 × 10−5 and average structural similarity index (SSIM) was 0.997 while the error of both beam range and width was within 1 mm FWHM. For the three measured SEB x‐ray images, the MSE was no worse than 5.5 × 10−3 and SSIM was no worse than 0.980 while the error of the beam range and width was 2 mm and 5 mm FWHM, respectively.

Conclusions

We have demonstrated the advantages of predicting dose images from not only simulated data but also measured data using our deep learning approach.
RARE two‐point Dixon with dual bandwidths
Authors: Rydén Henric , Berglund Johan , Norbeck Ola , Avventi Enrico , Sprenger Tim , van Niekerk Adam , Skare Stefan
Published: April 2020

Purpose

To investigate the impact of dual readout bandwidths (dBW) in a dual echo fat/water acquisition and describe a dBW‐rapid acquisition relaxation enhanced, or turbo spin echo sequence where the concept is used to improve SNR by removing dead times between refocusing pulses and avoiding redundant Chemical‐shift encoded.

Methods

Cramér‐Rao bounds and Monte Carlo simulations were used to investigate a two‐point fat/water model where the difference in bandwidths is incorporated. In vivo images were acquired at 1.5 and 3 T with the dBW‐rapid acquisition relaxation enhanced, or turbo spin echo sequence. Typical bandwidth ratios were 1:2. SNR was compared with a single bandwidth sequence under identical scan parameters at 3T.

Results

Monte Carlo simulations and Cramér‐Rao analysis demonstrate that number of signal averages can be improved with dual bandwidths compared to conventional single bandwidth acquisitions. The dBW‐rapid acquisition relaxation enhanced, or turbo spin echo sequence can acquire images with high readout resolutions with well‐conditioned sampling. An SNR improvement of 52% was measured, in line with the theoretical gain of 54%.

Conclusions

The proposed dBW‐rapid acquisition relaxation enhanced, or turbo spin echo sequence is a highly SNR‐efficient two‐point rapid acquisition relaxation enhanced, or turbo spin echo sequence without dead times, and can acquire images at higher resolutions than current vendor‐supplied alternatives.
Echo planar time‐resolved imaging with subspace reconstruction and optimized spatiotemporal encoding
Authors: Dong Zijing , Wang Fuyixue , Reese Timothy G. , Bilgic Berkin , Setsompop Kawin
Published: April 2020

Purpose

To develop new encoding and reconstruction techniques for fast multi‐contrast/quantitative imaging.

Methods

The recently proposed Echo Planar Time‐resolved Imaging (EPTI) technique can achieve fast distortion‐ and blurring‐free multi‐contrast/quantitative imaging. In this work, a subspace reconstruction framework is developed to improve the reconstruction accuracy of EPTI at high encoding accelerations. The number of unknowns in the reconstruction is significantly reduced by modeling the temporal signal evolutions using low‐rank subspace. As part of the proposed reconstruction approach, a B0‐update algorithm and a shot‐to‐shot B0 variation correction method are developed to enable the reconstruction of high‐resolution tissue phase images and to mitigate artifacts from shot‐to‐shot phase variations. Moreover, the EPTI concept is extended to 3D k‐space for 3D GE‐EPTI, where a new “temporal‐variant” of CAIPI encoding is proposed to further improve performance.

Results

The effectiveness of the proposed subspace reconstruction was demonstrated first in 2D GESE EPTI, where the reconstruction achieved higher accuracy when compared to conventional B0‐informed GRAPPA. For 3D GE‐EPTI, a retrospective undersampling experiment demonstrates that the new temporal‐variant CAIPI encoding can achieve up to 72× acceleration with close to 2× reduction in reconstruction error when compared to conventional spatiotemporal‐CAIPI encoding. In a prospective undersampling experiment, high‐quality whole‐brain
and tissue phase maps at 1 mm isotropic resolution were acquired in 52 seconds at 3T using 3D GE‐EPTI with temporal‐variant CAIPI encoding.

Conclusion

The proposed subspace reconstruction and optimized temporal‐variant CAIPI encoding can further improve the performance of EPTI for fast quantitative mapping.
Relationship of Effective Size to Hatchery Supplementation and Habitat Connectivity in a Simulated Population of Rio Grande Silvery Minnow
Authors: Carson Evan W. , Osborne Megan J. , Turner Thomas F.
Published: April 2020

Simultaneous management actions often are used to improve the status of imperiled species, yet the effects of these actions can be difficult to determine. The endangered Rio Grande Silvery Minnow Hybognathus amarus is a short-lived fish with a dispersive life history and thus requires—but does not occupy—unfragmented habitat for recruitment and survival. We used Rio Grande Silvery Minnow as a model system for an individual-based simulation study to evaluate responses of genetic effective size to hatchery supplementation and fish passage in a managed population. Simulations were designed to test effects of fish passage on the relationship between estimates of inbreeding (NeI) and variance (NeV) effective sizes, which differ consistently (NeI >> NeV) in long-term genetic-monitoring data from hatchery-supplemented Rio Grande Silvery Minnow populations. Values of different effective population size measures should be identical in a demographically stable and connected (admixed) population but can differ substantially under nonequilibrium conditions. When a barrier prevented upstream dispersal, NeI was associated negatively with rate of downstream dispersal and positively with supplementation rate, whereas NeV was associated negatively with both. This mirrored observations from Rio Grande Silvery Minnow. Individual effects of dispersal and supplementation, however, were difficult to discern due to significant interaction between these factors. When connectivity was restored, NeI and NeV depended on supplementation rate, with positive association between NeI and supplementation rate versus a negative association for NeV and interaction terms, and effects of dispersal were nonsignificant. Although fish passage did not alter the difference between NeI and NeV, our study suggests that for Rio Grande Silvery Minnow, and potentially other intensively managed species in regulated rivers, fish passage may help to distinguish effects of management actions, such as supplementation, from effects of other demographic influences. More generally, explicit analytical consideration of differences in effective population size estimates can provide important details of genetic responses to management.
Numerical comparison of Rayleigh and Love full waveform inversion in characterizing soil spatial variability for near‐surface engineering applications
Authors: Mahvelati Siavash , Coe Joseph Thomas
Published: April 2020

The use of surface wave testing for near‐surface engineering applications has increased in recent years. Typical surface wave analysis is based on the dispersion of surface waves in one‐dimensional layered models. One‐dimensional models are inappropriate for measurements at sites with appreciable lateral variability, a likely scenario in many engineering applications. Use of such models can subsequently undermine the reliability and accuracy of the surface wave results. Full waveform inversion (FWI) is a high‐resolution imaging technique that is proven to outperform the conventional dispersion‐based analysis of surface waves. Much of the near‐surface literature has focused on full waveform inversion of Rayleigh waves developed by the interaction of primary‐ and vertically polarized shear waves (P‐SV), and the capabilities of surface waves generated by horizontally polarized shear waves (Love waves) in mapping near‐surface spatial variabilities have not been fully explored. In this numerical study, full waveform inversion of Rayleigh and Love waves was performed on two different spatially correlated Gaussian random fields (meanVSof 200 and 500 m/s) to mimic the natural spatial variability of geologic materials. Each soil structure was produced at a low and high level of stiffness variability. Two sources with different frequency contents, 25 and 50 Hz, were used to evaluate the effects of source characteristics on the resolution of Rayleigh and Love waveform inversions. The inverted results from the high‐velocity domain demonstrated that Love waveform inversion using high‐frequency seismic sources outperforms Rayleigh full waveform inversion in detecting the shape and the velocities of horizontally deposited geologic materials. Results from the low‐velocity domain also confirmed that Love full waveform inversion was comparable or superior to Rayleigh full waveform inversion, though the performance difference was less significant. However, the 25‐Hz frequency inversions yielded superior results than the 50‐Hz frequency inversions for the low‐velocity domain because the dominant wavelength of the high‐frequency signals becomes so small that it offers an impractically small investigation depth.
Tumour‐suppressive effect of oestrogen receptor β in colorectal cancer patients, colon cancer cells, and a zebrafish model
Authors: Topi Geriolda , Satapathy Shakti Ranjan , Dash Pujarini , Fred Mehrabi Syrina , Ehrnström Roy , Olsson Roger , Lydrup Marie‐Louise , Sjölander Anita
Published: April 2020

Oestrogen receptor β (ERβ) has been suggested to have anti‐proliferative and anti‐tumour effects in breast and prostate cancer cells, but other studies have indicated its tumour‐promoting effects. Understanding the complex effects of this receptor in different contexts requires further study. We reported that high ERβ expression is independently associated with improved prognosis in female colorectal cancer (CRC) patients. Herein, we investigated the possible anti‐tumour effect of ERβ and its selective agonist. CRC patients with high ERβ expression had significantly higher levels of membrane‐associated β‐catenin, cysteinyl leukotriene receptor 2 (CysLT2R), and 15‐hydroxyprostaglandin dehydrogenase (15‐PGDH), which have anti‐tumour effects, but lower levels of nuclear β‐catenin, cysteinyl leukotriene receptor 1 (CysLT1R), and cyclooxygenase‐2 (COX‐2), which have tumour‐promoting effects. These interesting findings were further supported by two different publicly available CRC mRNA datasets that showed a significant positive correlation between ERβ expression and 15‐PGDH and CysLT2R expression and a negative correlation between ERβ expression and β‐catenin, CysLT1R, and COX‐2 expression. We next evaluated ERβ expression in three different colon cancer mouse models; ERβ expression was negatively correlated with tumourigenesis. Furthermore, treatment with the ERβ‐agonist ERB‐041 reduced CysLT1R, active β‐catenin, and COX‐2 levels but increased phospho‐β‐catenin, CysLT2R, and 15‐PGDH levels in HCT‐116, Caco‐2, and SW‐480 colon cancer cells compared to vehicle‐treated cells. Interestingly, ERB‐041‐treated cells showed significantly decreased migration, survival, and colonosphere formation and increased apoptotic activity, as indicated by increased CASPASE‐3 and apoptotic blebs. Finally, patients with low ERβ expression had significantly more distant metastasis at the time of diagnosis than patients with high ERβ expression. Therefore, we studied the effects of ERB‐041‐treated colon cancer cells in a zebrafish xenograft model. We found significantly less distant metastasis of ERB‐041‐treated cells compared to vehicle‐treated cells. These results further support ERβʼs anti‐tumour role in CRC and the possible use of its agonist in CRC patients. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
Evaluation of VTP‐50469, a menin‐MLL1 inhibitor, against Ewing sarcoma xenograft models by the pediatric preclinical testing consortium
Authors: Kurmasheva Raushan T. , Bandyopadhyay Abhik , Favours Edward , Pozo Vanessa Del , Ghilu Samson , Phelps Doris A. , McGeehan Gerard M. , Erickson Stephen W. , Smith Malcolm A. , Houghton Peter J.
Published: April 2020

Background

VTP‐50469 is a potent inhibitor of the menin‐MLL1 interaction and is implicated in signaling downstream of EWSR1‐FLI1.

Procedure

VTP‐50469 was evaluated against seven Ewing sarcoma (EwS) xenograft models and in vitro against EwS cell lines.

Results

VTP‐50469 showed limited antitumor activity, statistically significantly slowing tumor progression in four tumor models but with no evidence of tumor regression. In vitro, the IC50 concentration was 10 nM for the mixed lineage leukemia (MLL)‐rearranged leukemia cell line MV4;11, but > 3 μM for EwS cell lines.

Conclusions

In contrast to its high level of activity against MLL1‐rearranged leukemia xenografts, VTP‐50469 shows little activity against EwS models.