bluuebunny/crossref_metadata_2025 huggingface dataset:
Selectively Visualizing the Hidden Modes in Random Lasers for Secure Communication
Authors: Shi Xiaoyu , Song Wanting , Guo Dan , Tong Junhua , Zhai Tianrui
Published: August 2021

Toward a higher degree of secure communication, great efforts have been made to develop encryption and anticounterfeiting strategies. In particular, optical encryption with high complexity has become one of the most significant approaches. To strengthen optical information security, the concept of a spectral encryption approach is proposed based on selectively visualized spectral modes in random lasers. By coupling with external whispering gallery mode cavity, hidden localized lasing modes with special multiple‐peaks spectra are selected from phase‐correlated random lasers with smooth single‐peak spectra. The selectively visualized localized modes are utilized for spectral encryption of secure information. The encoded spectral modes that are hidden in phase‐correlated modes with identical spectra can only be selectively recognized by a special external coupler. This multiplex encryption strategy is super for the simple operation, low cost, and high security, supplying a new approach for further applications in secure communication and anticounterfeiting.
Mutation and methylation profiles of ectopic and eutopic endometrial tissues
Authors: Li Lihong , Antero Maria Facadio , Zhang Ming , Chu Tiffany , Seckin Tamer , Ayhan Ayse , Pisanic Thomas , Wang Tian‐Li , Cope Leslie , Segars James , Shih Ie‐Ming
Published: August 2021

Adenomyosis and peritoneal endometriosis are common gynecologic lesions; they are characterized by aberrant locations of normal‐appearing endometrium in myometrium and peritoneal surface, respectively. Both ectopic lesions are speculated to originate from uterine eutopic endometrium, which is composed of epithelium and stroma, but how these two different tissue types co‐evolve in ectopic locations remains unclear. Here, we analyzed exome‐wide mutations and global methylation in microdissected epithelium and stroma separately in paired adenomyosis, peritoneal endometriosis, and endometrium to investigate their relationship. Analyses of somatic mutations and their allele frequencies indicate monoclonal development not only in epithelium but also in the stroma of adenomyosis and peritoneal endometriosis. Our preliminary phylogenetic study suggests a plausible clonal derivation in epithelium and stroma of both ectopic and eutopic endometrium from the same founder epithelium‐stroma progenitor cells. While a patient‐specific methylation landscape is evident, adenomyosis epithelium and stroma can be distinguished from normal‐appearing eutopic endometrium epigenetically. In summary, endometrial stroma, like its epithelial counterpart, could be clonal and both ectopic and eutopic endometrium following divergent evolutionary trajectories. Our data also warrant future investigations into the role of endometrial stroma in the pathobiology of endometrium‐related disorders. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Characterization/mechanical behavior of AgCuOSnO2 composites: Experimental and finite element study
Authors: Li Jintao , Yang Minjie , Zhou Xiaolong
Published: August 2021

Herein, the effects of different content of SnO2 on the stress, strain, and microstructure of AgCuO(10)SnO2(x = 2,5,8) composites during hot extrusion were studied by using finite element analysis and compared with the actual hot extrusion experiment. The results show that cubic CuO gradually becomes fibrous mainly due to shear strain during hot extrusion, but monoclinic CuO and SnO2 only produce slight deformation. After hot extrusion, the reinforced phases CuO and SnO2 are redistributed to make the microstructure more uniform, which is in good agreement with the actual experimental results. In addition, by comparing the mechanical properties of samples with different content of SnO2, when the SnO2 content is 5%, AgCuOSnO2 has the highest conductivity, strain, and tensile strength.
Growth of fixed mindset from elementary to middle school: Its relationship with trajectories of academic behavior engagement and academic achievement
Authors: Kim Myung‐Seop , Park Soowon
Published: August 2021

This study investigated students' fixed mindset trajectories using 6‐year longitudinal data from the 4th grade (elementary school) to the 9th grade (middle school). The longitudinal associations between the trajectories and academic achievement with behavioral engagement as a mediator were examined using a piecewise latent growth model. The Gyeonggi Education Panel Study with 3531 Korean students was used. Fixed mindset and school engagement were measured six times at 1‐year intervals. The average score of the 9th‐grade math, English, and Korean test scores were used as the outcome variable. The results showed that the fixed mindset slightly decreased during the elementary school period (4th–6th grade) but increased in the middle school (7th–9th grade). The initial level of fixed mindset negatively predicted academic achievement through the low initial level of behavior engagement (i.e., effort exerted, attention, and involvement in academics). The slope of a fixed mindset in the elementary school period did not influence academic achievement in the 9th grade. Conversely, the slope of a fixed mindset in the middle school period affected academic achievement through the slope of behavior engagement in the middle school period. The results indicated that trajectory patterns of fixed mindset were differentiated depending on the school level. An increase in students' fixed mindset in middle school plays a significant role in decreasing classroom engagement and academic achievement.
Differential nuclease sensitivity profiling uncovers a drought responsive change in maize leaf chromatin structure for two large retrotransposon derivatives, Uloh and Vegu
Authors: Park Minkyu , Williams Delvin S. , Turpin Zachary M. , Wiggins ZaDarreyal J. , Tsolova Violeta M. , Onokpise Oghenekome U. , Bass Hank W.
Published: August 2021

Plant chromatin dynamics are generally recognized as playing a role in the genomic response to environmental stress. Although stress‐induced transcriptional activities of LTR‐retrotransposons have been reported, whether the stress response can be detected at the level of chromatin structure for LTR‐retrotransposons is largely unknown. Using differential nuclease sensitivity profiling, we identified that two out of 29 maize LTR‐retrotransposon families change their chromatin structure in response to drought stress in leaf tissue. The two LTR‐retrotransposon families, uloh and vegu, are classified as nonautonomous LTR‐retrotransposons. Differently from other families, the chromatin structure of these two families shifted from more open in normal conditions to more closed following drought stress. Although uloh and vegu lack sequence similarity, most of them shared an intriguing feature of having a new and uncharacterized insertion of a DNA sequence near one side of an LTR. In the uloh family, nine members with a strong drought response also exhibited a drought‐induced reduction of published H3K4me3 histone modification in the inserted DNA region, implicating this modification in the chromatin structural changes. Our results provide new insight into how LTR‐retrotransposons can alter their chromatin structure following stress response in plants.
Step‐by‐step comparison of ordinary differential equation and agent‐based approaches to pharmacokinetic‐pharmacodynamic models
Authors: Truong Van Thuy , Baverel Paul G. , Lythe Grant D. , Vicini Paolo , Yates James W. T. , Dubois Vincent F. S.
Published: August 2021

Mathematical models in oncology aid in the design of drugs and understanding of their mechanisms of action by simulation of drug biodistribution, drug effects, and interaction between tumor and healthy cells. The traditional approach in pharmacometrics is to develop and validate ordinary differential equation models to quantify trends at the population level. In this approach, time‐course of biological measurements is modeled continuously, assuming a homogenous population. Another approach, agent‐based models, focuses on the behavior and fate of biological entities at the individual level, which subsequently could be summarized to reflect the population level. Heterogeneous cell populations and discrete events are simulated, and spatial distribution can be incorporated. In this tutorial, an agent‐based model is presented and compared to an ordinary differential equation model for a tumor efficacy model inhibiting the pERK pathway. We highlight strengths, weaknesses, and opportunities of each approach.
Separation of Ultra‐High‐Density Cell Suspension via Elasto‐Inertial Microfluidics
Authors: Kwon Taehong , Choi Kyungyong , Han Jongyoon
Published: August 2021

Separation of high‐density suspension particles at high throughput is crucial for many chemical, biomedical, and environmental applications. In this study, elasto‐inertial microfluidics is used to manipulate ultra‐high‐density cells to achieve stable equilibrium positions in microchannels, aided by the inherent viscoelasticity of high‐density cell suspension. It is demonstrated that ultra‐high‐density Chinese hamster ovary cell suspension (>26 packed cell volume% (PCV%), >95 million cells mL−1) can be focused at distinct lateral equilibrium positions under high‐flow‐rate conditions (up to 10 mL min−1). The effect of flow rates, channel dimensions, and cell densities on this unique focusing behavior is studied. Cell clarification is further demonstrated using this phenomenon, from 29.7 PCV% (108.1 million cells mL−1) to 8.3 PCV% (33.2 million cells mL−1) with overall 72.1% reduction efficiency and 10 mL min−1 processing rate. This work explores an extreme case of elasto‐inertial particle focusing where ultra‐high‐density culture suspension is efficiently manipulated at high throughput. This result opens up new opportunities for practical applications of high‐particle‐density suspension manipulation.
Fast Leaps between Millisecond Confinements Govern Ase1 Diffusion along Microtubules
Authors: Bujak Łukasz , Holanová Kristýna , García Marín Antonio , Henrichs Verena , Barvík Ivan , Braun Marcus , Lánský Zdeněk , Piliarik Marek
Published: August 2021

Diffusion is the most fundamental mode of protein translocation within cells. Confined diffusion of proteins along the electrostatic potential constituted by the surface of microtubules, although modeled meticulously in molecular dynamics simulations, has not been experimentally observed in real‐time. Here, interferometric scattering microscopy is used to directly visualize the movement of the microtubule‐associated protein Ase1 along the microtubule surface at nanometer and microsecond resolution. Millisecond confinements of Ase1 and fast leaps between these positions of dwelling preferentially occurring along the microtubule protofilaments are resolved, revealing Ase1's mode of diffusive translocation along the microtubule's periodic surface. The derived interaction potential closely matches the tubulin‐dimer periodicity and the distribution of the electrostatic potential on the microtubule lattice. It is anticipated that mapping the interaction landscapes for different proteins on microtubules, finding plausible energetic barriers of different positioning and heights, can provide valuable insights into regulating the dynamics of essential cytoskeletal processes, such as intracellular cargo trafficking, cell division, and morphogenesis, all of which rely on diffusive translocation of proteins along microtubules.
Yttrium Vanadium Oxide–Poly(3,4‐ethylenedioxythiophene) Composite Cathode Material for Aqueous Zinc‐Ion Batteries
Authors: Kumankuma‐Sarpong James , Guo Wei , Fu Yongzhu
Published: August 2021

The development of metal ion‐intercalated active materials for excellent electrochemical performance in rechargeable aqueous zinc‐ion batteries (AZIBs) is challenging. The structure instability and intrinsic electrostatic repulsion of the lattice framework cause structural breakdown and low‐rate performance. In response to these problems, yttrium vanadium oxide–poly(3,4‐ethylenedioxythiophene) (PEDOT@YVO) composite is reported as stable cathode material for AZIBs. The introduction of PEDOT in YVO nanorods improves the crystalline structure with an enlarged interplanar lattice spacing of 3.4 Å. The PEDOT@YVO composite electrode demonstrates effective electric conductivity and a higher initial specific capacity of 308.5 mAh g−1 than that (125.5 mAh g−1) of the pure YVO at 0.2 C rate. It also features a long‐term stable discharge–charge cycle performance of 4000 cycles with a capacity retention of 79.2% at 1C rate, better than YVO (29.4 mAh g−1). The oxygen vacancies and improved electrical conductivity of the composite account for the invigorated electrochemical performance. Consequently, this work reveals another avenue for constructing unique electrodes to enhance the electrochemical properties of AZIBs.
A Hybrid Nanofiber/Paper Cell Culture Platform for Building a 3D Blood–Brain Barrier Model
Authors: Huang Kaixiang , Castiaux Andre D. , Podicheti Ram , Rusch Douglas B. , Martin R. Scott , Baker Lane A.
Published: August 2021

The blood–brain barrier (BBB) protects the central nervous system from toxins and pathogens in the blood by regulating permeation of molecules through the barrier interface. In vitro BBB models described to date reproduce some aspects of BBB functionality, but also suffer from incomplete phenotypic expression of brain endothelial traits, difficulty in reproducibility and fabrication, or overall cost. To address these limitations, a 3D BBB model based on a hybrid paper/nanofiber scaffold is described. The cell culture platform utilizes lens paper as a framework to accommodate 3D culture of astrocytes. An electrospun nanofiber layer is coated onto one face of the paper to mimic the basement membrane and support growth of an organized 2D layer of endothelial cells (ECs). Human induced pluripotent stem cell‐derived ECs and astrocytes are co‐cultured to develop a human BBB model. Morphological and spatial organization of model are validated with confocal microscopy. Measurements of transendothelial resistance and permeability demonstrate the BBB model develops a high‐quality barrier and responds to hyperosmolar treatments. RNA‐sequencing shows introduction of astrocytes both regulates EC tight junction proteins and improves endothelial phenotypes related to vasculogenesis. This model shows promise as a model platform for future in vitro studies of the BBB.
Advanced data integration in banking, financial, and insurance software in the age of COVID‐19
Authors: Maiti Moinak , Vuković Darko , Mukherjee Amrit , Paikarao Pavan D. , Yadav Janardan Krishna
Published: August 2021

This study contributes to our understanding of how the emergence of the COVID‐19 pandemic changes the global Banking Financial Services and Insurance (BFSI) landscape. Before the COVID‐19 pandemic, BFSIs corporate strategy was solely aligned to the quest for operational efficiency. However, during the ongoing COVID‐19 pandemic, global BFSIs are forced to adopt digital transformation in their operations due to a rise in transaction volumes. The ongoing COVID‐19 pandemic already triggers holistic innovations concerning the global BFSI's product, process, concept, trend, or idea. Thus, the BFSI cannot survive without efficient and innovative system software for global operations. The study plots the hype cycle to identify relevant technologies to deal with real‐world business problems. The hype cycle indicates that the need for advanced data integration is growing and COVID‐19 pandemic has already triggered it. The study argues that the incorporation of data integration might be challenging initially for BFSIs but eventually it may result in an efficient model to handle these types of pandemic or unexpected circumstances.
Enhanced Strength and Toughness of Low‐Carbon Bainitic Steel by Refining Prior Austenite Grains and Austempering Below Ms
Authors: Yao Chunxia , Lan Huifang , Tao Zhen , Misra Raja Devesh Kumar , Du Linxiu
Published: August 2021

Austempering is conducted below and above martensite start temperature (Ms) at the fine and coarse prior austenite grain size (PAGS), respectively, in a low‐carbon bainitic steel, and the relationship between multiphase microstructure and mechanical properties is investigated. The study indicates that refinement of bainite laths can be obtained by decreasing the PAGS and/or austempering temperature from above to below Ms. The former reduces bainite content, and increases the volume fraction of retained austenite (RA), thereby obtaining higher uniform elongation and strain hardening exponent. However, the latter effectively decreases the size and amount of blocky RA, as well as bainite content and conversely increases the ratio of volume fraction of film RA to that of blocky RA, which leads to significant improvement in yield strength and impact toughness. In addition, the variant selection is relatively weak with the decrease in the PAGS and austempering temperature, which has a beneficial effect on toughness. Furthermore, an outstanding combination of mechanical properties (1070 MPa yield strength, 1466 MPa tensile strength, total elongation of 11.68%, and V‐notch impact toughness at 20 and −40 °C of 78 and 44 J cm−2, respectively) is achieved by austempering below Ms in the finer PAGS.
Micro–Nanostructure‐Assisted Luminescence in Perovskite Devices
Authors: Tang Ying-Yi , Shen Yang , Wang Jing-Kun , Qian Xiao-Yan , Guo Ming-Lei , Li Yan-Qing , Tang Jian-Xin
Published: August 2021

Metal halide perovskite (MHP) materials have demonstrated great advantages over conventional semiconductors for the next‐generation optoelectronics on account of their outstanding photophysical properties and facile solution processability. Among all the related researches, the suitable micro–nanostructures have been proven to be a direct and effective optical and photophysical management strategy, which is essential for improving the luminescent characteristics of MHP‐based luminescent optoelectronics, including light‐emitting diodes (LEDs) and lasers. Herein, the developments of representative optical micro–nanostructures for perovskite luminescence with different architectures are first introduced, including metal nanoparticles, 1D Bragg gratings, 2D nanostructures with and without periodicity, and MHP nanocrystals. Notably, the fabrication techniques of various counterparts in micro–nanostructures are systematically reviewed. Moreover, the recent practical applications of micro–nanostructures in MHP‐based materials and luminescent optoelectronics are discussed in details, which mainly involves localized surface plasmon resonance (LSPR)‐derived luminescence improvement, optical outcoupling manipulation, and stimulated light emission via optical micro–nanocavity. Lastly, the challenges and perspectives for micro–nanostructures toward future's MHP‐based luminescence applications are summarized.
Rational Design of Near‐Infrared Aza‐Platinum‐Dipyrromethene‐Based Nanophototherapy Agent with Multistage Enhancement for Synergistic Antitumor Therapeutics
Authors: Xu Yunjian , Zhao Menglong , Zhou Yucheng , Wang Jiawei , Li Mingdang , Li Feiyang , Lv Wen , Liu Shujuan , Zhao Qiang
Published: August 2021

The development of innovative synergistic phototherapy (SPT) agent with excellent photodynamic therapy (PDT) and photothermal therapy (PTT) effects for efficient antitumor is of great significance. However, the low photothermal conversion efficiency or low singlet oxygen yield of SPT agent during the phototherapy process will result in inefficient tumor therapy. Herein, a new near‐infrared (NIR) SPT agent based on aza‐platinum‐dipyrromethene dye (D‐3) with synergistic PDT and PTT effects is rationally designed and synthesized by the metallization and halogenation of aza‐dipyrromethene simultaneously. The introduction of iodine atoms and Pt(II) ion to aza‐dipyrromethene skeleton can not only effectively promote the excited electrons to undergo intersystem crossing process for improving singlet oxygen (1O2) generation capability, but also inhibit radiative transition process for boosting photothermal conversion properties. For biological exploration, the biocompatible D‐3 nanomaterials (APIDNs) with excellent concentration‐dependent photoacoustic and photothermal properties are prepared, thus visibly guiding synergetic PDT and PTT effects for inhibiting the growth of tumor cells in vivo. This work demonstrates the superior therapy effects of APIDNs and its negligible dark cytotoxicity. The novel strategy reported in this work will offer a new way to design new‐generation NIR aza‐metal‐dipyrromethene‐based dyes for developing superior SPT agents.
Prenatal diagnosis and outcome of fetuses with isolated agenesis of septum pellucidum: cohort study and meta‐analysis
Authors: Di Pasquo E. , Kuleva M. , Arthuis C. , Morganelli G. , Ormitti F. , Millischer A.‐E. , Grevent D. , Ville Y. , Ghi T. , Salomon L. J.
Published: August 2021

Objective

To evaluate the postnatal outcome of children with a prenatal diagnosis of apparently isolated agenesis of the septum pellucidum (ASP).

Methods

A retrospective cohort study of cases of prenatally diagnosed ASP followed in two tertiary centers and a meta‐analysis combining data from the cohort study with data from published studies identified in a systematic review were carried out. Only cases with apparently isolated ASP on antenatal ultrasound and/or magnetic resonance imaging and with available postnatal follow‐up data were considered eligible for inclusion. The following outcomes were analyzed: incidence of chromosomal anomalies, agreement between antenatal and postnatal findings, overall incidence of septo‐optic dysplasia (SOD) and incidence of major neurological disability (motor, language, coordination or behavioral disorder or epilepsy) in non‐SOD children. The incidence of SOD in infants with apparently normal optic pathways on antenatal imaging was also evaluated.

Results

Fifteen cases of isolated ASP, with median postnatal follow‐up of 36 months (range, 12–60 months), were selected from the two centers. Six previously published studies met the inclusion criteria for the systematic review and a total of 78 cases were eligible for the analysis, including the 15 cases from our series. Genetic tests were carried out antenatally in 30 fetuses, of which two had an abnormal result (pooled proportion, 9.0% (95% CI, 1.8–20.7%); I2 = 0%). Additional or discordant imaging findings were noted postnatally in 9/70 (pooled proportion, 13.7% (95% CI, 3.5–29.0%); I2 = 63.9%) cases. Of all 78 neonates with available follow‐up, SOD was diagnosed postnatally in 14 (pooled proportion, 19.4% (95% CI, 8.6–33.2%); I2 = 51.2%). In 60 cases, the optic pathways were considered to be normal on antenatal imaging, and six of these (pooled proportion, 9.1% (95% CI, 1.1–24.0%); I2 = 62.0%) were diagnosed postnatally with SOD. Of the 46 infants with available neurological follow‐up who were not affected by SOD, a major neurological disability was diagnosed in three (pooled proportion, 6.5% (95% CI, 0.5–18.6%); I2 = 40.1%).

Conclusions

In the vast majority of cases with a prenatal diagnosis of apparently isolated ASP, the prognosis is favorable. However, an additional anomaly is detected after birth in about 14% of cases and has a negative impact on clinical outcome. Detailed antenatal assessment of the brain and optic pathways is strongly recommended in order to identify the presence of associated anomalies. Antenatal visualization of apparently normal optic pathways does not rule out SOD. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.
Longitudinal assessment of spiral artery and intravillous arteriole blood flow and adverse pregnancy outcome
Authors: Odibo A. O. , Kayisli U. , Lu Y. , Kayisli O. , Schatz F. , Odibo L. , Chen H. , Bronsteen R. , Lockwood C. J.
Published: August 2021

Objective

Superb microvascular imaging (SMI) has been shown to improve visualization of small vessels by suppressing global motions while preserving low‐flow components, such as the microvessels in the placenta. We sought to determine if SMI‐aided visualization of flow velocity waveforms in the spiral arteries (SA) and intravillous fetal arterioles (IVA) could predict fetal growth restriction (FGR), gestational hypertension (GH) and/or pre‐eclampsia (PE).

Methods

This was a prospective longitudinal study of singleton pregnancies without fetal anomaly, receiving prenatal care in one of two medical centers over a 5‐year period. Using SMI‐aided color Doppler, SA and IVA flow velocity was measured at three timepoints: 11 + 0 to 14 + 0, 18 + 0 to 22 + 6 and 28 + 0 to 34 + 6 weeks of gestation. SA and IVA flow velocity waveforms were reported as resistance indices (RI). RI values were analyzed using multilevel modeling; individual regression curves were estimated and combined to obtain the reference intervals for SA‐RI and IVA‐RI in uncomplicated pregnancies. The primary clinical outcome was FGR and secondary outcomes were PE and GH. FGR was defined as estimated fetal weight < 10th percentile. Student's t‐test was used to compare deviation from expected RI between normal and complicated pregnancies.

Results

Among 540 pregnancies included in the analysis, 18 (3.3%) had FGR, 31 (5.7%) PE and 61 (11.3%) GH. In uncomplicated pregnancies, the SA‐RI decreased progressively with advancing gestation, whereas the IVA‐RI increased with gestational age. In the third trimester, the mean SA‐RI and IVA‐RI values were significantly higher in the FGR group compared with pregnancies that did not develop FGR, while the mean SA‐RI was significantly higher in PE compared with non‐PE pregnancies. There was no significant difference in mean SA‐RI or IVA‐RI between pregnancies with vs those without GH at any gestational age. When all three adverse outcomes were combined, SA‐RI was significantly higher in pregnancies with these outcomes when compared to uncomplicated pregnancies in the third trimester (mean ± SD, 0.29 ± 0.12 vs 0.26 ± 0.12; P = 0.02). In screening for FGR using SA‐RI, the areas under the receiver‐operating‐characteristics curves (AUC) were 0.68, 0.73 and 0.73 in the first, second and third trimesters, respectively. The respective AUCs for IVA‐RI were 0.72, 0.72 and 0.73 for each trimester.

Conclusions

SA‐RI and IVA‐RI, measured using SMI technology, were significantly higher in pregnancies at risk for FGR in late gestation. Larger studies are needed to determine if SA and IVA flow are reliable predictors of adverse pregnancy outcome. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.
Prevalence of supratentorial anomalies assessed by magnetic resonance imaging in fetuses with open spina bifida
Authors: Trigo L. , Eixarch E. , Bottura I. , Dalaqua M. , Barbosa A. A. , De Catte L. , Demaerel P. , Dymarkowski S. , Deprest J. , Lapa D. A. , Aertsen M. , Gratacos E.
Published: August 2021

Objectives

To determine the prevalence of brain anomalies at the time of preoperative magnetic resonance imaging (MRI) assessment in fetuses eligible for prenatal open spina bifida (OSB) repair, and to explore the relationship between brain abnormalities and features of the spinal defect.

Methods

This was a retrospective cross‐sectional study, conducted in three fetal medicine centers, of fetuses eligible for OSB fetal surgery repair between January 2009 and December 2019. MRI images obtained as part of the presurgical assessment were re‐evaluated by two independent observers, blinded to perinatal results, to assess: (1) the type and area of the defect and its anatomical level; (2) the presence of any structural central nervous system (CNS) anomaly and abnormal ventricular wall; and (3) fetal head and brain biometry. Binary regression analyses were performed and data were adjusted for type of defect, upper level of the lesion (ULL), gestational age (GA) at MRI and fetal medicine center. Multiple logistic regression analysis was performed in order to identify lesion characteristics and brain anomalies associated with a higher risk of presence of abnormal corpus callosum (CC) and/or heterotopia.

Results

Of 115 fetuses included, 91 had myelomeningocele and 24 had myeloschisis. Anatomical level of the lesion was thoracic in seven fetuses, L1–L2 in 13, L3–L5 in 68 and sacral in 27. Median GA at MRI was 24.7 (interquartile range, 23.0–25.7) weeks. Overall, 52.7% of cases had at least one additional brain anomaly. Specifically, abnormal CC was observed in 50.4% of cases and abnormality of the ventricular wall in 19.1%, of which 4.3% had nodular heterotopia. Factors associated independently with higher risk of abnormal CC and/or heterotopia were non‐sacral ULL (odds ratio (OR), 0.51 (95% CI, 0.26–0.97); P = 0.043), larger ventricular width (per mm) (OR, 1.23 (95% CI, 1.07–1.43); P = 0.005) and presence of abnormal cavum septi pellucidi (OR, 3.76 (95% CI, 1.13–12.48); P = 0.031).

Conclusions

Half of the fetuses assessed for OSB repair had an abnormal CC and/or an abnormal ventricular wall prior to prenatal repair. The likelihood of brain abnormalities was increased in cases with a non‐sacral lesion and wider lateral ventricles. These findings highlight the importance of a detailed preoperative CNS evaluation of fetuses with OSB. © 2021 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.
Influence of fibroids on cell‐free DNA screening accuracy
Authors: Scott F. , Menezes M. , Smet M. E. , Carey K. , Hardy T. , Fullston T. , Rolnik D. L. , McLennan A.
Published: August 2021

Objective

Cell‐free DNA (cfDNA) screening assesses both maternal and placental cfDNA. Fibroids are common and release cfDNA into maternal serum. Genetic abnormality is seen in 50% of fibroids. We aimed to assess the impact of fibroids on the accuracy of genome‐wide cfDNA screening.

Methods

This was a prospective cohort study of singleton pregnancies examined at one of two centers in Melbourne and Sydney, Australia, between 1 November 2019 and 31 December 2020. All cases underwent pretest ultrasound examination to confirm an ongoing pregnancy of at least 10 weeks' gestation, and, at this stage, the number and volume of any uterine fibroid were documented. Genome‐wide cfDNA screening was performed to detect all copy‐number variants (CNV) > 7 megabases. The incidence of a false‐positive result was compared between cases with and those without fibroids.

Results

Over the 14‐month study period, 13 184 patients underwent cfDNA screening, of whom 1017 (7.7%) had fibroids. Fibroids were not identified in any of the 17 participants who had a false‐positive result for chromosomes 13, 18, 21, X or Y. Ninety‐five (0.7%) cases were screen‐positive for subchromosomal aberration (SA), rare autosomal trisomy (RAT) or multiple abnormalities (MA), with 10 of these cases having a fetal genetic abnormality. The incidence of a false‐positive RAT, MA or SA result was significantly higher in participants with fibroids (20/1017 (2.0%)) than in those without fibroids (64/12 167 (0.5%)). Women with fibroids were approximately six times as likely to have a false‐positive result for SA, and this was associated positively with both fibroid number and volume.

Conclusions

Most women with fibroids do not have an abnormal result on genome‐wide cfDNA screening. However, CNVs due to fibroids are associated with false‐positive SA findings, although fibroids do not appear to influence cfDNA screening accuracy for the common autosomal trisomies or sex‐chromosomal abnormalities. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.
Clinical phenotypes for risk stratification in small‐for‐gestational‐age fetuses
Authors: Ruiz‐Martinez S. , Delgado J. L. , Paules C. , Cavallaro A. , De Paco C. , Villar J. , Papageorghiou A. , Oros D.
Published: August 2021

Objective

To evaluate whether clinical phenotypes of small‐for‐gestational‐age (SGA) fetuses can be identified and used for adverse perinatal outcome risk stratification to facilitate clinical decision‐making.

Methods

This was a multicenter observational cohort study conducted in two tertiary care university hospitals. SGA fetuses were classified according to maternal, fetal and placental conditions using a two‐step cluster algorithm, in which fetuses with more than one condition were assigned to the cluster associated with the highest mortality risk. Delivery and perinatal outcomes were compared using chi‐square test among SGA clusters, and the associations between outcomes and each cluster were evaluated by calculating odds ratios (OR), adjusted for gestational age.

Results

The study included 17 631 consecutive singleton pregnancies, of which 1274 (7.2%) were defined as SGA at birth according to INTERGROWTH‐21st standards. Nine SGA clinical phenotypes were identified using a predefined conceptual framework. All delivery and perinatal outcomes analyzed were significantly different among the nine phenotypes. The whole SGA cohort had a three‐times higher risk of perinatal mortality compared with non‐SGA fetuses (1.4% vs 0.4%; P < 0.001). SGA clinical phenotypes exhibited three patterns of perinatal mortality risk: the highest risk was associated with congenital anomaly (8.3%; OR, 17.17 (95% CI, 2.17–136.12)) and second‐ or third‐trimester hemorrhage (8.3%; OR, 9.94 (95% CI, 1.23–80.02)) clusters; medium risk was associated with gestational diabetes (3.8%; OR, 9.59 (95% CI, 1.27–72.57)), preterm birth (3.2%; OR, 4.65 (95% CI, 0.62–35.01)) and intrauterine growth restriction (3.1%; OR, 5.93 (95% CI, 3.21–10.95)) clusters; and the lowest risk was associated with the remaining clusters. Perinatal mortality rate did not differ between SGA fetuses without other clinical conditions (54.1% of SGA fetuses) and appropriate‐for‐gestational‐age fetuses (0.1% vs 0.4%; OR, 0.41 (95% CI, 0.06–2.94); P = 0.27). SGA combined with other obstetric pathologies increased significantly the risk of perinatal mortality, as demonstrated by the increased odds of perinatal death in SGA cases with gestational diabetes compared to non‐SGA cases with the same condition (OR, 24.40 (95% CI, 1.31–453.91)).

Conclusions

We identified nine SGA clinical phenotypes associated with different patterns of risk for adverse perinatal outcome. Our findings suggest that considering clinical characteristics in addition to ultrasound findings could improve risk stratification and decision‐making for management of SGA fetuses. Future clinical trials investigating management of fetuses with SGA should take into account clinical information in addition to Doppler parameters and estimated fetal weight. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.
Moduli stabilisation and the statistics of axion physics in the landscape
Authors: Broeckel Igor , Cicoli Michele , Maharana Anshuman , Singh Kajal , Sinha Kuver
Published: August 2021

Abstract

String theory realisations of the QCD axion are often said to belong to the anthropic window where the decay constant is around the GUT scale and the initial misalignment angle has to be tuned close to zero. In this paper we revisit this statement by studying the statistics of axion physics in the string landscape. We take moduli stabilisation properly into account since the stabilisation of the saxions is crucial to determine the physical properties of the corresponding axionic partners. We focus on the model-independent case of closed string axions in type IIB flux compactifications and find that their decay constants and mass spectrum feature a logarithmic, instead of a power-law, distribution. In the regime where the effective field theory is under control, most of these closed string axions are ultra-light axion-like particles, while axions associated to blow-up modes can naturally play the role of the QCD axion. Hence, the number of type IIB flux vacua with a closed string QCD axion with an intermediate scale decay constant and a natural value of the misalignment angle is only logarithmically suppressed. In a recent paper we found that this correlates also with a logarithmic distribution of the supersymmetry breaking scale, providing the intriguing indication that most, if not all, of the phenomenologically interesting quantities in the string landscape might feature a logarithmic distribution.
Vectorial integer bootstrapping: flexible integer estimation with application to GNSS
Authors: Teunissen P. J. G. , Massarweh L. , Verhagen S.
Published: August 2021

In this contribution, we extend the principle of integer bootstrapping (IB) to a vectorial form (VIB). The mathematical definition of the class of VIB-estimators is introduced together with their pull-in regions and other properties such as probability bounds and success rate approximations. The vectorial formulation allows sequential block-by-block processing of the ambiguities based on a user-chosen partitioning. In this way, flexibility is created, where for specific choices of partitioning, tailored VIB-estimators can be designed. This wide range of possibilities is discussed, supported by numerical simulations and analytical examples. Further guidelines are provided, as well as the possible extension to other classes of estimators.
CD16xCD33 Bispecific Killer Cell Engager (BiKE) as potential immunotherapeutic in pediatric patients with AML and biphenotypic ALL
Authors: Reusing Sarah B. , Vallera Dan A. , Manser Angela R. , Vatrin Titus , Bhatia Sanil , Felices Martin , Miller Jeffrey S. , Uhrberg Markus , Babor Florian
Published: August 2021

Similar to pediatric acute myeloid leukemia (AML) the subgroup of biphenotypic acute lymphoblastic leukemia (ALL) is a rare complex entity with adverse outcome, characterized by the surface expression of CD33. Despite novel and promising anti-CD19 targeted immunotherapies such as chimeric antigen receptor T cells and bispecific anti-CD19/CD3 antibodies, relapse and resistance remain a major challenge in about 30% to 60% of patients. To investigate the potential role of the fully humanized bispecific antibody CD16 × CD33 (BiKE) in children with CD33+ acute leukemia, we tested whether the reagent was able to boost NK cell effector functions against CD33+ AML and biphenotypic ALL blasts. Stimulation of primary NK cells from healthy volunteers with 16 × 33 BiKE led to increased cytotoxicity, degranulation and cytokine production against CD33+ cell lines. Moreover, BiKE treatment significantly increased degranulation, IFN-γ and TNF-α production against primary ALL and AML targets. Importantly, also NK cells from leukemic patients profited from restoration of effector functions by BiKE treatment, albeit to a lesser extent than NK cells from healthy donors. In particular, those patients with low perforin and granzyme expression showed compromised cytotoxic function even in the presence of BiKE. In patients with intrinsic NK cell deficiency, combination therapy of CD16xCD33 BiKE and allogeneic NK cells might thus be a promising therapeutic approach. Taken together, CD16xCD33 BiKE successfully increased NK cell effector functions against pediatric AML and biphenotypic ALL blasts and constitutes a promising new option for supporting maintenance therapy or “bridging” consolidation chemotherapy before hematopoietic stem cell transplantation.
Dynamic switch of immunity and antitumor effects of metformin in rat spontaneous esophageal carcinogenesis
Authors: Takei Ryohei , Miyashita Tomoharu , Takada Satoshi , Tajima Hidehiro , Ninomiya Itasu , Takamura Hiroyuki , Fushida Sachio , Harashima Ai , Munesue Seiichi , Yagi Shintaro , Inaki Noriyuki , Ohta Tetsuo , Yamamoto Yasuhiko
Published: August 2021

Chronic inflammation contributes to tumor development by creating a local microenvironment that facilitates neoplastic transformation and potentiates the progression of cancer. Esophageal cancer (EC) is an inflammation-associated malignancy with a poor prognosis. The nature of the switch between chronic inflammation of the esophagus and EC-related immunological changes remains unclear. Here, we examined the dynamic alterations of immune cells at different stages of chronic esophagitis, Barrett’s esophagus (BE) and EC using an esophageal spontaneous carcinogenesis rat model. We also investigated the anticancer effects of metformin. To stimulate EC carcinogenesis, chronic gastroduodenal reflux esophagitis via esophagojejunostomy was induced in 120 rats in metformin-treated and non-treated (control) groups. After 40 weeks, BE and EC developed in 96.7% and 63.3% of the control group, and in 66.7% and 23.3% of the metformin-treated group, respectively. Flow cytometric analysis demonstrated that the balance of M1/M2-polarized or phospho-Stat3-positive macrophages, regulatory T, cytotoxic T, natural killer (NK), NK T cells, and Th17 T cells was dynamically changed at each stage of the disease and were resolved by metformin treatment. These findings clarify the immunity in esophageal carcinogenesis and suggest that metformin could suppress this disease by improving the immunosuppressive tumor microenvironment and immune evasion.
Is There a Role for Topical Swallowed Steroids upon Emergency Room Admission for Suspected Food Bolus Obstruction in Eosinophilic Esophagitis?
Authors: Schreiner Philipp , Greuter Thomas , Tatu Aurora , Keller Dagmar I. , Straumann Alex , Biedermann Luc
Published: August 2021

Since most pharmacological treatments in case of esophageal food impaction (EFI) are unsuccessful, an endoscopy is usually required to resolve EFI. We present the first results of a budesonide orodispersible tablet (BOT) as a medical treatment option before endoscopy. We evaluated all patients with a suspected EFI to receive BOT before emergent endoscopy at a tertiary hospital between March 2019 and June 2020. A total of eight patients received BOT before endoscopy. Mean age was 50.1 years and 87.5% were male. In 38% (3/8) of patients the EFI resolved without endoscopic intervention. No adverse events occurred. After endoscopy, a diagnosis of EoE was established in 75%. This case series demonstrate the potential of BOT as medical rescue therapy in case of EFI.
Clinical effectiveness of gasless laparoscopic surgery for abdominal conditions: systematic review and meta-analysis
Authors: Aruparayil N. , Bolton W. , Mishra A. , Bains L. , Gnanaraj J. , King R. , Ensor T. , King N. , Jayne D. , Shinkins B.
Published: August 2021

Background

In high-income countries, laparoscopic surgery is the preferred approach for many abdominal conditions. Conventional laparoscopy is a complex intervention that is challenging to adopt and implement in low resource settings. This systematic review and meta-analysis evaluate the clinical effectiveness of gasless laparoscopy compared to conventional laparoscopy with CO2 pneumoperitoneum and open surgery for general surgery and gynaecological procedures.

Methods

A search of the MEDLINE, EMBASE, Global Health, AJOL databases and Cochrane Library was performed from inception to January 2021. All randomised (RCTs) and comparative cohort (non-RCTs) studies comparing gasless laparoscopy with open surgery or conventional laparoscopy were included. The primary outcomes were mortality, conversion rates and intraoperative complications. Secondary outcomes: operative times and length of stay. The inverse variance random-effects model was used to synthesise data.

Results

63 studies were included: 41 RCTs and 22 non-RCTs (3,620 patients). No procedure-related deaths were reported in the studies. For gasless vs conventional laparoscopy there was no difference in intraoperative complications for general RR 1.04 [CI 0.45–2.40] or gynaecological surgery RR 0.66 [0.14–3.13]. In the gasless laparoscopy group, the conversion rates for gynaecological surgery were high RR 11.72 [CI 2.26–60.87] when compared to conventional laparoscopy. For gasless vs open surgery, the operative times were longer for gasless surgery in general surgery RCT group MD (mean difference) 10 [CI 0.64, 19.36], but significantly shorter in the gynaecology RCT group MD − 18.74 [CI − 29.23, − 8.26]. For gasless laparoscopy vs open surgery non-RCT, the length of stay was shorter for gasless laparoscopy in general surgery MD − 3.94 [CI − 5.93, − 1.95] and gynaecology MD − 1.75 [CI − 2.64, − 0.86]. Overall GRADE assessment for RCTs and Non-RCTs was very low.

Conclusion

Gasless laparoscopy has advantages for selective general and gynaecological procedures and may have a vital role to play in low resource settings.
Current experimental disease-modifying therapeutics for multiple system atrophy
Authors: Lemos Miguel , Wenning Gregor K. , Stefanova Nadia
Published: August 2021

Multiple system atrophy (MSA) is a challenging neurodegenerative disorder with a difficult and often inaccurate early diagnosis, still lacking effective treatment. It is characterized by a highly variable clinical presentation with parkinsonism, cerebellar ataxia, autonomic dysfunction, and pyramidal signs, with a rapid progression and an aggressive clinical course. The definite MSA diagnosis is only possible post-mortem, when the presence of distinctive oligodendroglial cytoplasmic inclusions (GCIs), mainly composed of misfolded and aggregated α-Synuclein (α-Syn) is demonstrated. The process of α-Syn accumulation and aggregation within oligodendrocytes is accepted one of the main pathological events underlying MSA. However, MSA is considered a multifactorial disorder with multiple pathogenic events acting together including neuroinflammation, oxidative stress, and disrupted neurotrophic support, among others. The discussed here treatment approaches are based on our current understanding of the pathogenesis of MSA and the results of preclinical and clinical therapeutic studies conducted over the last 2 decades. We summarize leading disease-modifying approaches for MSA including targeting α-Syn pathology, modulation of neuroinflammation, and enhancement of neuroprotection. In conclusion, we outline some challenges related to the need to overcome the gap in translation between preclinical and clinical studies towards a successful disease modification in MSA.
Spinocerebellar ataxias (SCAs) caused by common mutations
Authors: Müller Ulrich
Published: August 2021

The term SCA refers to a phenotypically and genetically heterogeneous group of autosomal dominant spinocerebellar ataxias. Phenotypically they present as gait ataxia frequently in combination with dysarthria and oculomotor problems. Additional signs and symptoms are common and can include various pyramidal and extrapyramidal signs and intellectual impairment. Genetic causes of SCAs are either repeat expansions within disease genes or common mutations (point mutations, deletions, insertions etc.). Frequently the two types of mutations cause indistinguishable phenotypes (locus heterogeneity). This article focuses on SCAs caused by common mutations. It describes phenotype and genotype of the presently 27 types known and discusses the molecular pathogenesis in those 21 types where the disease gene has been identified. Apart from the dominant types, the article also summarizes findings in a variant caused by mutations in a mitochondrial gene. Possible common disease mechanisms are considered based on findings in the various SCAs described.