bluuebunny/crossref_metadata_2025 huggingface dataset:
Two methods to study inelastic neutron-scattering measurements based on ω

n
(q) versus S(q, ω) applied to the magnetic open honeycomb lattice Tb2Ir3Ga9
Authors: Fishman Randy S , Ostrouchov George , Ye Feng
Published: January 2022

This work describes two methods to fit the inelastic neutron-scattering spectrum S(q, ω) with wavevector q and frequency ω. The common and well-established method extracts the experimental spin-wave branches ω

n
(q) from the measured spectra S(q, ω) and then minimizes the difference between the observed and predicted frequencies. When n branches of frequencies are predicted but the measured frequencies overlap to produce only m < n branches, the weighted average of the predicted frequencies must be compared to the observed frequencies. A penalty is then exacted when the width of the predicted frequencies exceeds the width of the observed frequencies. The second method directly compares the measured and predicted intensities S(q, ω) over a grid {q

i
, ω

j
} in wavevector and frequency space. After subtracting background noise from the observed intensities, the theoretical intensities are scaled by a simple wavevector-dependent function that reflects the instrumental resolution. The advantages and disadvantages of each approach are demonstrated by studying the open honeycomb material Tb2Ir3Ga9.
Computational perspective on recent advances in quantum electronics: from electron quantum optics to nanoelectronic devices and systems
Authors: Weinbub Josef , Kosik Robert
Published: January 2022

Quantum electronics has significantly evolved over the last decades. Where initially the clear focus was on light–matter interactions, nowadays approaches based on the electron’s wave nature have solidified themselves as additional focus areas. This development is largely driven by continuous advances in electron quantum optics, electron based quantum information processing, electronic materials, and nanoelectronic devices and systems. The pace of research in all of these areas is astonishing and is accompanied by substantial theoretical and experimental advancements. What is particularly exciting is the fact that the computational methods, together with broadly available large-scale computing resources, have matured to such a degree so as to be essential enabling technologies themselves. These methods allow to predict, analyze, and design not only individual physical processes but also entire devices and systems, which would otherwise be very challenging or sometimes even out of reach with conventional experimental capabilities. This review is thus a testament to the increasingly towering importance of computational methods for advancing the expanding field of quantum electronics. To that end, computational aspects of a representative selection of recent research in quantum electronics are highlighted where a major focus is on the electron’s wave nature. By categorizing the research into concrete technological applications, researchers and engineers will be able to use this review as a source for inspiration regarding problem-specific computational methods.
Construction of an exosome-functionalized graphene oxide based composite bionic smart drug delivery system and its anticancer activity
Authors: Chen Qi , Che Chengchuan , Liu Jinfeng , Gong Zhijin , Si Meiru , Yang Shanshan , Yang Ge
Published: January 2022

Graphene oxide has covalently modified by chito oligosaccharides and γ-polyglutamic acid to form GO-CO-γ-PGA, which exhibits excellent performance as a drug delivery carrier, but this carrier did not have the ability to actively target. In this study, the targeting property of breast cancer tumor cell exosomes was exploited to give GO-CO-γ-PGA the ability to target breast tumor cells (MDA-MB-231), and the drug mitoxantrone (MIT) was loaded to finally form EXO-GO-CO-γ-PGA-MIT with an encapsulation efficiency of 73.02%. The pH response of EXO-GO-CO-γ-PGA showed a maximum cumulative release rate of 56.59% (pH 5.0, 120 h) and 6.73% (pH 7.4, 120 h) for MIT at different pH conditions. In vitro cellular assays showed that EXO-GO-CO-γ-PGA-MIT was more potent in killing MDA-MB-231 cells due to its targeting ability and had a significantly higher pro-apoptotic capacity compared to GO-CO-γ-PGA-MIT. The results showed that this bionic nano-intelligent drug delivery system has good drug slow release function and it can increase the local drug concentration of tumor and enhance the pro-apoptotic ability of MIT, so this newly synthesized bionic drug delivery carriers (EXO-GO-CO-γ-PGA-MIT) has potential application in breast cancer treatment.
Dual-center co-doped and mixed ratiometric LuVO4:Nd3+/Yb3+ nanothermometers
Authors: Kolesnikov Ilya E , Afanaseva Elena V , Kurochkin Mikhail A , Vaishlia Elena I , Kolesnikov Evgenii Yu , Lähderanta Erkki
Published: January 2022

During last decade luminescence thermometry has become a widely studied research field due to its potential applications for real time contactless temperature sensing where usual thermometers cannot be used. Special attention is paid to the development of accurate and reliable thermal sensors with simple reading. To address existing problems of ratiometric thermometers based on thermally-coupled levels, LuVO4:Nd3+/Yb3+ thermal sensors were studied as a proof-of-concept of dual-center thermometer obtained by co-doping or mixture. Both approaches to create a dual-center sensor were compared in terms of energy transfer efficiency, relative sensitivity, and temperature resolution. Effect of excitation mechanism and Yb3+ doping concentration on thermometric performances was also investigated. The best characteristics of S
r = 0.34% K−1@298 K and ΔT = 0.2 K were obtained for mixed phosphors upon host excitation.
FID-calibrated simultaneous multi-slice fast spin echo with long trains of hard pulses
Authors: Lim Eun Ji , Sohn Chul-Ho , Shin Taehoon , Park Jaeseok
Published: January 2022

Objective. To develop a novel, free-induction-decay (FID)-calibrated single-shot simultaneous multi-slice fast spin echo (SMS-FSE) with very long hard pulse trains for high encoding efficiency and low energy deposition. Approach. The proposed single-shot SMS-FSE employs a mixed pulse configuration in which a long excitation pulse that is spatially multi-band (MB) selective is used in conjunction with short spatially nonselective refocusing pulses. To alleviate energy deposition to tissues while reducing signal modulation along the echo train, variable low flip angles with signal prescription are utilized in the refocusing pulse train. A time-efficient FID calibration and correction method is introduced before aliased voxels in the slice direction are resolved. Simulations and experiments are performed to demonstrate the feasibility of the proposed method as an alternative to conventional HASTE for generating T
2-weighted images. Main results. Compared with conventional HASTE, the proposed method enhances imaging speed effectively by an MB factor up to 5 without apparent loss of image contrast while successfully eliminating FID artifacts. Significance. We successfully demonstrated the feasibility of the proposed method as an encoding- and energy-efficient alternative to conventional HASTE for generation of T
2-weighted contrast.
Metal-as-insulation HTS coils
Authors: Lécrevisse Thibault , Chaud Xavier , Fazilleau Philippe , Genot Clément , Song Jung-Bin
Published: January 2022

In this article, we summarize what we have learned about metal-as-insulation (MI) winding behavior and technical challenges. High-temperature superconductor (HTS) materials are highly thermally stable. This feature compared to classical low temperature superconductor (LTS) enables the use of MI technology to improve the protection against quenches. We firstly present a review of what has been done worldwide since 2011, which is the first time that a co-winding of a metallic tape without insulation was used in HTS pancake coils. In this review we also focus on the turn-to-turn contact resistivity parameter and the ranges obtained by groups worldwide. Then, we give details of our NOUGAT insert, a LNCMI-CEA-Néel Institute MI HTS insert built in 2018. We describe the specific conception of the magnet including the compact magnetic shielding. The high number of tests performed in high resistive background fields between 2018 and 2021 gives us a unique data set on this technology for ultra-high field (UHF) magnets; even in case of a background field fast drop at 19 T. This magnet is the first REBCO solenoid of this size using this technology, and tested intensively at such high magnetic fields (up to 32.5 T) so far. Finally, we discuss about the self-protection feature of MI coils and we propose a passive protection way for high turn-to-turn resistivity values.
Simulating of X-states and the two-qubit XYZ Heisenberg system on IBM quantum computer
Authors: Shahbeigi Fereshte , Karimi Mahsa , Karimipour Vahid
Published: January 2022

Two qubit density matrices which are of X-shape, are a natural generalization of Bell Diagonal States (BDSs) recently simulated on the IBM quantum device. We generalize the previous results and propose a quantum circuit for simulation of a general two qubit X-state, implement it on the same quantum device, and study its entanglement for several values of the extended parameter space. We also show that their X-shape is approximately robust against noisy quantum gates. To further physically motivate this study, we invoke the two-spin Heisenberg XYZ system and show that for a wide class of initial states, it leads to dynamical density matrices which are X-states. Due to the symmetries of this Hamiltonian, we show that by only two qubits, one can simulate the dynamics of this system on the IBM quantum computer.
EMHD hybrid squeezing nanofluid flow with variable features and irreversibility analysis
Authors: Ramzan Muhammad , Riasat Saima , Alotaibi Hammad
Published: January 2022

This study discusses the entropy generation analysis of electro-magneto hydrodynamics (EMHD) hybrid nanofluid copper oxide-aluminum oxide/ethylene glycol (CuO–Al2O3/C2H6O2) flow amidst two rotating disks in a porous media having variable thermophysical features. The addition of the surface catalyzed to the homogeneous-heterogeneous reactions shorten the reaction time that may be taken as a novel aspect of the undertaken EMHD hybrid nanofluid squeezing flow. The inimitability of the assumed model is supplemented by considering the simultaneous effects of the variable thermal conductivity and viscosity. To simplify the governing flow model, suitable conversions are used to accurately translate the obtained partial differential equations to ordinary differential equations. The flow and energy transfer characteristics are computed and sketched graphically by using the Keller box scheme. The outcomes reveal that the drag force in radial and tangential directions depict the opposing trend for variable viscosity parameter. Furthermore, the normal magnetic and transverse electric fields play an essential role in the alignment of the nanoparticles throughout the flow field. The validation of the envisaged model is also a part of this study.
MeRIPseqPipe: an integrated analysis pipeline for MeRIP-seq data based on Nextflow
Authors: Bao Xiaoqiong , Zhu Kaiyu , Liu Xuefei , Chen Zhihang , Luo Ziwei , Zhao Qi , Ren Jian , Zuo Zhixiang
Published: January 2022

MeRIPseqPipe is an integrated and automatic pipeline that can provide users a friendly solution to perform in-depth mining of MeRIP-seq data. It integrates many functional analysis modules, range from basic processing to downstream analysis. All the processes are embedded in Nextflow with Docker support, which ensures high reproducibility and scalability of the analysis. MeRIPseqPipe is particularly suitable for analyzing a large number of samples at once with a simple command. The final output directory is structured based on each step and tool. And visualization reports containing various tables and plots are provided as HTML files.

Availability and implementation

MeRIPseqPipe is freely available at https://github.com/canceromics/MeRIPseqPipe.

Supplementary information

Supplementary data are available at Bioinformatics online.
Exposure to perfluorooctanoic acid leads to promotion of pancreatic cancer
Authors: Kamendulis Lisa M , Hocevar Jessica M , Stephens Mikayla , Sandusky George E , Hocevar Barbara A
Published: January 2022

Pancreatic cancer is the fourth leading cause of cancer deaths in the United States. Perfluorooctanoic acid (PFOA), a persistent environmental pollutant, has been shown to induce pancreatic acinar cell tumors in rats. Human epidemiologic studies have linked PFOA exposure to adverse chronic health effects including several types of cancer. Previously, we demonstrated that PFOA induces oxidative stress and focal ductal hyperplasia in the mouse pancreas. Here, we evaluated whether PFOA promotes pancreatic cancer using the LSL-KRasG12D;Pdx-1 Cre (KC) mouse model of pancreatic cancer. KC mice were exposed to 5 ppm PFOA in drinking water starting at 8 weeks of age and analyzed at 6 and 9 months of age. At the 6-month time point, PFOA exposure increased pancreatic intraepithelial neoplasia (PanIN) area by 58%, accompanied by a 2-fold increase in lesion number. Although PanIN area increased at 9 months, relative to 6 months, no treatment effect was observed. Collagen deposition was enhanced by PFOA at both the 6- and 9-month time points. PFOA also induced oxidative stress in the pancreas evidenced by elevated antioxidant activity of superoxide dismutase (Sod), catalase and thioredoxin reductase, and a ~3-fold increase in Sod1 mRNA and protein levels at 6 months. Although antioxidant activity was not enhanced by PFOA exposure at the 9-month time point, increased pancreatic oxidative damage was observed. Collectively, these results show that PFOA elicited temporal increases in PanIN lesion area and desmoplasia concomitant with the induction of oxidative stress, demonstrating that it functions to promote pancreatic cancer progression.
Sexually Transmitted Infection Transmission Dynamics During the Coronavirus Disease 2019 (COVID-19) Pandemic Among Urban Gay, Bisexual, and Other Men Who Have Sex With Men
Authors: Schumacher Christina M , Thornton Nicole , Wagner Jessica , Tilchin Carla , Ghanem Khalil G , Hamill Matthew M , Latkin Carl , Rompalo Anne , Ruhs Sebastian , Greenbaum Adena , Jennings Jacky M
Published: January 2022

Background

The impact of coronavirus disease 2019 (COVID-19) mitigation measures on sexually transmitted infection (STI) transmission and racial disparities remains unknown. Our objectives were to compare sex and drug risk behaviors, access to sexual health services, and STI positivity overall and by race during the COVID-19 pandemic compared with pre-pandemic among urban sexual minority men (MSM).

Methods

Sexually active MSM aged 18–45 years were administered a behavioral survey and STI testing every 3-months. Participants who completed at least 1 during-pandemic (April 2020–December 2020) and 1 pre-pandemic study visit (before 13 March 2020) that occurred less than 6 months apart were included. Regression models were used to compare during- and pre-pandemic visit outcomes.

Results

Overall, among 231 MSM, reports of more than 3 sex partners declined(pandemic-1: adjusted prevalence ratio 0.68; 95% confidence interval: .54–.86; pandemic-2: 0.65, .51–.84; pandemic-3: 0.57, .43–.75), substance use decreased (pandemic-1: 0.75, .61–.75; pandemic-2: 0.62, .50–.78; pandemic-3: 0.61, .47–.80), and human immunodeficiency virus/preexposure prophylaxis care engagement (pandemic-1: 1.20, 1.07–1.34; pandemic-2: 1.24, 1.11–1.39; pandemic-3: 1.30, 1.16–1.47) increased. STI testing decreased (pandemic-1: 0.68, .57–.81; pandemic-2: 0.78, .67–.92), then rebounded (pandemic-3: 1.01, .87–1.18). Nei­ther Chlamydia (pandemic-2: 1.62, .75–3.46; pandemic-3: 1.13, .24–1.27) nor gonorrhea (pandemic-2: 0.87, .46 1.62; pandemic-3: 0.56, .24–1.27) positivity significantly changed during vs pre-pandemic. Trends were mostly similar among Black vs. non-Black MSM.

Conclusions

We observed sustained decreases in STI risk behaviors but minimal change in STI positivity during compared with pre-pandemic. Our findings underscore the need for novel STI prevention strategies that can be delivered without in-person interactions.
Discovering potential interactions between rare diseases and COVID-19 by combining mechanistic models of viral infection with statistical modeling
Authors: López-Sánchez Macarena , Loucera Carlos , Peña-Chilet María , Dopazo Joaquín
Published: January 2022

Recent studies have demonstrated a relevant role of the host genetics in the coronavirus disease 2019 (COVID-19) prognosis. Most of the 7000 rare diseases described to date have a genetic component, typically highly penetrant. However, this vast spectrum of genetic variability remains yet unexplored with respect to possible interactions with COVID-19. Here, a mathematical mechanistic model of the COVID-19 molecular disease mechanism has been used to detect potential interactions between rare disease genes and the COVID-19 infection process and downstream consequences. Out of the 2518 disease genes analyzed, causative of 3854 rare diseases, a total of 254 genes have a direct effect on the COVID-19 molecular disease mechanism and 207 have an indirect effect revealed by a significant strong correlation. This remarkable potential of interaction occurs for >300 rare diseases. Mechanistic modeling of COVID-19 disease map has allowed a holistic systematic analysis of the potential interactions between the loss of function in known rare disease genes and the pathological consequences of COVID-19 infection. The results identify links between disease genes and COVID-19 hallmarks and demonstrate the usefulness of the proposed approach for future preventive measures in some rare diseases.
Matching to Categories: Learning and Compliance Costs in Administrative Processes
Authors: Moynihan Donald , Giannella Eric , Herd Pamela , Sutherland Julie
Published: January 2022

A perennial task for the state is the creation and policing of categories. State-created categories have real world impacts on the public. The consequences of racial categorizations, for example, are well-documented. We examine a less studied consequence of state categorization, which are the administrative burdens created when individuals attempt to match themselves to state-created categories. Matching requires time and effort, and failure to match to an advantageous category can mean a loss of material benefits. The matching problem may sometimes result from obscure categories, or an overwhelming number of categories. The matching problem is also amplified when the state uses identity categories—such as self-employed or unemployed, a retiree, parent, spouse or disabled—where individuals hold pre-existing beliefs about such identities that map poorly onto equivalent state categorizations. To study the matching problem and ways to reduce it, we undertook a field experiment in a California welfare program, CalFresh, the state version of the Supplemental Nutrition Assistance Program (SNAP). Claimants often fail to select into the category of “self-employed” even though it would be more favorable for them to do so. We show how a more intuitive presentation of information about the category and its benefits increased the rate of those identifying as self-employed from 8.8% to 12.1%, approximately one-third. We also show that providing a simple self-attestation template to convey information about self-employment status, a means of reducing compliance costs while meeting state documentation requirements, increased the number of claimants providing an acceptable form of documentation to match to the category. The results show that people frequently lack an intuitive understanding of state categories, that the presentation of categories can reduce this matching problem, and that the state can make it easier to document the match.
Pattern of chromosomal aberrations persisting over 30 years in a Chernobyl Nuclear Power Plant accident survivor: study using mFISH
Authors: Nikitina Victoriya , Nugis Vladimir , Astrelina Tatiyana , Zheglo Diana , Kobzeva Irina , Kozlova Mariya , Galstyan Irina , Lomonosova Elena , Zhanataev Aliy , Karaseva Tatiyana , Samoylov Alexander S
Published: January 2022

The long-term in vivo cytogenetic effects of high-dose radiation exposure can be traced in accidentally irradiated persons, and particularly useful for developing strategies of monitoring and therapy of such patients, as well as for elucidating the fundamental aspects of hematopoiesis and radiobiology. Using 24-color fluorescent in situ hybridization (mFISH), we analysed the frequency and the spectrum of chromosomal aberrations (CA) in peripheral blood lymphocytes of the Chernobyl Nuclear Power Plant (NPP) accident victim 30, 31, 32 and 33 years after acute accidental exposure to high-dose gamma radiation of the whole body. Totally, 993 metaphase cells were analyzed (or 219, 272, 258, 244 cells each year), of which 297 were aberrant. Our study demonstrated a constant aberrant cell frequency at 28% in 2016–2018 years, while in 2019, a significant increase up to 35% occurred due to contribution of significantly elevated frequency of simple aberrations in the absence of evident recent genotoxic factors. Four clonal aberrations were detected, three of which persisted for more than one year at a frequency up to 2.5% of analyzed cells. The distribution of 731 breakpoints per individual chromosomes was nearly proportional to their physical length, excepting Chromosomes 13 and 20, which were significantly breakpoint-deficient compared to the genome median rate. Monitoring of the long-term effects on chromosomal instability caused by radiation exposure is important for understanding and predicting the long-term effects of ionizing radiation.
Black hole–galaxy scaling relations in FIRE: the importance of black hole location and mergers
Authors: Çatmabacak Onur , Feldmann Robert , Anglés-Alcázar Daniel , Faucher-Giguère Claude-André , Hopkins Philip F , Kereš Dušan
Published: January 2022

The concurrent growth of supermassive black holes (SMBHs) and their host galaxies remains to be fully explored, especially at high redshift. While often understood as a consequence of self-regulation via AGN feedback, it can also be explained by alternative SMBH accretion models. Here, we expand on previous work by studying the growth of SMBHs with the help of a large suite of cosmological zoom-in simulations (MassiveFIRE) that are part of the Feedback in Realistic Environments (FIRE) project. The growth of SMBHs is modelled in post-processing with different black hole accretion models, placements, and merger treatments, and validated by comparing to on-the-fly calculations. Scaling relations predicted by the gravitational torque-driven accretion (GTDA) model agree with observations at low redshift without the need for AGN feedback, in contrast to models in which the accretion rate depends strongly on SMBH mass. At high redshift, we find deviations from the local scaling relations in line with previous theoretical results. In particular, SMBHs are undermassive, presumably due to stellar feedback, but start to grow efficiently once their host galaxies reach M* ∼ 1010M⊙. We analyse and explain these findings in the context of a simple analytic model. Finally, we show that the predicted scaling relations depend sensitively on the SMBH location and the efficiency of SMBH merging, particularly in low-mass systems. These findings highlight the relevance of understanding the evolution of SMBH-galaxy scaling relations to predict the rate of gravitational wave signals from SMBH mergers across cosmic history.
Magnetic field topology, chemical spot distributions, and photometric variability of the Ap star φ Draconis
Authors: Kochukhov O , Papakonstantinou N , Neiner C
Published: January 2022

The primary component of the multiple star φ Dra is one of the brightest magnetic chemically peculiar stars in the northern sky. Here, we report results of a comprehensive study of the rotational photometric variability, binarity, magnetic field geometry, and surface chemical spot structure for this star. We derived a precise photometric rotational period of 1.71650213(21) d based on 1 yr of TESS nearly continuous space observations and discovered modulation of the stellar light curve with the phase of the 127.9-d binary orbit due to the light time travel effect. We revised parameters of the binary orbit and detected spectroscopic contribution of the secondary. A tomographic mapping technique was applied to the average intensity and circular polarization profiles derived from Narval high-resolution spectropolarimetric observations. This analysis yielded a detailed map of the global magnetic field topology together with the surface distributions of Si, Cr, and Fe abundances. Magnetic mapping demonstrates that the surface field structure of φ Dra is dominated by a distorted dipolar component with a peak field strength of 1.4 kG and a large asymmetry between the poles. Chemical maps show an enhancement of Cr, Fe and, to a lesser extent, Si in a series of spots encircling intersections of the magnetic and rotational equators. These chemical spot geometries do not directly correlate with either the local field strength or the field inclination.
Improved galactic foreground removal for B-mode detection with clustering methods
Authors: Puglisi Giuseppe , Mihaylov Gueorgui , Panopoulou Georgia V , Poletti Davide , Errard Josquin , Puglisi Paola A , Vianello Giacomo
Published: January 2022

Characterizing the sub-mm Galactic emission has become increasingly critical especially in identifying and removing its polarized contribution from the one emitted by the cosmic microwave background (CMB). In this work, we present a parametric foreground removal performed on to sub-patches identified in the celestial sphere by means of spectral clustering. Our approach takes into account efficiently both the geometrical affinity and the similarity induced by the measurements and the accompanying errors. The optimal partition is then used to parametrically separate the Galactic emission encoding thermal dust and synchrotron from the CMB one applied on two nominal observations of forthcoming experiments from the ground and from the space. Moreover, the clustering is performed on tracers that are different from the data used for component separation, e.g. the spectral index maps of dust and synchrotron. Performing the parametric fit singularly on each of the clustering derived regions results in an overall improvement: both controlling the bias and the uncertainties in the CMB B-mode recovered maps. We finally apply this technique using the map of the number of clouds along the line of sight, $\mathcal {N}_c$, as estimated from H i emission data and perform parametric fitting on to patches derived by clustering on this map. We show that adopting the $\mathcal {N}_c$ map as a tracer for the patches related to the thermal dust emission, results in reducing the B-mode residuals post-component separation. The code is made publicly available https://github.com/giuspugl/fgcluster.
A complex network of interactions governs DNA methylation at telomeric regions
Authors: Farrell Colin , Vaquero-Sedas María I , Cubiles María D , Thompson Michael , Vega-Vaquero Alejandro , Pellegrini Matteo , Vega-Palas Miguel A
Published: January 2022

DNA methylation modulates telomere function. In Arabidopsis thaliana, telomeric regions have a bimodal chromatin organization with unmethylated telomeres and methylated subtelomeres. To gain insight into this organization we have generated TAIR10-Tel, a modified version of the Arabidopsis reference genome with additional sequences at most chromosome ends. TAIR10-Tel has allowed us to analyse DNA methylation at nucleotide resolution level in telomeric regions. We have analysed the wild-type strain and mutants that encode inactive versions of all currently known relevant methyltransferases involved in cytosine methylation. These analyses have revealed that subtelomeric DNA methylation extends 1 to 2 kbp from Interstitial Telomeric Sequences (ITSs) that abut or are very near to telomeres. However, DNA methylation drops at the telomeric side of the telomere-subtelomere boundaries and disappears at the inner part of telomeres. We present a comprehensive and integrative model for subtelomeric DNA methylation that should help to decipher the mechanisms that govern the epigenetic regulation of telomeres. This model involves a complex network of interactions between methyltransferases and subtelomeric DNA sequences.
Dicer dependent tRNA derived small RNAs promote nascent RNA silencing
Authors: Di Fazio Arianna , Schlackow Margarita , Pong Sheng Kai , Alagia Adele , Gullerova Monika
Published: January 2022

In mammalian cells, small non-coding RNAs (sncRNAs) negatively regulate gene expression in a pathway known as RNA interference (RNAi). RNAi can be categorized into post-transcriptional gene silencing (PTGS), which involves the cleavage of target messenger RNA (mRNA) or inhibition of translation in the cytoplasm, and transcriptional gene silencing (TGS), which is mediated by the establishment of repressive epigenetic marks at target loci. Transfer RNAs (tRNAs), which are essential for translation, can be processed into small ncRNAs, termed tRNA-derived small RNAs (tsRNAs). The biogenesis of tsRNAs and their role in gene expression regulation has not yet been fully understood. Here, we show that Dicer dependent tsRNAs promote gene silencing through a mechanism distinct from PTGS and TGS. tsRNAs can lead to downregulation of target genes by targeting introns via nascent RNA silencing (NRS) in nuclei. Furthermore, we show that Ago2 slicer activity is required for this mechanism. Synthetic tsRNAs can significantly reduce expression of a target gene at both RNA and protein levels. Target genes regulated by NRS are associated with various diseases, which further underpins its biological significance. Finally, we show that NRS is evolutionarily conserved and has the potential to be explored as a novel synthetic sRNA based therapeutic.
Lifelong effect of therapy in young patients with the COL4A5 Alport missense variant p.(Gly624Asp): a prospective cohort study
Authors: Boeckhaus Jan , Hoefele Julia , Riedhammer Korbinian M , Nagel Mato , Beck Bodo B , Choi Mira , Gollasch Maik , Bergmann Carsten , Sonntag Joseph E , Troesch Victoria , Stock Johanna , Gross Oliver
Published: January 2022

Background

Angiotensin-converting enzyme inhibitors (ACEis) have evolved as a first-line therapy for delaying end-stage renal failure (ESRF) in Alport syndrome (AS). The present study tested the hypothesis of a superior nephroprotective potential of an early ACEi intervention, examining a cohort with the COL4A5 missense variant p.(Gly624Asp).

Methods

In this observational cohort study (NCT02378805), 114 individuals with the identical gene variant were explored for age at ESRF and life expectancy in correlation with treatment as endpoints.

Results

All 13 untreated hemizygous patients developed ESRF (mean age 48.9 ± 13.7 years), as did 3 very late treated hemizygotes (51.7 ± 4.2 years), with a mean life expectancy of 59.2 ± 9.6 years. All 28 earlier-treated [estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2] hemizygous patients were still alive and still had not reached ESRF. Therapy minimized the annual loss of their GFR, similar to the annual loss in healthy individuals. Of 65 heterozygotes, 4 untreated individuals developed ESRF at an age of 53.3 ± 20.7 years. None of the treated heterozygous females developed ESRF.

Conclusions

For the first time, this study shows that in AS, early therapy in individuals with missense variants might have the potential to delay renal failure for their lifetime and thus to improve life expectancy and quality of life without the need for renal replacement therapy. Some treated patients have reached their retirement age with still-functioning kidneys, whereas their untreated relatives have reached ESRF at the same or a younger age. Thus, in children with glomerular haematuria, early testing for Alport-related gene variants could lead to timely nephroprotective intervention.
Benefits of Adjuvant Chemotherapy Differ by Menopausal Status in Women with HR+/HER2- Early Breast Cancer, 1-3 Positive Nodes, and a Low Recurrence Score
Authors: Jacobson Anne
Published: January 2022

Adjuvant chemotherapy is beneficial for premenopausal women-and not postmenopausal women-with HR-positive, HER2-negative, early breast cancer with 1-3 lymph nodes and a recurrence score of 0-25, according to updated results from the phase III RxPonder study.
Use of 18F-fluorodeoxyglucose positron emission tomography to standardize clinical trial recruitment in Takayasu’s arteritis
Authors: Quinn Kaitlin A , Alessi Hugh D , Ponte Cristina , Rose Emily , Ahlman Mark A , Redmond Christopher , Luo Yiming , Bolek Ertugrul Cagri , Langford Carol A , Merkel Peter A , Grayson Peter C
Published: January 2022

Objectives

To assess whether data from 18F-fluorodeoxyglucose (FDG) PET should be incorporated into eligibility criteria for clinical trials in Takayasu’s arteritis (TAK).

Methods

The study was conducted in two parts. Part one was an international online survey among physicians with experience managing TAK to determine, using clinical vignettes, whether FDG-PET data influence decisions about enrolment in trials. Part two used patient data from an observational cohort study in TAK to assess agreement regarding decisions about enrolment into trials, based on clinical assessment with and without incorporation of FDG-PET data.

Results

In part one, 68 physicians responded to the survey. Most physicians had used FDG-PET to diagnose TAK (82%) or monitor disease activity (66%). In vignettes representing active clinical disease, FDG-PET findings increased physician confidence in disease assessment and reduced outlier assessments. The greatest variability in decisions regarding enrolment into trials was observed in vignettes representing constitutional symptoms alone and elevated acute-phase reactants. In these cases, FDG-PET findings influenced decisions about enrolment and improved physician confidence. In multivariable models, FDG-PET findings were 1.29 times more strongly associated with enrolment decisions compared with levels of acute-phase reactants. In part two, incorporation of FDG-PET data significantly improved agreement about enrolment decisions between raters [inter-rater reliability (IRR) = 0.68 (95% CI 0.67, 0.69) to IRR = 0.88 (95% CI 0.87, 0.89); P < 0.01].

Conclusions

Incorporation of FDG-PET data into assessment of TAK influences decisions about enrolment of patients into trials, improves physician confidence about clinical assessment and could help reduce variability in study populations. Future trials in TAK should consider incorporating FDG-PET data into eligibility criteria.
Interaction between the proprietary base theory and subrogation—‘It WAS mine’, ‘It HAD BEEN mine’, but IS it yours?
Authors: Chong Conrad
Published: January 2022

The law of restitution has developed rapidly in recent decades. Many concepts have been created, refined, and diminished. The proprietary base theory is one of the concepts that is increasingly marginalized. This article examines this theory and advocates its rejuvenation. By analysing the decision Menelaou v Bank of Cyprus UK Ltd, the interaction between the proprietary base theory and the principle of equitable subrogation is dissected. This article concludes that the proprietary base theory can clarify uncertainties in subrogation cases involving proprietary claims and remains an important tool in relevant litigations.
Early Experience Using a New Robotic Microsurgical System for Lymphatic Surgery
Authors: Lindenblatt Nicole , Grünherz Lisanne , Wang Anna , Gousopoulos Epameinondas , Barbon Carlotta , Uyulmaz Semra , Giovanoli Pietro
Published: January 2022

Robotic microsurgery has emerged as a new technology with potential benefits for reconstructive surgery. We report the first-in-human use of the Symani surgical system to perform lympho-venous and arterial anastomosis for lymphatic reconstruction. In five patients, 10 robot-assisted anastomoses were performed. Next to lympho-venous anastomoses, two patients received a free vascularized lymph node transfer. Motion scaling was set to 10×. Visualization was either achieved with a 3D system or an optical microscope. All anastomoses were patent as confirmed by ICG. Despite a longer time to perform the first anastomoses with the robot, we observed a decline in duration of anastomosis. Among the advantages of the system were a high accuracy in placing the stitches even in very small and fragile vessels or when performing anastomoses with size mismatches. The challenges encountered included the lack of a touch sensation and the necessity to develop a “see-feel.” This could be achieved surprisingly well because the force necessary to close dilator and needle holder via the manipulators was perceived as comparable to using conventional micro instruments. Our data confirm feasibility and safety of the robotic system to perform lymphatic surgery. Larger patient cohorts and inclusion of surgeons at different training levels will be necessary to investigate the true potential of robotics in microsurgery. In addition, robot-assisted surgery shows a promising potential in opening up new frontiers in reconstructive microsurgery (eg, the reliable performance of anastomoses on even smaller blood and lymphatic vessels or on structures deeper within the body cavities—eg, the thoracic duct).
Hospitalized Children With Common Human Coronavirus Clinical Impact of Codetected Respiratory Syncytial Virus and Rhinovirus
Authors: Heimdal Inger , Valand Jonas , Krokstad Sidsel , Moe Nina , Christensen Andreas , Risnes Kari , Nordbø Svein Arne , Døllner Henrik
Published: January 2022

Background:

The clinical impact of common human coronavirus (cHCoV) remains unclear. We studied the clinical manifestations of pediatric cHCoV infections and the possible modifying effects of codetected human rhinovirus (RV) and respiratory syncytial virus (RSV).

Methods:

We used data from an 11-year-long prospective study of hospitalized children with community-acquired respiratory tract infections. Nasopharyngeal aspirates were analyzed with real-time polymerase chain reaction assay for cHCoV OC43, NL63, HKU1 and 229E, and 15 other respiratory viruses. We assessed disease severity based on the clinical factors hospitalization length, oxygen requirement, other respiratory support and supplementary fluids.

Results:

cHCoV was detected in 341 (8%) of 4312 children. Among 104 children with single cHCoV detections, 58 (56%) had lower respiratory tract infection (LRTI) and 20 (19%) developed severe disease. The proportion with severe disease was lower among single cHCoV detections compared with single RSV detections (338 of 870; 39%), but similar to single RV detections (136 of 987; 14%). Compared with single cHCoV, codetected cHCoV-RSV was more often associated with LRTI (86 of 89; 97%) and severe disease (adjusted odds ratio, 3.3; 95% confidence interval: 1.6–6.7). LRTI was more frequent in codetected cHCoV-RV (52 of 68; 76%) than single cHCoV, but the risk of severe disease was lower (adjusted odds ratios, 0.3; 95% confidence interval: 0.1–1.0).

Conclusions:

cHCoV was associated with severe LRTI in hospitalized children. Viral codetections were present in two-thirds. Codetections of cHCoV-RV were associated with lower proportions of severe disease, suggesting a modifying effect of RV on HCoV.
Variation in Patient-Reported Outcomes in Young and Old Patients Up to 4 to 6 Years After Arthroscopic Partial Meniscectomy
Authors: Tayfur Beyza , Pihl Kenneth , Varnum Claus , Lohmander Stefan , Englund Martin , Thorlund Jonas Bloch
Published: January 2022

Objective:

To assess the variation in changes in patient-reported outcomes 4 to 6 years after arthroscopic partial meniscectomy (APM).

Design:

Prospective cohort study.

Setting:

Orthopedic departments at public hospitals.

Patients:

Patients (n = 447) from the Knee Arthroscopy Cohort Southern Denmark undergoing APM.

Interventions:

All patients underwent APM.

Main Outcome Measures:

Change in KOOS4 scores from baseline before surgery to ∼5 years (range 4-6 years) after surgery. KOOS4 is the average aggregated score of 4 of 5 of the Knee injury and Osteoarthritis Outcome Score (KOOS) excluding the activities of daily living subscale (minimal clinical important improvement ∼10 points). A mixed linear model adjusted for sex and body mass index was used to assess change from baseline to ∼5-year follow-up. Change in KOOS4 was divided into 5 categories based on change from baseline to ∼5-year follow-up: <0 points, 0 to 9 points, 10 to 19 points, 20 to 29 points, and ≥30 points.

Results:

On average, patient-reported outcomes continued to improve from baseline to ∼5-year follow-up (mean KOOS4 change: 26, 95% CI, 24-28). Proportions in the different response groups were <0 points (12%), 0 to 9 points (13%), 10 to 19 points (16%), 20 to 29 points (19%), and ≥30 points (40%), with no difference between younger (≤40 years, n = 75) and older (>40 years, n = 337) patients (P = 0.898).

Conclusions:

Patient-reported outcomes on average improved up to ∼5 years after APM; however, large variability was observed. The similar variability in younger and older patients questions the assumption that younger patients with traumatic injuries experience larger benefits from APM.
Management Practices for Asparaginase-associated Coagulopathy: A Survey of Pediatric Oncologists
Authors: Greenmyer Jacob R. , Wyatt Kirk D. , Rodriguez Vilmarie , Ashrani Aneel A. , Warad Deepti
Published: January 2022

Background:

Coagulopathy and thrombosis are well-described complications of asparaginase therapy. However, treatment practices in pediatric hematology/oncology (PHO) patients vary widely as evidence-based guidelines for clinical management of these complications in this population are lacking.

Objective:

The objective of this study was to assess management practices of asparaginase-related coagulopathy by pediatric hematologist/oncologist attending physicians.

Design/Method:

Email survey sent to 2327 PHO physicians primarily practicing in the United States.

Results:

Two hundred eighty-five (12.2%) attending physicians completed the survey. Only 4.6% (n=13/285) routinely prescribe prophylactic anticoagulation during induction chemotherapy for leukemia. Slightly more than half (n=145/250, 50.9%) of all providers perform baseline coagulation studies. Most providers that were surveyed (n=185/285, 64.9%) only replete coagulant factors if the patient experiences bleeding or bruising. One hundred thirty (n=130/285, 45.6%) physicians replace low fibrinogen. The median fibrinogen replacement was 100 mg/dL (range: 40 to 200 mg/dL) with the median target of at least 100 mg/dL (range: 50 to 200 mg/dL). A minority of physicians (n=39/250, 13.7%) replace low antithrombin. The median antithrombin cutoff activity level was 60% (range: 40% to 100%) with a median target of 75% (range: 40% to 125%).

Conclusions:

There is a significant variation in PHO physician practices for monitoring and management of asparaginase-associated hemostatic derangements. Evidence-based guidelines have the potential to standardize practices.
Case Report: Occult Macular Dystrophy
Authors: Toland Ashley
Published: January 2022

SIGNIFICANCE

This case report discusses a case of suspected occult macular dystrophy, which is an underrecognized but not rare subtype of cone dystrophy. Increasing clinician recognition of occult macular dystrophy will lead to increased accurate diagnosis of affected patients.

PURPOSE

A clinical presentation and diagnosis of a case of suspected occult macular dystrophy, as well as background information and management, are reported.

CASE REPORT

A 44-year-old White man reported long-standing decreased vision and photophobia in both eyes. Examination revealed a bilateral reduction in best-corrected visual acuity, abnormal color vision, central visual field defects, and subtle disruption of subfoveal photoreceptor integrity on optical coherence tomography with a normal fundus appearance. The multifocal electroretinogram showed decreased perifoveal responses, whereas both the photopic and scotopic full-field electroretinograms were normal. This distinctive electroretinogram response pattern was critical in the diagnosis of occult macular dystrophy.

CONCLUSIONS

Reduced visual acuity with a normal clinical examination result is commonly encountered in patients with occult macular dystrophy. Therefore, clinicians must be aware of occult macular dystrophy and order appropriate testing to accurately identify cases of occult macular dystrophy. Without thorough evaluation, patients may be easily misdiagnosed with other etiologies of vision loss.
Case Series: Tattoo-associated Uveitis
Authors: Peterson Aaron S. , Patterson Anthony W.
Published: January 2022

SIGNIFICANCE

Tattoo-associated uveitis describes simultaneous tattoo inflammation and uveitis. Multiple cases exist in the literature related to systemic sarcoidosis or a delayed hypersensitivity reaction; however, there is no consensus on etiology. Clinicians should consider new tattoos as an associated factor for patients presenting with a new uveitis.

PURPOSE

In this retrospective review case series, two African American men with simultaneous tattoo inflammation and bilateral anterior uveitis were examined. Systemic sarcoidosis was suspected as the leading differential in both cases; however, laboratory evidence and imaging did not confirm a sarcoidosis diagnosis. Both patients were therefore suspected to have tattoo-associated uveitis.

CASE REPORTS

Acute anterior uveitis was diagnosed in 24- and 42-year-old African American men who presented with bilateral uveitis and inflammation of tattoos received greater than 1 year before the onset of symptoms. One patient presented with granulomatous ocular signs, whereas the other did not. Both patients received skin biopsies of their tattoos confirming noncaseating granulomas. Both patients had unremarkable radiological chest scans and were treated with topical and oral corticosteroids but only had complete inflammatory resolution after removal of their tattoos. After tattoo removal, neither patient experienced recurrent inflammation.

CONCLUSIONS

Simultaneous tattoo granuloma and uveitis is well supported by literature evidence. It is suspected that both patients either had a localized sarcoidosis reaction or had tattoo-associated uveitis due to a delayed-type hypersensitivity reaction caused by an unknown antigen in the tattoo ink.
Myeloid Sarcoma Involving the Testis in Adults: Clonal Evolution of Acute Myeloid Leukemia
Authors: Nichols Meredith M. , Cook James R. , Bosler David S. , Rogers Heesun J. , Philip John K.S.S. , Jogenpally Narender R. , Reynolds Jordan P. , Robertson Scott , Cotta Claudiu V.
Published: January 2022

To describe the clinical, histologic, immunophenotypic, and genetic characteristics of myeloid sarcoma (MS) diagnosed in the testes of adults, 3 cases were identified, and information on their presentation, clinical features, treatment, and outcome was retrieved from the medical records. In addition, histologic, immunophenotypic, and molecular characteristics were reviewed. This showed that all patients had a previous history of acute myeloid leukemia (AML), in 2 cases diagnosed >10 years before the testicular lesions. In 1 case, there was bilateral involvement, while in 2, involvement was unilateral. The neoplastic cells showed evidence of cytogenetic/molecular clonal evolution in all cases, 1 of which also had significant immunophenotypic changes. A mutational profile including NPM1 p.Trp288Cysfs*12, IDH1 p.Arg132His NRAS p.Gly12Asp was seen in 2 of the 3 cases. Concurrent bone marrow involvement by a myeloid neoplasm was diagnosed in 2 patients, in 1, there was AML in the second 8% blasts. These patients progressed rapidly after MS and had a dismal outcome. The patient with no concurrent bone marrow disease had a favorable outcome. In conclusion, MS involving the testes of adults is a rare event, and it may represent the clonal evolution of AML.