bluuebunny/crossref_metadata_2025 huggingface dataset:
Roles of miR-592-3p and Its Target Gene, TMEFF1, in the Nucleus Accumbens During Incubation of Morphine Craving
Authors: Xie Bing , Zhang Jingjing , Ma Chunling , Yu Hailei , Ni Zhiyu , Cong Bin , Wen Di
Published: January 2022

Background

Prolonged forced abstinence from morphine can increase cue-induced cravings for the drug, contributing to a persistent vulnerability to relapse. Previous studies have identified the implications of aberrant microRNA (miRNA) regulation in the pathogenesis of morphine addiction, but the changes in miRNA expression during the incubation of morphine craving are still unknown.

Methods

Nucleus accumbens (NAc)-specific altered miRNA transcriptomics was determined in a mouse model of cue-induced incubation of morphine craving following a next-generation sequencing method and verified by RT-qPCR. Bioinformatics analysis was performed to predict the target gene of selected miRNA, and the protein expression of the target gene was detected by western blot. A dual-luciferase assay was performed to confirm the binding sites, and gain- and loss-of-function strategy was applied to understand the mechanism of miRNA and its target gene.

Results

The miR-592-3p observed to be downregulated in the NAc core was linked to the incubation of morphine craving, and a dual-luciferase assay was performed to confirm the binding sites of miR-592-3p in its target gene, tomoregulin-1 (TMEFF1). Also, gain- and loss-of-function analyses revealed that the inhibition of miR-592-3p expression in the NAc core negatively regulated TMEFF1 expression, thereby enhancing the incubation of morphine craving; however, the overexpression of miR-592-3p in the NAc core resulted in a decreased expression of TMEFF1, thereby reducing the incubation of morphine craving.

Conclusion

Our findings demonstrated that miR-592-3p can improve the incubation of morphine craving by targeting TMEFF1, and thus, it holds a therapeutic potential to inhibit opioid craving.
On the Hölder Estimate of Kähler–Ricci Flow
Authors: Chu Jianchun , Lee Man-Chun
Published: January 2022

It is conjectured by Song–Tian that the normalized Kähler–Ricci flow on compact Kähler manifolds with semi-ample canonical line bundle is uniformly smooth away from the singular fibers. In this work, we adapt the method in the work of Hein–Tosatti on collapsing Calabi–Yau metrics and obtain a uniform spatial Hölder estimate along the normalized Kähler–Ricci flow for all time away from the singular fiber.
Rapid Cytokine Release Assays for Analysis of Severe Acute Respiratory Syndrome Coronavirus 2–Specific T Cells in Whole Blood
Authors: Törnell Andreas , Grauers Wiktorin Hanna , Ringlander Johan , Arabpour Mohammad , Nilsson Malin R , Nilsson Staffan , Kiffin Roberta , Lindh Magnus , Lagging Martin , Hellstrand Kristoffer , Martner Anna
Published: January 2022

Background

Waning of immunoglobulin G (IgG) antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) complicates the diagnosis of past infection. The durability of T-cell memory against SARS-CoV-2 remains unclear, and most current T-cell protocols are unsuited for large-scale automation.

Methods

Whole-blood samples from 31 patients with verified past coronavirus disease 2019 (COVID-19) and 46 controls, of whom 40 received COVID-19 vaccine, were stimulated with peptides spanning the nucleocapsid (NC) or spike 1 (S1) regions of SARS-CoV-2 and analyzed for interferon γ in supernatant plasma. Diagnostic accuracy of these assays was evaluated against serum anti-NC and anti–receptor-binding domain S1-IgG.

Results

Induction of interferon γ in whole blood by NC or S1 peptides diagnosed past COVID-19 with high accuracy (area under the receiver operating characteristic curve, 0.93 and 0.95, respectively). In accordance with previous studies, NC-IgG levels rapidly waned with only 5 of 17 patients (29%) remaining seropositive >180 days after infection. By contrast, NC peptide–induced T-cell memory responses remained in 13 of 17 study participants (76%) >180 days after infection (P = .01 for comparison with NC-IgG; McNemar test). After 2 vaccine doses, all 18 donors exhibited S1-specific T-cell memory.

Conclusions

Cytokine release assays for the monitoring of T-cell memory in whole blood may be useful for evaluating complications following unverified past COVID-19 and for long-term assessment of vaccine-induced T-cell immunity.

Clinical Trials Registration

EudraCT 2021-000349-42.
Relationship Between Anxiety, Depression, and Susceptibility to Severe Acute Respiratory Syndrome Coronavirus 2 Infection: Proof of Concept
Authors: Vedhara Kavita , Ayling Kieran , Jia Ru , Fairclough Lucy , Morling Joanne R , Ball Jonathan K , Knight Holly , Blake Holly , Corner Jessica , Denning Chris , Bolton Kirsty , Jackson Hannah , Coupland Carol , Tighe Patrick
Published: January 2022

Background

Psychological factors can influence susceptibility to viral infections. We examined whether such influences are evident in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.

Methods

Participants (n = 102) completed measures of anxiety, depression, positive mood, and loneliness and provided a blood sample for the measurement of antibodies to the SARS-CoV-2 spike and nucleocapsid proteins.

Results

SARS-CoV-2 was significantly negatively associated with anxiety and depression. The model remained significant after adjustment for age and gender, although anxiety and depression were no longer significant independent predictors.

Conclusions

These findings offer early support for the hypothesis that psychological factors may influence susceptibility to SARS-CoV-2 infection.
Daily Variation in Sampled Densities ofIxodes scapularisandAmblyomma americanum(Acari: Ixodidae) Nymphs at a Single Site—Implications for Assessing Acarological Risk
Authors: Schulze Terry L , Jordan Robert A
Published: January 2022

The public health challenge posed by tick-borne disease (TBD) has increased efforts to characterize the spatial and temporal distribution of ticks and associated pathogens to better focus tick control strategies and personal protection measures. We describe variability in nymphal Ixodes scapularis Say and Amblyomma americanum (L.) density derived from daily drag sampling at a single location in New Jersey over 4 yr and explore how observed differences in daily collections might affect the estimation of acarological risk. We found significant variability in the density of host-seeking nymphs that could suggest substantially different rates of human-tick encounters depending on sampling date, habitat, and ambient weather conditions. The spatial and temporal variability in the distribution of 2 sympatric tick species with different host preferences and questing strategies, suggests that to produce results that are comparable among sites across the area sampled, surveillance efforts may be limited to shorter collection seasons, fewer sites or less sampling effort (fewer plots or fewer visits) per site, and a geographic scope that minimizes the potential temporal and spatial biases indicated here. Our results illustrate that evaluation of models of tick distribution or relative acarological risk based on surveillance data requires a full description of the diversity of habitats sampled and the conditions under which sampling is performed. The array of factors that affect tick host-seeking and that could bias interpretation of sampling results emphasizes the need to standardize sampling protocols and for more caution when interpreting tick sampling data collected over large temporal and spatial scales.
Differences in functional traits among distinct populations of the plant invaderBunias orientalis
Authors: Binama Blaise , Müller Caroline
Published: January 2022

Plants that expand their range and become invasive in other areas may shift several functional traits in response to specific environments. However, local conditions at the place of origin may have shaped the functional traits, which may to some extent remain visible in plants growing in new habitats. The present study aimed to explore the trait variation in different plant populations of native, invasive and naturalized status of Bunias orientalis grown in common conditions in relation to the climatic conditions at their place of origin. Seeds of B. orientalis were collected from 12 populations (4 per status) in 8 countries and grown under standardized conditions in a common field garden. The variation in several functional traits related to phenology, growth and reproduction was compared among status and among populations. Phenology did not differ according to status. However, several plants of the native populations, originating from areas with low annual temperatures, did not start flowering. Plants of the invasive populations produced more leaves than natives, potentially indicating their vigor in building up vegetative biomass. Number and mass of silicles and other growth traits did not differ among status groups but varied among populations. Some of the variation in functional traits may be explained by long-term adaptations to local conditions at the areas of origin and genetic diversity, while other environmental factors differing in the novel environment may contribute to a high trait variation.
Links between autophagy and lipid droplet dynamics
Authors: Xu Changcheng , Fan Jilian
Published: January 2022

Autophagy is a catabolic process in which cytoplasmic components are delivered to vacuoles or lysosomes for degradation and nutrient recycling. Autophagy-mediated degradation of membrane lipids provides a source of fatty acids for the synthesis of energy-rich, storage lipid esters such as triacylglycerol (TAG). In eukaryotes, storage lipids are packaged into dynamic subcellular organelles, lipid droplets. In times of energy scarcity, lipid droplets can be degraded via autophagy in a process termed lipophagy to release fatty acids for energy production via fatty acid β-oxidation. On the other hand, emerging evidence suggests that lipid droplets are required for the efficient execution of autophagic processes. Here, we review recent advances in our understanding of metabolic interactions between autophagy and TAG storage, and discuss mechanisms of lipophagy. Free fatty acids are cytotoxic due to their detergent-like properties and their incorporation into lipid intermediates that are toxic at high levels. Thus, we also discuss how cells manage lipotoxic stresses during autophagy-mediated mobilization of fatty acids from lipid droplets and organellar membranes for energy generation.
When rain collides with plants—patterns and forces of drop impact and how leaves respond to them
Authors: Roth-Nebelsick Anita , Konrad Wilfried , Ebner Martin , Miranda Tatiana , Thielen Sonja , Nebelsick James H
Published: January 2022

Raindrop impact on leaves is a common event which is of relevance for numerous processes, including the dispersal of pathogens and propagules, leaf wax erosion, gas exchange, leaf water absorption, and interception and storage of rainwater by canopies. The process of drop impact is complex, and its outcome depends on many influential factors. The wettability of plants has been recognized as an important parameter which is itself complex and difficult to determine for leaf surfaces. Other important parameters include leaf inclination angle and the ability of leaves to respond elastically to drop impact. Different elastic motions are initiated by drop impact, including local deformation, flapping, torsion, and bending, as well as ‘swinging’ of the petiole. These elastic responses, which occur on different time scales, can affect drop impact directly or indirectly, by changing the leaf inclination. An important feature of drop impact is splashing, meaning the fragmentation of the drop with ejection of satellite droplets. This process is promoted by the kinetic energy of the drop and leaf traits. For instance, a dense trichome cover can suppress splashing. Basic drop impact patterns are presented and discussed for a number of different leaf types, as well as some exemplary mosses.
The prototype X-ray binary GX 339–4: using TeV γ-rays to assess LMXBs as Galactic cosmic ray accelerators
Authors: Kantzas D , Markoff S , Lucchini M , Ceccobello C , Grinberg V , Connors R M T , Uttley P
Published: January 2022

Since the discovery of cosmic rays (CRs) over a century ago, their origin remains an open question. Galactic CRs with energy up to the knee (1015 eV) are considered to originate from supernova remnants, but this scenario has recently been questioned due to lack of TeV γ-ray counterparts in many cases. Extragalactic CRs, on the other hand, are thought to be associated with accelerated particles in the relativistic jets launched by supermassive accreting black holes at the centre of galaxies. Scaled down versions of such jets have been detected in X-ray binaries hosting a stellar black hole (BHXBs). In this work, we investigate the possibility that the smaller scale jets in transient outbursts of low-mass BHXBs could be sources of Galactic CRs. To better test this scenario, we model the entire electromagnetic spectrum of such sources focusing on the potential TeV regime, using the ‘canonical’ low-mass BHXB GX 339–4 as a benchmark. Taking into account both the leptonic radiative processes and the γ-rays produced via neutral pion decay from inelastic hadronic interactions, we predict the GeV and TeV γ-ray spectrum of GX 339–4 using lower frequency emission as constraints. Based on this test-case of GX 339–4, we investigate whether other, nearby low-mass BHXBs could be detected by the next-generation very-high-energy γ-ray facility the Cherenkov Telescope Array, which would establish them as additional and numerous potential sources of CRs in the Galaxy.
Magnetic field sustained by the elastic force in neutron star crusts
Authors: Kojima Yasufumi , Kisaka Shota , Fujisawa Kotaro
Published: January 2022

We investigate the magneto–elastic equilibrium of a neutron star crust and magnetic energy stored by the elastic force. The solenoidal motion driven by the Lorentz force can be controlled by the magnetic elastic force, so that conditions for the magnetic field strength and geometry are less restrictive. For equilibrium models, the minor solenoidal part of the magnetic force is balanced by a weak elastic force because the irrotational part is balanced by the dominant gravity and pressure forces. Therefore, a strong magnetic field may be confined in the interior, regardless of poloidal or toroidal components. We numerically calculated axially symmetric models with the maximum shear–strain and found that a magnetic energy >1046 erg can be stored in the crust, even for a normal surface dipole-field-strength (<1013 G). The magnetic energy much exceeds the elastic energy (1044−1045 erg). The shear–stress spatial distribution revealed that the elastic structure is likely to break down near the surface. In particular, the critical position is highly localized at a depth less than 100 m from the surface.
Unprecedented change in the position of four radio sources
Authors: Titov Oleg , Frey Sándor , Melnikov Alexey , Lambert Sébastien , Shu Fengchun , Xia Bo , González Javier , Tercero Belén , Gulayev Sergey , Weston Stuart , Natusch Tim
Published: January 2022

Astrometric positions of radio-emitting active galactic nuclei (AGNs) can be determined with sub-milliarcsec accuracy using very long baseline interferometry (VLBI). The usually small apparent proper motion of distant extragalactic targets allow us to realize the fundamental celestial reference frame with VLBI observations. However, long-term astrometric monitoring may reveal extreme changes in some AGN positions. Using new VLBI observations in 2018–2021, we show here that four extragalactic radio sources (3C 48, CTA 21, 1144+352, 1328+254) have a dramatic shift in their positions by 20–130 mas over two decades. For all four sources, the apparent positional shift is caused by their radio structure change.
Stellar evolution and tidal dissipation in REBOUNDx
Authors: Baronett Stanley A , Ferich Noah , Tamayo Daniel , Steffen Jason H
Published: January 2022

To study the post-main sequence evolution of the Solar system and exoplanetary systems more accurately and efficiently, we introduce two new features to reboundx, an extended library for the N-body integrator rebound. The first is a convenient parameter interpolator for coupling different physics and integrators using numerical splitting schemes. The second implements a constant time lag model for tides without evolving spins. We demonstrate various uses of these features using stellar evolution data from mesa (Modules for Experiments in Stellar Astrophysics) as an example. The results of our tests agree with several studies in the literature on post-main sequence orbital evolution, and our convergence and performance studies, respectively, demonstrate our implementations’ accuracy and efficiency. These additional effects are publicly available as of reboundx’s latest release.
The high-velocity clouds above the disc of the outer Milky Way: misty precipitating gas in a region roiled by stellar streams
Authors: Tripp Todd M
Published: January 2022

The high-velocity clouds (HVCs) in the outer Milky Way at 20° < l < 190° have similar spatial locations, metallicities, and kinematics. Moreover, their locations and kinematics are coincident with several extraplanar stellar streams. The HVC origins may be connected to the stellar streams, either stripped directly from them or precipitated by the aggregate dynamical roiling of the region by the stream progenitors. This paper suggests that these HVCs are ‘misty’ precipitation in the stream wakes based on the following observations. New high-resolution (2.6 km s−1) ultraviolet spectroscopy of the QSO H1821+643 resolves what appears to be a single HVC absorption cloud (at 7 km s−1 resolution) into five components with T ≲ 3 × 104 K. Photoionization models can explain the low-ionization components but require some depletion of refractory elements by dust, and model degeneracies allow a large range of metallicity. High-ionization absorption lines (Si iv, C iv, and O vi) are kinematically aligned with the lower-ionization lines and cannot be easily explained with photoionization or equilibrium collisional ionization; these lines are best matched by non-equilibrium rapidly cooling models, i.e. condensing/precipitating gas, with high metallicity and a significant amount of H i. Both the low- and high-ionization phases have low ratios of cooling time to freefall time and cooling time to sound-crossing time, which enables fragmentation and precipitation. The H1821+643 results are corroborated by spectroscopy of six other nearby targets that likewise show kinematically correlated low- and high-ionization absorption lines with evidence of dust depletion and rapid cooling.
Stellar rotation rates in Kepler eccentric (heartbeat) binaries obtained from r-mode signatures
Authors: Saio Hideyuki , Kurtz Donald W
Published: January 2022

R-mode oscillations in a rotating star produce characteristic signatures in a Fourier amplitude spectrum at frequencies related with the rotation frequency, which can be, in turn, used to obtain the surface rotation rate of the star. Some binary stars observed by Kepler indicate the presence of r modes that are probably excited by the tidal effect. In this paper, we have obtained stellar rotation periods in 20 eccentric (heartbeat) binaries with r-mode signatures. The majority of the rotation periods are found to be comparable to pseudo-synchronous periods, in which the angular velocity of rotation is similar to the angular orbital motion of the companion at periastron. In particular, for the heartbeat stars with orbital periods longer than about 8 d, all but one agree with pseudo-synchronous rotation. In contrast to a previous investigation by Zimmerman et al., our result supports the pseudo-synchronisation theory developed by Hut.
Common envelopes in massive stars: towards the role of radiation pressure and recombination energy in ejecting red supergiant envelopes
Authors: Lau Mike Y M , Hirai Ryosuke , González-Bolívar Miguel , Price Daniel J , De Marco Orsola , Mandel Ilya
Published: January 2022

We perform 3D hydrodynamical simulations of a common-envelope event involving a 12$\, \rm {M}_{\odot }$ red supergiant donor. Massive stars are expected to be qualitatively different from low-mass stars as their envelopes have significant support from radiation pressure, which increases both the final separation and amount of mass ejected through the common-envelope interaction. We perform adiabatic simulations that include radiation energy through the equation of state, which results in ejecting 60 per cent more mass (up to two thirds of the total envelope mass becoming unbound, or more) and yield a 10 per cent larger final separation compared to simulations that assume an ideal gas. When also including recombination energy, we find that at least three quarters of the envelope, and possibly the entire envelope, may be unbound. The final separation further increases by almost 20 per cent. The additional amount of ejected material is mainly due to energy injected from helium recombination. Hydrogen recombination plays a comparatively small role, as it mainly occurs in gas that has already become unbound. We conclude that the internal energy of the envelope can be a significant energy source for ejecting the common envelope, but ultimately radiation transport and convection need to be included.
Can phantom transition at z ∼ 1 restore the Cosmic concordance?
Authors: Zhou Zhihuan , Liu Gang , Mu Yuhao , Xu Lixin
Published: January 2022

The tension among inferences of Hubble constant (H0) is found in a large array of data sets combinations. Modification to the late expansion history is the most direct solution to this discrepancy. In this work, we examine the viability of restoring the cosmological concordance with a novel version of transitional dark energy (TDE). The main anchors for the cosmic distance scale: cosmic microwave background (CMB) radiation, baryon acoustic oscillation (BAO), and Type Ia supernova (SNe Ia) calibrated by Cepheids form a ‘impossible trinity’, i.e. it’s plausible to reconcile with any two of the three but unlikely to accommodate them all. Particularly, the tension between BAO and the calibrated SNe Ia cannot be reconciled within the scenarios of late dark energy. Nevertheless, our analysis suggests that the TDE model can reconcile with CMB and SNe Ia calibrated by its absolute magnitude (MB) when the equation of state (EoS) of DE transits around z ∼ 1. Meanwhile, we see a positive sign that the EoS transits with the inclusion of a local prior on MB, whereas the opposite is true without the MB prior.
FishmiRNA: An Evolutionarily Supported MicroRNA Annotation and Expression Database for Ray-Finned Fishes
Authors: Desvignes Thomas , Bardou Philippe , Montfort Jérôme , Sydes Jason , Guyomar Cervin , George Simon , Postlethwait John H , Bobe Julien
Published: January 2022

MicroRNAs (miRNAs) are important post-transcriptional regulators of gene expression involved in countless biological processes and are widely studied across metazoans. Although miRNA research continues to grow, the large community of fish miRNA researchers lacks exhaustive resources consistent among species. To fill this gap, we developed FishmiRNA, an evolutionarily supported miRNA annotation and expression database for ray-finned fishes: www.fishmirna.org. The self-explanatory database contains detailed, manually curated miRNA annotations with orthology relationships rigorously established by sequence similarity and conserved syntenies, and expression data provided for each detected mature miRNA. In just few clicks, users can download the annotation and expression database in several convenient formats either in its entirety or a subset. Simple filters and Blast search options also permit the simultaneous exploration and visual comparison of expression data for up to any ten mature miRNAs across species and organs. FishmiRNA was specifically designed for ease of use to reach a wide audience.
Dissecting the genotype-phenotype correlation of COL4A5 gene mutation and its response to renin-angiotensin-aldosterone system blockers in Chinese male patients with Alport syndrome
Authors: Di Hongling , Zhang Jiahui , Gao Erzhi , Zheng Chunxia , Huang Xianghua , Wang Qing , Yu Xiaomin , Liu Zhihong
Published: January 2022

Background

Alport syndrome (AS) is an inherited type IV collagen–related disorder with an irreversible tendency to progress to end-stage renal disease (ESRD). X-linked AS (XLAS) is caused by mutations in the COL4A5 gene. The aim of this study was to investigate the effects of underlying mutations on clinical manifestations and the response to therapy in XLAS.

Methods

We conducted a retrospective cohort study of 187 Chinese male patients with XLAS confirmed by pathological examination and genetic analysis. The Kaplan–Meier method and Cox proportional hazards model were used to assess the age and risk of progression to ESRD under different genotypes and treatment conditions.

Results

A strong relationship between transcript type and renal outcome was observed, with the median age of ESRD onset being 22 years for truncating mutations and 39 years for non-truncating mutations. The response of affected patients to renin–angiotensin–aldosterone system (RAAS) blockers was genotype-associated. This therapy delayed the onset of ESRD by 16 years in patients with non-truncating mutations and 3 years in patients with truncating mutations. The efficacy of RAAS blockers functioned in a time-dependent manner, with a 7% reduction in the risk of progression to ESRD per each 6-month increase in treatment duration [hazard ratio 0.93 (95% confidence interval 0.89–0.96); P < 0.001].

Conclusions

Clinical features and response to RAAS blockers were observed to be strongly correlated with the genotypes of male XLAS patients. Genotyping of COL4A5 gene mutations is essential and is a useful tool to assess the prognosis of AS patients.
RtNet: a deep hybrid neural network for the identification of acute rejection and chronic allograft nephropathy after renal transplantation using multiparametric MRI
Authors: Zhi Rui , Zhang Xiao-Dong , Hou Ying , Jiang Ke-Wen , Li Qiao , Zhang Jing , Zhang Yu-Dong
Published: January 2022

Background

Reliable diagnosis of the cause of renal allograft dysfunction is of clinical importance. The aim of this study is to develop a hybrid deep-learning approach for determining acute rejection (AR), chronic allograft nephropathy (CAN) and renal function in kidney-allografted patients by multimodality integration.

Methods

Clinical and magnetic resonance imaging (MRI) data of 252 kidney-allografted patients who underwent post-transplantation MRI between December 2014 and November 2019 were retrospectively collected. An end-to-end convolutional neural network, namely RtNet, was designed to discriminate between AR, CAN and stable renal allograft recipient (SR), and secondarily, to predict the impaired renal graft function [estimated glomerular filtration rate (eGFR) ≤50 mL/min/1.73 m2]. Specially, clinical variables and MRI radiomics features were integrated into the RtNet, resulting in a hybrid network (RtNet+). The performance of the conventional radiomics model RtRad, RtNet and RtNet+ was compared to test the effect of multimodality interaction.

Results

Out of 252 patients, AR, CAN and SR was diagnosed in 20/252 (7.9%), 92/252 (36.5%) and 140/252 (55.6%) patients, respectively. Of all MRI sequences, T2-weighted imaging and diffusion-weighted imaging with stretched exponential analysis showed better performance than other sequences. On pairwise comparison of resulting prediction models, RtNet+ produced significantly higher macro-area-under-curve (macro-AUC) (0.733 versus 0.745; P = 0.047) than RtNet in discriminating between AR, CAN and SR. RtNet+ performed similarly to the RtNet (macro-AUC, 0.762 versus 0.756; P > 0.05) in discriminating between eGFR ≤50 mL/min/1.73 m2 and >50 mL/min/1.73 m2. With decision curve analysis, adding RtRad and RtNet to clinical variables resulted in more net benefits in diagnostic performance.

Conclusions

Our study revealed that the proposed RtNet+ model owned a stable performance in revealing the cause of renal allograft dysfunction, and thus might offer important references for individualized diagnostics and treatment strategy.
Integrating morphologic and molecular histopathological features through whole slide image registration and deep learning
Authors: Faust Kevin , Lee Michael K , Dent Anglin , Fiala Clare , Portante Alessia , Rabindranath Madhumitha , Alsafwani Noor , Gao Andrew , Djuric Ugljesa , Diamandis Phedias
Published: January 2022

Background

Modern molecular pathology workflows in neuro-oncology heavily rely on the integration of morphologic and immunohistochemical patterns for analysis, classification, and prognostication. However, despite the recent emergence of digital pathology platforms and artificial intelligence-driven computational image analysis tools, automating the integration of histomorphologic information found across these multiple studies is challenged by large files sizes of whole slide images (WSIs) and shifts/rotations in tissue sections introduced during slide preparation.

Methods

To address this, we develop a workflow that couples different computer vision tools including scale-invariant feature transform (SIFT) and deep learning to efficiently align and integrate histopathological information found across multiple independent studies. We highlight the utility and automation potential of this workflow in the molecular subclassification and discovery of previously unappreciated spatial patterns in diffuse gliomas.

Results

First, we show how a SIFT-driven computer vision workflow was effective at automated WSI alignment in a cohort of 107 randomly selected surgical neuropathology cases (97/107 (91%) showing appropriate matches, AUC = 0.96). This alignment allows our AI-driven diagnostic workflow to not only differentiate different brain tumor types, but also integrate and carry out molecular subclassification of diffuse gliomas using relevant immunohistochemical biomarkers (IDH1-R132H, ATRX). To highlight the discovery potential of this workflow, we also examined spatial distributions of tumors showing heterogenous expression of the proliferation marker MIB1 and Olig2. This analysis helped uncover an interesting and unappreciated association of Olig2 positive and proliferative areas in some gliomas (r = 0.62).

Conclusion

This efficient neuropathologist-inspired workflow provides a generalizable approach to help automate a variety of advanced immunohistochemically compatible diagnostic and discovery exercises in surgical neuropathology and neuro-oncology.
Nicotine Content in Swedish-Type Snus Sold in Norway From 2005 to 2020
Authors: Vedøy Tord Finne , Lund Karl Erik
Published: January 2022

Introduction

Use of snus (moist smokeless tobacco) is widespread in Scandinavia and increasingly popular in the U.S. Snus products vary in terms of product design, portion size, and nicotine content. The aim of this study was to examine variations in the nicotine content in snus sold on the Norwegian market from 2005 to 2020.

Methods

We calculated the nicotine content in dry snus in milligram per gram (mg/g) and milligram per serving (mg/s), weighted by the products’ market share from data on nicotine content, water content, and portion size (both for portion and loose snus) for the ten most sold snus products from each of the three largest manufacturers in 2005, 2010, 2015, and 2020.

Results

In all snus products combined, the nicotine content per gram snus (mg/g) increased from 16.3 to 24.1, while nicotine per serving (mg/s) was stable around 13.0. In portion snus, the nicotine content increased for both mg/g and mg/s, most notably from 2005 to 2010. In loose snus, mg/g decreased marginally, while mg/s was stable throughout the period.

Conclusions

In a period with increasing snus use, the nicotine content in snus increased per gram snus, but not per serving. The stability in nicotine per serving is likely due to a decreasing market share of loose snus which accounted for 54% of the snus products in 2005 and 5% in 2020, and which traditionally has a high content of nicotine per serving.

Implications

Use of snus is popular in Scandinavia, most notably in Sweden and Norway, but also increasingly common in Finland, especially among young adults. There are no prior market-based studies of variations in the nicotine content in Swedish snus over time. We found that the average amount of nicotine per gram snus sold on the Norwegian market increased in the period 2005 to 2020, most notably from 2005 to 2010, while the amount of nicotine per serving was stable in the same period, primarily due to a decreasing share of loose snus.
Effects of Marijuana Use on Smokers Switching to E-Cigarettes in a Randomized Clinical Trial
Authors: Rice Myra , Nollen Nicole L , Ahluwalia Jasjit S , Benowitz Neal , Woodcock Anna , Pulvers Kim
Published: January 2022

Introduction

Co-use of tobacco and marijuana is common, and research suggests that marijuana use may be a barrier to smoking cessation. Research to date has not evaluated how marijuana use affects e-cigarette switching behaviors and related outcomes in a harm reduction trial.

Aims and Methods

This secondary analysis includes African American (48%) and Latinx (52%) adult smokers randomized to the e-cigarette group (N = 114) of a harm reduction clinical trial from 2018 to 2019. Participants were provided JUUL e-cigarettes and encouraged to make an exclusive switch for 6 weeks. Our primary outcome was cigarettes smoked per week. Secondary health outcomes were e-cigarette substitution (calculated by measuring e-cigarette pod use), expired carbon monoxide (CO), and respiratory symptoms. Marijuana products were recorded at three timepoints and coded for combustion.

Results

Marijuana use during the study (n = 52, 46%) was not associated with week 6 cigarettes smoked or e-cigarette substitution, and combustible marijuana use was not associated with week 6 respiratory symptoms (ps > .05). After controlling for cigarettes smoked at week 6, combustible marijuana use was significantly associated with a 4.4 ppm increase in CO compared with no use of marijuana (p = .001).

Conclusions

Marijuana use was not a barrier to switching to e-cigarettes in this 6-week trial. Marijuana use contributed to elevated CO, reflecting greater exposure to toxic combustion products, beyond the effects of cigarette smoking. Marijuana co-use may increase risk of adverse health outcomes and may be a confounding factor when using CO as an endpoint to bioverify exclusive e-cigarette use.

Implications

This is the first known study to examine the effects of marijuana use on smokers switching to e-cigarettes. Marijuana use was not a barrier to cigarette reduction in a 6-week randomized clinical trial. Marijuana use uniquely contributed to higher carbon monoxide among cigarette smokers, indicating greater exposure to toxic combustion products, which could increase risk of adverse health outcomes. Furthermore, combustible marijuana use may be a confounding factor when CO is used as an endpoint to bioverify exclusive e-cigarette use.
BBX17 Interacts with CO and Negatively Regulates Flowering Time in Arabidopsis thaliana
Authors: Xu Xiaorui , Xu Jingya , Yuan Chen , Chen Qianqian , Liu Qinggang , Wang Xuming , Qin Cheng
Published: January 2022

Floral transition, the change from vegetative growth to reproductive development, is dramatic in flowering plants. Here, we show that one subgroup III member of the B-box (BBX) family, BBX17, is a repressor of floral transition under long-day conditions. BBX17 contains a B-box domain and a CCT domain. Although the phenotype of the BBX17 loss-of-function plants was comparable to that of wild-type plants, BBX17-overexpression plants displayed a delayed-flowering phenotype under long-day conditions. The delayed-flowering phenotype was not the result of an altered CONSTANS (CO) expression level but rather the repression of the FLOWERING LOCUS T (FT) expression level. BBX17 physically associated with CO and repressed its ability to control FT expression. Furthermore, the BBX17 protein degraded in the dark, but irradiating seedlings with white, blue, red or far-red light stabilized the BBX17 level. We also proved that the degradation of BBX17 was via 26S proteasome and requires COP1. Thus, BBX17 acts as a key factor in the CO–FT regulatory system to control Arabidopsis thaliana flowering.
Low temperature inhibits anthocyanin accumulation in strawberry fruit by activating FvMAPK3-induced phosphorylation of FvMYB10 and degradation of Chalcone Synthase 1
Authors: Mao Wenwen , Han Yu , Chen Yating , Sun Mingzhu , Feng Qianqian , Li Li , Liu Liping , Zhang Kaikai , Wei Lingzhi , Han Zhenhai , Li Bingbing
Published: January 2022

Low temperature causes poor coloration of strawberry (Fragaria sp.) fruits, thus greatly reducing their commercial value. Strawberry fruits accumulate anthocyanins during ripening, but how low temperature modulates anthocyanin accumulation in plants remains largely unknown. We identified MITOGEN-ACTIVATED PROTEIN KINASE3 (FvMAPK3) as an important negative regulator of anthocyanin accumulation that mediates the poor coloration of strawberry fruits in response to low temperature. FvMAPK3 activity was itself induced by low temperature, leading to the repression of anthocyanin accumulation via two mechanisms. Activated FvMAPK3 acted as the downstream target of MAPK KINASE4 (FvMKK4) and SUCROSE NONFERMENTING1-RELATED KINASE2.6 (FvSnRK2.6) to phosphorylate the transcription factor FvMYB10 and reduce its transcriptional activity. In parallel, FvMAPK3 phosphorylated CHALCONE SYNTHASE1 (FvCHS1) to enhance its proteasome-mediated degradation. These results not only provide an important reference to elucidate the molecular mechanisms underlying low-temperature-mediated repression of anthocyanin accumulation in plants, but also offer valuable candidate genes for generating strawberry varieties with high tolerance to low temperature and good fruit quality.
A cascade of bHLH-regulated pathways programs maize anther development
Authors: Nan Guo-Ling , Teng Chong , Fernandes John , O'Connor Lily , Meyers Blake C , Walbot Virginia
Published: January 2022

The spatiotemporal development of somatic tissues of the anther lobe is necessary for successful fertile pollen production. This process is mediated by many transcription factors acting through complex, multi-layered networks. Here, our analysis of functional knockout mutants of interacting basic helix–loop–helix genes Ms23, Ms32, basic helix–loop–helix 122 (bHLH122), and bHLH51 in maize (Zea mays) established that male fertility requires all four genes, expressed sequentially in the tapetum (TP). Not only do they regulate each other, but also they encode proteins that form heterodimers that act collaboratively to guide many cellular processes at specific developmental stages. MS23 is confirmed to be the master factor, as the ms23 mutant showed the earliest developmental defect, cytologically visible in the TP, with the most drastic alterations in premeiotic gene expression observed in ms23 anthers. Notably, the male-sterile ms23, ms32, and bhlh122-1 mutants lack 24-nt phased secondary small interfering RNAs (phasiRNAs) and the precursor transcripts from the corresponding 24-PHAS loci, while the bhlh51-1 mutant has wild-type levels of both precursors and small RNA products. Multiple lines of evidence suggest that 24-nt phasiRNA biogenesis primarily occurs downstream of MS23 and MS32, both of which directly activate Dcl5 and are required for most 24-PHAS transcription, with bHLH122 playing a distinct role in 24-PHAS transcription.
The Mediating Effect of Perceived Injustice and Pain Catastrophizing in the Relationship of Pain on Fatigue and Sleep in Breast Cancer Survivors: A Cross-Sectional Study
Authors: Lahousse Astrid , Ivakhnov Sergei , Nijs, PhD Jo , Beckwée, PhD David , Cools, PhD Wilfried , Fernández de las Peñas, PhD César , Roose Eva , Leysen, PhD Laurence
Published: January 2022

Objective

Multidimensional aspects of pain have raised awareness about cognitive appraisals, such as perceived injustice (PI) and pain catastrophizing (PC). It has been demonstrated that they play an important role in patients’ pain experience. However, the mediating effect of these appraisals has not been investigated in breast cancer survivors (BCS), nor have they been related to fatigue and sleep.

Methods

Cross-sectional data from 128 BCS were analysed by structural path analysis with the aim to examine the mediating effect of PI and PC in the relationship of pain on fatigue and sleep.

Results

The indirect mediating effects of PI on fatigue (CSI*PI = 0.21; P < .01 and VAS*PI = 1.19; P < .01) and sleep (CSI*PI = 0.31; P < .01 and VAS*PI = 1.74; P < .01) were found significant for both pain measures (Central Sensitization Inventory [CSI] and Visual Analogue Scale [VAS]). PC, on the other hand, only mediated the relationship between pain measured by VAS and fatigue (VAS*PC = 0.80; P = .03). Positive associations were found, indicating that higher pain levels are positively correlated with PI and PC, which go hand in hand with higher levels of fatigue and sleep problems.

Conclusions

PI is an important mediator in the relationship of pain on fatigue and sleep, while PC is a mediator on fatigue after cancer treatment. These findings highlight that both appraisals are understudied and open new perspectives regarding treatment strategies in BCS.
Evaluation of the radon adsorption efficiency of activated carbon fiber using tetrafluoromethane
Authors: Kotsar Y , Nakano Y , Takeuchi Y , Miuchi K
Published: January 2022

The radioactive noble gas radon-222 (222Rn) is one of the most significant background sources in various types of rare event experiments, such as direct dark matter searches, neutrinoless double-beta decay searches, and neutrino experiments. Previously, a method to measure $\rm {}^{222}Rn$ concentration in purified air, argon, and xenon gases at a level of $\rm 1 \, mBq/m^{3}$ was established. Since other detector media are used in these experiments, there is a potential need to expand the study for other types of gases. In this paper the performance of an 80 liter $\rm {}^{222}Rn$ detector filled with tetrafluoromethane ($\rm CF_4$) gas, which is used for a direct dark matter search experiment, NEWAGE, was measured. The calibration factor of the detector for the $\rm CF_4$ gas was measured and its dependence on the absolute humidity was investigated. We also employed activated carbon fiber to evaluate its 222Rn adsorption efficiency in CF4, which was found to be $82.7\pm 0.1(\text{stat.})\pm 2.3(\text{syst.})\%$ at 0.10 MPa. For pressures lower than atmospheric pressure, we found that adsorption efficiency rises with lower pressure, and it is equal to $93.7\pm 0.3(\text{stat.})\pm 3.9(\text{syst.})\%$ at 0.03 MPa.
Degree of Safety Against Falls Provided by 4 Different Prosthetic Knee Types in People With Transfemoral Amputation: A Retrospective Observational Study
Authors: Palumbo Pierpaolo , Randi Pericle , Moscato Serena , Davalli Angelo , Chiari Lorenzo
Published: January 2022

Objective

People with transfemoral amputation have balance and mobility problems and are at high risk of falling. An adequate prosthetic prescription is essential to maximize their functional levels and enhance their quality of life. This study aimed to evaluate the degree of safety against falls offered by different prosthetic knees.

Methods

A retrospective study was conducted using data from a center for prosthetic fitting and rehabilitation. Eligible individuals were adults with unilateral transfemoral amputation or knee disarticulation. The prosthetic knee models were grouped into 4 categories: locked knees, articulating mechanical knees (AMKs), fluid-controlled knees (FK), and microprocessor-controlled knees (MPK). The outcome was the number of falls experienced during inpatient rehabilitation while wearing the prosthesis. Association analyses were performed with mixed-effect Poisson models. Propensity score weighting was used to adjust causal estimates for participant confounding factors.

Results

Data on 1486 hospitalizations of 815 individuals were analyzed. Most hospitalizations (77.4%) were related to individuals with amputation due to trauma. After propensity score weighting, the knee category was significantly associated with falls. People with FK had the highest rate of falling (incidence rate = 2.81 falls per 1000 patient days, 95% CI = 1.96 to 4.02). FK significantly increased the risk of falling compared with MPK (incidence rate ratio [IRRFK-MPK] = 2.44, 95% CI = 1.20 to 4.96). No other comparison among knee categories was significant.

Conclusions

Fluid-controlled prosthetic knees expose inpatients with transfemoral amputation to higher incidence of falling than MPK during rehabilitation training.

Impact

These findings can guide clinicians in the selection of safe prostheses and reduction of falls in people with transfemoral amputation during inpatient rehabilitation.
Retinal Cell Transplantation, Biomaterials, and In Vitro Models for Developing Next-generation Therapies of Age-related Macular Degeneration
Authors: Rizzolo Lawrence J , Nasonkin Igor O , Adelman Ron A
Published: January 2022

Retinal pigment epithelium (RPE) cells grown on a scaffold, an RPE patch, have potential to ameliorate visual impairment in a limited number of retinal degenerative conditions. This tissue-replacement therapy is suited for age-related macular degeneration (AMD), and related diseases. RPE cells must be transplanted before the disease reaches a point of no return, represented by the loss of photoreceptors. Photoreceptors are specialized, terminally differentiated neurosensory cells that must interact with RPE’s apical processes to be functional. Human photoreceptors are not known to regenerate. On the RPE’s basal side, the RPE transplant must induce the reformation of the choriocapillaris, thereby re-establishing the outer blood-retinal barrier. Because the scaffold is positioned between the RPE and choriocapillaris, it should ideally degrade and be replaced by the natural extracellular matrix that separates these tissues. Besides biodegradable, the scaffolds need to be nontoxic, thin enough to not affect the focal length of the eye, strong enough to survive the transplant procedure, yet flexible enough to conform to the curvature of the retina. The challenge is patients with progressing AMD treasure their remaining vision and fear that a risky surgical procedure will further degrade their vision. Accordingly, clinical trials only treat eyes with severe impairment that have few photoreceptors to interact with the transplanted patch. Although safety has been demonstrated, the cell-replacement mechanism and efficacy remain difficult to validate. This review covers the structure of the retina, the pathology of AMD, the limitations of cell therapy approaches, and the recent progress in developing retinal therapies using biomaterials.