bluuebunny/crossref_metadata_2025 huggingface dataset:
Family Adjustment to Pediatric Hematopoietic Stem Cell Transplant During COVID-19
Authors: Chardon Marie L , Klages Kimberly L , Joffe Naomi E , Pai Ahna L H
Published: September 2021

Objective

The COVID-19 pandemic has been difficult for families across the world due to fears about infection risk, increased social isolation, and significant changes in family roles and routines. Families with a child undergoing pediatric hematopoietic stem cell transplant (HCT) may be at even greater risk for poor adjustment during COVID-19 given their child’s increased risk for infection. The purpose of the current study was to qualitatively examine the impact of COVID-19 on family adjustment during pediatric HCT to inform clinical care.

Methods

Twenty-nine caregivers of children (≤12 years) who underwent an HCT within the past 2 years completed semi-structured qualitative interviews and demographic questionnaires in the first 4 months following initial COVID-19 quarantine.

Results

Twenty-two themes emerged from the interviews using grounded theory methodology. Although nearly half of caregivers described COVID-19 as a stressor, 69% of caregivers reported adequate adjustment to COVID-19. Caregivers generally attributed their positive adjustment to HCT preparing the family for COVID-19 and more difficult adjustment to increased physical or social isolation and COVID-19 amplifying germ fears. The child’s HCT treatment status also had important implications on family adjustment to COVID-19.

Conclusions

Results suggest that families undergoing pediatric HCT are uniquely prepared to cope with the impacts of a global pandemic; however, families experiencing certain risk factors (e.g., more recent transplant, impaired access to social support, reduced access to coping tools) may experience poorer adjustment during pandemics such as COVID-19 and may benefit from increased psychosocial support from their healthcare team.
Light Therapy for QoL/Depression in AYA With Cancer: A Randomized Trial
Authors: LaRosa Kayla N , MacArthur Erin , Wang Fang , Zhang Hui , Pan Haitao , Brigden Jane , Pappo Alberto , Wilson Matthew W , Crabtree Valerie McLaughlin
Published: September 2021

Objective

Secondary outcomes from a published feasibility and acceptability trial were examined to explore the effect of bright white light (BWL) on quality of life (QoL) and depressive symptoms compared to dim red light (DRL) control in adolescents and young adults (AYAs) receiving cancer-directed therapy.

Methods

Fifty-one AYAs (12–22 years, 51% male) newly diagnosed with cancer were randomized to receive 8 weeks of BWL (n = 26) or DRL (n = 25). The CDI-2 (total score, negative mood/physical symptoms, interpersonal problems, ineffectiveness, and negative self-esteem) and parent- and self-report PedsQL (total score and subscales of physical, emotional, social, and school QoL) were completed at multiple timepoints.

Results

BWL produced improvements in self-reported total depression (d = −.64; 95% confidence interval [CI] = −1.26, −0.01), negative self-esteem (d = −.80; 95% CI = −1.43, −.14), negative mood/physical symptoms (d = −.73; 95% CI = −1.36, −0.08), ineffectiveness (d = −.43; 95% CI = −1.04, .19), total self-reported QoL (d = .41; 95% CI = −.16, .96), emotional (d = .78; 95% CI = .19, 1.37), school functioning (d = .48; 95% CI = −.09, 1.04), and parent-reported school functioning (d = .66; 95% CI = 0.02, 1.33). BWL reported a greater rate of improvement than DRL for total depression (β = .49, p < .05) and self-esteem (β = .44, p < .05), and parent-reported school functioning (β = −1.68, p < .05).

Conclusions

BWL improved QoL and depressive symptoms for AYAs with cancer. These findings will inform larger randomized controlled trials.
Galactic bar resonances inferred from kinematically hot stars in Gaia EDR3
Authors: Kawata Daisuke , Baba Junichi , Hunt Jason A S , Schönrich Ralph , Ciucă Ioana , Friske Jennifer , Seabroke George , Cropper Mark
Published: September 2021

Using a numerical simulation of an isolated barred disc galaxy, we first demonstrate that the resonances of the inner bar structure induce more prominent features in the action space distribution for the kinematically hotter stars, which are less sensitive to the local perturbation, such as the transient spiral arms. Then, we analyse the action distribution for the kinematically hotter stars selected from the Gaia EDR3 data as the stars with higher values of radial and vertical actions. We find several resonance features, including two new features, in the angular momentum distribution similar to what are seen in our numerical simulations. We show that the bar pattern speeds of about Ωbar ∼ 34 and 42 km s−1 kpc−1 explain all these features equally well. The resonance features we find correspond to the inner 4:1, co-rotation (CR), outer 4:1, outer Lindblad, and outer 4:3 (CR, outer 4:1, outer Lindblad, outer 4:3, and outer 1:1) resonances, when Ωbar ∼ 34 (42) km s−1 kpc−1 is assumed.
Resonant and non-resonant relaxation of globular clusters
Authors: Fouvry Jean-Baptiste , Hamilton Chris , Rozier Simon , Pichon Christophe
Published: September 2021

Globular clusters contain a finite number of stars. As a result, they inevitably undergo secular evolution (‘relaxation’) causing their mean distribution function (DF) to evolve on long time-scales. On one hand, this long-term evolution may be interpreted as driven by the accumulation of local deflections along each star’s mean field trajectory – so-called ‘non-resonant relaxation’ (NR). On the other hand, it can be thought of as driven by non-local, collectively dressed, and resonant couplings between stellar orbits, a process termed ‘resonant relaxation’ (RR). In this paper, we consider a model globular cluster represented by a spherical, isotropic isochrone DF, and compare in detail the predictions of both RR and NR theories against tailored direct N-body simulations. In the space of orbital actions (namely the radial action and total angular momentum), we find that both RR and NR theories predict the correct morphology for the secular evolution of the cluster’s DF, although the NR theory overestimates the amplitude of the relaxation rate by a factor of ∼2. We conclude that the secular relaxation of hot isotropic spherical clusters is not dominated by collectively amplified large-scale potential fluctuations, despite the existence of a strong ℓ = 1 damped mode. Instead, collective amplification affects relaxation only marginally even on the largest scales. The predicted contributions to relaxation from smaller scale fluctuations are essentially the same from RR and NR theories.
Chemical abundances in Seyfert galaxies – VII. Direct abundance determination of neon based on optical and infrared emission lines
Authors: Armah Mark , Dors O L , Aydar C P , Cardaci M V , Hägele G F , Feltre Anna , Riffel R , Riffel R A , Krabbe A C
Published: September 2021

For the first time, neon abundance has been derived in the narrow line region from a sample of Seyfert 2 nuclei. In view of this, we compiled from the literature fluxes of optical and infrared (IR) narrow emission lines for 35 Seyfert 2 nuclei in the local universe ($z \:\lesssim \:0.06$). The relative intensities of emission lines were used to derive the ionic and total neon and oxygen abundances through electron temperature estimations (Te-method). For the neon, abundance estimates were obtained by using both Te-method and IR-method. Based on photoionization model results, we found a lower electron temperature [$t_{\rm e}({\rm Ne\, \small {III}})$] for the gas phase where the Ne2 + is located in comparison with t3 for the O2 + ion. We find that the differences (D) between Ne2 +/H+ ionic abundances calculated from IR-method and Te-method (assuming t3 in the Ne2 +/H+ derivation) are similar to the derivations in star-forming regions (SFs) and they are reduced by a mean factor of ∼3 when $t_{\rm e}({\rm Ne\, \small {III}})$ is considered. We propose a semi-empirical Ionization Correction Factor (ICF) for the neon, based on [Ne ii]12.81$\rm{\mu m}$, [Ne iii]15.56$\rm{\mu m}$, and oxygen ionic abundance ratios. We find that the average Ne/H abundance for the Seyfert 2s sample is nearly 2 times higher than similar estimate for SFs. Finally, for the very high metallicity regime (i.e. [$\rm 12+log(O/H)\: \gtrsim \: 8.80$]) an increase in Ne/O with O/H is found, which likely indicates secondary stellar production for the neon.
Selecting accreted populations: metallicity, elemental abundances, and ages of the Gaia-Sausage-Enceladus and Sequoia populations
Authors: Feuillet Diane K , Sahlholdt Christian L , Feltzing Sofia , Casagrande Luca
Published: September 2021

Identifying stars found in the Milky Way as having formed in situ or accreted can be a complex and uncertain undertaking. We use Gaia kinematics and APOGEE elemental abundances to select stars belonging to the Gaia-Sausage-Enceladus (GSE) and Sequoia accretion events. These samples are used to characterize the GSE and Sequoia population metallicity distribution functions, elemental abundance patterns, age distributions, and progenitor masses. We find that the GSE population has a mean [Fe/H] ∼ −1.15 and a mean age of 10–12 Gyr. GSE has a single sequence in [Mg/Fe] versus [Fe/H] consistent with the onset of SN Ia Fe contributions and uniformly low [Al/Fe] of ∼−0.25 dex. The derived properties of the Sequoia population are strongly dependent on the kinematic selection. We argue the selection with the least contamination is Jϕ/Jtot < −0.6 and (Jz − JR)/Jtot < 0.1. This results in a mean [Fe/H] ∼ −1.3 and a mean age of 12–14 Gyr. The Sequoia population has a complex elemental abundance distribution with mainly high-[Mg/Fe] stars. We use the GSE [Al/Fe] versus [Mg/H] abundance distribution to inform a chemically based selection of accreted stars, which is used to remove possible contaminant stars from the GSE and Sequoia samples.
The CRL4DTL E3 ligase induces degradation of the DNA replication initiation factor TICRR/TRESLIN specifically during S phase
Authors: Wittig Kimberlie A , Sansam Courtney G , Noble Tyler D , Goins Duane , Sansam Christopher L
Published: September 2021

A DNA replication program, which ensures that the genome is accurately and wholly replicated, is established during G1, before the onset of S phase. In G1, replication origins are licensed, and upon S phase entry, a subset of these will form active replisomes. Tight regulation of the number of active replisomes is crucial to prevent replication stress-induced DNA damage. TICRR/TRESLIN is essential for DNA replication initiation, and the level of TICRR and its phosphorylation determine the number of origins that initiate during S phase. However, the mechanisms regulating TICRR protein levels are unknown. Therefore, we set out to define the TICRR/TRESLIN protein dynamics throughout the cell cycle. Here, we show that TICRR levels are high during G1 and dramatically decrease as cells enter S phase and begin DNA replication. We show that degradation of TICRR occurs specifically during S phase and depends on ubiquitin ligases and proteasomal degradation. Using two targeted siRNA screens, we identify CRL4DTL as a cullin complex necessary for TICRR degradation. We propose that this mechanism moderates the level of TICRR protein available for replication initiation, ensuring the proper number of active origins as cells progress through S phase.
OncoSplicing: an updated database for clinically relevant alternative splicing in 33 human cancers
Authors: Zhang Yangjun , Yao Xiangyang , Zhou Hui , Wu Xiaoliang , Tian Jianbo , Zeng Jin , Yan Libin , Duan Chen , Liu Haoran , Li Heng , Chen Ke , Hu Zhiquan , Ye Zhangqun , Xu Hua
Published: September 2021

Alternative splicing (AS) represents a crucial method in mRNA level to regulate gene expression and contributes to the protein complexity. Abnormal splicing has been reported to play roles in several diseases, including cancers. We developed the OncoSplicing database for visualization of survival-associated and differential alternative splicing in 2019. Here, we provide an updated version of OncoSplicing for an integrative view of clinically relevant alternative splicing based on 122 423 AS events across 33 cancers in the TCGA SpliceSeq project and 238 558 AS events across 32 cancers in the TCGA SplAdder project. The new version of the database contains several useful features, such as annotation of alternative splicing-associated transcripts, survival analysis based on median and optimal cut-offs, differential analysis between TCGA tumour samples and adjacent normal samples or GTEx normal samples, pan-cancer views of alternative splicing, splicing differences and results of Cox’PH regression, identification of clinical indicator-relevant and cancer-specific splicing events, and downloadable splicing data in the SplAdder project. Overall, the substantially updated version of OncoSplicing (www.oncosplicing.com) is a user-friendly and registration-free database for browsing and searching clinically relevant alternative splicing in human cancers.
Visual Attention to the Source Matters: Using Eye Tracking to Understand the FDA’s ‘Every Try Counts’ Campaign Message Effectiveness
Authors: Kim Sojung Claire , Zhao Xiaoquan , Brophy Nate S , Walker Matthew W , Alexander Tesfa N
Published: September 2021

Introduction

Visual attention is a crucial mechanism in health messaging and campaign persuasiveness. Little is known about how visual attention may translate into cessation-related outcomes in tobacco public education campaigns.

Methods

Using the eye-tracking technology, this study investigated the relationships among visual attention, cognitive and affective message responses, and cessation-related outcomes (readiness to quit, intentions to quit, and intentions to seek cessation information). Four different posters from the Every Try Counts (ETC) campaign were used as message stimuli. A total of 80 adult current smokers participated. The associations between their behavioral eye gaze patterns and self-reported message responses and cessation-related outcomes were examined.

Results

Half of the sample (49.4%) were male, and 46.8% were White—with ages ranging from 18 to 36 years old (M = 21.22, SD = 2.86). Roughly 41% were daily smokers, and 78% had attempted quitting in the previous year. When exposed to campaign ads, only fixation on the FDA logo showed consistent positive relationships with cognitive and affective message responses. Mediation analyses revealed significant indirect effects of fixation on the FDA logo on quitting and information-seeking intentions mainly through positive affective message responses.

Conclusions

Visual attention to the FDA logo played an important role in the effects of ETC campaign messages.

Implications

This study contributes new evidence on the relationship of visual attention, message responses, and ETC campaign outcomes. The current findings suggest that highlighting FDA as a campaign sponsor in the visual display may enhance the effectiveness of FDA tobacco education messages.
Crustal Derivation of theca. 475 Ma Eppawala Carbonatites in Sri Lanka
Authors: Wang Jing , Su Ben-Xun , Chen Chen , Ferrero Silvio , Malaviarachchi Sanjeewa P K , Sakyi Patrick Asamoah , Yang Yue-Heng , Dharmapriya P L
Published: September 2021

Although a mantle origin of carbonatites has long been advocated, a few carbonatite bodies with crustal fingerprints have been identified. The Eppawala carbonatites in Sri Lanka are more similar to orogenic carbonatites than those formed in stable cratons and within plate rifts. They occur within the Pan-African orogenic belt and have a formation age of ca. 475 Ma newly obtained in this study with no contemporary mantle-related magmatism. These carbonatites have higher (87Sr/86Sr)i ratios (0·70479–0·70524) and more enriched Nd and Hf isotopic compositions than carbonatites reported in other parts of the world. Model ages (1·3–2·0 Ga) of both Nd and Hf isotopes [apatite ɛNd(t) = −9·2 to −4·7; rutile εHf(t) = −22·0 to −8·02] are in the age range of metamorphic basement in Sri Lanka, and the carbon and oxygen isotopic compositions (δ13CPDB = −2·36 to −1·71; δ18OSMOW = 13·91–15·13) lie between those of mantle-derived carbonatites and marble. These crustal signatures are compatible with the chemistry of accessory minerals in the carbonatites, such as Ni-free olivine and Al- and Cr-poor rutile. Modeling results demonstrate that the Eppawala carbonatite magmas originated from a mixture of basement gneisses and marbles, probably during regional metamorphism. This interpretation is supported by the occurrence of the carbonatites along, or near, the axes of synforms and antiforms where granitic gneiss and marble are exposed. Therefore, we propose that the Eppawala carbonatites constitute another rare example of a carbonatitic magma that was derived from melting of a sedimentary carbonate protolith. Our findings suggest that other orogenic carbonatites with similar features should be re-examined to re-evaluate their origin.
N-hydroxypipecolic acid-induced transcription requires the salicylic acid signaling pathway at basal SA levels
Authors: Nair Aswin , Goyal Isha , Voß Edgar , Mrozek Pascal , Prajapati Sabin , Thurow Corinna , Tietze Lutz , Tittmann Kai , Gatz Christiane
Published: September 2021

Systemic acquired resistance (SAR) is a plant immune response established in uninfected leaves after colonization of local leaves with biotrophic or hemibiotrophic pathogens. The amino acid-derived metabolite N-hydroxypipecolic acid (NHP) travels from infected to systemic leaves, where it activates salicylic acid (SA) biosynthesis through the isochorismate pathway. The resulting increased SA levels are essential for induction of a large set of SAR marker genes and full SAR establishment. In this study, we show that pharmacological treatment of Arabidopsis thaliana with NHP induces a subset of SAR-related genes even in the SA induction-deficient2 (sid2/isochorismate synthase1) mutant, which is devoid of NHP-induced SA. NHP-mediated induction is abolished in sid2-1 NahG plants, in which basal SA levels are degraded. The SA receptor NON-EXPRESSOR OF PATHOGENESIS-RELATED GENES1 (NPR1) and its interacting TGACG SEQUENCE-SPECIFIC BINDING PROTEIN (TGA) transcription factors are required for the NHP-mediated induction of SAR genes at resting SA levels. Isothermal titration analysis determined a KD of 7.9 ± 0.5 µM for the SA/NPR1 complex, suggesting that basal levels of SA would not bind to NPR1 unless yet unknown potentially NHP-induced processes increase the affinity. Moreover, the nucleocytoplasmic protein PHYTOALEXIN DEFICIENT4 is required for a slight NHP-mediated increase in NPR1 protein levels and NHP-induced expression of SAR-related genes. Our experiments have unraveled that NHP requires basal SA and components of the SA signaling pathway to induce SAR genes. Still, the mechanism of NHP perception remains enigmatic.
Two stripe rust effectors impair wheat resistance by suppressing import of host Fe–S protein into chloroplasts
Authors: Wang Xiaodong , Zhai Tong , Zhang Xingmin , Tang Chunlei , Zhuang Rui , Zhao Haibin , Xu Qiang , Cheng Yulin , Wang Jianfeng , Duplessis Sébastien , Kang Zhensheng , Wang Xiaojie
Published: September 2021

Several effectors from phytopathogens usually target various cell organelles to interfere with plant defenses, and they generally contain sequences that direct their translocation into organelles, such as chloroplasts. In this study, we characterized a different mechanism for effectors to attack chloroplasts in wheat (Triticum aestivum). Two effectors from Puccinia striiformis f. sp. tritici (Pst), Pst_4, and Pst_5, inhibit Bax-mediated cell death and plant immune responses, such as callose deposition and reactive oxygen species (ROS) accumulation. Gene silencing of the two effectors induced significant resistance to Pst, demonstrating that both effectors function as virulence factors of Pst. Although these two effectors have low sequence similarities and lack chloroplast transit peptides, they both interact with TaISP (wheat cytochrome b6–f complex iron–sulfur subunit, a chloroplast protein encoded by nuclear gene) in the cytoplasm. Silencing of TaISP impaired wheat resistance to avirulent Pst and resulted in less accumulation of ROS. Heterogeneous expression of TaISP enhanced chloroplast-derived ROS accumulation in Nicotiana benthamiana. Co-localization in N. benthamiana and western blot assay of TaISP content in wheat chloroplasts show that both effectors suppressed TaISP from entering chloroplasts. We conclude that these biotrophic fungal effectors suppress plant defenses by disrupting the sorting of chloroplast protein, thereby limiting host ROS accumulation and promoting fungal pathogenicity.
The transcription factor ORA59 exhibits dual DNA binding specificity that differentially regulates ethylene- and jasmonic acid-induced genes in plant immunity
Authors: Yang Young Nam , Kim Youngsung , Kim Hyeri , Kim Su Jin , Cho Kwang-Moon , Kim Yerin , Lee Dong Sook , Lee Myoung-Hoon , Kim Soo Young , Hong Jong Chan , Kwon Sun Jae , Choi Jungmin , Park Ohkmae K
Published: September 2021

Jasmonic acid (JA) and ethylene (ET) signaling modulate plant defense against necrotrophic pathogens in a synergistic and interdependent manner, while JA and ET also have independent roles in certain processes, e.g. in responses to wounding and flooding, respectively. These hormone pathways lead to transcriptional reprogramming, which is a major part of plant immunity and requires the roles of transcription factors. ET response factors are responsible for the transcriptional regulation of JA/ET-responsive defense genes, of which ORA59 functions as a key regulator of this process and has been implicated in the JA-ET crosstalk. We previously demonstrated that Arabidopsis (Arabidopsis thaliana) GDSL LIPASE 1 (GLIP1) depends on ET for gene expression and pathogen resistance. Here, promoter analysis of GLIP1 revealed ERELEE4 as the critical cis-element for ET-responsive GLIP1 expression. In a yeast one-hybrid screening, ORA59 was isolated as a specific transcription factor that binds to the ERELEE4 element, in addition to the well-characterized GCC box. We found that ORA59 regulates JA/ET-responsive genes through direct binding to these elements in gene promoters. Notably, ORA59 exhibited a differential preference for GCC box and ERELEE4, depending on whether ORA59 activation is achieved by JA and ET, respectively. JA and ET induced ORA59 phosphorylation, which was required for both activity and specificity of ORA59. Furthermore, RNA-seq and virus-induced gene silencing analyses led to the identification of ORA59 target genes of distinct functional categories in JA and ET pathways. Our results provide insights into how ORA59 can generate specific patterns of gene expression dynamics through JA and ET hormone pathways.
Transverse susceptibility and resonance absorption of an anti-ferromagnetic spin wave interacting with a phonon reservoir
Authors: Saeki Mizuhiko
Published: September 2021

A form of the transverse magnetic susceptibility for an anti-ferromagnetic spin system interacting with a phonon reservoir is derived employing the TCLE method (a method in which the admittance of a physical system is directly derived from time-convolutionless equations with external driving terms) in terms of the non-equilibrium thermo-field dynamics (NETFD) in the spin-wave approximation. The region valid for the lowest spin-wave approximation is numerically investigated in detail, and the transverse susceptibility for the anti-ferromagnetic system of one-dimensional infinite spins of magnitude $S = 2$ is numerically studied in that region. It is confirmed that the effects of the memory and initial correlation for the spin system and phonon reservoir, which are represented by the interference terms in the TCLE method, increase the power absorption in the resonance region. In the region valid for the lowest spin-wave approximation, it is shown that the line half-width $\Delta \omega_{\mathrm{RF}}$ of the power absorption in the resonance region for a transversely rotating magnetic field increases as the temperature $T$ rises, and decreases as the uniaxial anisotropy energy $\hbar K$ of the $z$ direction increases or as the wave number $k$ becomes large, and also that the line peak-height $H_{\mathrm{RF}}$ of the power absorption in the resonance region for the transverse magnetic field decreases as $T$ rises and increases as $\hbar K$ increases or as $k$ becomes large. According to analytic considerations, it is anticipated that $\Delta \omega_{\mathrm{RF}}$ and $H_{\mathrm{RF}}$ vary approximately as $\Delta \omega_{\mathrm{RF}} \approx \{A_k + B_k \bar{n} (\omega_{{\mathrm{R}} k} )\} \{ \bar{n}(\omega_{{\mathrm{R}} k}) + \,1\}$ and $H_{\mathrm{RF}} \propto \{A_k + B_k \bar{n}(\omega_{{\mathrm{R}} k})\}^{- 1} \{ \bar{n}(\omega_{{\mathrm{R}} k}) + 1\}^{- 1}$, with $\bar{n}(\omega_{{\mathrm{R}} k}) = \{ \exp(\hbar \omega_{{\mathrm{R}} k}/ (k_{\mathrm{B}} T)) -1 \}^{- 1}$, where $\omega_{{\mathrm{R}} k}$ is the characteristic frequency of the phonon reservoir. Here, $A_k$ is a positive quantity dependent on the Zeeman frequency, the spin magnitude, and the anisotropy energy of the spin system, and $B_k$ is a positive quantity dependent on the anisotropy energy. At low temperatures ($k_{\mathrm{B}} T \ll \hbar \omega_{{\mathrm{R}} k}$), it is anticipated that $\Delta \omega_{\mathrm{RF}}$ and $H_{\mathrm{RF}}$ vary approximately as $\Delta \omega_{\mathrm{RF}} \approx A_k \exp\{((A_k + B_k)/ A_k) \exp(- \hbar \omega_{{\mathrm{R}} k}/ (k_{\mathrm{B}} T))\}$ and $H_{\mathrm{RF}} \propto A_k^{- 1} \exp\{- ((A_k + B_k)/ A_k) \exp(- \hbar \omega_{{\mathrm{R}} k}/ (k_{\mathrm{B}} T))\}$.
Response to secukinumab on synovitis using Power Doppler ultrasound in psoriatic arthritis: 12-week results from a phase III study, ULTIMATE
Authors: D’Agostino Maria Antonietta , Schett Georg , López-Rdz Alejandra , Šenolt Ladislav , Fazekas Katalin , Burgos-Vargas Ruben , Maldonado-Cocco Jose , Naredo Esperanza , Carron Philippe , Duggan Anne-Marie , Goyanka Punit , Boers Maarten , Gaillez Corine
Published: September 2021

Objectives

To investigate the dynamics of response of synovitis to IL-17A inhibition with secukinumab in patients with active PsA using Power Doppler ultrasound.

Methods

The randomized, placebo-controlled, Phase III ULTIMATE study enrolled PsA patients with active ultrasound synovitis and clinical synovitis and enthesitis having an inadequate response to conventional DMARDs and naïve to biologic DMARDs. Patients were randomly assigned to receive either weekly subcutaneous secukinumab (300 or 150 mg according to the severity of psoriasis) or placebo followed by 4-weekly dosing thereafter. The primary outcome was the mean change in the ultrasound Global EULAR and OMERACT Synovitis Score (GLOESS) from baseline to week 12. Key secondary endpoints included ACR 20 and 50 responses.

Results

Of the 166 patients enrolled, 97% completed 12 weeks of treatment (secukinumab, 99%; placebo, 95%). The primary end point was met, and the adjusted mean change in GLOESS was higher with secukinumab than placebo [−9 (0.9) vs −6 (0.9), difference (95% CI): −3 (−6, −1); one-sided P=0.004] at week 12. The difference in GLOESS between secukinumab and placebo was significant as early as one week after initiation of treatment. All key secondary endpoints were met. No new or unexpected safety findings were reported.

Conclusion

This unique ultrasound study shows that apart from improving the signs and symptoms of PsA, IL-17A inhibition with secukinumab leads to a rapid and significant reduction of synovitis in PsA patients.

Trial registration

ClinicalTrials.gov; NCT02662985.
Experience Effects in Finance: Foundations, Applications, and Future Directions
Authors: Malmendier Ulrike
Published: September 2021

This article establishes four key findings of the growing literature on experience effects in finance: (i) the long-lasting imprint of past experiences on beliefs and risk taking; (ii) recency effects; (iii) the domain-specificity of experience effects; and (iv) imperviousness to information that is not experience-based. I first discuss the neuroscientific foundations of experience-based learning and sketch a simple model of its role in the stock market based on Malmendier et al. (2020a, b). I then distill the empirical findings on experience effects in stock-market investment, trade dynamics, and international capital flows, highlighting these four key features. Finally, I contrast models of belief formation that rely on “learned information” with models accounting for the neuroscience evidence on synaptic tagging and memory formation, and provide directions for future research.
TYPICAL VALUES OF DOSIMETRIC DATA FOR CARDIAC FLUOROSCOPY-GUIDED PROCEDURES IN A SOUTH AFRICAN TEACHING HOSPITAL
Authors: Sothmann P J , Groenewald W A , Doubell A F , Pitcher R D
Published: September 2021

Currently there are limited diagnostic reference level (DRL) data for South African (SA) public sector cardiac fluoroscopy-guided procedures (FGPs). A 4-y retrospective study of dosimetric data on 6265 patients determined typical values (50th percentile) of dosimetric data for the seven most frequent cardiac FGPs at a SA teaching hospital. Kerma-area-product (KAP), reference point air Kerma (Ka,r) and fluoroscopy time (FT) were, respectively, calculated for coronary angiography (CA) (n = 1935; 61Gy.cm2, 624 mGy, 5 min); CA with left ventriculography (n = 1687; 85Gy.cm2, 840 mGy, 3.9 min), valve screening (n = 129; 6Gy.cm2, 164 mGy, 2.3 min), percutaneous coronary intervention (n = 1922; 145Gy.cm2, 1569 mGy, 11.9 min), pacemaker implantation (n = 432; 9Gy.cm2, 100 mGy, 6.5 min), pericardial tap (n = 115; 1.9Gy.cm2, 18 mGy, 1.5 min) and transcatheter aortic valve implantation (n = 45; 65Gy.cm2, 658 mGy, 14.1 min). This work presents the largest SA public sector cardiac FGP dosimetric data to date and provides a key resource for future work in this domain.
UNCERTAINTY ASSOCIATED WITH THE USE OF SOFTWARE SOLUTIONS UTILIZING DICOM RDSR FOR SKIN DOSE ASSESSMENT IN INTERVENTIONAL RADIOLOGY AND CARDIOLOGY
Authors: Krajinović Marko , Vujisić Miloš , Ciraj-Bjelac Olivera
Published: September 2021

Purpose

The purpose of this work is to provide a comprehensive analysis of uncertainties associated with the use of software solutions utilizing DICOM RDSRs for skin dose assessment in the interventional fluoroscopic environment.

Methods and Results

Three different scenarios have been defined for determining the overall uncertainty, each with a specific assumption on the maximum deviations of factors affecting the calculated dose. Relative expanded uncertainty has been calculated using two approaches: the law of propagation of uncertainty and the propagation of distributions based on the Monte Carlo method. According to the propagation of uncertainty, it is estimated that the lowest possible relative expanded uncertainty of ~13% (at the 95% level of confidence, i.e. with the coverage factor of k = 2 assuming normal distribution) could only be achieved if all sources of uncertainties are carefully controlled, whereas maximum relative expanded uncertainty could reach up to 61% if none of the influencing parameters are controlled properly. When the influencing parameters are reasonably well-controlled, realistic relative expanded uncertainty amounts to 28%. Values for the relative expanded uncertainty obtained from the Monte Carlo propagation of distributions concur with the results obtained from the propagation of uncertainty to within 3% in all three considered scenarios, validating the assumption of normality.

Conclusions

The overall skin dose relative uncertainty has been found to range from 13 to 61%, emphasizing the importance of adequate analysis and control of all relevant uncertainty sources.
AtMC1 Associates With LSM4 to Regulate Plant Immunity Through Modulating Pre-mRNA Splicing
Authors: Wang Shune , Xue Mei , He Chan , Shen Danyu , Jiang Chunhao , Zhao Hongwei , Niu Dongdong
Published: September 2021

Alternative splicing of pre-mRNAs is an important gene regulatory mechanism shaping the transcriptome. AtMC1 is an Arabidopsis thaliana type I metacaspase that positively regulates the hypersensitive response. Here, we found that AtMC1 is involved in the regulation of plant immunity to the bacterial pathogen Pseudomonas syringae pv. tomato DC3000 and is physically associated with Sm-like4 (LSM4), which is involved in pre-mRNA splicing. AtMC1 and LSM4 protein levels both increased with their coexpression as compared with their separate expression in vivo. Like AtMC1, LSM4 negatively regulates plant immunity to P. syringae pv. tomato DC3000 infection. By RNA sequencing, AtMC1 was shown to modulate the splicing of many pre-mRNAs, including 4CL3, which is a negative regulator of plant immunity. Thus, AtMC1 plays a regulatory role in pre-mRNA splicing, which might contribute to AtMC1-mediated plant immunity.

[Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Establishment of an Artificial Inoculation Method of Ustilaginoidea virens Without Damaging the Rice Panicle Sheaths
Authors: Hu Xianfeng , Wang Jian , Li Rongyu , Wu Xiaomao , Gao Xiubing , Li Ming
Published: September 2021

Rice false smut (RFS) is a destructive disease of rice worldwide caused by Ustilaginoidea virens. Nevertheless, there is a lack of efficient and stable artificial inoculation method to simulate the natural infection of U. virens, which is an important factor limiting further research on the pathogen. The purpose of this study was to establish an artificial inoculation method, which can simulate the natural infection process of U. virens without destroying the panicle sheath structure of rice. In this research, rice plants were inoculated by soaking roots at the seedling stage, spraying at the tillering stage, injecting at the booting stage, and again spraying at the flowering stage to determine the appropriate artificial inoculation time. Meanwhile, the panicle sheath instillation method and the injection inoculation method were compared. The results show that stages 6 to 8 of young panicle differentiation are an important period for U. virens infection. There were no significant differences in the mean rates of infected panicles, mean rates of infected grains, and maximum infected grains per panicle between the two inoculation methods. However, the frequency of RFS ball occurrence at the upper part of the panicles was significantly higher on the spikelets inoculated by the injection method than that of spikelets inoculated by natural infection and panicle sheath instillation. Therefore, panicle sheath instillation method was more similar to the natural infection of U. virens in the field. This research exhibited an innovative artificial inoculation method for identification of U. virens pathogenicity and evaluation of rice resistance against RFS.
Validation of the labeled magnitude scale for the assessment of itch intensity in patients with chronic pruritus
Authors: Zeidler Claudia , Röchter Marvin , Ständer Sonja , Pereira Manuel P.
Published: September 2021

Introduction:

The visual analogue scale (VAS), the numerical rating scale (NRS), and the verbal rating scale (VRS) are routinely used to assess pruritus intensity. However, these scales have limitations, especially the ceiling effect of linear scales (VAS, NRS) and the reduced sensitivity to change of the VRS. In the labeled magnitude scale (LMS) consisting of a vertical line with verbal anchors distributed quasi-logarithmically, the ceiling effect is reduced, allowing a higher discriminative assessment at the higher end of the scale.

Methods:

A total of 172 patients completed the LMS twice within 30–60 minutes to assess the reliability of the scale, as well as the NRS and VAS for analyses of convergent validity. Sensitivity to change of the LMS was investigated by analyzing changes in scores after a twice-daily application of an emollient containing menthoxypropanediol for 14 days.

Results:

Test-retest reliability was excellent for the LMS assessing average (Cronbach α: 0.955) and worst (Cronbach α: 0.945) pruritus intensity in the last 24 hours, while strong to very strong correlations were observed between the LMS and NRS assessing the worst (r=0.783) and average (r=0.808) pruritus intensity, respectively. Treatment with an emollient lead to a significant decrease in LMS scores (P<0.01). In patients with severe pruritus at baseline (VRS ≥3), we recorded a 30.2% improvement of average pruritus intensity using the LMS compared with a 25.0% improvement using the NRS and a 27.8% improvement of worst pruritus intensity using the LMS compared with an 11.1% improvement with the NRS. Most patients considered the LMS an appropriate instrument to assess pruritus intensity (89.6%) and would use it again (91.9%).

Discussion:

The LMS is an appropriate well-accepted instrument to assess CP. It is especially useful to detect variations in pruritus intensity in patients with severe CP.
Trends in Covid-19 hospital mortality in women and men
Authors: Ayerbe Luis , Risco-Risco Carlos , Martínez-Urbistondo Diego , Caro-Tinoco María Elena , Ayis Salma
Published: September 2021

Introduction

It remains unclear if the development of health services, clinical management, and scientific evidence, during the pandemic is associated with better medical outcomes, sustained in the long term, for Covid-19 patients of each gender. This study presents the trends in mortality associated with Covid-19 for women and men during the first year of the pandemic.

Methods

This study was based in 17 Spanish hospitals. Sociodemographic, clinical, and mortality data from all patients with Covid-19, who had been discharged alive, or had died after being admitted, between March 2020 and February 2021, were used.

The association between time of admission and mortality was examined with multivariate logistic regression models.

Results

3390 Covid-19 patients were included in the study, of which 1330 were women, the age was M(SD): 66.55(16.55) Death was reported for 451 patients. There was a significant decreasing trend in mortality by time of admission for the whole year with an OR: 0.86(0.77-0.96) p=0.005. No significant trend in mortality for women was observed OR: 1.00(0.85-1.19) p=0.959, while there was a significant decreasing trend for men OR: 0.78 (0.68-0.90) p=0.001

Discussion

The health policies put in place, the scientific evidence developed by researchers, and the experienced acquired by clinicians, are likely to explain this improvement in mortality. More epidemiological and clinical studies addressing trends of mortality in patients with different sociodemographic and clinical profile and the improvement of clinical outcomes are required. Future research may address the safety and efficacy of interventions specifically in female patients.
Incidence of COVID-19 reinfection among Midwestern healthcare employees
Authors: Rivelli Anne , Fitzpatrick Veronica , Blair Christopher , Copeland Kenneth , Richards Jon
Published: September 2021

Importance

Given the overwhelming worldwide rate of infection and the disappointing pace of vaccination, addressing reinfection is critical. Understanding reinfection, including protection longevity after natural infection, will allow us to better know the prospect of herd immunity, which hinges on the assumption that natural infection generates sufficient, protective immunity. The primary aim of this paper is to provide data on SARS-CoV-2 reinfection over a 10-month period.

Objective

The primary objective of this study is to establish the incidence of reinfection of COVID-19 among healthcare employees who experienced a prior COVID-19 infection.

Design

This observational cohort study followed a convenience sample of 2,625 participants who experienced a COVID-19 infection for subsequent COVID-19 infection.

Setting

Healthcare employees were recruited across a large Midwestern healthcare system. Positive PCR test results were administered and recorded by the system-affiliated lab serving Illinois and Wisconsin.

Participants

Adult healthcare system employees who enrolled in a research study focused on SARS-CoV-2 antibodies (N = 16,357) and had at least one positive PCR test result between March 1, 2020 and January 10, 2021 were included (N = 2,625).

Exposure

Positive PCR test for SARS-CoV-2

Main Outcome(s) and Measure(s)

The primary outcome is incidence of COVID-19 reinfection, defined by current CDC guidelines (i.e. subsequent COVID-19 infection ≥ 90 days from prior infection). COVID-19 recurrence, defined as subsequent COVID-19 infection after prior infection irrespective of time, is also described.

Results

Of 2,625 participants who experienced at least one COVID-19 infection during the 10-month study period, 156 (5.94%) experienced reinfection and 540 (20.57%) experienced recurrence after prior infection. Median days were 126.50 (105.50-171.00) to reinfection and 31.50 (10.00-72.00) to recurrence. Incidence rate of COVID-19 reinfection was 0.35 cases per 1,000 person-days, with participants working in COVID-clinical and clinical units experiencing 3.77 and 3.57 times, respectively, greater risk of reinfection relative to those working in non-clinical units. Incidence rate of COVID-19 recurrence was 1.47 cases per 1,000 person-days.

Conclusions and Relevance

This study supports the consensus that COVID-19 reinfection, defined as subsequent infection ≥ 90 days after prior infection, is rare, even among a sample of healthcare workers with frequent exposure.
Evaluating strategies for spatial allocation of vaccines based on risk and centrality
Authors: Singer Benjamin J , Thompson Robin N , Bonsall Michael B
Published: September 2021

When vaccinating a large population in response to an invading pathogen, it is often necessary to prioritise some individuals to be vaccinated first. One way to do this is to choose individuals to vaccinate based on their location. Methods for this prioritisation include strategies which target those regions most at risk of importing the pathogen, and strategies which target regions with high centrality on the travel network. We use a simple infectious disease epidemic model to compare a risk-targeting strategy to two different centrality-targeting strategies based on betweenness centrality and random walk percolation centrality, respectively. We find that the relative effectiveness of these strategies in reducing the total number of infections varies with the basic reproduction number of the pathogen, travel rates, structure of the travel network, and vaccine availability. We conclude that, when a pathogen has high spreading capacity, or when vaccine availability is limited, centrality-targeting strategies should be considered as an alternative to the more commonly used risk-targeting strategies.
High risk landscapes of Japanese encephalitis virus outbreaks in India converge on wetlands, rainfed agriculture, wild Ardeidae, and domestic pigs
Authors: Walsh Michael G. , Pattanaik Amrita , Vyas Navya , Saxena Deepak , Webb Cameron , Sawleshwarkar Shailendra , Mukhopadhyay Chiranjay
Published: September 2021

Japanese encephalitis constitutes a significant burden of disease across Asia, particularly in India, with high mortality in children. This zoonotic mosquito-borne disease is caused by theFlavivirus, Japanese encephalitis virus (JEV), and circulates in wild ardeid bird and domestic pig reservoirs both of which generate sufficiently high viremias to infect vector mosquitoes, which can then subsequently infect humans. The landscapes of these hosts, particularly in the context of anthropogenic ecotones and resulting wildlife-livestock interfaces, are poorly understood and thus significant knowledge gaps in the epidemiology and infection ecology of JEV persist, which impede optimal control and prevention of outbreaks. The current study investigated the landscape epidemiology of JEV outbreaks in India over the period 2010 to 2020 based on national human disease surveillance data. Outbreaks were modelled as an inhomogeneous Poisson point process. Outbreak risk was strongly associated with the habitat suitability of ardeid birds and pig density, and shared landscapes between fragmented rainfed agriculture and both river and freshwater marsh wetlands. Moreover, risk scaled with Ardeidae habitat suitability, but was consistent across scale with respect to pig density and rainfed agriculture-wetland mosaics. The results from this work provide a more complete understanding of the landscape epidemiology and infection ecology of JEV in India and suggest important priorities for control and prevention across fragmented terrain comprised of wildlife-livestock interface that favours spillover to humans.
Local patterns of spread of influenza A(H3N2) virus in coastal Kenya over a one-year period revealed through virus sequence data
Authors: Owuor D. Collins , Ngoi Joyce M. , Nyasimi Festus M. , Murunga Nickson , Nyiro Joyce U. , Garten Rebecca , Barnes John R. , Chaves Sandra S. , Nokes D. James , Agoti Charles N.
Published: September 2021

Background

The patterns of spread of influenza A viruses in local populations in tropical and sub-tropical regions are unclear due to sparsity of representative spatiotemporal sequence data.

Methods

We sequenced and analyzed 58 influenza A(H3N2) virus genomes sampled between December 2015 and December 2016 from nine health facilities within the Kilifi Health and Demographic Surveillance System (KHDSS), a predominantly rural region, covering approximately 891 km2along the Kenyan coastline. The genomes were compared with 1,571 contemporaneous global sequences from 75 countries.

Results

We observed at least five independent introductions of A(H3N2) viruses into the region during the one-year period, with the importations originating from Africa, Europe, and North America. We also inferred 23 virus location transition events between the nine facilities included in the study. International virus imports into the study area were captured at the facilities of Chasimba, Matsangoni, Mtondia, and Mavueni, while all four exports from the region were captured from the Chasimba facility, all occurring to Africa destinations. A strong spatial clustering of virus strains at all locations was observed associated with local evolution.

Conclusion

Our study shows that influenza A(H3N2) virus epidemics in local populations appear to be characterized by limited introductions followed by significant local spread and evolution.
Interpretable Brain Disease Classification and Relevance-Guided Deep Learning
Authors: Tinauer Christian , Heber Stefan , Pirpamer Lukas , Damulina Anna , Schmidt Reinhold , Stollberger Rudolf , Ropele Stefan , Langkammer Christian
Published: September 2021

Deep neural networks are increasingly used for neurological disease classification by MRI, but the networks’ decisions are not easily interpretable by humans. Heat mapping by deep Taylor decomposition revealed that (potentially misleading) image features even outside of the brain tissue are crucial for the classifier’s decision. We propose a regularization technique to train convolutional neural network (CNN) classifiers utilizing relevance-guided heat maps calculated online during training. The method was applied using T1-weighted MR images from 128 subjects with Alzheimer’s disease (mean age=71.9±8.5 years) and 290 control subjects (mean age=71.3±6.4 years). The developed relevance-guided framework achieves higher classification accuracies than conventional CNNs but more importantly, it relies on less but more relevant and physiological plausible voxels within brain tissue. Additionally, preprocessing effects from skull stripping and registration are mitigated. With the interpretability of the decision mechanisms underlying CNNs, these results challenge the notion that unprocessed T1-weighted brain MR images in standard CNNs yield higher classification accuracy in Alzheimer’s disease than solely atrophy.