bluuebunny/crossref_metadata_2025 huggingface dataset:
Chronic bee paralysis virus exploits host antimicrobial peptides and alters gut microbiota composition to facilitate viral infection
Authors: Deng Yanchun , Yang Sa , Zhang Li , Chen Chenxiao , Cheng Xuefen , Hou Chunsheng
Published: March 2024

The significance of gut microbiota in regulating animal immune response to viral infection is increasingly recognized. However, how chronic bee paralysis virus (CBPV) exploits host immune to disturb microbiota for its proliferation remains elusive. Through histopathological examination, we discovered that the hindgut harbored the highest level of CBPV, and displayed visible signs of damages. The metagenomic analysis showed that a notable reduction in the levels of Snodgrassella alvi and Lactobacillus apis, and a significant increase in the abundance of the opportunistic pathogens such as Enterobacter hormaechei and Enterobacter cloacae following CBPV infection. Subsequent co-inoculation experiments showed that these opportunistic pathogens facilitated the CBPV proliferation, leading to accelerated mortality in bees and exacerbation of bloated abdomen symptoms after CBPV infection. The expression level of antimicrobial peptide (AMP) was found to be significantly up-regulated by over 1000 times in response to CBPV infection, as demonstrated by subsequent transcriptome and quantitative real-time PCR investigations. In particular, through correlation analysis and a bacteriostatic test revealed that the AMPs did not exhibit any inhibitory effect against the two opportunistic pathogens. However, they did demonstrate inhibitory activity against S. alvi and L. apis. Our findings provide different evidence that the virus infection may stimulate and utilize the host’s AMPs to eradicate probiotic species and facilitate the proliferation of opportunistic bacteria. This process weakens the intestinal barrier and ultimately resulting in the typical bloated abdomen.
Economic Globalization's Polycrisis
Authors: Helleiner Eric
Published: March 2024

In this article, I suggest that economic globalization is experiencing a particularly serious kind of crisis: a “polycrisis.” Use of this term has proliferated recently but with many meanings. I propose that it be defined as a cluster of distinct crises that interact in ways that they and/or their effects tend to reinforce each other. This core definition enables the identification of distinct types of polycrises that capture multiple uses of the term to date. These types vary according to the spatiality, temporality, and level of generality of each polycrisis as well as the traits of its constituent crises. The analytical utility of the term, when defined in this way, is to encourage scholars to analyze interconnections between different kinds of crises across various issue areas and to reject monocausal analyses of crisis clusters they study. Applying this understanding of the concept to the study of economic globalization, I focus on five constituent crises that are contributing to its current polycrisis. This application of the term highlights yet another type of polycrisis, illustrating the importance of the conceptual issues raised above. The article concludes with some cautions about efforts to predict economic globalization's future and about ways in which polycrisis discourse may serve political projects.
Central Bankers in Crisis: Interpersonal Trust, Cooperation, and the Creation of the Fed Swap Network during the 2008 Global Financial Crisis
Authors: Sahasrabuddhe Aditi
Published: March 2024

How do policymakers respond to global crises? I argue that interpersonal trust enables policymakers to engage in ad hoc cooperation, in conditions of crisis and uncertainty. Leaders’ differentiated ties by degree—of stronger, looser, or absent—interpersonal trust influenced economies’ access to Federal Reserve swap lines over costlier unilateral and multilateral alternatives during the 2008 Global Financial Crisis. Using this framework, I re-examine the emergence of the Fed swap network. I triangulate evidence from elite interviews with central bankers in office during the crisis, and transcripts of Fed meetings. My findings highlight the role of interpersonal trust as an operating variable in shaping patterns of international cooperation and problematize the politics of technocratic governance. While necessary and successful, these crisis management policies reinforce global hierarchies and exacerbate the democratic deficit in central banking. This article thus draws attention to the contentious and undemocratic foundations of the global financial safety net.
Canon and Cultural Negotiation
Authors: Hick Darren Hudson , Derksen Craig
Published: March 2024

By questions of “canon,” we mean questions of what is fictionally true of some character, story, or world. What is canon is treated as authoritative or official, usually by creators and fans alike. But disputes about canon have arisen as storytellers and publishers have sought to capitalize on the popularity of their characters, churning out more and more stories to meet public demand, and at the same time engaging with growing fan bases. As audiences have become more involved, and as fictional worlds have become messier, the authoritative nature of canon—and who authorizes it—has begun to erode. In this paper, we characterize canon as an article in the evolving relation between authors and audiences. More specifically, we characterize canon as an intangible good, subject to a form of cultural negotiation, resting on a power relation between producers and consumers of fictions. In Part I, we consider the author’s evolving role, and the rights of the creator to a story, character, or world. In Part II, we discuss the emerging activities of fans, particularly as they weigh on issues of canon. In Part III, we discuss canon as being subject to cultural negotiation, highlighting the importance of power dynamics in this negotiation.
Seed-borne bacterial synthetic community resists seed pathogenic fungi and promotes plant growth
Authors: Luo De-Lin , Huang Shi-Yi , Ma Chen-Yu , Zhang Xiang-Yu , Sun Kai , Zhang Wei , Dai Chuan-Chao
Published: March 2024

Aims

In this study, the control effects of synthetic microbial communities composed of peanut seed bacteria against seed aflatoxin contamination caused by Aspergillus flavus and root rot by Fusarium oxysporum were evaluated.

Methods and results

Potentially conserved microbial synthetic communities (C), growth-promoting synthetic communities (S), and combined synthetic communities (CS) of peanut seeds were constructed after 16S rRNA Illumina sequencing, strain isolation, and measurement of plant growth promotion indicators. Three synthetic communities showed resistance to root rot and CS had the best effect after inoculating into peanut seedlings. This was achieved by increased defense enzyme activity and activated salicylic acid (SA)-related, systematically induced resistance in peanuts. In addition, CS also inhibited the reproduction of A. flavus on peanut seeds and the production of aflatoxin. These effects are related to bacterial degradation of toxins and destruction of mycelia.

Conclusions

Inoculation with a synthetic community composed of seed bacteria can help host peanuts resist the invasion of seeds by A. flavus and seedlings by F. oxysporum and promote the growth of peanut seedlings.
Nonthermal plasma air disinfection for the inactivation of airborne microorganisms in an experimental chamber and indoor air
Authors: Li Ye , Wei Lanfen , Lin Junming , Xie Zhongyi , Lu Longxi , Pan Xieshang , Xu Ji , Cai Ran
Published: March 2024

Aims

Airborne transmission of diseases presents a serious threat to human health, so effective air disinfection technology to eliminate microorganisms in indoor air is very important. This study evaluated the effectiveness of a non-thermal plasma (NTP) air disinfector in both laboratory experiments and real environments.

Methods and results

An experimental chamber was artificially polluted with a bioaerosol containing bacteria or viruses. Additionally, classroom environments with and without people present were used in field tests. Airborne microbial and particle concentrations were quantified. A 3.0 log10 reduction in the initial load was achieved when a virus-containing aerosol was disinfected for 60 min and a bacteria-containing aerosol was disinfected for 90 min. In the field test, when no people were present in the room, NTP disinfection decreased the airborne microbial and particle concentrations (P < 0.05). When people were present in the room, their constant activity continuously contaminated the indoor air, but all airborne indicators decreased (P < 0.05) except for planktonic bacteria (P = 0.094).

Conclusions

NTP effectively inactivated microorganisms and particles in indoor air.
Decomposing and simplifying the Fracture Risk Assessment Tool—a module from the Taiwan-specific calculator
Authors: Li Chia-Chun , Liu I-Ting , Cheng Tien-Tsai , Liang Fu-Wen , Sun Zih-Jie , Chang Yin-Fan , Chang Chin-Sung , Yang Yi-Ching , Lu Tsung-Hsueh , Kuo Li-Chieh , Wu Chih-Hsing
Published: March 2024

The Fracture Risk Assessment Tool (FRAX®) is a widely utilized country-specific calculator for identifying individuals with high fracture risk; its score is calculated from 12 variables, but its formulation is not publicly disclosed. We aimed to decompose and simplify the FRAX® by utilizing a nationwide community survey database as a reference module for creating a local assessment tool for osteoporotic fracture community screening in any country. Participants (n = 16384; predominantly women (75%); mean age = 64.8 years) were enrolled from the Taiwan OsteoPorosis Survey, a nationwide cross-sectional community survey collected from 2008 to 2011. We identified 11 clinical risk factors from the health questionnaires. BMD was assessed via dual-energy X-ray absorptiometry in a mobile DXA vehicle, and 10-year fracture risk scores, including major osteoporotic fracture (MOF) and hip fracture (HF) risk scores, were calculated using the FRAX®. The mean femoral neck BMD was 0.7 ± 0.1 g/cm2, the T-score was −1.9 ± 1.2, the MOF was 8.9 ± 7.1%, and the HF was 3.2 ± 4.7%. Following FRAX® decomposition with multiple linear regression, the adjusted R2 values were 0.9206 for MOF and 0.9376 for HF when BMD was included and 0.9538 for MOF and 0.9554 for HF when BMD was excluded. The FRAX® demonstrated better prediction for women and younger individuals than for men and elderly individuals after sex and age stratification analysis. Excluding femoral neck BMD, age, sex, and previous fractures emerged as 3 primary clinical risk factors for simplified FRAX® according to the decision tree analysis in this study population. The adjusted R2 values for the simplified country-specific FRAX® incorporating 3 premier clinical risk factors were 0.8210 for MOF and 0.8528 for HF. After decomposition, the newly simplified module provides a straightforward formulation for estimating 10-year fracture risk, even without femoral neck BMD, making it suitable for community or clinical osteoporotic fracture risk screening.
Outcomes of a mandatory non-medical switch of infliximab to a biosimilar for inflammatory bowel disease in British Columbia, Canada
Authors: Hoang Thomas Tam , Reid Jacqueline , Galorport Cherry , Bressler Brian , Leung Yvette , Rosenfeld Greg
Published: March 2024

Background

Despite infliximab biosimilars becoming widely used in inflammatory bowel disease (IBD) patients, real-world non-medical switching is sparse. A biosimilar non-medical switch was launched in British Columbia in 2019, the first Canadian province to do so, from Remicade to an approved biosimilar (CT-P13 or SB2).

Aims

This study aims to obtain real-world evidence evaluating the clinical outcomes of non-medical switching from Remicade to the infliximab biosimilars.

Methods

This is a retrospective observational study of stable IBD patients from the IBD Centre of BC who underwent the non-medical infliximab switch. The primary outcome is treatment continuation at 12 ± 2 months post-switch. Secondary outcomes include frequency of loss of response, adverse events, and immunogenicity within the first 12 months post-switch. A control group of patients maintained on the originator served as a comparison.

Results

Patients in the biosimilar switch group (n = 264) and originator group (n = 99), show similar demographics and disease characteristics. There was no difference in infliximab continuation between the biosimilar group (94.9%) and the originator group (90.1%) (P = 0.18). Reasons for discontinuation of infliximab included loss of response (4.04% vs 4.91%), immunogenicity (1.01% vs 0.75%), or adverse effect (1.01% vs 2.3%) in the infliximab originator vs biosimilar switch group, respectively. Similarly, no differences in safety or efficacy were observed between patients switched to CT-P13 or SB2.

Conclusions

Non-medical biosimilar switch of infliximab demonstrates similar clinical outcomes compared to originator molecule continuation for therapy of IBD. These data support the safety and efficacy of non-medical infliximab switching in IBD patients.
Multi-strategy augmented Harris Hawks optimization for feature selection
Authors: Zhao Zisong , Yu Helong , Guo Hongliang , Chen Huiling
Published: March 2024

In the context of increasing data scale, contemporary optimization algorithms struggle with cost and complexity in addressing the feature selection (FS) problem. This paper introduces a Harris hawks optimization (HHO) variant, enhanced with a multi-strategy augmentation (CXSHHO), for FS. The CXSHHO incorporates a communication and collaboration strategy (CC) into the baseline HHO, facilitating better information exchange among individuals, thereby expediting algorithmic convergence. Additionally, a directional crossover (DX) component refines the algorithm's ability to thoroughly explore the feature space. Furthermore, the soft-rime strategy (SR) broadens population diversity, enabling stochastic exploration of an extensive decision space and reducing the risk of local optima entrapment. The CXSHHO's global optimization efficacy is demonstrated through experiments on 30 functions from CEC2017, where it outperforms 15 established algorithms. Moreover, the paper presents a novel FS method based on CXSHHO, validated across 18 varied datasets from UCI. The results confirm CXSHHO's effectiveness in identifying subsets of features conducive to classification tasks.
Evolution of individual variation in a competitive trait: a theoretical analysis
Authors: Reinhold Klaus , Eigentler Lukas , Kikuchi David W
Published: March 2024

When competitive traits are costly, negative frequency dependence can maintain genetic variance. Most theoretical studies examining this problem assume binary polymorphisms, yet most trait variation in wild populations is continuous. We propose that continuous trait variation can result from continuous variation in resource quality and that, specifically, the shape of the resource distribution determines trait maintenance. We used an individual-based model to test which conditions favour the stable maintenance of variation and which cause temporal fluctuations in trait values. This approach, inspired by contrasting outcomes of previous studies regarding variance and fluctuations in trait values, clearly showed a decisive role played by the shape of resource distributions. Under extreme conditions, e.g., the absence of resource variation or with very scarce resources for weak competitors, traits evolved to a single non-competitive or highly competitive strategy, respectively. Most other distributions led to strong temporal fluctuations on trait values or the maintenance of stable, standing variation. Our results thus explain the contradicting outcomes of previous theoretical studies and, at the same time, provide hypotheses to explain the maintenance of genetic variation and individual differences. We suggest ways to empirically test the proposed effects of resource variation on trait maintenance.
Evaluating the use of common grasses by the wheat stem sawfly (Hymenoptera: Cephidae) and its native parasitoids in rangeland and Conservation Reserve Program grasslands
Authors: Rand Tatyana A , Kula Robert R , Gaskin John F
Published: March 2024

The wheat stem sawfly, Cephus cinctus Norton (Hymenoptera: Cephidae), is a major pest of wheat (Triticum aestivum L., Poales: Poaceae) across the northern Great Plains of North America. Cephus cinctus has a wide host range, attacking numerous wild grasses and cultivated cereals in crop and grassland habitats, where it is, in turn, attacked by 2 native braconid parasitoids. Quantitative assessments of C. cinctus infestation and parasitism levels in different grass species across the full spectrum of available hosts are important in assessing the extent to which grasslands, or specific constituent grass species, may be reservoirs of pests or parasitoids moving into wheat. We quantified infestation and parasitism levels in over 25,000 stems collected from 17 grass species and wheat spanning 35 sites in central Montana, United States, over 2 yr. Infestation levels in 5 grass species, primarily wheatgrasses, were high (38%–65%) and similar to the levels observed in wheat (55%). In contrast, the majority of grass species (12 of 17) had significantly lower levels of infestation (<10%), suggesting that most grasses are not important reservoirs of C. cinctus. Parasitism levels in highly infested wheatgrasses were, on average, 3 times higher than those in cultivated wheat, suggesting that these grasses could provide important conservation habitat for parasitoids. Future work examining the relative performance of pests and parasitoids in these grasses will be important in gauging their relative value as plant materials to bolster parasitoid conservation in reseeded grassland habitats.
Chemical and transcriptomic analyses of leaf trichomes from Cistus creticus subsp. creticus reveal the biosynthetic pathways of certain labdane-type diterpenoids and their acetylated forms
Authors: Papanikolaou Antigoni S , Papaefthimiou Dimitra , Matekalo Dragana , Karakousi Christina-Vasiliki , Makris Antonios M , Kanellis Angelos K
Published: March 2024

Labdane-related diterpenoids (LRDs), a subgroup of terpenoids, exhibit structural diversity and significant commercial and pharmacological potential. LRDs share the characteristic decalin–labdanic core structure that derives from the cycloisomerization of geranylgeranyl diphosphate (GGPP). Labdanes derive their name from the oleoresin known as ‘Labdanum’, ‘Ladano’, or ‘Aladano’, used since ancient Greek times. Acetylated labdanes, rarely identified in plants, are associated with enhanced biological activities. Chemical analysis of Cistus creticus subsp. creticus revealed labda-7,13(E)-dien-15-yl acetate and labda-7,13(E)-dien-15-ol as major constituents. In addition, novel labdanes such as cis-abienol, neoabienol, ent-copalol, and one as yet unidentified labdane-type diterpenoid were detected for the first time. These compounds exhibit developmental regulation, with higher accumulation observed in young leaves. Using RNA-sequencing (RNA-seq) analysis of young leaf trichomes, it was possible to identify, clone, and eventually functionally characterize labdane-type diterpenoid synthase (diTPS) genes, encoding proteins responsible for the production of labda-7,13(E)-dien-15-yl diphosphate (endo-7,13-CPP), labda-7,13(E)-dien-15-yl acetate, and labda-13(E)-ene-8α-ol-15-yl acetate. Moreover, the reconstitution of labda-7,13(E)-dien-15-yl acetate and labda-13(E)-ene-8α-ol-15-yl acetate production in yeast is presented. Finally, the accumulation of LRDs in different plant tissues showed a correlation with the expression profiles of the corresponding genes.
Waveform reconstruction of core-collapse supernova gravitational waves with ensemble empirical mode decomposition
Authors: Yuan Yong , Fan Xi-Long , Lü Hou-Jun , Sun Yang-Yi , Lin Kai
Published: March 2024

Gravitational waves (GWs) from core-collapse supernovae (CCSNe) have been proposed as a probe to investigate the physical properties inside supernovae. However, how to search for and extract the GW signals from CCSNe remains an open question owing to their complicated time–frequency structure. In this paper, we apply the ensemble empirical mode decomposition (EEMD) method to decompose and reconstruct simulated GW data generated by the magnetorotational mechanism and the neutrino-driven mechanism within the Advanced LIGO, using the match score as the criterion for assessing the quality of the reconstruction. The results indicate that by decomposing the data, the sum of the first six intrinsic mode functions (IMFs) can be used as the reconstructed waveform. To determine the probability that our reconstructed waveform corresponds to a real GW waveform, we calculate the false alarm probability of reconstruction (FAPR). By setting the threshold of the match score to be 0.75, we obtain the FAPRs of GW sources at distances of 5 and 10 kpc to be 6 × 10−3 and 1 × 10−2, respectively. If we normalize the maximum amplitude of the GW signal to 5 × 10−21, the FAPR at this threshold is 4 × 10−3. Furthermore, in our study, the reconstruction distance is not equivalent to the detection distance. When the strain of GWs reaches 7 × 10−21, and the match score threshold is set at 0.75, we can reconstruct GW waveforms up to approximately 36 kpc.
CSST large-scale structure analysis pipeline: I. Constructing reference mock galaxy redshift surveys
Authors: Gu Yizhou , Yang Xiaohu , Han Jiaxin , Wang Yirong , Li Qingyang , Tan Zhenlin , Jiang Wenkang , Wang Yaru , Wang Jiaqi , Katsianis Antonios , Xu Xiaoju , Xu Haojie , Hong Wensheng , Mo Houjun , Wen Run , Zheng Xianzhong , Shi Feng , Zhang Pengjie , Zhai Zhongxu , Liu Chengze , Wang Wenting , Zu Ying , Guo Hong , Zhang Youcai , Lu Yi , Zheng Yi , Han Yunkun , Zou Hu , Wang Xin , Wei Chengliang , Li Ming , Luo Yu
Published: March 2024

In this paper, we set out to construct a set of reference mock galaxy redshift surveys (MGRSs) for the future Chinese Space-station Survey Telescope (CSST) observation, where subsequent survey selection effects can be added and evaluated. This set of MGRSs is generated using the dark matter subhaloes extracted from a high-resolution Jiutian N-body simulation of the standard lambda-cold dark matter cosmogony with Ωm = 0.3111, ΩΛ = 0.6889, and σ8 = 0.8102. The simulation has a box size of 1 h−1Gpc, and consists of 61443 particles with mass resolution $3.723 \times 10^{8} \:h^{-1}\rm M_\odot$. In order to take into account the effect of redshift evolution, we first use all 128 snapshots in the Jiutian simulation to generate a light-cone halo/subhalo catalogue. Next, galaxy luminosities are assigned to the main and subhalo populations using the subhalo abundance matching (SHAM) method with the DESI (Dark Energy Spectroscopic Instrument) z-band luminosity functions at different redshifts. Multiband photometries, as well as images, are then assigned to each mock galaxy using a 3D parameter space nearest-neighbour sampling of the DESI LS (Legacy Imaging Survey) observational galaxies and groups. Finally, the CSST and DESI LS survey geometry and magnitude limit cuts are applied to generate the required MGRSs. As we have checked, this set of MGRSs can generally reproduce the observed galaxy luminosity/mass functions within 0.1 dex for galaxies with L > 108  h-2 L⊙ (or M* > 108.5 h-2M⊙) and within 1σ level for galaxies with L < 108 h-2 L⊙ (or M* < 108.5 h-2 M⊙). Together with the CSST slitless spectra and redshifts for our DESI LS seed galaxies that are under construction, we will set out to test various slitless observational selection effects in subsequent probes.
Searching for local features in primordial power spectrum using genetic algorithms
Authors: Lodha Kushal , Pinol Lucas , Nesseris Savvas , Shafieloo Arman , Sohn Wuhyun , Fasiello Matteo
Published: March 2024

We present a novel methodology for exploring local features directly in the primordial power spectrum using a genetic algorithm pipeline coupled with a Boltzmann solver and Cosmic Microwave Background data (CMB). After testing the robustness of our pipeline using mock data, we apply it to the latest CMB data, including Planck 2018 and CamSpec PR4. Our model-independent approach provides an analytical reconstruction of the power spectra that best fits the data, with the unsupervised machine learning algorithm exploring a functional space built off simple ‘grammar’ functions. We find significant improvements upon the simple power-law behaviour, by Δχ2 ≲ −21, consistently with more traditional model-based approaches. These best-fits always address both the low-ℓ anomaly in the TT spectrum and the residual high-ℓ oscillations in the TT, TE, and EE spectra. The proposed pipeline provides an adaptable tool for exploring features in the primordial power spectrum in a model-independent way, providing valuable hints to theorists for constructing viable inflationary models that are consistent with the current and upcoming CMB surveys.
Characterization of starspots on a young M-dwarf K2-25: multiband observations of stellar photometric variability and planetary transits
Authors: Mori Mayuko , Ikuta Kai , Fukui Akihiko , Narita Norio , de Leon Jerome P , Livingston John H , Ikoma Masahiro , Kawai Yugo , Kawauchi Kiyoe , Murgas Felipe , Palle Enric , Parviainen Hannu , Rodríguez Gareb Fernández , Terada Yuka , Watanabe Noriharu , Tamura Motohide
Published: March 2024

Detailed atmospheric characterization of exoplanets by transmission spectroscopy requires careful consideration of stellar surface inhomogeneities induced by star-spots. This effect is particularly problematic for planetary systems around M-dwarfs, and their spot properties are not fully understood. We investigated the stellar activity of the young M-dwarf K2-25 and its effect on transit observations of the sub-Neptune K2-25 b. From multiband monitoring observations of stellar brightness variability using ground-based telescopes and Transiting Exoplanets Survey Satellite, we found that the temperature difference between the spots and photosphere is <190 K and the spot covering fraction is <61 per cent (2σ). We also investigated the effect of starspot activity using multiepoch, multiband transit observations. We rule out cases with extremely low spot temperatures and large spot covering fractions. The results suggest that spots could distort the transmission spectrum of K2-25 b by as much as ∼100 ppm amplitude, corresponding to the precision of JWST/NIRSPEC of the target. Our study demonstrates that simultaneous multiband observations with current instruments can constrain the spot properties of M-dwarfs with good enough precision to support atmospheric studies of young M-dwarf planets via transmission spectroscopy.
S-phase checkpoint prevents leading strand degradation from strand-associated nicks at stalled replication forks
Authors: Bugallo Alberto , Sánchez Mar , Fernández-García María , Segurado Mónica
Published: March 2024

The S-phase checkpoint is involved in coupling DNA unwinding with nascent strand synthesis and is critical to maintain replication fork stability in conditions of replicative stress. However, its role in the specific regulation of leading and lagging strands at stalled forks is unclear. By conditionally depleting RNaseH2 and analyzing polymerase usage genome-wide, we examine the enzymology of DNA replication during a single S-phase in the presence of replicative stress and show that there is a differential regulation of lagging and leading strands. In checkpoint proficient cells, lagging strand replication is down-regulated through an Elg1-dependent mechanism. Nevertheless, when checkpoint function is impaired we observe a defect specifically at the leading strand, which was partially dependent on Exo1 activity. Further, our genome-wide mapping of DNA single-strand breaks reveals that strand discontinuities highly accumulate at the leading strand in HU-treated cells, whose dynamics are affected by checkpoint function and Exo1 activity. Our data reveal an unexpected role of Exo1 at the leading strand and support a model of fork stabilization through prevention of unrestrained Exo1-dependent resection of leading strand-associated nicks after fork stalling.
Sex-Dependent Occlusive Cardiovascular Disease Effects of Short-Term Thirdhand Smoke Exposure
Authors: Qadri Shahnaz , Maia Ana Carolina R G , Ali Hamdy E A , Alarabi Ahmed B , Alshbool Fatima Z , Khasawneh Fadi T
Published: March 2024

Introduction

Thirdhand smoke (THS) is associated with many public health and disease concerns, such as respiratory illness, cancer, lipidemia, and cardiovascular disease (CVD). We have previously shown that a moderate to long-term exposure to THS increases the risk of thrombosis. However, whether short-term exposure to THS would produce any effects remains to be discovered. Therefore, this study investigated the impact of 1-month THS exposure on platelet function, in vivo and in vitro, and on cytokine response, in a sex-dependent manner.

Aims and Methods

Secondhand smoke or clean air (CA) exposed upholstery materials for 1 week were kept in cages housed with 5–6 mice, and the procedure was repeated for 4 weeks. These THS-exposed mice were evaluated for thrombogenesis and platelet function assays. In addition, cytokines expression was evaluated from pooled serum.

Results

Compared to the CA group, THS exposure significantly shortened the tail bleeding time and carotid artery thrombus formation. Moreover, the female mice appeared more sensitive to THS exposure than males. Furthermore, platelet aggregation, dense granule secretion, and P-selectin activation markers were significantly elevated due to THS exposure. In addition, high-throughput screening showed at least 30 cytokines differentially modulated by THS in females relative to 26 in male mice.

Conclusions

Collectively, these results demonstrate that 1 month of THS exposure represents a high health risk, in part, by triggering a prothrombotic phenotype that appears to be more significant in females, who are at a much higher risk for occlusive CVD. Additionally, changes in cytokine levels mediate some of the THS-induced occlusive effects.

Implications

This study revealed that THS exposure for 1 month is detrimental to the cardiovascular health of both sexes; however, females could be more aggressively affected than males. In addition, interleukins and chemokines could be critical factors for initiating prothrombotic activity due to THS exposure.
Osimertinib in Patients With Treatment-Naive EGFR-Mutant Non-small Cell Lung Cancer: Overall Survival, Post-progression Management and Budget Impact Analysis in Real-World
Authors: Pasello Giulia , Lorenzi Martina , Scattolin Daniela , Del Conte Alessandro , Cecere Fabiana , Pavan Alberto , Macerelli Marianna , Polo Valentina , Pilotto Sara , Santarpia Mariacarmela , Cumerlato Enrico , Da Ros Valentina , Targato Giada , Bortolami Alberto , Bonanno Laura , Ferro Alessandra , Dal Maso Alessandro , Frega Stefano , Guarneri Valentina
Published: March 2024

Introduction

The observational multicenter prospective FLOWER study (NCT04965701) confirmed effectiveness and safety of osimertinib in the real-world (RW) management of untreated EGFR-mutant advanced non-small cell lung cancer (aNSCLC) patients.

Methods

Herein, we report updated survival data, post-progression management, cost/effectiveness and budget impact (BI) of osimertinib compared with a RW population receiving gefitinib or erlotinib.

Results

Overall, 189 Caucasian patients receiving first-line osimertinib were included. After a follow-up of 20.7 months, 74(39.2%) patients discontinued osimertinib, median time-to-treatment discontinuation (mTTD) was 27.9 months, overall survival 36.8 months. At progression, tissue biopsy was performed in 29 (56.9%), liquid biopsy in 15 (29.4%) and both in 7 (13.7%) cases. The most frequent resistant mechanism was MET amplification (N = 14, 29.8%). At data cutoff, 13 (6.9%) patients were continuing osimertinib beyond progression; 52 (67.5%) received second-line treatment; no further treatments were administered in 25 (32.5%) cases. Thirty-three (63.4%) patients received chemotherapy, 12(23.1%) TKIs combination. Cost–effectiveness analysis showed a total cost per patient based on RW mTTD of 98,957.34€, 21,726.28€ and 19,637.83€ for osimertinib, erlotinib and gefitinib, respectively. The incremental cost-effectiveness ratio (ICER)/month for osimertinib was 359,806.0€/life-year-gained (LYG) and 197,789.77€/LYG compared to erlotinib and gefitinib. For osimertinib, the BI-gap between RW-TTD and theoretical-TTD was 16,501.0€ per patient.

Conclusions

This updated analysis confirms the effectiveness of osimertinib in RW. Although the ICER of osimertinib seems not cost-effective, additional costs for the management of disease progression to old generation TKIs were not considered in this study. The BI-gap suggests RW mTTD as a more reliable measure for expense estimation.
Crisis, corruption and state-led development in the making of the Mexican drug trade
Authors: Morris Nathaniel
Published: March 2024

The state of Durango has long been a centre of Mexican heroin production and an important node in transnational drug trafficking networks. As early as 1944, it was the site of one of the biggest drug busts in Mexican history, when an opium poppy plantation the size of 325 football pitches, irrigated by a purpose-built aqueduct, was discovered in the state’s northern mountains. By the mid 1970s, a combination of kinship ties and concrete connected these poppy fields directly with the US drug market hub of Chicago, Illinois, along a route known as the ‘heroin highway’, which helped Mexico become the supplier of 90 per cent of US heroin. But how did a poor, underpopulated and overwhelmingly rural state become a major player in the billion-dollar US–Mexican drug trade? This article shows that in Durango, the rise of heroin production and trafficking were integral aspects of local processes of social, political and economic modernization. Stimulated by the Mexican and US governments’ promotion of infrastructural improvements and mass migration, and protected by representatives of Mexico’s post-revolutionary political system, the drug trade in turn fuelled further ‘licit’ economic development, making it part of the very foundation of Mexico as we know it today.
Panel Conditioning Biases in the Current Population Survey’s Food Security Supplement
Authors: Warren John Robert , Himmelstern Jessie , Halpern-Manners Andrew
Published: March 2024

We estimate the extent to which the methodological problem called panel conditioning biases the federal government’s estimates of the prevalence of food insecurity in the United States. To do so, we use 2002 through 2020 data from the Current Population Survey’s Food Security Supplement—the same data used to produce the federal government’s annual statistics about food insecurity. We take advantage of the CPS’s rotating panel design feature to estimate the effects of panel conditioning. By comparing CPS respondents who participated in the Food Security Supplement in each of two consecutive years but who—strictly by chance—were selected to begin the CPS one year apart, we both approximate an experimental design and derive estimates of panel conditioning that are purged of biases from panel attrition. For the 200,000+ unique households in our sample, the treatment is having previously participated in the Food Security Supplement; the outcome is participants’ subsequent responses to survey questions about food security. We find that in nearly every year people in the treatment group—that is, the group of people who have previously responded to the Food Security Supplement—are less likely to be food insecure than people responding for the first time. These differences are statistically significant and large in magnitude. We conclude that the federal government’s estimates of the prevalence of food insecurity in America are substantially biased; depending on the mechanism underlying panel conditioning, the true prevalence of food insecurity may be substantially higher or lower than officially reported.
Thermal Larmor Radiation
Authors: Ievlev Evgenii , Good Michael R R
Published: March 2024

Thermal radiation is found from a moving point charge along a special, globally defined, continuous accelerated trajectory. The calculation is entirely classical (despite the appearance of ℏ) but is shown to have an immediate connection to quantum field theory via the moving mirror model. A precise recipe is given for the functional mathematical identity of the electron–mirror duality that allows one to map between (1) the classical radiation of an ordinary accelerating point charge in 3+1 Minkowski spacetime and (2) the quantum radiation of a moving mirror in 1+1 flat spacetime, for a given rectilinear trajectory.
Toward a cultural sociology of taxation
Authors: Braunstein Ruth
Published: March 2024

This article advances calls for a cultural sociology of taxation by arguing that Zelizer’s theory of how monetary exchanges perform ‘relational work’ can be applied to taxpaying. Based on a review of research on taxpaying in the USA, I show this approach offers insight into a disparate set of puzzles about taxation including: why the USA continues to require income tax returns; why anti-tax sentiment persists even at low tax rates; why anti-government conservatives support some social spending; and whether linking taxpaying to citizenship promotes solidarity or racialized hierarchies. Recognizing that taxpaying involves relational work also reveals continuities with other forms of monetary exchange; and supplies evidence that relational work is performed at higher levels of relational abstraction than previously understood. While this article only gestures toward these possibilities, I hope it stimulates future research that fulfills the new fiscal sociology’s aspirations for a cultural sociology of taxation.
Electroencephalography connectome changes in chronic insomnia disorder are correlated with neurochemical signatures
Authors: Yu Liyong , Peng Wei , Lin Wenting , Luo Yucai , Hu Daijie , Zhao Guangli , Xu Hao , Dou Zeyang , Zhang Qi , Hong Xiaojuan , Yu Siyi
Published: March 2024

Study Objectives

This study aimed to investigate the alterations in resting-state electroencephalography (EEG) global brain connectivity (GBC) in patients with chronic insomnia disorder (CID) and to explore the correlation between macroscale connectomic variances and microscale neurotransmitter distributions.

Methods

We acquired 64-channel EEG from 35 female CID patients and 34 healthy females. EEG signals were source-localized using individual brain anatomy and orthogonalized to mitigate volume conduction. Correlation coefficients between band-limited source-space power envelopes of the DK 68 atlas were computed and averaged across regions to determine specific GBC values. A support vector machine (SVM) classifier utilizing GBC features was employed to differentiate CID patients from controls. We further used Neurosynth and a 3D atlas of neurotransmitter receptors/transporters to assess the cognitive functions and neurotransmitter landscape associated with CID cortical abnormality maps, respectively.

Results

CID patients exhibited elevated GBC within the medial prefrontal cortex and limbic cortex, particularly at the gamma carrier frequency, compared to controls (pFDR < .05). GBC patterns were found to effectively distinguish CID patients from controls with a precision of 90.8% in the SVM model. The cortical abnormality maps were significantly correlated with meta-analytic terms like “cognitive control” and “emotion regulation.” Notably, GBC patterns were associated with neurotransmitter profiles (pspin < .05), with neurotransmitter systems such as norepinephrine, dopamine, and serotonin making significant contributions.

Conclusions

This work characterizes the EEG connectomic profile of CID, facilitating the cost-effective clinical translation of EEG-derived markers. Additionally, the linkage between GBC patterns and neurotransmitter distribution offers promising avenues for developing targeted treatment strategies for CID.
Italian resident individuals with interests in Liechtenstein entities: notes on Italian income taxes—Part 2
Authors: Quartana Claudio , Bolis Lodovico
Published: March 2024

It is not uncommon for Italian resident taxpayers to resort to Liechtenstein entities for taking advantage of the benefits that they can offer, like asset protection, confidentiality and favorable taxation. After having dealt, inter alia, with Liechtenstein foundations and establishments in Part 1, Part 2 focuses on the holding of participations in Liechtenstein limited companies by Italian resident individuals. In this regard, the tax treatment of dividends, capital gains and “the Italian Controlled Foreign Companies regime” are addressed. Finally, a few remarks are made on some income tax planning opportunities and criticalities in light of the Italian tax legislative framework described in Part 1 and Part 2.
Subcutaneous Furosemide: A Novel to Euvolemia
Authors: Cheikhali Ryan , Kalish Chloe , Maksymiuk Victoria , Nasereldin Mohamed , Bahl Sameer , Frishman Willi H. , Aronow Wilbert S. , Pan Stephen
Published: March 2024

Furoscix, a subcutaneous pH-neutral formulation of furosemide, obtained US Food and Drug Administration approval in October 2022 for adult patients with New York Heart Association class II and class III chronic heart failure. This approval marks an anticipated potential shift in the traditional management of decongestive therapy in chronic heart failure patients from the confines of the hospital to more accessible outpatient or home-based care. In this review, we will summarize existing evidence regarding the use of subcutaneous furosemide in comparison to both oral and intravenous formulations, highlighting the demonstrable benefits of its application in both outpatient and inpatient settings, and also discuss several factors that may limit its use.
Loudness Balancing Optimization for Better Speech Intelligibility, Music Perception, and Spectral Temporal Resolution in Cochlear Implant Users
Authors: Deniz Burcu , Deniz Rişvan , Ataş Ahmet
Published: March 2024

Hypothesis

The behaviorally based programming with loudness balancing (LB) would result in better speech understanding, spectral–temporal resolution, and music perception scores, and there would be a relationship between these scores.

Background

Loudness imbalances at upper stimulation levels may cause sounds to be perceived as irregular, gravelly, or overly echoed and may negatively affect the listening performance of the cochlear implant (CI) user. LB should be performed after fitting to overcome these problems.

Methods

The study included 26 unilateral Med-EL CI users. Two different CI programs based on the objective electrically evoked stapedial reflex threshold (P1) and the behaviorally program with LB (P2) were recorded for each participant. The Turkish Matrix Sentence Test (TMS) was applied to evaluate speech perception; the Random Gap Detection Test (RGDT) and Spectral-Temporally Modulated Ripple Test (SMRT) were applied to evaluate spectral temporal resolution skills; the Mini Profile of Music Perception Skills (mini-PROMS) and Melodic Contour Identification (MCI) tests were applied to evaluate music perception, and the results were compared.

Results

Significantly better scores were obtained with P2 in TMS tests performed in noise and quiet. SMRT scores were significantly correlated with TMS in quiet and noise, and mini-PROMS sound perception results. Although better scores were obtained with P2 in the mini-PROMS total score and MCI, a significant difference was found only for MCI.

Conclusion

The data from the current study showed that equalization of loudness across CI electrodes leads to better perceptual acuity. It also revealed the relationship between speech perception, spectral–temporal resolution, and music perception.
Both major xanthophyll cycles present in nature can provide Non-Photochemical Quenching in the model diatomPhaeodactylum tricornutum
Authors: Giossi Chiara E. , Wünsch Marie A. , Dautermann Oliver , Schober Alexander F. , Buck Jochen M. , Kroth Peter G. , Lohr Martin , Lepetit Bernard
Published: March 2024

Xanthophyll cycling contributes to photoprotection by regulating Non-Photochemical Quenching (NPQ). While most photosynthetic eukaryotes including land plants use the violaxanthin cycle, some algae like diatoms and haptophytes rely on the diadinoxanthin cycle for photoprotection. These algae also contain minor amounts of violaxanthin cycle pigments, serving as precursors in xanthophylls biosynthesis. Both cycles are catalyzed by the enzymes violaxanthin de-epoxidase (VDE) and zeaxanthin epoxidase (ZEP). Here, we characterized the role ofVDEand different ZEP-encoding paralogs (ZEP2andZEP3) in the model diatomPhaeodactylum tricornutum. While knockout ofVDEandZEP3significantly impaired the diadinoxanthin cycle, lack ofZEP2led to sustained accumulation of the violaxanthin cycle instead of diadinoxanthin cycle pigments under high irradiance, with no negative effect on NPQ capacity. We demonstrate that both major xanthophyll cycles present in nature can function with comparable efficiency within the same species, offering a new perspective on the evolution of xanthophyll-mediated photoprotection.
Optical characterization of molecular interaction strength in protein condensates
Authors: Beck Timon , van der Linden Lize-Mari , Borcherds Wade M. , Kim Kyoohyun , Schlüßler Raimund , Müller Paul , Franzmann Titus , Möckel Conrad , Goswami Ruchi , Leaver Mark , Mittag Tanja , Alberti Simon , Guck Jochen
Published: March 2024

Biomolecular condensates have been identified as a ubiquitous means of intracellular organization, exhibiting very diverse material properties. However, techniques to characterize these material properties and their underlying molecular interactions are scarce. Here, we introduce two optical techniques – Brillouin microscopy and quantitative phase imaging (QPI) – to address this scarcity. We establish Brillouin shift and linewidth as measures for average molecular interaction and dissipation strength, respectively, and we used QPI to obtain the protein concentration within the condensates. We monitored the response of condensates formed by FUS and by the low-complexity domain of hnRNPA1 (A1-LCD) to altering temperature and ion concentration. Conditions favoring phase separation increased Brillouin shift, linewidth, and protein concentration. In comparison to solidification by chemical crosslinking, the ion-dependent aging of FUS condensates had a small effect on the molecular interaction strength inside. Finally, we investigated how sequence variations of A1-LCD, that change the driving force for phase separation, alter the physical properties of the respective condensates. Our results provide a new experimental perspective on the material properties of protein condensates. Robust and quantitative experimental approaches such as the presented ones will be crucial for understanding how the physical properties of biological condensates determine their function and dysfunction.
In search of visual opsin ofLissachatina fulica:in silicoprediction
Authors: Dominova Irina N. , Fedotov Daniil A. , Shirina Svetlana , Zikin Vladimir , Zhukov Valerii V.
Published: March 2024

Here we present a complex study of possible visual opsin ofL. fulica. 8 candidate sequences were chosen for visual opsin protein and only one (Afu005002) was confirmed as a possible candidate after domain search, structural (structures were stimulated with AlphaFold2) and BLAST analysis. In order to evaluate spectroscopic properties of the Afu005002 protein, we have computed excitation energy and intensity of the main absorption band using QM/MM methodology at the ADC(2) level of theory. The theoretically predicted position of the main absorption maxima shows a good agreement with available experimental data.