bluuebunny/crossref_metadata_2025 huggingface dataset:
Viral Genomic Variation and the Severity of Genital Herpes Simplex Virus-2 Infection as Quantified by Shedding Rate: A Viral Genome-Wide Association Study
Authors: Casto Amanda M , Song Hoseung , Xie Hong , Selke Stacy , Roychoudhury Pavitra , Wu Michael C , Wald Anna , Greninger Alexander L , Johnston Christine
Published: May 2024

Background

The clinical severity of genital herpes simplex virus-2 (HSV-2) infection varies widely among infected persons with some experiencing frequent genital lesions while others are asymptomatic. The viral genital shedding rate is closely associated with, and has been established as, a surrogate marker of clinical severity.

Methods

To assess the relationship between viral genetics and shedding, we assembled a set of 145 persons who had the severity of their genital herpes quantified through determination of their HSV genital shedding rate. An HSV-2 sample from each person was sequenced and biallelic variants among these genomes were identified.

Results

We found no association between metrics of genome-wide variation in HSV-2 and shedding rate. A viral genome-wide association study identified the minor alleles of 3 individual unlinked variants as significantly associated with higher shedding rate (P < 8.4 × 10−5): C44973T (A512T), a nonsynonymous variant in UL22 (glycoprotein H); A74534G, a synonymous variant in UL36 (large tegument protein); and T119283C, an intergenic variant. We also found an association between the total number of minor alleles for the significant variants and shedding rate (P = 6.6 × 10−7).

Conclusions

These results add to a growing body of literature for HSV suggesting a connection between viral genetic variation and clinically important phenotypes of infection.
Effects of a manganese complex with lysine and glutamic acid on growth performance, manganese deposition, and emission, antioxidant capacity and metacarpal strength in weaned piglets
Authors: Qi Keke , Deng Bo , Ma Qian , Ji Fei , Wu Jie , Zhang Cheng , Xu Ziwei
Published: May 2024

The present study sought to assess the effects of manganese complexes with lysine and glutamic acid (Mn-LG) as manganese (Mn) sources on growth performance, trace element deposition, antioxidant capacity, and metacarpal strength in weaned piglets. The study involved 288 healthy Duroc × Landrace × Yorkshire piglets that were weaned at 25 to 28 d of age and weighed 8.66 ± 0.96 kg. These piglets were randomly divided into six groups: a control group (Mn-LG-0, receiving a basal diet without Mn supplementation), a Mn sulfate group (basal diet supplemented with 40 mg·kg−1 diet of Mn, Mn-S-40 group), and four Mn-LG groups (Mn-LG-20, Mn-LG-40, Mn-LG-60, Mn-LG-80, supplemented with 20, 40, 60, and 80 mg·kg−1 Mn from Mn-LG in the basal diet). Grouping began at weaning on the 0th day of the experiment. The corn–soybean-based basal diet during the early (days 0 to 14) and late (days 15 to 42) phases of the experiment contained 20.88 and 30.12 mg·kg−1 Mn, respectively. Blood samples were collected on days 14 and 42, and pigs were sacrificed for sample collection on day 42. The results indicated no significant differences in average daily gain, average daily feed intake, or feed-to-gain ratio among the groups (P > 0.05). The diarrhea rates of all Mn-LG groups and the Mn-S-40 group were significantly lower in the 0 to 14 d and during the entire experimental period than in the Mn-LG-0 group (P < 0.001). The Mn-LG-40 group exhibited a significant increase in liver Mn concentration and serum Mn superoxide dismutase (Mn-SOD) activity on day 42 (P < 0.01), as well as a significant decrease in fecal Mn concentration (P < 0.05), compared to those of the Mn-S-40 group. Significant differences (P < 0.05) were detected in the serum, liver, and fecal Mn concentrations, as well as in the serum and liver Mn-SOD activity, across the different Mn-LG groups. The serum and fecal Mn concentrations and serum Mn-SOD activity increased linearly or quadratically (P < 0.01) with increasing Mn-LG supplementation. No significant differences (P > 0.05) were found in kidney, heart, or metacarpal bone Mn concentrations or in bone strength indices. In summary, compared with the Mn-LG-0 diet, dietary supplementation with Mn-LG enhanced serum Mn deposition and Mn-SOD activity and decreased the incidence of diarrhea. Additionally, the fecal Mn concentration was lower in the Mn-LG group than in the inorganic group at equivalent dosages.
Functional characterization of the InR/PI3K/AKT signaling pathway in female reproduction of the predatory bug Cyrtorhinus lividipennis (Hemiptera: Miridae)
Authors: Hu Kui , Jin Rong , Liu Jianqi , Zhu Jun , Dai Wei , Wang Ying , Li Yao , Liu Fang
Published: May 2024

The insulin signaling (IIS) pathway plays a key role in the regulation of various physiological functions in animals. However, the involvement of IIS pathway in the reproduction of natural enemy insects remains enigmatic. Here, 3 key genes (named ClInR, ClPI3K, and ClAKT) related to IIS pathway were cloned from Cyrtorhinus lividipennis (Reuter) (Hemiptera: Miridae), an important natural enemy in the rice ecosystem. These 3 proteins had the typical features of corresponding protein families and shared high similarity with their respective homologs from the Hemipteran species. The ClInR, ClPI3K, and ClAKT were highly expressed in the adult stage. Tissue distribution analysis revealed that ClInR, ClPI3K, and ClAKT were highly expressed in the midgut and ovary of adults. Silencing of ClInR, ClPI3K, and ClAKT caused 92.1%, 72.1%, and 57.8% reduction in the expression of ClVg, respectively. Depletion of these 3 genes impaired vitellogenin synthesis and ovary development. Moreover, the fecundity in the dsInR, dsPI3K, and dsAKT injected females were 53.9%, 50.8%, and 48.5% lower than the control treatment, respectively. These results indicated that ClInR, ClPI3K, and ClAKT are of great importance for the reproduction of C. lividipennis. Our results advance the knowledge about the molecular mechanism of reproduction regulation in natural enemy insects.
Waveform inversion with structural regularizing constraint based on gradient decomposition
Authors: Wang Ziying , Wang Jianhua , Sun Wenbo , Huang Jianping , Li Zhenchun , Wang Yandong
Published: May 2024

Full waveform inversion (FWI) can simultaneously update low-to-medium wavenumber velocity components and high-wavenumber velocity components. However, if seismic data lack large-offset data and effective low-frequency components, FWI updates will be dominated by high-wavenumber velocity perturbation. Meanwhile, providing that the initial model is inaccurate, inversion will have the problem of local minima. In this study, FWI is developed with structural regularizing constraint based on gradient decomposition (RGDFWI). By correlating the separated forward wavefield and backward wavefield with specific propagating direction, the FWI gradient is decomposed into a tomography-mode gradient and migration-mode gradient. We propose an optimized strategy taking full advantage of the two modes of FWI gradient. On the one hand, we use the tomography-mode gradient to enhance low-to-medium wavenumber updates. On the other hand, we use the migration-mode gradient to apply structural regularizing constraint by estimating structure dip and adding sparsity constraint in the seislet domain. During the inversion process, high-wavenumber structural information constrains and guides low-wavenumber model updates. The results of two numerical tests, the Marmousi model test and Overthrust model test, validate the optimized strategy, which can produce a better initial velocity model for FWI. The inversion finally generates a high-precision and high-resolution velocity model.
Investigation on the vibration characteristics of rock based on circular plate and cylinder models: dimension, geometric shape and boundary condition
Authors: Zhang Zhao , Liu Bing , Liu Jianlin
Published: May 2024

The declaration on the “natural frequency of rock” exists in many engineering areas, and it has caused many misunderstandings. Different from the mass-spring model usually used, the circular plate and cylinder models are respectively established to clarify the relationship between the vibration characteristics (including the natural frequency and vibration mode) and their influencing factors of rock by modal analysis. The effect of the dimension, geometric shape and boundary condition on the vibration characteristics of rock with plate structure is investigated, in which the semi-analytical solutions agree well with the simulation results. By using the cylinder model based upon the Lamé–Navier equation, the effect of such influencing factors on the vibration characteristics of the block rock sample is further studied and verified by numerical simulation and experimental results. The results suggest that the natural frequency of “rock” (including the experimental rock sample) is strongly dependent on the dimension, geometric shape and boundary condition. The resonance frequency observed in the excitation experiment is not only closely associated with the natural frequency of a specific order but also dependent on the dominance of the particular vibration mode. These findings contribute to a better understanding of the rock-breaking mechanism under dynamic loads with a certain excitation frequency.
Impairment in a member of AP2/ERF and F-box family protein enhances complete panicle exsertion in rice
Authors: Ballichatla Suneel , C. G. Gokulan , Barbadikar Kalyani M , Hake Anil A , Potupureddi Gopi , Guha Pritam Kanti , Phule Amol S , Magar Nakul D , Balija Vishalakshi , Awalellu Komal , Kokku Premalatha , Golla Suresh , Raman Meenakshi Sundaram , Ayyangari Phani Padmakumari , Gouri Shankar Laha , Ponnuvel Senguttuvel , Lella Venkata SubbaRao , Patel Hitendra K , Sonti Ramesh Venkata , Maganti Sheshu Madhav
Published: May 2024

Complete panicle exsertion (CPE) is an economically important quantitative trait that contributes to grain yield in rice. We deployed an integrated approach for understanding the molecular mechanism of CPE using a stable ethyl methanesulfonate mutant line, CPE-109 of the Samba Mahsuri (SM) variety of rice (Oryza sativa), which exhibits CPE. Two consistent genomic regions were identified for CPE through quantitative trait locus (QTL) mapping [qCPE-4 (28.24–31.22 Mb) and qCPE-12 (2.30–3.18 Mb)] and QTL-sequencing [chr 4 (31.21–33.69 Mb) and chr 12 (0.12–3.15 Mb)]. Two non-synonymous single nucleotide polymorphisms, namely KASP 12–12 (T→C; chr12:1269983) in Os12g0126300, encoding an AP2/ERF transcription factor, and KASP 12–16 (G→A; chr12:1515198) in Os12g0131400, encoding an F-box domain-containing protein, explained 81.05% and 59.61% of the phenotypic variance, respectively, and exhibited strong co-segregation with CPE in F2 mapping populations, advanced generation lines, and CPE-exhibiting SM mutants through KASP assays. Down-regulation of these genes in CPE-109 compared with SM (wild type) was observed in transcriptome sequencing of flag leaves, which was validated through qRT-PCR. We propose that the abrogation of Os12g0126300 and Os12g0131400 in CPE-109 combinatorially influences down-regulation of ethylene biosynthetic genes, Os01g0192900 (ACC synthase) and Os05g0497300 (ethylene-responsive factor-2), and up-regulation of a gibberellic acid synthetic gene, Os06g0569900 (ent-kaurene synthase) and the two cytokinin biosynthetic genes Os07g0486700 (cytokinin-O-glucosyltransferase 2) and Os10g0479500 (similar to carboxy-lyase), which results in complete panicle exsertion.
Mapping the Milky Way with LAMOST – IV. The large Galactic disc extending to 35 kpc
Authors: Tian Hao , Liu Chao , Li Jiadong , Zhang Bo
Published: May 2024

We investigate extent of the disc in both vertical and radial directions by separately analysing the density and azimuthal velocity distributions using 31116 M giant stars selected from LAMOST DR5. We first measure the metallicities, radial velocities, and the distances with precision of 0.26 dex, 5.01 km s−1, and 20.8 per cent, respectively. Then, a Bayesian method is applied to model the distributions of the outer Galaxy including components of the thin, thick discs and the halo, to obtain the scale height and azimuthal velocity distributions for the thin and thick discs as a function of galactocentric distance R. The density profile of the thin disc shows that it extends out to R ∼ 35 kpc, beyond which there are no M giant stars in the halo except for Sagittarius Stream members. By using azimuthal velocity to trace the thin disc out to 26 kpc from the Galactic Centre, we show that both the density profile and azimuthal velocity decrease with Galactocentric distance R. In both the density and azimuthal velocity distributions, there is a significant breakpoint at a galactocentric distance of R ∼ 14 kpc. The scale height distribution shows that the thin disc is significantly flared, consistent with previous works. We also find that there is no significant thick disc (as traced by M giant stars) in the outer region beyond R ∼ 15.5 kpc.
Faraday rotation as a probe of radio galaxy environment in RMHD AGN jet simulations
Authors: Jerrim L A , Shabala S S , Yates-Jones P M , Krause M G H , Turner R J , Anderson C S , Stewart G S C , Power C , Rodman P E
Published: May 2024

Active galactic nuclei (AGNs) play an integral role in galaxy formation and evolution by influencing galaxies and their environments through radio jet feedback. Historically, interpreting observations of radio galaxies and quantifying radio jet feedback has been challenging due to degeneracies between their physical parameters. In particular, it is well established that different combinations of jet kinetic power and environment density can yield indistinguishable radio continuum properties, including apparent size and Stokes I luminosity. We present an approach to breaking this degeneracy by probing the line-of-sight environment with Faraday rotation. We study this effect in simulations of three-dimensional relativistic magnetohydrodynamic AGN jets in idealized environments with turbulent magnetic fields. We generate synthetic Stokes I emission and Faraday rotation measure (RM) maps, which enable us to distinguish between our simulated sources. We find enhanced RMs near the jet head and lobe edges. We show that increasing the environment density and the average cluster magnetic field strength broadens the distribution of Faraday rotation measure values. We study the depolarization properties of our sources, finding that the hotspot regions depolarize at lower frequencies than the lobes. We quantify the effect of depolarization on the RM distribution, finding that the frequency at which the source is too depolarized to measure the RM distribution accurately is a probe of environmental properties. This technique offers a range of new opportunities for upcoming surveys, including probing radio galaxy environments and determining more accurate estimates of the AGN feedback budget.
Effectiveness of halo and galaxy properties in reducing the scatter in the stellar-to-halo mass relation
Authors: Pei Wenxiang , Guo Qi , Shao Shi , He Yi , Gu Qing
Published: May 2024

The stellar-to-halo mass relation (SHMR) is a fundamental relationship between galaxies and their host dark matter haloes. In this study, we examine the scatter in this relation for primary galaxies in the semi-analytic l-galaxies model and two cosmological hydrodynamical simulations, EAGLE (Evolution and Assembly of Galaxies and their Environments) and TNG100-1. We find that in low-mass haloes, more massive galaxies tend to reside in haloes with higher concentration, earlier formation time, greater environmental density, earlier major mergers, and, to have older stellar populations, which is consistent with findings in various studies. Quantitative analysis reveals the varying significance of halo and galaxy properties in determining SHMR scatter across simulations and models. In EAGLE and TNG100-1, halo concentration and formation time primarily influence SHMR scatter for haloes with $M_{\rm h}\lt 10^{12}{\, \rm M_\odot }$, but the influence diminishes at high mass. Baryonic processes play a more significant role in LGal. For haloes with $M_{\rm h} \lt 10^{11}{\, \rm M_\odot }$ and $10^{12}{\, \rm M_\odot }\lt M_{\rm h}\lt 10^{13}{\, \rm M_\odot }$, the main drivers of scatter are galaxy star formation rate and age. In the $10^{11.5}{\, \rm M_\odot }\lt M_{\rm h} \lt 10^{12}{\, \rm M_\odot }$ range, halo concentration and formation time are the primary factors. And for haloes with $M_{\rm h} \gt 10^{13}{\, \rm M_\odot }$, supermassive black hole mass becomes more important. Interestingly, it is found that active galactic nucleus feedback may increase the amplitude of the scatter and decrease the dependence on halo properties at high masses.
Multiple chemical tracers finally unveil the intricate NGC 1333 IRAS 4A outflow system. FAUST XVI
Authors: Chahine Layal , Ceccarelli Cecilia , De Simone Marta , Chandler Claire J , Codella Claudio , Podio Linda , López-Sepulcre Ana , Sakai Nami , Loinard Laurent , Bouvier Mathilde , Caselli Paola , Vastel Charlotte , Bianchi Eleonora , Cuello Nicolás , Fontani Francesco , Johnstone Doug , Sabatini Giovanni , Hanawa Tomoyuki , Zhang Ziwei E , Aikawa Yuri , Busquet Gemma , Caux Emmanuel , Durán Aurore , Herbst Eric , Ménard François , Segura-Cox Dominique , Svoboda Brian , Balucani Nadia , Charnley Steven , Dulieu François , Evans Lucy , Fedele Davide , Feng Siyi , Hama Tetsuya , Hirota Tomoya , Isella Andrea , Jímenez-Serra Izaskun , Lefloch Bertrand , Maud Luke T , Maureira María José , Miotello Anna , Moellenbrock George , Nomura Hideko , Oba Yasuhiro , Ohashi Satoshi , Okoda Yuki , Oya Yoko , Pineda Jaime , Rimola Albert , Sakai Takeshi , Shirley Yancy , Testi Leonardo , Viti Serena , Watanabe Naoki , Watanabe Yoshimasa , Zhang Yichen , Yamamoto Satoshi
Published: May 2024

The exploration of outflows in protobinary systems presents a challenging yet crucial endeavour, offering valuable insights into the dynamic interplay between protostars and their evolution. In this study, we examine the morphology and dynamics of jets and outflows within the IRAS 4A protobinary system. This analysis is based on ALMA observations of SiO(5–4), H2CO(30, 3–20, 3), and HDCO(41, 4–31, 3) with a spatial resolution of ∼150 au. Leveraging an astrochemical approach involving the use of diverse tracers beyond traditional ones has enabled the identification of novel features and a comprehensive understanding of the broader outflow dynamics. Our analysis reveals the presence of two jets in the redshifted emission, emanating from IRAS 4A1 and IRAS 4A2, respectively. Furthermore, we identify four distinct outflows in the region for the first time, with each protostar, 4A1 and 4A2, contributing to two of them. We characterize the morphology and orientation of each outflow, challenging previous suggestions of bends in their trajectories. The outflow cavities of IRAS 4A1 exhibit extensions of 10 and 13 arcsec with position angles (PA) of 0° and -12°, respectively, while those of IRAS 4A2 are more extended, spanning 18 and 25 arcsec with PAs of 29° and 26°. We propose that the misalignment of the cavities is due to a jet precession in each protostar, a notion supported by the observation that the more extended cavities of the same source exhibit lower velocities, indicating they may stem from older ejection events.
guppy i: a code for reducing the storage requirements of cosmological simulations
Authors: Mansfield Philip , Abel Tom
Published: May 2024

As cosmological simulations have grown in size, the permanent storage requirements of their particle data have also grown. Even modest simulations present a major logistical challenge for the groups which run these boxes and researchers without access to high performance computing facilities often need to restrict their analysis to lower quality data. In this paper, we present guppy, a compression algorithm and code base tailored to reduce the sizes of dark matter-only cosmological simulations by approximately an order of magnitude. guppy is a ‘lossy’ algorithm, meaning that it injects a small amount of controlled and uncorrelated noise into particle properties. We perform extensive tests on the impact that this noise has on the internal structure of dark matter haloes, and identify conservative accuracy limits which ensure that compression has no practical impact on single-snapshot halo properties, profiles, and abundances. We also release functional prototype libraries in C, Python, and Go for reading and creating guppy data.
rAAV capsid mutants eliminate leaky expression from DNA donor template for homologous recombination
Authors: Ling Chen , Yu Chenghui , Wang Cong , Yang Ming , Yang Hengbin , Yang Keying , He Yun , Shen Yajie , Tang Shiyi , Yu Xiaomin , Zhou Zhengjun , Zhou Shaolai , Zhou Jian , Zhu Liqing , Li Jixi
Published: May 2024

Precise genomic editing through the combination of CRISPR/Cas systems and recombinant adeno-associated virus (rAAV)-delivered homology directed repair (HDR) donor templates represents a powerful approach. However, the challenge of effectively suppressing leaky transcription from the rAAV vector, a phenomenon associated to cytotoxicity, persists. In this study, we demonstrated substantial promoter activities of various homology arms and inverted terminal repeats (ITR). To address this issue, we identified a novel rAAV variant, Y704T, which not only yields high-vector quantities but also effectively suppresses in cis mRNA transcription driven by a robust promoter. The Y704T variant maintains normal functionality in receptor interaction, intracellular trafficking, nuclear entry, uncoating, and second-strand synthesis, while specifically exhibiting defects in transcription. Importantly, this inhibitory effect is found to be independent of ITR, promoter types, and RNA polymerases. Mechanistic studies unveiled the involvement of Valosin Containing Protein (VCP/p97) in capsid-mediated transcription repression. Remarkably, the Y704T variant delivers HDR donor templates without compromising DNA replication ability and homologous recombination efficiency. In summary, our findings enhance the understanding of capsid-regulated transcription and introduce novel avenues for the application of the rAAV-CRISPR/Cas9 system in human gene therapy.
GCMS-ID: a webserver for identifying compounds from gas chromatography mass spectrometry experiments
Authors: Wakoli Julia , Anjum Afia , Sajed Tanvir , Oler Eponine , Wang Fei , Gautam Vasuk , LeVatte Marcia , Wishart David S
Published: May 2024

GCMS-ID (Gas Chromatography Mass Spectrometry compound IDentifier) is a webserver designed to enable the identification of compounds from GC–MS experiments. GC–MS instruments produce both electron impact mass spectra (EI-MS) and retention index (RI) data for as few as one, to as many as hundreds of different compounds. Matching the measured EI-MS, RI or EI-MS + RI data to experimentally collected EI-MS and/or RI reference libraries allows facile compound identification. However, the number of available experimental RI and EI-MS reference spectra, especially for metabolomics or exposomics-related studies, is disappointingly small. Using machine learning to accurately predict the EI-MS spectra and/or RIs for millions of metabolomics and/or exposomics-relevant compounds could (partially) solve this spectral matching problem. This computational approach to compound identification is called in silico metabolomics. GCMS-ID brings this concept of in silico metabolomics closer to reality by intelligently integrating two of our previously published webservers: CFM-EI and RIpred. CFM-EI is an EI-MS spectral prediction webserver, and RIpred is a Kovats RI prediction webserver. We have found that GCMS-ID can accurately identify compounds from experimental RI, EI-MS or RI + EI-MS data through matching to its own large library of >1 million predicted RI/EI-MS values generated for metabolomics/exposomics-relevant compounds. GCMS-ID can also predict the RI or EI-MS spectrum from a user-submitted structure or annotate a user-submitted EI-MS spectrum. GCMS-ID is freely available at https://gcms-id.ca/.
Volenrelaxin (LY3540378) increases renal plasma flow: a randomized Phase 1 trial
Authors: Tham Lai San , Heerspink Hiddo J L , Wang Xiaojun , Verdino Petra , Saifan Chadi G , Benson Eric A , Goldsmith Paul , Wang Zhenzhong , Testani Jeffrey M , Haupt Axel , Sam Flora , Cherney David Z I
Published: May 2024

Background

Volenrelaxin is a half-life-extended recombinant human relaxin protein developed for improving kidney perfusion and cardiorenal function. This study assessed the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of volenrelaxin following single- and multiple-ascending doses (SAD and MAD) administration.

Methods

In this Phase 1, four-part, randomized, double-blinded, placebo-controlled SAD and MAD study in healthy participants, SAD participants (n = 56) received an intravenous or subcutaneous dose of volenrelaxin or placebo in a dose-ascending manner. MAD participants (n = 77) received volenrelaxin or placebo subcutaneously once weekly for 5 weeks. Effective renal plasma flow (ERPF) and measured glomerular filtration rate (mGFR) were determined by para-aminohippurate and iohexol clearance, respectively.

Results

Volenrelaxin demonstrated an extended half-life and increased acute and chronic placebo-adjusted ERPF change from baseline by 50% and 44%, respectively (P < .0001). mGFR was unchanged, while filtration fraction and afferent/efferent renal arteriolar resistances were reduced. Systolic and diastolic blood pressures decreased, and pulse rate increased with increasing volenrelaxin exposures, demonstrating maximal model-derived placebo-adjusted changes (90% confidence interval) of –6.16 (–8.04, –4.28) mmHg, –6.10 (–7.61, –4.58) mmHg and +4.39 (+3.38, +5.39) bpm, respectively. Adverse events were mild, with no difference in orthostatic hypotension between volenrelaxin and placebo.

Conclusion

Volenrelaxin was well-tolerated, safe and suitable for weekly subcutaneous dosing. Volenrelaxin showed a sustained improvement in kidney perfusion upon repeated dosing, supporting further clinical development in chronic kidney disease and chronic heart failure.

Clinical trial registration

NCT04768855.
Impact of New York City Cigarette Floor Price Policy on Reducing Smoking Disparities
Authors: Ma Haijing , Golden Shelley D
Published: May 2024

Introduction

In 2017, New York City (NYC) passed a minimum floor price law (MFPL) to raise the minimum price of a pack of cigarettes to $13.00. Evaluation of the MFPL in NYC is limited and has yet to examine its potential as a proequity policy.

Aims and Methods

Data (n = 20 241; prepolicy n = 15 037, postpolicy n = 5204) were obtained from the New York State Adult Tobacco Survey, a quarterly repeated cross-sectional survey. Using the Difference-in-Differences approach, we compared changes in reported cigarette prices, cigarette consumption, and smoking status among NYC residents before and after policy implementation to changes in the same outcomes among residents in the rest of the state (ROS) over the same period.

Results

For some smokers, cigarette price increased in NYC for the postpolicy period; moreover, prices increased more in NYC than in ROS. NYC smokers who reported higher income, more education, or White or “Other” race, reported a bigger price increase than their ROS counterparts. Cigarette consumption decreased more in the postpolicy period for people in the ROS, in general and among certain groups. Everyday smoking status decreased similarly in both NYC and ROS, whereas someday smoking status decreased primarily in the ROS during the analysis period.

Conclusions

Cigarette prices in NYC increased after the 2017 MFPL; these increases were greater than those occurring elsewhere in the state, suggesting the policy might be a factor in the change. However, the increases were concentrated among relatively higher-priced purchases, and groups with lower smoking prevalence. Changes in smoking status and cigarette consumption did not correspond to study hypotheses.

Implications

This study provides an empirical analysis of a real-world policy in tobacco control. It examines the potential of the MFPL in NYC as a proequity policy. Findings extend the current MFPL literature and suggest that they may be able to raise cigarette prices for some purchases, but also may have a limited impact on smoking behaviors.
Inflation-overshooting commitment: an analysis using a macroeconomic model
Authors: Kawamoto Takuji , Nakajima Jouchi , Mikami Tomoaki
Published: May 2024

This article examines the effectiveness of the makeup strategy for Japan’s economy, where inflation expectations formation is known to be largely adaptive. We build a small-scale macroeconomic model and conduct simulation analysis to study the implications of adopting the makeup strategy for early achievement of the inflation target and the incurring costs. Simulation results show that when the inflation rate has been below the target, it is effective to stabilize average inflation by offsetting the past inflation misses over some makeup windows and that when the natural rate of interest is lower, the optimal makeup window becomes longer.
Unleashing patient voices: empowering adverse event assessment with complete patient-reported outcomes
Authors: Phung Thi Hanh , Bradford Natalie , Pitt Erin , Alexander Kimberly
Published: May 2024

The 124-item patient reported-outcome common terminology criteria for adverse events (PRO-CTCAE) questionnaire, assessing 78 symptoms, is widely used in cancer clinical trials to identify side effects. However, its regular use in routine cancer care is rarely reported. We aimed to investigate the feasibility of weekly PRO-CTCAE completion over 9 weeks in a prospective study with 30 patients with cancer undergoing chemotherapy. Participants were asked to complete electronic surveys with reminders, but no feedback or incentives. Only 136 (50%) of the planned 270 time points at which a PRO-CTCAE self-report was expected were completed, with an additional 21 (8%) partially completed, and represents a failure to achieve the expected level of completion. Patients reported experiencing up to 51 and a median of 30 symptoms across all time points, highlighting the complexity of symptom assessment in acute cancer care. While weekly implementation of the PRO-CTCAE may not be feasible outside of clinical trial settings, this study highlights the breadth of symptoms experienced.
Frequency of HLA-A*02:01 in the Brazilian population and its impact on uveal melanoma systemic treatment
Authors: de Melo Andreia Cristina , Lucena Evandro , de Oliveira Danielli Cristina Muniz , Viola João P B
Published: May 2024

Uveal melanoma is a rare malignancy originating from extracutaneous melanocytes on the uveal layer of the eyes. The incidence varies depending on the ethnic and racial global distribution, as uveal melanoma is more frequently diagnosed in non-Hispanic White subjects when compared with Hispanic, Asian, or Black individuals. Despite all the local effective management of uveal melanoma, roughly 50% of the cases will develop distant metastases. For these cases, the historical median overall survival is around 12 months. Recently, tebentafusp became the first therapy to receive Food and Drug Administration approval following a phase 3 trial demonstrating a continued long-term benefit for overall survival among adult HLA-A*02:01-positive patients with previously untreated metastatic uveal melanoma. Since 2021, high-resolution sequence-based HLA typing has been considered the gold standard for determining HLA alleles and haplotypes for the Brazilian Bone Marrow Donor Registry (REDOME) donors. To depict the HLA-A*02:01-positivity in Brazilian individuals, the REDOME database was queried out for the donors included from 2021 to 2023 and tested for HLA in high-resolution platforms. A total of 203, 44 donors were included and the frequency of the HLA-A*02:01 was 21.01%, much lower compared to the frequency in North Americans and Europeans (around 45%). Despite tebentafusp has demonstrated promising results in the treatment of uveal melanoma, the number of patients to benefit from this new approach can strongly vary by ethnic and racial issues. New strategies for the systemic treatment of advanced uveal melanoma have to be developed and tested as this disease still represents an unmet medical need.
Verbal disputes about the content of experience
Authors: Speaks Jeff
Published: May 2024

A verbal dispute is one in which the disputants agree on all of the facts about the intended subject matter of the dispute and disagree only about how to use certain terms. This paper explores the possibility that the dispute between particularists and generalists about the contents of perceptual experience is a verbal dispute. The aim is less to provide a knockdown argument for the conclusion that this dispute is merely verbal than to show how difficult it is to uncover a substantive dispute between the two sides. A concluding section asks whether the argument generalizes beyond the particularism/generalism dispute to other prominent disputes in contemporary philosophy of mind.
Information Spillovers and Sovereign Debt: Theory Meets the Eurozone Crisis
Authors: Cole Harold L , Neuhann Daniel , Ordoñez Guillermo
Published: May 2024

We develop a theory of information spillovers in sovereign bond markets in which investors can learn about default risk before trading in primary and secondary markets. If primary markets are structured as multi-unit discriminatory-price auctions, an endogenous winner’s curse leads to strategic complementarities in information acquisition. Shocks to default risk in one country may trigger crisis episodes with widespread information acquisition, sharp increases in the level and volatility of yields in risky countries, low and stable yields in safe countries, market segmentation, and arbitrage profits between primary and secondary markets. These predictions are consistent with the dynamics of auction informativeness during the Eurozone Sovereign Debt Crisis, which we measure using the reaction of secondary market yields to primary market yields.
Does Pricing Carbon Mitigate Climate Change? Firm-Level Evidence from the European Union Emissions Trading System
Authors: Colmer Jonathan , Martin Ralf , Muûls Mirabelle , Wagner Ulrich J
Published: May 2024

In theory, market-based regulatory instruments correct market failures at least cost. However, evidence on their efficacy remains scarce. Using administrative data, we estimate that, on average, the European Union Emissions Trading System (EU ETS)—the world’s first and largest market-based climate policy—induced regulated manufacturing firms to reduce carbon dioxide emissions by 14–16% with no detectable contractions in economic activity. We find no evidence of outsourcing to unregulated firms or markets; instead, firms made targeted investments, reducing the emissions intensity of production. These results indicate that the EU ETS induced global emissions reductions, a necessary and sufficient condition for mitigating climate change. We show that the absence of any negative economic effects can be rationalized in a model where pricing the externality induces firms to make fixed-cost investments in energy-saving capital that reduce marginal variable costs.
The Dynamics of Loan Sales and Lender Incentives
Authors: Gryglewicz Sebastian , Mayer Simon , Morellec Erwan
Published: May 2024

How much of a loan should a lender retain, and how do loan sales affect loan performance? We address these questions in a model in which a lender originates loans that it can sell to investors. The lender reduces default risk through screening at origination and monitoring after origination, but is subject to moral hazard. The optimal lender-investor contract can be implemented by requiring the lender to initially retain a share of the loan that it gradually sells to investors, rationalizing loan sales after origination. The model generates novel predictions linking loan and lender characteristics to initial retention, sales dynamics, and loan performance.
Ramosetron as an add-on therapy for refractory fibromyalgia: a randomized, double-blind, placebo-controlled trial
Authors: Park Dong-Jin , Jeong Hyemin , Choi Sung-Eun , Kang Ji-Hyoun , Lee Jung-Kil , Lee Shin-Seok
Published: May 2024

Objective

This study aimed to assess the efficacy and safety of intravenous ramosetron for pain relief in patients with fibromyalgia (FM) unresponsive to conventional treatments.

Methods

In this prospective, double-blind, placebo-controlled trial, 80 FM patients were randomly allocated to receive either placebo (n = 40) or ramosetron (n = 40) at a dosage of 0.3 mg/day intravenously for five consecutive days. The primary outcome was the reduction in pain intensity at the end of the treatment period, evaluated using a visual analogue scale (VAS). Secondary outcome measures included the FM Impact Questionnaire, Beck Depression Inventory (BDI), Multi-Dimensional Health Assessment Questionnaire (MDHAQ), EQ-5D and State-Trait Anxiety Inventory on days 5 (end of treatment), 7, 10 and 28. Safety was continuously monitored throughout the study.

Results

At the end of the treatment phase, the ramosetron group demonstrated a significantly greater reduction in VAS pain scores compared with the placebo group (1.18 ± 1.60 vs 0.54 ± 1.59, P < 0.05). Additionally, the ramosetron group exhibited significant improvements in BDI (4.42 ± 5.18 vs 1.33 ± 4.87, P < 0.05) and MDHAQ pain scale (0.37 ± 0.74 vs 0.04 ± 0.52, P < 0.05) scores. However, these improvements in pain VAS and BDI scores were not sustained through day 28. The safety profile of ramosetron was favorable, with gastrointestinal symptoms, particularly constipation, being the most commonly reported adverse events.

Conclusions

Intravenous administration of ramosetron provided safe and effective short-term relief of pain intensity in FM patients with inadequate response to standard treatments.
The Role of Social Deprivation and Cannabis Use in Explaining Variation in the Incidence of Psychotic Disorders: Findings From the EU-GEI Study
Authors: Brink Vera , Andleeb Humma , Gayer-Anderson Charlotte , Arango Celso , Arrojo Manuel , Berardi Domenico , Bernardo Miquel , Bobes Julio , Del-Ben Cristina Marta , Ferraro Laura , de Haan Lieuwe , La Barbera Daniele , La Cascia Caterina , Lasalvia Antonio , Llorca Pierre-Michel , Menezes Paolo Rossi , Pignon Baptiste , Sanjuán Julio , Santos José Luis , Selten Jean-Paul , Tarricone Ilaria , Tortelli Andrea , Tripoli Giada , Velthorst Eva , Rutten Bart P F , van Os Jim , Quattrone Diego , Murray Robin M , Jones Peter B , Morgan Craig , Di Forti Marta , Jongsma Hannah E , Kirkbride James B
Published: May 2024

Background and Hypothesis

Recent findings suggest the incidence of first-episode psychotic disorders (FEP) varies according to setting-level deprivation and cannabis use, but these factors have not been investigated together. We hypothesized deprivation would be more strongly associated with variation in FEP incidence than the prevalence of daily or high-potency cannabis use between settings.

Study Design

We used incidence data in people aged 18–64 years from 14 settings of the EU-GEI study. We estimated the prevalence of daily and high-potency cannabis use in controls as a proxy for usage in the population at-risk; multiple imputations by chained equations and poststratification weighting handled missing data and control representativeness, respectively. We modeled FEP incidence in random intercepts negative binomial regression models to investigate associations with the prevalence of cannabis use in controls, unemployment, and owner-occupancy in each setting, controlling for population density, age, sex, and migrant/ethnic group.

Study Results

Lower owner-occupancy was independently associated with increased FEP (adjusted incidence rate ratio [aIRR]: 0.76, 95% CI: 0.61–0.95) and non-affective psychosis incidence (aIRR: 0.68, 95% CI: 0.55–0.83), after multivariable adjustment. Prevalence of daily cannabis use in controls was associated with the incidence of affective psychoses (aIRR: 1.53, 95% CI: 1.02–2.31). We found no association between FEP incidence and unemployment or high-potency cannabis use prevalence. Sensitivity analyses supported these findings.

Conclusions

Lower setting-level owner-occupancy and increased prevalence of daily cannabis use in controls independently contributed to setting-level variance in the incidence of different psychotic disorders. Public health interventions that reduce exposure to these harmful environmental factors could lower the population-level burden of psychotic disorders.
Dios y la Nación: The 1837 Revolt and the Maladministration of Mexican New Mexico
Authors: Saionz Matthew
Published: May 2024

This article examines the revolt of 1837 in New Mexico within the context of Mexico City’s inattention to the North after Mexican independence and the destabilizing effects of U.S. commercial expansion. An analysis tracing the origins of the uprising to its suppression in January 1838 suggests that New Mexico’s unrest had less to do with a federalist movement for autonomy or separatism than it did a rejection of ineffective governance and mismanagement common to both federalist and centralist regimes. More specifically, rebelling nuevomexicanos challenged the prevailing political economy of New Mexico sustained by what can be called the commercial order. This haphazard coalition of wealthy nuevomexicanos, American traders, and officials provided just enough revenue to maintain the basic functions of government; but, in their devotion to the overland trade between the United States and Mexico, New Mexican administrators enacted policies that promoted wars with Navajos and jeopardized the livelihoods of nuevomexicanos who relied on subsistence agriculture and the borderlands trade with independent Indians. Nuevomexicanos in 1837 ultimately rose up against not only the commercial order, but also the national government whose neglect after 1821 helped to engender and then perpetuate the maladministration of New Mexico.
Embracing failure: Nurturing learning and well-being in anesthesiology and perioperative medicine
Authors: Higgins K. Elliott , Vinson Amy E. , Petrini Laura , Kotha Rohini , Black Stephanie A.
Published: May 2024

Failure, ubiquitous in life and medical practice, offers myriad opportunities for learning and growth alongside challenges to overall well-being. In this article, we explore the nature of failure, it’s sources and impacts in perioperative medicine, and the specific challenges it brings to trainee well-being. With a deeper understanding of the societal, psychological and cognitive determinants and effects of failure, we propose solutions in order to harness the opportunities inherent in failures to create brave and supportive learning environments conducive to both education and well-being.
Anesthesia Blunts Carbon Dioxide Effects on Glymphatic Cerebrospinal Fluid Dynamics in Mechanically Ventilated Rats
Authors: Persson Niklas Daniel Åke , Lohela Terhi J. , Mortensen Kristian Nygaard , Rosenholm Marko , Li Qianliang , Weikop Pia , Nedergaard Maiken , Lilius Tuomas O.
Published: May 2024

Background

Impaired glymphatic clearance of cerebral metabolic products and fluids contribute to traumatic and ischemic brain edema and neurodegeneration in preclinical models. Glymphatic perivascular cerebrospinal fluid flow varies between anesthetics possibly due to changes in vasomotor tone and thereby in the dynamics of the periarterial cerebrospinal fluid (CSF)–containing space. To better understand the influence of anesthetics and carbon dioxide levels on CSF dynamics, this study examined the effect of periarterial size modulation on CSF distribution by changing blood carbon dioxide levels and anesthetic regimens with opposing vasomotor influences: vasoconstrictive ketamine–dexmedetomidine (K/DEX) and vasodilatory isoflurane.

Methods

End-tidal carbon dioxide (ETco
2) was modulated with either supplemental inhaled carbon dioxide to reach hypercapnia (Etco
2, 80 mmHg) or hyperventilation (Etco
2, 20 mmHg) in tracheostomized and anesthetized female rats. Distribution of intracisternally infused radiolabeled CSF tracer 111In-diethylamine pentaacetate was assessed for 86 min in (1) normoventilated (Etco
2, 40 mmHg) K/DEX; (2) normoventilated isoflurane; (3) hypercapnic K/DEX; and (4) hyperventilated isoflurane groups using dynamic whole-body single-photon emission tomography. CSF volume changes were assessed with magnetic resonance imaging.

Results

Under normoventilation, cortical CSF tracer perfusion, perivascular space size around middle cerebral arteries, and intracranial CSF volume were higher under K/DEX compared with isoflurane (cortical maximum percentage of injected dose ratio, 2.33 [95% CI, 1.35 to 4.04]; perivascular size ratio 2.20 [95% CI, 1.09 to 4.45]; and intracranial CSF volume ratio, 1.90 [95% CI, 1.33 to 2.71]). Under isoflurane, tracer was directed to systemic circulation. Under K/DEX, the intracranial tracer distribution and CSF volume were uninfluenced by hypercapnia compared with normoventilation. Intracranial CSF tracer distribution was unaffected by hyperventilation under isoflurane despite a 28% increase in CSF volume around middle cerebral arteries.

Conclusions

K/DEX and isoflurane overrode carbon dioxide as a regulator of CSF flow. K/DEX could be used to preserve CSF space and dynamics in hypercapnia, whereas hyperventilation was insufficient to increase cerebral CSF perfusion under isoflurane.

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Association of Neighborhood Opportunity, Race, and Ethnicity with Pediatric Day-of-surgery Cancellations: A Cohort Study
Authors: Willer Brittany L. , Mpody Christian , Tobias Joseph D. , Nafiu Olubukola O. , Jimenez Nathalia
Published: May 2024

Background

Day-of-surgery cancellations impede healthcare access and contribute to inequities in pediatric healthcare. Socially disadvantaged families have many risk factors for surgical cancellation, including low health literacy, transportation barriers, and childcare constraints. These social determinants of health are captured by the Child Opportunity Index 2.0, a national quantification of neighborhood-level characteristics that contribute to a child’s vulnerability to adversity. This study examined the association of neighborhood opportunity with pediatric day-of-surgery cancellations.

Methods

A retrospective cohort study of children younger than 18 yr of age scheduled for ambulatory surgery at a tertiary pediatric hospital between 2017 and 2022 was conducted. Primary addresses were geocoded to determine Child Opportunity Index 2.0 neighborhood opportunity. Log-binomial regression was used to estimate the relative risk of day-of-surgery cancellation comparing different levels of neighborhood opportunity. This study also estimated the relative risk of cancellations associated with race and ethnicity, by neighborhood opportunity.

Results

Overall, the incidence of day-of-surgery cancellation was 3.8%. The incidence of cancellation was lowest in children residing in very-high-opportunity neighborhoods and highest in children residing in very-low-opportunity neighborhoods (2.4% vs. 5.7%, P < 0.001). The adjusted relative risk of day-of-surgery cancellation in very-low-opportunity neighborhoods compared to very-high-opportunity neighborhoods was 2.24 (95% CI, 2.05 to 2.44; P < 0.001). The results showed statistical evidence of an interaction of Children’s Opportunity Index with race and ethnicity. In very-low-opportunity neighborhoods, Black children had 1.48 times greater risk of day-of-surgery cancellation than White children (95% CI, 1.35 to 1.63; P < 0.001). Likewise, in very-high-opportunity neighborhoods, Black children had 2.17 times greater risk of cancellation (95% CI, 1.75 to 2.69; P < 0.001).

Conclusions

This study found a strong relationship between pediatric day-of-surgery cancellation and neighborhood opportunity. Black children at every level of opportunity had the highest risk of cancellation, suggesting that there are additional factors that render them more vulnerable to neighborhood disadvantage.

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