bluuebunny/crossref_metadata_2025_split huggingface dataset:
First-in-human trial evaluating safety and pharmacokinetics of AT-752, a novel nucleotide prodrug with pan-serotype activity against dengue virus
Authors: Zhou Xiao-Jian , Lickliter Jason , Montrond Maureen , Ishak Laura , Pietropaolo Keith , James Dayle , Belanger Bruce , Horga Arantxa , Hammond Janet 
Published: March 2024

ABSTRACT

AT-752 is a novel guanosine nucleotide prodrug inhibitor of the dengue virus (DENV) polymerase with sub-micromolar, pan-serotype antiviral activity. This phase 1, double-blind, placebo-controlled, first-in-human study evaluated the safety, tolerability, and pharmacokinetics of ascending single and multiple oral doses of AT-752 in healthy subjects. AT-752 was well tolerated when administered as a single dose up to 1,500 mg or when administered as multiple doses up to 750 mg three times daily (TID). No serious adverse events occurred, and the majority of treatment-emergent adverse events were mild in severity and resolved by the end of the study. In those receiving single ascending doses of AT-752, no pharmacokinetic sensitivity was observed in Asian subjects, and no food effect was observed. Plasma exposure of the guanosine nucleoside metabolite AT-273, the surrogate of the active triphosphate metabolite of the drug, increased with increasing dose levels of AT-752 and exhibited a long half-life of approximately 15–25 h. Administration of AT-752 750 mg TID led to a rapid increase in plasma levels of AT-273 exceeding the target
in vitro
90% effective concentration (EC
90
) of 0.64 µM in inhibiting DENV replication, and maintained this level over the treatment period. The favorable safety and pharmacokinetic results support the evaluation of AT-752 as an antiviral for the treatment of dengue in future clinical studies.

Registered at ClinicalTrials.gov (
NCT04722627
).
Coding-complete genomic sequence of a rhinovirus C-32 in a human nasal swab sample that tested false positive in a SARS-CoV-2 antigen test
Authors: Moquin Tracey L. , Subramaniam Kuttichantran , Lednicky John A. 
Published: March 2024

ABSTRACT

Rhinovirus-A was previously shown to cause false-positive results in a Japanese SARS-CoV-2 antigen test. We report that a false-positive result was obtained in a specimen with rhinovirus C-32 that had been tested using an American SARS-CoV-2 antigen test.
Prognostic value of poly-microorganisms detected by droplet digital PCR and pathogen load kinetics in sepsis patients: a multi-center prospective cohort study
Authors: Zhao Yuanhan , Lin Ke , Zhang Haocheng , Zhang Yanliang , Li Shaling , Zhang Shengguo , Zhang Wei , Zhou Aiming , Zhuang Yangyang , Chen Jie , Wu Caixia , Zhou Wei , He Xiaoju , Yue Qiaoyan , Zhang Meng , Huang Yan , Li Liang , Hong Liang , Cai Fujing , Huang Lisu , Ruan Zhengshang , Xu Shanshan , Zhang Yan , Chen Xiaohua , Chen Jie , Ye Ying , Bian Tingting , Li Jiabin , Yin Jun , Li Xiang , Jiang Lijing , Lei Chen , Liu Jun , Zhang Ying , Jin Jialin , Ai Jingwen , Pan Jingye , Zhang Wenhong 
Published: March 2024

ABSTRACT

This study aimed to investigate the prognostic value of a novel droplet digital polymerase chain reaction (DDPCR) assay in sepsis patients. In this prospective cohort study, univariable and multivariable Cox regressions were used to assess risk factors for 28-day mortality. We also monitored pathogen load together with clinical indicators in a subgroup of the cohort. A total of 107 sepsis patients with positive baseline DDPCR results were included. Detection of poly-microorganisms [adjusted hazard ratio (HR) = 3.19; 95% confidence interval (CI) = 1.34–7.62;
P
= 0.009], high Charlson Comorbidity Index (CCI) score (adjusted HR = 1.14; 95% CI = 1.01–1.29;
P
= 0.041), and Sequential Organ Failure Assessment (SOFA) score (adjusted HR = 1.18; 95% CI = 1.05–1.32;
P
= 0.005) at baseline were independent risk factors for 28-day mortality while initial pathogen load was not associated (adjusted HR = 1.17; 95% CI = 0.82–1.66;
P
= 0.385). Among 63 patients with serial DDPCR results, an increase in pathogen load at days 6–8 compared to baseline was a risk factor for 28-day mortality (
P
= 0.008). Also, pathogen load kinetics were significantly different between day-28 survivors and nonsurvivors (
P
= 0.022), with a decline overtime only in survivors and an increase from days 3 and 4 to days 6–8 in nonsurvivors. Using DDPCR technique, we found that poly-microorganisms detected and increased pathogen load a week after sepsis diagnosis were associated with poor prognosis.

IMPORTANCE
This prospective study was initiated to explore the prognostic implications of a novel multiplex PCR assay in sepsis. Notably, our study was the largest cohort of sepsis with droplet digital polymerase chain reaction pathogen monitoring to date, allowing for a comprehensive evaluation of the prognostic significance of both pathogen species and load. We found that detection of poly-microorganisms was an independent risk factors for 28-day mortality. Also, pathogen load increase 1 week after sepsis diagnosis was a risk factor for 28-day mortality, and differential pathogen load kinetics were identified between day-28 survivors and nonsurvivors. Overall, this study demonstrated that pathogen species and load were highly correlated with sepsis prognosis. Patients exhibiting conditions mentioned above face a more adverse prognosis, suggesting the potential need for an escalation of antimicrobial therapy.

Registered at ClinicalTrials.gov (
NCT05190861
).
When the Trojan horse is unable to reach inside the city: investigation of the mechanism of resistance behind the first reported cefiderocol-resistant
E. coli
in Canada
Authors: Barker Kevin R. , Rebick Gabriel W. , Fakharuddin Ken , MacDonald Clayton , Mulvey Michael R. , Mataseje Laura F. 
Published: March 2024

ABSTRACT

Gram-negative metallo-β-lactamase-producing bacteria can be extremely problematic, especially when found to be extensively drug-resistant (XDR). Cefiderocol is a novel antimicrobial that has been shown to overcome most carbapenemases, with very rare resistance reported to date. Within our institution, two multidrug-resistant and one XDR strains were isolated from a patient who recently emigrated from India. Each isolate underwent whole-genome sequencing to resolve plasmids and determine phylogenetics, strain typing, and mechanisms of resistance. The XDR
E. coli
was ST167, harbored NDM-5,
cirA
and PBP3 mutations, consistent with cefiderocol resistance. Our study suggests that the NDM region is required in conjunction with
cirA
and PBP3 mutations. It is not clear why; however, our study did determine a potential novel iron-transport region unique to the cefiderocol-resistant isolate. This is the first characterized cefiderocol-resistant
E.coli
reported from Canada. Health centers should be on alert for this clone.

IMPORTANCE

The development of cefiderocol, a novel siderophore cephalosporin, has provided additional options to the treatment of extensively drug-resistant (XDR) Gram-negative bacteria. Resistance to cefiderocol is poorly understood and only recently described. Here, we describe a case of a patient with recent travel to India harboring three
Escherichia coli
isolates, one resistant and two susceptible to cefiderocol. Two isolates are highly similar genetically, allowing the mechanism of resistance to be described more closely. The importance of this manuscript contributes both globally to the understanding of cefiderocol resistance in
E. coli
as well as nationally as this is the first resistant case reported in Canada. This is especially concerning as cefiderocol is not currently approved in Canada. The implications of reporting emerging resistance to new antimicrobials for XDR Gram negatives are impactful to infectious disease specialists, clinical microbiologists, physicians, and public health.
Ortho-positronium annihilation processes in Y zeolites under different environments by measurements of the energy spectra of the positron annihilation radiation
Authors: Noguchi Haruka , Chiari Luca 
Published: March 2024

AbstractMeasurements of the energy distribution of the positron annihilation radiation in Y zeolites are carried out to elucidate the various ortho-positronium annihilation processes that take place in these microporous materials and relate them to the ortho-positronium lifetime components observed by positron annihilation lifetime spectroscopy in earlier studies. Y zeolites with various Si/Al ratios in the range from 2.6 to 40 are investigated under a controlled atmosphere of N2 gas and after exposure to the atmosphere. The ortho-positronium annihilation modes are characterized by analyzing the γ-ray spectra through the use of the f3γ index, which represents the fraction of 3γ-annihilation, and the S parameter. The proportion of ortho-positronium self-annihilation is found to be no less than 15% in N2 gas, but drastically decreases by the physisorption of water molecules and possibly positronium spin exchange interaction with oxygen in the atmosphere. The presence of water molecules suppresses ortho-positronium intrinsic annihilation and, at the same time, promotes ortho-positronium pick-off annihilation in the pores. Similarly, the S parameter rises due to an increased contribution from para-positronium annihilation and ortho-positronium pick-off annihilation, which is also consistent with the physisorption of water and positronium spin exchange. In conjunction with the previously measured ortho-positronium lifetime components, the specific ortho-positronium annihilation sites and processes in these porous materials under different environments are determined and a complete picture of the ortho-positronium behavior in Y zeolites is obtained.
Graphical abstract
Cryptanalysis and improvement of efficient multiparty quantum secret sharing based on a novel structure and single qubits
Authors: Gao Gan 
Published: March 2024

AbstractIn the paper (EPJ Quant. Technol. 10:29, 2023), Kuo et al. proposed a multiparty quantum secret sharing protocol based on a novel structure and single qubits. Owing to the absence of an entanglement state, the proposed protocol is more practical than other quantum secret sharing protocols which use entanglement properties. Therefore, we study the security of the proposed protocol and find there exists a security loophole in the n-party ($n\geq 4$
n
≥
4
) secret sharing case in it, that is, two dishonest agents can collude to obtain (part of) Alice’s secret without the help of the other agents. In order to overcome the security loophole, we give an improved protocol and make a security analysis for it. By calculating, the qubit efficiency of the three-party case in it is equal to $\frac{1}{8}$

1

8

, which is higher than that in Hillery et al.’s protocol (Phys. Rev. A 59:1829, 1999).
Control of NLO and photocatalysis properties based on the use of Sn-doped ZnO thin films for optoelectronics applications
Authors: Abed S. , Djaaboube H. , Aouati R. , Bouaballou A. , Bouchouit K. , Andrushchak A. , Wielgosz R. , Taboukhat S. , Sahraoui B. 
Published: March 2024

Thin films of zinc oxide (ZnO) have unique properties that make them suitable for various applications. In this study, we used a spray pyrolysis process to develop undoped ZnO and ZnO doped with Sn thin films on a glass substrate. We aimed to investigate the effect of Sn concentration on the optical, nonlinear optical, and structural properties of ZnO:Sn thin films. X-ray diffraction analysis revealed that all the deposited ZnO thin films exhibit polycrystalline hexagonal structures well-oriented along the c-axis. The obtained films were transparent in the visible range, with a transmittance between 70% and 80%. The optical energy bandgap values for the films varied from 3.16 eV to 3.29 eV. We also determined the second- and third-order nonlinear susceptibilities, which decreased with increasing Sn concentration. We investigated the photocatalytic activity of the ZnO-doped Sn thin films using methylene blue dye under visible light. Sn doping enhanced the photocatalytic activity of ZnO thin films, with constant rate values of 0.00046 and 0.00074 min[Formula: see text] for ZnO and ZnO:Sn thin films, respectively.
Hedging rainfall risk: An illustrative analysis of rainfall index-based futures contracts
Authors: Dileep N. , Kotreshwar G. 
Published: March 2024

Various studies have attempted to explore rainfall index (RI)-based derivatives as a tool to hedge rainfall risk. But no study delved into the issue to discuss the potential deployment of those tools for hedging rainfall risk on a model based on RI-based futures (RIBFs). An illustrative analysis of RIBFs contracts as hedging instruments has been undertaken in this study. The study is fundamentally based on empirical data. A brief account of the rainfall risk profile is presented to indicate the risk diversification opportunity. Besides, the results of an analysis of the correlation between the RI and the stock market index are projected to establish the RI as a unique asset class. The monsoon rainfall data for 50 years, i.e., from 1971 to 2020 have been considered. The Sensex and Nifty stock market indices data covered a period of 30 years, from 1991 to 2020. The study used correlation, the GARCH (1,1) model, and ratio analysis to test the hypotheses. A hypothetical insurance company representing major stakeholders in need of rainfall risk hedging has been taken as an example for evaluating the utility of RIBFs contracts as hedging tools. The results reveal that the party buying RIBFs contracts can significantly reduce the loss of revenue due to adverse monsoon outcomes.
Outdoor Light at Night, Air Pollution, and Risk of Cerebrovascular Disease: A Cohort Study in China
Authors: Wu Yonghao , Shen Peng , Yang Zongming , Yu Luhua , Xu Lisha , Zhu Zhanghang , Li Tiezheng , Luo Dan , Lin Hongbo , Shui Liming , Tang Mengling , Jin Mingjuan , Chen Kun , Wang Jianbing 
Published: March 2024

BACKGROUND:
We sought to explore the associations of outdoor light at night (LAN) and air pollution with the risk of cerebrovascular disease (CeVD).

METHODS:
We included a total of 28 302 participants enrolled in Ningbo, China from 2015 to 2018. Outdoor LAN and air pollution were assessed by Satellite-derived images and land-use regression models. CeVD cases were confirmed by medical records and death certificates and further subdivided into ischemic and hemorrhagic stroke. Cox proportional hazard models were used to estimate hazard ratios and 95% CIs.

RESULTS:

A total of 1278 CeVD cases (including 777 ischemic and 133 hemorrhagic stroke cases) were identified during 127 877 person-years of follow-up. In the single-exposure models, the hazard ratios for CeVD were 1.17 (95% CI, 1.06–1.29) for outdoor LAN, 1.25 (1.12–1.39) for particulate matter with an aerodynamic diameter ≤2.5 µm, 1.14 (1.06–1.22) for particulate matter with aerodynamic diameter ≤10 μm, and 1.21 (1.06–1.38) for NO
2
in every interquartile range increase. The results were similar for ischemic stroke, whereas no association was observed for hemorrhagic stroke. In the multiple-exposure models, the associations of outdoor LAN and PM with CeVD persisted but not for ischemic stroke. Furthermore, no interaction was observed between outdoor LAN and air pollution.

CONCLUSIONS:
Levels of exposure to outdoor LAN and air pollution were positively associated with the risk of CeVD. Furthermore, the detrimental effects of outdoor LAN and air pollution might be mutually independent.
Long-term treatment with lasmiditan in patients with migraine: post hoc analysis of treatment patterns and outcomes from the open-label extension of the CENTURION randomized trial
Authors: Komori Mika , Ozeki Akichika , Tanji Yuka , Kamiki Eriko , Krege John H. , Li Lily Qian , Suzuki Shiho , Shibata Mamoru , Takeshima Takao 
Published: March 2024

Abstract
Background
The objective of this analysis was to gain new insights into the patient characteristics and other factors associated with lasmiditan usage and clinical outcomes under conditions resembling the real-world setting.

Methods
This was a post hoc analysis of data from the 12-month, open-label extension (OLE) of the phase 3, double-blind, randomized, controlled CENTURION trial, which examined the efficacy and safety of lasmiditan as acute treatment across four migraine attacks. Patients completing the main study who treated ≥ 3 attacks could continue in the OLE. The initial lasmiditan dose was 100 mg, with dose adjustments to 50 mg or 200 mg allowed at the investigator’s discretion. Patient and clinical characteristics were summarized by dosing pattern and completion status. Safety was assessed based on adverse event (AE) frequency by number of doses.

Results
In total, 445 patients treated ≥ 1 migraine attacks with lasmiditan during the OLE, 321 of whom (72.1%) completed the study. Forty-seven percent of patients remained on the 100-mg initial dose during the OLE whereas 20.2% used both 100 mg and 50 mg, 30.6% used both 100 mg and 200 mg, and 6 (1.3%) used multiple dose levels. All dosing patterns were associated with clinical and patient-reported improvement; however, the 100-mg group had the highest proportion of patients reporting improvement in the Patient Global Impression of Change – Migraine Headache Condition (56.5% vs 33.4%–52.2%). In comparison, all three groups that made dose adjustments had higher rates of completion compared to the 100-mg group (72.1%–83.3% vs 68.9%). The frequency of AEs decreased with continued use of lasmiditan. Concomitant triptans and lasmiditan use did not increase AE frequency.

Conclusions
Based on high persistence and patient satisfaction rates, the 100-mg dose appears optimal for most patients. For those who adjusted dose levels, dose adjustments appeared beneficial to improve efficacy or tolerability, retaining patients on treatment. Collectively, the data suggest that patients who experienced efficacy continued to use lasmiditan regardless of the occurrence or frequency of AEs, and continued use appeared associated with fewer AEs.

Trial registration
European Union Drug Regulating Authorities Clinical Trials Database (EudraCT): 2018–001661-17; ClinicalTrials.gov: NCT03670810; registration date: September 12, 2018.

Graphical Abstract
Automated content analysis as a tool to compare content in sexual selection research with examples of sexual selection in evolutionary biology textbooks: implications for teaching the nature of science
Authors: Jackson J. Kasi , Fuselier Linda , Eason Perri 
Published: March 2024

Abstract
Background
We used college-level evolution textbooks to examine the presentation of sexual selection research—a field with ongoing debates related to sex, sexuality and gender identity. Many classic sexual selection concepts have been criticized for androcentrism and other forms of gender-sex bias, specifically for de-emphasizing the female role in reproductive behaviors and over-reliance on gender-sex binaries. These classic concepts are fundamentally captured in the idea that animal reproductive-related behaviors can be grouped in sex roles (e.g. competitive males and selective females). Recently developed alternative concepts provide a more nuanced understanding of the flexibility of sexual and reproductive-related behaviors, stemming in part from growing attention to a broader range of female behavior. To assess whether students are receiving content reflecting these insights, we measured the congruence between textbook content and the scientific literature, using insects as a case study because of the importance of this group in the development of sexual selection theory, its prevalence in current sexual selection research, and the number of insect examples included in textbooks. We first coded textbook content for sexual selection concepts. We used automated content analysis to analyze a database of citations, keywords and abstracts in sexual selection research published between 1990 and 2014, inclusive of the period covered by the textbooks.

Results
The textbooks and research literatures prioritized the same taxa (e.g., fruit flies) and sex roles as embodied in classic sexual selection theory. Both the research literature and some textbooks acknowledge androcentrism and other forms of gender-sex bias in classic sexual selection paradigms, especially competitive male and selective female sex roles. Yet, while the research literature included alternative models, textbooks neglected these alternatives, even when researchers had studied both classic and alternative views in the same insect.

Conclusions
We recommend using this kind of analysis of textbook content to engage students in a conversation around the social factors that impact knowledge construction, a key part of the epistemological understanding they need for a robust grasp of the Nature of Science and of evolutionary theory.
Identification and functional analysis of the LEAFY gene in longan flower induction
Authors: Jue Dengwei , Li Zhexin , Zhang Wenlin , Tang Jianmin , Xie Ting , Sang Xuelian , Guo Qigao 
Published: March 2024

Abstract
Background
Flowering at the right time is a very important factor affecting the stable annual yield of longan. However, a lack of knowledge of the regulatory mechanism and key genes of longan flowering restricts healthy development of the longan industry. Therefore, identifying relevant genes and analysing their regulatory mechanism are essential for scientific research and longan industry development.

Results
DlLFY (Dimocarpus longan LEAFY) contains a 1167 bp open reading frame and encodes 388 amino acids. The amino acid sequence has a typical LFY/FLO family domain. DlLFY was expressed in all tissues tested, except for the leaf, pericarp, and pulp, with the highest expression occurring in flower buds. Expression of DlLFY was significantly upregulated at the early flower induction stage in “SX” (“Shixia”). The results of subcellular localization and transactivation analysis showed that DlLFY is a typical transcription factor acting as a transcriptional activator. Moreover, overexpression of DlLFY in Arabidopsis promoted early flowering and restrained growth, resulting in reduced plant height and rosette leaf number and area in transgenic plants. DNA affinity purification sequencing (DAP-Seq) analysis showed that 13 flower-related genes corresponding to five homologous genes of Arabidopsis may have binding sites and be putative target genes. Among these five flower-related genes, only AtTFL1 (terminal flower 1) was strongly inhibited in transgenic lines.

Conclusion
Taken together, these results indicate that DlLFY plays a pivotal role in controlling longan flowering, possibly by interacting with TFL1.