bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Phase III Randomized Controlled Trial of Plitidepsin, a Marine-Derived Compound, in Hospitalized Adults With Moderate COVID-19
Authors: Landete Pedro , Caliman-Sturdza Olga-Adriana , Lopez-Martin Jose A , Preotescu Liliana , Luca Mihaela-Catalina , Kotanidou Anastasia , Villares Paula , Iglesias Shirley-Patricia , Guisado-Vasco Pablo , Saiz-Lou Elena-Maria , del Carmen Farinas-Alvarez Maria , de Lucas Esperanza Merino , Perez-Alba Eduardo , Cisneros Jose-Miguel , Estrada Vicente , Hidalgo-Tenorio Carmen , Poulakou Garyfallia , Torralba Miguel , Fortun Jesus , Garcia-Ocana Paula , Lemaignen Adrien , Marcos-Martin Miguel , Molina Maria , Paredes Roger , Perez-Rodriguez Maria Teresa , Raev Dimitar , Ryan Pablo , Meira Fernanda , Gomez Javier , Torres Nadia , Lopez-Mendoza Diego , Jimeno Jose , Varona Jose-Felipe 
Published: August 2024

Abstract

Background
Plitidepsin has shown potent preclinical activity against severe acute respiratory syndrome coronavirus 2 and was generally well tolerated in a phase I trial of hospitalized patients with coronavirus disease 2019 (COVID-19). NEPTUNO, a phase III, multicenter, randomized, controlled trial, was designed to evaluate the efficacy and safety of plitidepsin in the management of moderate COVID-19 in hospitalized adult patients.

Methods
Included patients had documented severe acute respiratory syndrome coronavirus 2 infection, required oxygen therapy, and had adequate organ function. The planned sample size was 609 patients. Patients were randomized 1:1:1 to at least 3 days of dexamethasone plus either plitidepsin (1.5 mg/day or 2.5 mg/day, for 3 days) or standard of care (control). The primary endpoint was the time to sustained withdrawal of supplemental oxygen. Secondary endpoints included time to sustained hospital discharge, clinical status, duration of oxygen support, percentage of patients requiring admission to the intensive care unit, and safety.

Results
After randomizing 205 patients, NEPTUNO was discontinued due to a notable drop in COVID-19–related hospitalizations. Available data suggest a 2-day improvement in the median time to sustained oxygen therapy discontinuation (5 vs 7 days) favoring both plitidepsin arms (hazard ratio, 1.37; 95% confidence interval, .96–1.96; P = .08 for plitidepsin 1.5 mg vs control; hazard ratio, 1.06; 95% confidence interval, .73–1.53; P = .78 for plitidepsin 2.5 mg vs control). Plitidepsin was generally well tolerated.

Conclusions
Despite the trial limitations, these results suggest that plitidepsin may have a positive benefit-risk ratio in the management of patients requiring oxygen therapy. Further studies with plitidepsin, including those in immunosuppressed patients, are warranted.
Results from this phase III trial suggest that plitidepsin, a first-in-class antiviral, may have a positive benefit-risk ratio in the management of hospitalized patients requiring oxygen therapy for moderate COVID-19.
Disentangling bottom-up and top-down controls on fish consumption of key prey in the Northeast US Shelf ecosystem
Authors: Gartland James , Latour Robert J 
Published: August 2024

Abstract
Exploited forage fishes serve a dual role in marine ecosystems by supporting directed fisheries and predator productivity, and thus both harvest and predatory removals should be accounted for when developing stock assessments and evaluating management trade-offs. Predator catch and stomach content data collected on the Northeast US Shelf from 1978 to 2019 by two fisheries-independent surveys were combined within multivariate spatiotemporal models to estimate time-series of consumptive removals during spring and fall for four commercially exploited prey; Atlantic herring (Clupea harengus), silver hake (Merluccius bilinearis), butterfish (Peprilus triacanthus), and longfin squid (Doryteuthis pealeii). Seasonal consumption trends were mostly synchronous for Atlantic herring and silver hake, asynchronous for butterfish and longfin squid, and predatory removals were generally greater during fall. Consumption has increased since the 1990s for all prey except Atlantic herring and butterfish during fall, which coincides with the widespread implementation of harvest constraints meant to rebuild predator and prey populations. These time-series were linked to hypothesized drivers using state-space regression models; prey availability (bottom-up; positive relationships) and commercial catch (top-down; primarily negative relationships) were the strongest predictors of consumption. Although the mechanisms underlying these relationships remain unresolved, these linkages highlight connections among the systemic drivers of productivity on the Northeast Shelf.
High-level ceftriaxone resistance due to transfer of penA allele 60.001 into endemic gonococcal lineages in Hangzhou, China
Authors: Yang Fan , Sun Xia , Fu Ying , Zhao Feng , Lin Xu’ai , Chen Yan , van der Veen Stijn 
Published: August 2024

Abstract

Objectives
Neisseria gonorrhoeae strains associated with the high-level ceftriaxone-resistant FC428 clone or containing its main resistance determinant, penA allele 60.001, have shown global transmission. In Hangzhou, China, 10% of the isolates were associated with the FC428 clone in 2019. Here, we investigated ceftriaxone resistance and the prevalence of FC428-associated strains in Hangzhou in 2020–22.

Methods
A total of 209 gonococcal isolates were investigated for antimicrobial susceptibility to ceftriaxone and other antibiotics by agar dilution method. Sequence types and penA alleles were determined by PCR and sequence analysis.

Results
Resistance to ceftriaxone (MIC &gt; 0.125 mg/L) was observed for 16% (33/209) of the isolates, whereas 6.7% (14/209) of the isolates displayed high-level ceftriaxone resistance (MIC = 1 mg/L). These 14 high-level ceftriaxone-resistant isolates and another isolate displaying an MIC = 0.25 mg/L contained penA allele 60.001, with eight of these isolates, all from 2020 to 2021 belonging to MLST ST1903, the sequence type commonly associated with the original FC428 clone. Importantly, the six penA allele 60.001-containing isolates from 2022 belonged to MLST ST8123, ST7365 and ST7367, which are among the most frequently encountered sequence types found in China. Therefore, these results indicate that endemic lineages in China have acquired penA allele 60.001.

Conclusions
Here, we report continued transmission of gonococcal strains associated with the FC428 clone or containing penA allele 60.001 in Hangzhou. A major concern for public health is the acquisition of penA allele 60.001 by successful endemic lineages, which might enhance the transmission of this high-level ceftriaxone resistance trait.
Feasibility study of a telehealth school-based behavioral parent training group program for attention-deficit/hyperactivity disorder
Authors: Chung Sara , Lai Jasmine , Hawkey Elizabeth J , Dvorsky Melissa R , Owens Elizabeth , Huston Emma , Pfiffner Linda J 
Published: August 2024

Abstract

Objective
To evaluate the feasibility and preliminary efficacy of Telehealth Behavioral Parent Training (T-BPT), a school telehealth group intervention for attention-deficit/hyperactivity disorder (ADHD) with a companion training program for school clinicians.

Methods
T-BPT was developed in an iterative three-phase design in partnership with community stakeholders during the COVID-19 pandemic. School clinicians (N = 4) delivered T-BPT over 8 weeks to parents (N = 21, groups of 5–6 per school) of children (Grades 2–5) with ADHD while simultaneously receiving training and consultation from PhD-level study trainers. A single-arm open trial was used to assess feasibility, engagement, and preliminary efficacy.

Results
Parents and school clinicians endorsed high feasibility, acceptability, and usability of T-BPT. Parent attendance was high (M = 94.6%) and a majority of parents (66.7%) attended all eight sessions. Preliminary outcomes indicate moderate to large reductions in parent-reported ADHD symptoms (ω2 = .36), functional and clinical global impairment (ω2s= .21 and .19, respectively), and distance learning challenges (ω2 = .22).

Conclusions
Results were in line with in-person delivery, indicating promising feasibility of school telehealth BPT groups. This study also provided further support for the feasibility of the remote training model for school clinicians. Implications of the commonly endorsed barriers and benefits beyond COVID-19 and relevance to under resourced communities are also discussed.
A general framework for regression with mismatched data based on mixture modelling
Authors: Slawski Martin , West Brady T , Bukke Priyanjali , Wang Zhenbang , Diao Guoqing , Ben-David Emanuel 
Published: August 2024

Abstract
The advent of the information age has revolutionized data collection and has led to a rapid expansion of available data sources. Methods of data integration are indispensable when a question of interest cannot be addressed using a single data source. Record linkage (RL) is at the forefront of such data integration efforts. Incentives for sharing linked data for secondary analysis have prompted the need for methodology accounting for possible errors at the RL stage. Mismatch error is a common consequence resulting from the use of nonunique or noisy identifiers at that stage. In this paper, we present a framework to enable valid postlinkage inference in the secondary analysis setting in which only the linked file is given. The proposed framework covers a variety of statistical models and can flexibly incorporate information about the underlying RL process. We propose a mixture model for linked records whose two components reflect distributions conditional on match status, i.e. correct or false match. Regarding inference, we develop a method based on composite likelihood and the expectation-maximization algorithm that is implemented in the R package pldamixture. Extensive simulations and case studies involving contemporary RL applications corroborate the effectiveness of our framework.
Lemon zinc finger protein ClSUP induces accumulation of reactive oxygen species and inhibits citrus yellow vein-clearing virus infection via interactions with ClDOF3.4
Authors: Liao Ping , Zeng Ting , Chen Yuan , Ding Dong-dong , Zhou Chang-yong , Zhou Yan 
Published: August 2024

Abstract
Citrus yellow vein-clearing virus (Potexvirus citriflavivenae; CYVCV) is an increasing threat to citrus cultivation. Notably, the role of zinc finger proteins (ZFPs) in mediating viral resistance in citrus plants is unclear. In this study, we demonstrated that ZFPs ClSUP and ClDOF3.4 enhanced citrus defense responses against CYVCV in Eureka lemon (Citrus limon ‘Eureka’). ClSUP interacted with the coat protein (CP) of CYVCV to reduce CP accumulation and inhibited its silencing suppressor function. Overexpression of CISUP triggered reactive oxygen species (ROS) and salicylic acid (SA) pathways, and enhanced resistance to CYVCV infection. In contrast, ClSUP silencing resulted in increased CP accumulation and down-regulated ROS and SA-related genes. ClDOF3.4 interacted with ClSUP to facilitate its interactions with CP. Furthermore, ClDOF3.4 synergistically regulated the accumulation of ROS and SA with ClSUP and accelerated down-regulation of CP accumulation. Transgenic plants co-expressing ClSUP and ClDOF3.4 significantly decreased the CYVCV. These findings provide a new reference for understanding the interaction mechanism between the host and CYVCV.
The Genetic Architecture of Recombination Rates is Polygenic and Differs Between the Sexes in Wild House Sparrows (Passer domesticus)
Authors: McAuley John B , Servin Bertrand , Burnett Hamish A , Brekke Cathrine , Peters Lucy , Hagen Ingerid J , Niskanen Alina K , Ringsby Thor Harald , Husby Arild , Jensen Henrik , Johnston Susan E 
Published: August 2024

Abstract
Meiotic recombination through chromosomal crossing-over is a fundamental feature of sex and an important driver of genomic diversity. It ensures proper disjunction, allows increased selection responses, and prevents mutation accumulation; however, it is also mutagenic and can break up favorable haplotypes. This cost–benefit dynamic is likely to vary depending on mechanistic and evolutionary contexts, and indeed, recombination rates show huge variation in nature. Identifying the genetic architecture of this variation is key to understanding its causes and consequences. Here, we investigate individual recombination rate variation in wild house sparrows (Passer domesticus). We integrate genomic and pedigree data to identify autosomal crossover counts (ACCs) and intrachromosomal allelic shuffling (r¯intra) in 13,056 gametes transmitted from 2,653 individuals to their offspring. Females had 1.37 times higher ACC, and 1.55 times higher r¯intra than males. ACC and r¯intra were heritable in females and males (ACC h2 = 0.23 and 0.11; r¯intra h2 = 0.12 and 0.14), but cross-sex additive genetic correlations were low (rA = 0.29 and 0.32 for ACC and r¯intra). Conditional bivariate analyses showed that all measures remained heritable after accounting for genetic values in the opposite sex, indicating that sex-specific ACC and r¯intra can evolve somewhat independently. Genome-wide models showed that ACC and r¯intra are polygenic and driven by many small-effect loci, many of which are likely to act in trans as global recombination modifiers. Our findings show that recombination rates of females and males can have different evolutionary potential in wild birds, providing a compelling mechanism for the evolution of sexual dimorphism in recombination.
Inflammatory Biomarker Reduction With Fostemsavir Over 96 Weeks in Heavily Treatment-Experienced Adults With Multidrug-Resistant HIV-1 in the BRIGHTE Study
Authors: Clark Andrew , Prakash Manyu , Chabria Shiven , Pierce Amy , Castillo-Mancilla Jose R , Wang Marcia , Du Fangfang , Tenorio Allan R 
Published: August 2024

Abstract

Background
Fostemsavir, a first-in-class attachment inhibitor that binds to the viral envelope protein gp120, is approved for heavily treatment-experienced persons with HIV-1 with limited treatment options. We explored changes in immunologic and coagulopathy parameters in the BRIGHTE study: a phase 3 trial that evaluated fostemsavir plus optimized background therapy in heavily treatment-experienced adults with multidrug-resistant HIV-1.

Methods
CD4+ T-cell count, CD4+/CD8+ ratio, soluble CD14, soluble CD163, and D-dimer levels were measured through 96 weeks in participants with 1 or 2 fully active antiretroviral agents available at screening. No formal statistical analyses were performed.

Results
Among 272 participants, increases were observed from baseline to week 96 in CD4+ T-cell count (mean increase, +205 cells/mm3) and CD4+/CD8+ ratio (mean increase, +0.24). The proportion of observed participants with a CD4+/CD8+ ratio ≥0.45 increased from 9% (25/272) at baseline to 40% (85/213) at week 96. From baseline to week 96, we also observed trends toward decreases in the following (mean [SD] change): soluble CD14, −738.2 (981.8) µg/L; soluble CD163, −138.0 (193.4) µg/L; and D-dimer, −0.099 (0.521) mg/L fibrinogen-equivalent units. Decreases in biomarkers were generally observed among subgroups by baseline disease characteristics, virologic response, and CD4+ T-cell count.

Conclusions
These data suggest that heavily treatment-experienced persons with multidrug-resistant HIV-1 treated with fostemsavir + optimized background therapy may have improvements in immune parameters, including markers of monocyte activation and coagulopathy.

Clinical Trials Registration
NCT02362503 (ClinicalTrials.gov; https://clinicaltrials.gov/study/NCT02362503).
Origins, belonging, and expectations: assessing resource compensation and reinforcement in academic educational trajectories
Authors: Burger Kaspar , Brack Nathan 
Published: August 2024

Abstract
Research has shown that socioeconomic and psychological resources may influence educational trajectories. There are still unanswered questions, however, about the unique roles of these resources and the interplay between them. We consider two such questions: First, how do major psychological resources—a sense of school belonging and optimistic future expectations—predict educational trajectories when controlling for the effect of socioeconomic resources? And, second, do these psychological resources compensate for lacking socioeconomic resources or do they reinforce the influence of socioeconomic resources on educational trajectories? We used data from a 15-year-long Swiss panel study (N = 1989) and investigated educational trajectories concerning individuals’ transitions from lower-secondary to academic upper-secondary education, and from there to university. Findings indicated that both socioeconomic and psychological resources were significantly associated with individuals’ probability of transitioning to academic upper-secondary education. We also uncovered some evidence of resource compensation between socioeconomic resources and future expectations, suggesting that optimistic expectations may buffer the adverse effect of scarce socioeconomic resources on educational attainment. Furthermore, we found that both the sense of school belonging and future expectations were significantly associated with individuals’ probability of transitioning to university. Overall, we conclude that psychological resources play a critical role in academically oriented educational trajectories and that they may partly compensate for the effects of limited socioeconomic resources on these trajectories.
Closing the Information Gap Between the Field and Scientific Literature for Improved Disease Management, with a Focus on Rice and Bacterial Blight
Authors: Loo Eliza P. I. , Szurek Boris , Arra Yugander , Stiebner Melissa , Buchholzer Marcel , Devanna B. N. , Vera Cruz Casiana M. , Frommer Wolf B. 
Published: August 2024

A path to sustainably reduce world hunger, food insecurity, and malnutrition is to close the crop yield gap and, particularly, lower losses due to pathogens. Breeding resistant crops is key to achieving this goal, which is an effort requiring collaboration among stakeholders, scientists, breeders, farmers, and policymakers. During a disease outbreak, epidemiologists survey the occurrence of a disease after which pathologists investigate mechanisms to stop an infection. Policymakers then implement strategies with farmers and breeders to overcome the outbreak. Information flow from the field to the lab and back to the field involves several processing hubs that require different information inputs. Failure to communicate the necessary information results in the transfer of meaningless data. Here, we discuss gaps in information acquisition and transfer between the field and laboratory. Using rice bacterial blight disease as an example, we discuss pathogen biology and disease resistance to point out the importance of reporting pathogen strains that caused an outbreak to optimize the deployment of resistant crop varieties. We examine differences between infection in the field and assays performed in the laboratory to draw awareness of possible misinformation concerning plant resistance or susceptibility. We discuss key data considered useful for reporting disease outbreaks, sampling bias, and suggestions for improving data quality. We also touch on the knowledge gap in the state-of-the-art literature regarding disease dispersal and transmission. We use a recent case study to exemplify the gaps mentioned. We conclude by highlighting potential actions that may contribute to food security and to closing the yield gap. [Formula: see text] Copyright © 2025 The Author(s). This is an open access article distributed under the CC BY 4.0 International license .
Improving access and outcomes for children with ADHD
Authors: Rowan Linda , Gary Annette , Geist Rebecca 
Published: August 2024

ABSTRACT
Attention-deficit hyperactivity disorder (ADHD) is a mental health condition characterized by inattentiveness, hyperactivity, and impulsivity as well as difficulties with social interaction, learning, and sometimes sleep. A variety of symptoms is possible, and three ADHD presentations have been defined. Owing to healthcare workforce shortages, particularly in mental health care, it is critical for family NPs and other primary care providers to possess accurate understanding of the disorder and its symptomatology, evaluation, diagnosis, and management in children and adolescents. In today's landscape, newer extended-release and long-acting stimulants support better medication administration and adherence, as well as maintain more consistent levels in the body throughout the day, for pediatric patients. This article aims to keep family NPs up to date in the latest in ADHD diagnosis and management to reduce patient barriers to care; it also provides NPs with critical information to convey to pediatric patients, their families, and their teachers during this back-to-school season.
Cardiovascular Effects of Increasing Positive End-expiratory Pressure in a Model of Left Ventricular Cardiogenic Shock in Female Pigs
Authors: Hørsdal Oskar Kjærgaard , Wethelund Kasper Lykke , Gopalasingam Nigopan , Lyhne Mads Dam , Ellegaard Mark Stoltenberg , Møller-Helgestad Ole Kristian , Ravn Hanne Berg , Wiggers Henrik , Christensen Steffen , Berg-Hansen Kristoffer 
Published: August 2024

Background:
Cardiogenic shock (CS) presents a medical challenge with limited treatment options. Positive end-expiratory pressure (PEEP) during mechanical ventilation has been linked with clinical benefits in patients with CS. This study investigated whether increasing PEEP levels could unload the left ventricle (LV) in CS in a large animal model of LV-CS.

Methods:
Left ventricle cardiogenic shock was induced in 26 female pigs (60 kg) by microsphere injections into the left main coronary artery. In one study, protocol PEEP was increased (5, 10, and 15 cm H2O) and then reverted (15, 10, and 5 cm H2O) in 3-min intervals. In another protocol, PEEP increments with higher granularity were conducted through 3-min intervals (5, 8, 10, 13, and 15 cm H2O). Hemodynamic measurements were performed at all PEEP levels during a healthy state and in LV-CS with LV pressure–volume loops. The primary endpoint was pressure–volume area. Secondary endpoints included other mechanoenergetic parameters and estimates of LV preload and afterload.

Results:
Cardiac output (CO) decreased significantly in LV-CS from 4.5 ± 1.0 to 3.1 ± 0.9 l/min (P < 0.001). Increasing PEEP resulted in lower pressure–volume area, demonstrating a 36 ± 3% decrease in the healthy state (P < 0.001) and 18 ± 3% in LV-CS (P < 0.001) at PEEP 15 cm H2O. These effects were highly reversible when PEEP was returned to 5 cm H2O. Although mean arterial pressure declined with higher PEEP, CO remained preserved during LV-CS (P = 0.339). Increasing PEEP caused reductions in key measures of LV preload and afterload during LV-CS. The right ventricular stroke work index was decreased with increased PEEP. Despite a minor increase in heart rate at PEEP levels of 15 cm H2O (71 beats/min vs. 75 beats/min, P < 0.05), total mechanical power expenditure (pressure–volume area normalized to heart rate) decreased at higher PEEP.

Conclusions:
Applying higher PEEP levels reduced pressure–volume area, preserving CO while decreasing mean arterial pressure. Positive end-expiratory pressure could be a viable LV unloading strategy if titrated optimally during LV-CS.