bluuebunny/crossref_metadata_2025_split huggingface dataset:
8 The influence of sepsis on the tissue penetration of piperacillin-tazobactam in children: a microdialysis study in the juvenile pig
Authors: Hermans Eline , Meganck Freya , de Paepe Peter , Vande Walle Johan , de Cock Pieter , Devreese Mathias 
Published: May 2023

IntroductionAntibiotics are the cornerstone in the treatment of sepsis. Microdialysis (MD) data from adults suggest an impaired antibiotic tissue penetration in the case of sepsis. Tissue pharmacokinetics (PK) remain largely understudied in children. Juvenile pig models have proven to provide an accurate prediction of PK behavior in pediatric patients. This study aimed to investigate the influence of sepsis on antibiotic tissue penetration in a piglet model.MethodsIn 17 piglets, piperacillin (PIP) - tazobactam (TAZ) was administered (75 mg/kg IV over 30 minutes, 6h dosing interval) over 4 days. Blood and MD samples (muscle) were collected in first-dose (FD) and steady-state (SS) conditions. In 11 piglets a continuous LPS infusion (36h) was administered to induce a septic state. In the 6 control animals (no LPS) time effects during the study period were evaluated. Non-compartmental PK analysis was used to determine the tissue penetration (AUC-ratio tissue/plasma). The AUC ratios were pairwise compared between the healthy and septic states in each piglet, data are reported as mean ± SD.ResultsFor PIP, the AUC ratio in FD conditions was significantly lower in the septic state (0.84 ± 0.22) compared to the healthy baseline measurement (1.06 ± 0.46) (P = 0.042). In SS conditions, comparable results were found with an AUC ratio of 1.09 ± 0.27 during baseline and 0.80 ± 0.22 in the septic state (p=0.009). The results for TAZ were similar to PIP. There were no time effects found in the control group.ConclusionIn this juvenile piglet model, sepsis impaired the PIP-TAZ tissue penetration. The results of this study warrant further research into the tissue PK of septic children to optimize the antibiotic dosing in this population.
A cross-sectional study factors associated with resilience among medical staff in radiology departments during COVID-19, Riyadh, Kingdom of Saudi Arabia
Authors: Asiri Fatimah Khalid , Al Harbi Nouf Sahal , Alanazi Manal Abdullah , Aljuaid Mohammed M , Fahlevi Mochammad , Heidler Petra 
Published: May 2023

ObjectivesThis study aims to assess the level of resilience of medical workers in radiology departments in Riyadh, Kingdom of Saudi Arabia, during the COVID-19 outbreak and to explore associated factors.SettingMedical staff, including nurses, technicians, radiology specialists and physicians, working in radiology departments at government hospitals in Riyadh, Saudi Arabia during the COVID-19 outbreak.DesignA cross-sectional study.ParticipantsThe study was conducted among 375 medical workers in radiology departments in Riyadh, Kingdom of Saudi Arabia. The data collection took place from 15 February 2022 to 31 March 2022.ResultsThe total resilience score was 29.37±6.760 and the scores of each dimension showed that the higher mean score was observed in the domain of ‘flexibility’, while the lowest was observed in ‘maintaining attention under stress’. Pearson’s correlation analysis showed that there was a significant negative correlation between resilience and perceived stress (r=–0.498, p<0.001). Finally, based on multiple linear regression analysis, factors affecting resilience among participants are the availability of psychological hotline (available, B=2.604, p<0.050), knowledge of COVID-19 protective measures (part of understanding, B=−5.283, p<0.001), availability of adequate protective materials (partial shortage, B=−2.237, p<0.050), stress (B=−0.837, p<0.001) and education (postgraduate, B=−1.812, p<0.050).ConclusionsThis study sheds light on the level of resilience and the factors that contribute to resilience in radiology medical staff. Moderate levels of resilience call for health administrators to focus on developing strategies that can effectively help cope with workplace adversities.
Adolescent, caregiver and provider perspectives on tuberculosis treatment adherence: a qualitative study from Lima, Peru
Authors: Chiang Silvia S , Senador Liz , Altamirano Elmer , Wong Milagros , Beckhorn Catherine B , Roche Stephanie , Coit Julia , Oliva Rapoport Victoria Elena , Lecca Leonid , Galea Jerome T 
Published: May 2023

ObjectivesTo understand the perspectives of adolescents (10–19 years old), their caregivers and healthcare providers regarding factors that impact adherence to tuberculosis (TB) treatment among adolescents.DesignWe conducted in-depth interviews using semistructured interview guides based on the World Health Organization (WHO)’s Five Dimensions of Adherence framework, which conceptualises adherence as being related to the health system, socioeconomic factors, patient, treatment and condition. We applied framework thematic analysis.SettingBetween August 2018 and May 2019, at 32 public health centres operated by the Ministry of Health in Lima, Peru.ParticipantsWe interviewed 34 adolescents who completed or were lost to follow-up from treatment for drug-susceptible pulmonary TB disease in the preceding 12 months; their primary caregiver during treatment; and 15 nurses or nurse technicians who had ≥6 months’ experience supervising TB treatment.ResultsParticipants reported numerous treatment barriers, the most common of which were the inconvenience of health facility-based directly observed therapy (DOT), long treatment duration, adverse treatment events and symptom resolution. The support of adult caregivers was critical for helping adolescents overcome these barriers and carry out the behavioural skills (eg, coping with the large pill burden, managing adverse treatment events and incorporating treatment into daily routines) needed to adhere to treatment.ConclusionOur findings support a three-pronged approach to improve TB treatment adherence among adolescents: (1) reduce barriers to adherence (eg, home-based or community-based DOT in lieu of facility-based DOT, reducing pill burden and treatment duration when appropriate), (2) teach adolescents the behavioural skills required for treatment adherence and (3) strengthen caregivers’ ability to support adolescents.
Prevalence and associated factors of stunting and thinness among primary school-aged children in Gudeya Bila district, West Ethiopia: a cross-sectional study
Authors: Shama Adisu Tafari , Wakuma Obsa , Debelo Sidise , Terefa Dufera Rikitu , Cheme Melese Chego , Lema Matiyos , Biru Bayise , Geta Edosa Tesfaye 
Published: May 2023

ObjectivesThis study aimed to assess the prevalence and associated factors of stunting and thinness among primary school-age children in the Gudeya Bila district.Methods and analysisA community-based cross-sectional study was conducted in the Gudeya Bila district which is located in the Western part of Ethiopia. Among the calculated sample size of 561 school-aged children, 551 children were randomly selected by systematic random sampling technique and participated in this study. Critical illness, physical disability and the inability of caregivers to respond were exclusion criteria. Under-nutrition was the primary outcome while factors associated were the second outcome of this study. Semi-structured interviewer-administered questionnaires were used to collect the data while interview and body measurement were used as data collection techniques. Health Extension Workers collected the data. Data were entered into Epi Data V.3.1 and transported into SPSS V.24.0 software for data cleaning and analysis. Both bivariable and multivariable logistic regressions were run to identify the associated factors of under-nutrition. Model fitness was checked by using Hosmer-Lemeshow’s test. Variables with p values <0.05 were considered statistically significant in the multivariable logistic regression.Results and conclusionThe prevalence of stunting and thinness among primary school children was 8.2% (95% CI 5.6% to 10.6%) and 7.1% (95% CI 4.5% to 8.9%), respectively. Being male caregiver (adjusted OR (AOR)=4.26;95% CI 1.256% to 14.464%), family size ≥4 (AOR=4.65; 95% CI 1.8 51% to 11.696%), separated kitchen room (AOR=0.096; 95% CI 0.019 to 0.501) and hand washing after toilet use (AOR=0.152; 95% CI 0.035% to 0.667%) were significantly associated with stunting. Moreover, drinking coffee (AOR=2.25; 95% CI 1.968% to 5.243%) and child dietary diversity score <4 (AOR=2.54; 95% CI 1.721% to 8.939%) were significantly associated with thinness. Under-nutrition in this study was high compared with the global target of eradicating under-nutrition. Community-based nutritional education programmes and implementing health extension programmes are important to reduce the problem of under-nutrition to an undetectable level and to eradicate chronic under-nutrition.
Data from mWTX-330, an IL 12 INDUKINE Molecule, Activates and Reshapes Tumor-infiltrating CD8+ T and NK Cells to Generate Antitumor Immunity
Authors: Nirschl Christopher J. , Brodkin Heather R. , Domonkos Celesztina , Dwyer Connor J. , Hicklin Daniel J. , Ismail Nesreen , Seidel-Dugan Cynthia , Steiner Philipp , Steuert Zoe , Sullivan Jenna M. , Winston William M. , Salmeron Andres 
Published: May 2023

<div>Abstract<p>IL-12 is a pleotropic inflammatory cytokine that has broad stimulatory effects on various immune cell populations, making it an attractive target for cancer immunotherapy. However, despite generating robust antitumor activity in syngeneic murine tumor models, clinical administration of IL-12 has been limited by severe toxicity. mWTX-330 is a selectively inducible INDUKINE molecule comprised of a half-life extension domain and an inactivation domain linked to chimeric IL-12 by tumor protease–sensitive linkers. Systemic administration of mWTX-330 in mice was well tolerated, resulted in robust antitumor immunity in multiple tumor models, and preferentially activated tumor-infiltrating immune cells rather than immune cells present in peripheral tissues. Antitumor activity was dependent on in vivo processing of the protease cleavable linkers and required CD8+ T cells for full efficacy. Within the tumor, mWTX-330 increased the frequency of cross-presenting dendritic cells (DCs), activated natural killer (NK) cells, skewed conventional CD4+ T cells toward a T helper 1 (TH1) phenotype, drove regulatory T cells (Treg) fragility, and increased the frequency of polyfunctional CD8+ T cells. mWTX-330 treatment also increased the clonality of tumor-infiltrating T cells by expanding underrepresented T-cell receptor (TCR) clones, drove CD8+ T and NK cells towards increased mitochondrial respiration and fitness, and decreased the frequency of TOX+ exhausted CD8+ T cells within the tumor. A fully human version of this INDUKINE molecule was stable in human serum, was reliably and selectively processed by human tumor samples, and is currently in clinical development.
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Deconstructing Olfactory Epithelium Developmental Pathways in Olfactory Neuroblastoma
Authors: Finlay John B. , Abi Hachem Ralph , Jang David W. , Osazuwa-Peters Nosayaba , Goldstein Bradley J. 
Published: May 2023

Olfactory neuroblastoma is a rare tumor arising from the olfactory cleft region of the nasal cavity. Because of the low incidence of this tumor, as well as an absence of established cell lines and murine models, understanding the mechanisms driving olfactory neuroblastoma pathobiology has been challenging. Here, we sought to apply advances from research on the human olfactory epithelial neurogenic niche, along with new biocomputational approaches, to better understand the cellular and molecular factors in low- and high-grade olfactory neuroblastoma and how specific transcriptomic markers may predict prognosis. We analyzed a total of 19 olfactory neuroblastoma samples with available bulk RNA-sequencing and survival data, along with 10 samples from normal olfactory epithelium. A bulk RNA-sequencing deconvolution model identified a significant increase in globose basal cell (GBC) and CD8 T-cell identities in high-grade tumors (GBC from ∼0% to 8%, CD8 T cell from 0.7% to 2.2%), and significant decreases in mature neuronal, Bowman's gland, and olfactory ensheathing programs, in high-grade tumors (mature neuronal from 3.7% to ∼0%, Bowman's gland from 18.6% to 10.5%, olfactory ensheathing from 3.4% to 1.1%). Trajectory analysis identified potential regulatory pathways in proliferative olfactory neuroblastoma cells, including PRC2, which was validated by immunofluorescence staining. Survival analysis guided by gene expression in bulk RNA-sequencing data identified favorable prognostic markers such as SOX9, S100B, and PLP1 expression.Significance:Our analyses provide a basis for additional research on olfactory neuroblastoma management, as well as identification of potential new prognostic markers.
Retained Metabolic Flexibility of the Failing Human Heart
Authors: Watson William D. , Green Peregrine G. , Lewis Andrew J.M. , Arvidsson Per , De Maria Giovanni Luigi , Arheden Håkan , Heiberg Einar , Clarke William T. , Rodgers Christopher T. , Valkovič Ladislav , Neubauer Stefan , Herring Neil , Rider Oliver J. 
Published: May 2023

Background:
The failing heart is traditionally described as metabolically inflexible and oxygen starved, causing energetic deficit and contractile dysfunction. Current metabolic modulator therapies aim to increase glucose oxidation to increase oxygen efficiency of adenosine triphosphate production, with mixed results.

Methods:

To investigate metabolic flexibility and oxygen delivery in the failing heart, 20 patients with nonischemic heart failure with reduced ejection fraction (left ventricular ejection fraction 34.9±9.1) underwent separate infusions of insulin+glucose infusion (I+G) or Intralipid infusion. We used cardiovascular magnetic resonance to assess cardiac function and measured energetics using phosphorus-31 magnetic resonance spectroscopy. To investigate the effects of these infusions on cardiac substrate use, function, and myocardial oxygen uptake (MV
o
2
), invasive arteriovenous sampling and pressure–volume loops were performed (n=9).

Results:

At rest, we found that the heart had considerable metabolic flexibility. During I+G, cardiac glucose uptake and oxidation were predominant (70±14% total energy substrate for adenosine triphosphate production versus 17±16% for Intralipid;
P
=0.002); however, no change in cardiac function was seen relative to basal conditions. In contrast, during Intralipid infusion, cardiac long-chain fatty acid (LCFA) delivery, uptake, LCFA acylcarnitine production, and fatty acid oxidation were all increased (LCFA 73±17% of total substrate versus 19±26% total during I+G;
P
=0.009). Myocardial energetics were better with Intralipid compared with I+G (phosphocreatine/adenosine triphosphate 1.86±0.25 versus 2.01±0.33;
P
=0.02), and systolic and diastolic function were improved (LVEF 34.9±9.1 baseline, 33.7±8.2 I+G, 39.9±9.3 Intralipid;
P
<0.001). During increased cardiac workload, LCFA uptake and oxidation were again increased during both infusions. There was no evidence of systolic dysfunction or lactate efflux at 65% maximal heart rate, suggesting that a metabolic switch to fat did not cause clinically meaningful ischemic metabolism.

Conclusions:
Our findings show that even in nonischemic heart failure with reduced ejection fraction with severely impaired systolic function, significant cardiac metabolic flexibility is retained, including the ability to alter substrate use to match both arterial supply and changes in workload. Increasing LCFA uptake and oxidation is associated with improved myocardial energetics and contractility. Together, these findings challenge aspects of the rationale underlying existing metabolic therapies for heart failure and suggest that strategies promoting fatty acid oxidation may form the basis for future therapies.
A pattern of cognitive resource disruptions in childhood psychopathology
Authors: Stier Andrew J. , Cardenas-Iniguez Carlos , Kardan Omid , Moore Tyler M. , Meyer Francisco A. C. , Rosenberg Monica D. , Kaczkurkin Antonia N. , Lahey Benjamin B. , Berman Marc G. 
Published: May 2023

Abstract
The Hurst exponent (H) isolated in fractal analyses of neuroimaging time series is implicated broadly in cognition. Within this literature, H is associated with multiple mental disorders, suggesting that H is transdimensionally associated with psychopathology. Here, we unify these results and demonstrate a pattern of decreased H with increased general psychopathology and attention-deficit/hyperactivity factor scores during a working memory task in 1,839 children. This pattern predicts current and future cognitive performance in children and some psychopathology in 703 adults. This pattern also defines psychological and functional axes associating psychopathology with an imbalance in resource allocation between fronto-parietal and sensorimotor regions, driven by reduced resource allocation to fronto-parietal regions. This suggests the hypothesis that impaired working memory function in psychopathology follows from a reduced cognitive resource pool and a reduction in resources allocated to the task at hand.
Atmospheric Water Vapor Transport between Ocean and Land under Climate Warming
Authors: Wang Jialin , Pan Feifei , An Pingli , Han Guolin , Jiang Kang , Song Yu , Huang Na , Zhang Ziyuan , Ma Shangqian , Chen Xiao , Pan Zhihua 
Published: May 2023

Abstract
Global warming intensifies atmospheric water vapor transport between ocean and land, which increases the likelihood of extreme precipitation and floods. However, accurate estimations of water vapor exchange between ocean and land are difficult due to the lack of available data and effective methods. This study developed a novel eight-direction-vector decomposition algorithm for calculating water vapor flux between ocean and land based on the ERA5 dataset, and the results showed that global water vapor exchange between ocean and land had significantly increased in the past 40 years, except for Antarctica. During 1980–2018, the average annual net water vapor inflow from ocean to land (Qnet) was 44.68 × 1015 kg yr−1, and Qnet increased at a rate of 1.48 × 1015 kg yr−1 decade−1. The intensified atmospheric water vapor exchange between ocean and land was directly caused by the increase of atmospheric water vapor content, which largely depended on the rising air temperature, and it was found that water vapor flux between ocean and land increased by over 8% K−1 with the increasing air temperature at the global average. This study also identified El Niño–Southern Oscillation (ENSO) as an important contributor to the global ocean–land water vapor exchange anomalies. A strong El Niño event (MEI = 1) can result in a 1.36 × 1015 kg yr−1 (3.03%) decrease in Qnet, and a strong La Niña event (MEI = −1) can increase Qnet by 1.38 × 1015 kg yr−1 (3.09%). The eight-direction-vector decomposition algorithm was effective in ocean–land water vapor flux estimations at different spatial and temporal scales, which could provide great insights into the mechanisms of extreme precipitation events.

Significance Statement
This study developed a novel approach on water vapor flux estimation (i.e., the eight-direction-vector decomposition algorithm) and achieved a high-temporal–spatial-resolution estimation of water vapor flux between ocean and land. It was found that water vapor flux between ocean and land was intensified by increasing air temperature at a rate of 8% K−1, and El Niño yielded an anomaly low net water vapor input from ocean to land at the global scale. The algorithm developed in this study can be used for estimating water vapor fluxes at different spatial and temporal scales, which is crucial for evaluating the role of water vapor flux on formations for extreme weather (e.g., torrential rainstorms and heat waves) and climatic extremes (e.g., droughts and floods).
The Idealized Aquaplanet Maritime Continent Barrier Effect on the MJO Predictability
Authors: Kim Hyemi , Benedict James J. 
Published: May 2023

Abstract
Studies have indicated exaggerated Maritime Continent (MC) barrier effect in simulations of the Madden–Julian oscillation (MJO), a dominant source of subseasonal predictability in the tropics. This issue has plagued the modeling and operational forecasting communities for decades, while the sensitivity of MC barrier on MJO predictability has not been addressed quantitatively. In this study, perfect-model ensemble forecasts are conducted with an aquaplanet configuration of the Community Earth System Model version 2 (CESM2) in which both basic state and tropical modes of variability are reasonably simulated with a warm pool–like SST distribution. When water-covered terrain mimicking MC landmasses is added to the warm pool–like SST framework, the eastward propagation of the MJO is disturbed by the prescribed MC aqua-mountain. The MJO predictability estimate with the perfect-model experiment is about 6 weeks but reduces to about 4 weeks when the MJO is impeded by the MC aqua-mountain. Given that the recent operational forecasts show an average of 3–4 weeks of MJO prediction skill, we can conclude that improving the MJO propagation crossing the MC could improve the MJO skill to 5–6 weeks, close to the potential predictability found in this study (6 weeks). Therefore, more effort toward understanding and improving the MJO propagation is needed to enhance the MJO and MJO-related forecasts to improve the subseasonal-to-seasonal prediction.
Linearity of the Climate System Response to Raising and Lowering West Antarctic and Coastal Antarctic Topography
Authors: Pauling Andrew G. , Bitz Cecilia M. , Steig Eric J. 
Published: May 2023

Abstract
A hierarchy of general circulation models (GCMs) is used to investigate the linearity of the response of the climate system to changes in Antarctic topography. Experiments were conducted with a GCM with either a slab ocean or fixed SSTs and sea ice, in which the West Antarctic ice sheet (WAIS) and coastal Antarctic topography were either lowered or raised in an idealized way. Additional experiments were conducted with a fully coupled GCM with topographic perturbations based on an ice-sheet model in which the WAIS collapses. The response over the continent is the same in all model configurations and is mostly linear. In contrast, the response has substantial nonlinear elements over the Southern Ocean that depend on the model configuration and are due to feedbacks with sea ice, ocean, and clouds. The atmosphere warms near the surface over much of the Southern Ocean and cools in the stratosphere over Antarctica, whether topography is raised or lowered. When topography is lowered, the Southern Ocean surface warming is due to strengthened southward atmospheric heat transport and associated enhanced storminess over the WAIS and the high latitudes of the Southern Ocean. When topography is raised, Southern Ocean warming is more limited and is associated with circulation anomalies. The response in the fully coupled experiments is generally consistent with the more idealized experiments, but the full-depth ocean warms throughout the water column whether topography is raised or lowered. These results indicate that ice sheet–climate system feedbacks differ depending on whether the Antarctic ice sheet is gaining or losing mass.

Significance Statement
Throughout Earth’s history, the Antarctic ice sheet was at times taller or shorter than it is today. The purpose of this study is to investigate how the atmosphere, sea ice, and ocean around Antarctica respond to changes in ice sheet height. We find that the response to lowering the ice sheet is not the opposite of the response to raising it, and that in either case the ocean surface near the continent warms. When the ice sheet is raised, the ocean warming is related to circulation changes; when the ice sheet is lowered, the ocean warming is from an increase in southward atmospheric heat transport. These results are important for understanding how the ice sheet height and local climate evolve together through time.