bluuebunny/crossref_metadata_2025_split huggingface dataset:
Triacylglycerol stability limits futile cycles and inhibition of carbon capture in oil-accumulating leaves
Authors: Johnson Brandon S , Allen Doug K , Bates Philip D 
Published: March 2024

Abstract
Engineering plant vegetative tissue to accumulate triacylglycerols (TAG, e.g. oil) can increase the amount of oil harvested per acre to levels that exceed current oilseed crops. Engineered tobacco (Nicotiana tabacum) lines that accumulate 15% to 30% oil of leaf dry weight resulted in starkly different metabolic phenotypes. In-depth analysis of the leaf lipid accumulation and 14CO2 tracking describe metabolic adaptations to the leaf oil engineering. An oil-for-membrane lipid tradeoff in the 15% oil line (referred to as HO) was surprisingly not further exacerbated when lipid production was enhanced to 30% (LEAFY COTYLEDON 2 (LEC2) line). The HO line exhibited a futile cycle that limited TAG yield through exchange with starch, altered carbon flux into various metabolite pools and end products, and suggested interference of the glyoxylate cycle with photorespiration that limited CO2 assimilation by 50%. In contrast, inclusion of the LEC2 transcription factor in tobacco improved TAG stability, alleviated the TAG-to-starch futile cycle, and recovered CO2 assimilation and plant growth comparable to wild type but with much higher lipid levels in leaves. Thus, the unstable production of storage reserves and futile cycling limit vegetative oil engineering approaches. The capacity to overcome futile cycles and maintain enhanced stable TAG levels in LEC2 demonstrated the importance of considering unanticipated metabolic adaptations while engineering vegetative oil crops.
Cocaine diminishes functional network robustness and destabilizes the energy landscape of neuronal activity in the medial prefrontal cortex
Authors: Borzou Ahmad , Miller Sierra N , Hommel Jonathan D , Schwarz J M 
Published: March 2024

Abstract
We present analysis of neuronal activity recordings from a subset of neurons in the medial prefrontal cortex of rats before and after the administration of cocaine. Using an underlying modern Hopfield model as a description for the neuronal network, combined with a machine learning approach, we compute the underlying functional connectivity of the neuronal network. We find that the functional connectivity changes after the administration of cocaine with both functional-excitatory and functional-inhibitory neurons being affected. Using conventional network analysis, we find that the diameter of the graph, or the shortest length between the two most distant nodes, increases with cocaine, suggesting that the neuronal network is less robust. We also find that the betweenness centrality scores for several of the functional-excitatory and functional-inhibitory neurons decrease significantly, while other scores remain essentially unchanged, to also suggest that the neuronal network is less robust. Finally, we study the distribution of neuronal activity and relate it to energy to find that cocaine drives the neuronal network towards destabilization in the energy landscape of neuronal activation. While this destabilization is presumably temporary given one administration of cocaine, perhaps this initial destabilization indicates a transition towards a new stable state with repeated cocaine administration. However, such analyses are useful more generally to understand how neuronal networks respond to perturbations.
Into the Unknown: Conceptualizing the Experience of Uncertainty in Citizen–State Interactions
Authors: Cecchini Mathilde 
Published: March 2024

Abstract
It is often argued that uncertainty is an inherent characteristic of citizen–state interactions. It is therefore hardly surprising that many scholars of street-level bureaucracy have studied how frontline workers cope with and make discretionary decisions under uncertain conditions. However, citizens’ experiences of uncertainty have received limited attention in the street-level bureaucracy literature. This article argues that understanding citizens’ experiences of uncertainty is highly relevant because experiences of uncertainty are likely to affect mental well-being of individuals negatively. The article seeks to address this gap by building a conceptual framework for understanding and analyzing citizens’ experiences with uncertainty in state–citizen interactions based on theoretical insights from the existing literature and in-depth qualitative analysis of 20 narrative interviews with former coronavirus disease 2019 (COVID-19) patients and their relatives concerning their encounter with health authorities. The article proposes a conceptual framework that distinguishes between epistemic uncertainty and moral uncertainty. Epistemic uncertainty concerns uncertainty about empirical facts or knowledge. Moral uncertainty concerns uncertainty about values due to conflicting or competing norms and values. The article illustrates how these forms of uncertainty may arise before, during, and after citizens’ interaction with frontline workers.
The Rhetorical Post-presidency: Former Presidents as Elite Cue Givers
Authors: Winger Gregory H , Oliver Alex 
Published: March 2024

Abstract
Former presidents are not resigned to quiet anonymity but instead can remain prominent political actors long after exiting the White House. From Jimmy Carter's personal diplomacy to Donald Trump's caustic social media posts, ex-presidents continue to exercise considerable political power despite lacking any official role or governing authority. We argue that this continued post-presidential influence is an outgrowth of the informal powers of the presidency. A president's rhetorical prowess and ability to command national attention do not dissipate upon exiting office but instead form the basis for post-presidential influence. To test this theory, we conducted two survey experiments of former presidents as elite cue givers. We found that although effects are not uniform, statements attributed to former presidents can substantively alter the policy preferences of recipients. However, these effects appear to be highly individualistic and largely tied to copartisan recipients.
Most dynorphin neurons in the zona incerta-perifornical area are active in waking relative to non-rapid-eye movement and rapid-eye movement sleep
Authors: Shiromani Priyattam J , Vidal-Ortiz Aurelio 
Published: March 2024

Abstract
Dynorphin is an endogenous opiate localized in many brain regions and spinal cord, but the activity of dynorphin neurons during sleep is unknown. Dynorphin is an inhibitory neuropeptide that is coreleased with orexin, an excitatory neuropeptide. We used microendoscopy to test the hypothesis that, like orexin, the dynorphin neurons are wake-active. Dynorphin-cre mice (n = 3) were administered rAAV8-Ef1a-Con/Foff 2.0-GCaMP6M into the zona incerta-perifornical area, implanted with a GRIN lens (gradient reflective index), and electrodes to the skull that recorded sleep. One month later, a miniscope imaged calcium fluorescence in dynorphin neurons during multiple bouts of wake, non-rapid-eye movement (NREM), and rapid-eye movement (REM) sleep. Unbiased data analysis identified changes in calcium fluorescence in 64 dynorphin neurons. Most of the dynorphin neurons (72%) had the highest fluorescence during bouts of active and quiet waking compared to NREM or REM sleep; a subset (20%) were REM-max. Our results are consistent with the emerging evidence that the activity of orexin neurons can be classified as wake-max or REM-max. Since the two neuropeptides are coexpressed and coreleased, we suggest that dynorphin-cre-driven calcium sensors could increase understanding of the role of this endogenous opiate in pain and sleep.
Longitudinal study of childhood sleep trajectories and adolescent mental health problems
Authors: Touchette Evelyne , Fréchette-Boilard Gabrielle , Petit Dominique , Geoffroy Marie-Claude , Pennestri Marie-Hélène , Côté Sylvana , Tremblay Richard E , Petitclerc Amélie , Boivin Michel , Montplaisir Jacques 
Published: March 2024

Abstract

Study Objective
To investigate whether childhood sleep trajectories are associated with mental health symptoms such as social phobia, generalized anxiety, depression, attention deficit hyperactivity disorder (ADHD), conduct problems, and opposition at age 15.

Methods
A total of 2120 children took part in the Quebec Longitudinal Study of Child Development. Childhood sleep trajectories were computed from maternal reports at 2.5, 3.5, 4, 6, 8, 10, and/or 12 years. At age 15, 1446 adolescents filled out mental health and sleep questions. A path analysis model was assessed in the full sample.

Results
Four childhood nocturnal sleep duration trajectories were identified: (1) a short pattern (7.5%), (2) a short-increasing pattern (5.8%), (3) a 10 hours pattern (50.7%), and (4) an 11 hours pattern (36.0%). Three childhood sleep latency trajectories were found: (1) a short pattern (31.7%), (2) an intermediate pattern (59.9%), and (3) a long pattern (8.4%). Finally, two childhood wakefulness after sleep-onset trajectories were found: (1) a normative pattern (73.0%) and (2) a long pattern (27.0%). The path analysis model indicated that children following a long childhood sleep latency trajectory were more likely to experience symptoms of depression (β = 0.06, 95% CI: 0.01 to 0.12), ADHD (β = 0.07, 95% CI: 0.02 to 0.13), conduct problems (β = 0.05, 95% CI: 0.00 to 0.10) and opposition (β = 0.08, 95% CI: 0.02 to 0.13) at age 15.

Conclusions
This longitudinal study revealed that children presenting a long sleep latency throughout childhood are at greater risk of symptoms of depression, ADHD, conduct problems, and opposition in adolescence.
Becoming Humanist: Worldview Formation and the Emergence of Atheist Britain
Authors: Strhan Anna , Lee Lois , Shillitoe Rachael 
Published: March 2024

Abstract
It is widely accepted that the growth of “non-religious” identification and “non-belief” in God(s) in many societies is linked to changing religious socialization. However, existing research mapping these intergenerational changes has largely focused on religious decline or the loss of belief—“push” factors—rather than exploring the distinctive non-religious forms of life into which children are growing up, which may operate as “pull” factors. Drawing on a qualitative study conducted with children, their parents, and teachers in England, we demonstrate how children come to inhabit a “humanist condition” through socialization processes in which “pull” factors toward humanism play a significant role and even shape the nature of “push” factors. The significance of new worldviews also helps explain how participants combine humanism with diverse religious and non-religious beliefs and practices. We argue that socialization processes at home and at school are interwoven and can be hard to distinguish in practice.
Distinct taxonomic practices impact patterns of bird endemism in the South American Cerrado savannas
Authors: Lopes Leonardo E , Gonzaga Luiz P , Rodrigues Marcos , da Silva José Maria C 
Published: March 2024

Abstract
Identifying endemic species and the areas of endemism delimited by them is central to biogeography. However, the impact of distinct taxonomic approaches on these patterns is often neglected. We investigated how three different taxonomic approaches impact the patterns of bird endemism in the Cerrado. The first two approaches (at species and subspecies levels) were based on traditional taxonomy based on the biological species concept. The third approach was based on a revised alternative taxonomy that sought to identify evolutionarily significant units (ESUs). In this third approach, after identifying the endemic taxa using traditional taxonomy, we revised their validity, removing biologically meaningless entities. We then detected the areas of endemism delimited by these endemic taxa under the three taxonomic approaches. We found that traditional taxonomy at the species level underestimated bird endemism by ignoring some ESUs that were considered subspecies. In contrast, traditional taxonomy at the subspecies level overestimated bird endemism, leading to the recognition of spurious areas of endemism because several of the purported endemic subspecies were taxonomic artefacts. The revised taxonomy provided a more refined picture of patterns of avian endemism in the Cerrado, suggesting that the use of ESUs improves the results of biogeographical analysis.
Microsomal triglyceride transfer protein is necessary to maintain lipid homeostasis and retinal function
Authors: Grubaugh Catharina R. , Dhingra Anuradha , Prakash Binu , Montenegro Diego , Sparrow Janet R. , Daniele Lauren L. , Curcio Christine A. , Bell Brent A. , Hussain M. Mahmood , Boesze‐Battaglia Kathleen 
Published: March 2024

AbstractLipid processing by the retinal pigment epithelium (RPE) is necessary to maintain retinal health and function. Dysregulation of retinal lipid homeostasis due to normal aging or age‐related disease triggers lipid accumulation within the RPE, on Bruch's membrane (BrM), and in the subretinal space. In its role as a hub for lipid trafficking into and out of the neural retina, the RPE packages a significant amount of lipid into lipid droplets for storage and into apolipoprotein B (APOB)‐containing lipoproteins (Blps) for export. Microsomal triglyceride transfer protein (MTP), encoded by the MTTP gene, is essential for Blp assembly. Herein we test the hypothesis that MTP expression in the RPE is essential to maintain lipid balance and retinal function using the newly generated RPEΔMttp mouse model. Using non‐invasive ocular imaging, electroretinography, and histochemical and biochemical analyses we show that genetic depletion of Mttp from the RPE results in intracellular lipid accumulation, increased photoreceptor‐associated cholesterol deposits, and photoreceptor cell death, and loss of rod but not cone function. RPE‐specific reduction in Mttp had no significant effect on plasma lipids and lipoproteins. While APOB was decreased in the RPE, most ocular retinoids remained unchanged, with the exception of the storage form of retinoid, retinyl ester. Thus suggesting that RPE MTP is critical for Blp synthesis and assembly but is not directly involved in plasma lipoprotein metabolism. These studies demonstrate that RPE‐specific MTP expression is necessary to establish and maintain retinal lipid homeostasis and visual function.
A novel intracoronary hypothermia device reduces myocardial reperfusion injury in pigs
Authors: Pei Zhiqiang , Qiu Jin , Zhao Yongchao , Song Shuai , Wang Rui , Luo Wei , Cai Xingxing , Liu Bin , Chen Han , Yin Jiasheng , Weng Xinyu , Wu Yizhe , Li Chenguang , Shen Li , Ge Junbo 
Published: March 2024

Abstract

Background:
Hypothermia therapy has been suggested to attenuate myocardial necrosis; however, the clinical implementation as a valid therapeutic strategy has failed, and new approaches are needed to translate into clinical applications. This study aimed to assess the feasibility, safety, and efficacy of a novel selective intracoronary hypothermia (SICH) device in mitigating myocardial reperfusion injury.

Methods:
This study comprised two phases. The first phase of the SICH was performed in a normal porcine model for 30 minutes (n = 5) to evaluate its feasibility. The second phase was conducted in a porcine myocardial infarction (MI) model of myocardial ischemia/reperfusion which was performed by balloon occlusion of the left anterior descending coronary artery for 60 minutes and maintained for 42 days. Pigs in the hypothermia group (n = 8) received hypothermia intervention onset reperfusion for 30 minutes and controls (n = 8) received no intervention. All animals were followed for 42 days. Cardiac magnetic resonance analysis (five and 42 days post-MI) and a series of biomarkers/histological studies were performed.

Results:
The average time to lower temperatures to a steady state was 4.8 ± 0.8 s. SICH had no impact on blood pressure or heart rate and was safely performed without complications by using a 3.9 F catheter. Interleukin-6 (IL-6), tumor necrosis factor-α, C-reactive protein (CRP), and brain natriuretic peptide (BNP) were lower at 60 min post perfusion in pigs that underwent SICH as compared with the control group. On day 5 post MI/R, edema, intramyocardial hemorrhage, and microvascular obstruction were reduced in the hypothermia group. On day 42 post MI/R, the infarct size, IL-6, CRP, BNP, and matrix metalloproteinase-9 were reduced, and the ejection fraction was improved in pigs that underwent SICH.

Conclusions:
The SICH device safely and effectively reduced the infarct size and improved heart function in a pig model of MI/R. These beneficial effects indicate the clinical potential of SICH for treatment of myocardial reperfusion injury.
Associations of demographics, aggravating factors, comorbidities, and treatments with atopic dermatitis severity in China: A national cross-sectional study
Authors: Zhao Jiahui , Zhang Zhixin , Chen Hongguang , Dou Xia , Zhao Zuotao , Liu Lingling , Wang Yang , Li Hang 
Published: March 2024

Abstract

Background:
Atopic dermatitis (AD) is a chronic inflammatory skin disorder impacting populations worldwide, although its clinical characteristics and patient demographics remain uncharacterized in China. The aim of this study was to investigate the demographics, comorbidities, aggravating factors, and treatments in AD patients across different age groups in China.

Methods:
This cross-sectional study included Chinese AD patients from 205 hospitals spanning 30 provinces. Patients completed dermatologist-led surveys of general medical history, comorbidities, AD-related aggravating factors, and medications. Two-level mixed-ordered logistic regression was used to evaluate aggravating factors.

Results:
Overall, 16,838 respondents were included in the final analysis (age 30.9 ± 24.1 years). The proportion of severe AD was the highest in patients with AD onset at ≥60 years (26.73%). Allergic rhinitis and hypertension were the most common atopic and metabolism-related non-atopic comorbidities, respectively. AD severity was significantly associated with chronic urticaria, food allergies, and diabetes. Aggravating factors including foods, seasonal changes, and psychological factors were also linked to AD severity. The cross-sectional survey implied that severe AD may be related to the undertreatment of effective systemic or topical interventions.

Conclusion:
To enhance the management of AD, it is crucial to consider both aggravating factors and the increased utilization of systemic immunotherapy.

Registration:
ClinicalTrials.gov Identifier: NCT05316805, CORNERSTONE
Incidence, prevalence, and causes of spinal injuries in China, 1990–2019: Findings from the Global Burden of Disease Study 2019
Authors: Liu Chenjun , Xu Tingling , Xia Weiwei , Xu Shuai , Zhu Zhenqi , Zhou Maigeng , Liu Haiying 
Published: March 2024

Abstract

Background:
Spinal injuries are an urgent public health priority; nevertheless, no China-wide studies of these injuries exist. This study measured the incidence, prevalence, causes, regional distribution, and annual trends of spinal injuries in China from 1990 to 2019.

Methods:
We used data from the Global Burden of Diseases, Injuries, and Risk Factors Study 2019 to estimate the incidence and prevalence of spinal injuries in China. The data of 33 provincial-level administrative regions (excluding Taiwan, China) provided by the National Center for Chronic and Noncommunicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention (CDC) were use to systematically analyze the provincial etiology, geographical distribution, and annual trends of spinal injuries. The Bayesian meta-regression tool DisMod-MR 2.1 was used to ensure the consistency among incidence, prevalence, and mortality rates in each case.

Results:
From 1990 to 2019, the number of living patients with spinal injuries in China increased by 138.32%, from 2.14 million to 5.10 million, while the corresponding age-standardized prevalence increased from 0.20% (95% uncertainty interval [UI]: 0.18–0.21%) to 0.27% (95% UI: 0.26–0.29%). The incidence of spinal injuries in China increased by 89.91% (95% UI: 72.39–107.66%), and the prevalence increased by 98.20% (95% UI: 89.56–106.82%), both the most significant increases among the G20 countries; 71.00% of the increase could be explained by age-specific prevalence. In 2019, the incidence was 16.47 (95% UI: 12.08–22.00, per 100,000 population), and the prevalence was 358.30 (95% UI: 333.96–386.62, per 100,000 population). Based on the data of 33 provincial-level administrative regions provided by CDC, age-standardized incidence and prevalence were both highest in developed provinces in Eastern China. The primary causes were falls and road injuries; however, the prevalence and specific causes differed across provinces.

Conclusions:
In China, the overall disease burden of spinal injuries increased significantly during the past three decades but varied considerably according to geographical location. The primary causes were falls and road injuries; however, the prevalence and specific causes differed across provinces.
The novel rapid formulation of intravenous dantrolene (NPJ5008) versus standard dantrolene (Dantrium®)
Authors: Ng Kwet Shing Richard H. , Clayton Lucy B. , Smith Samuel L. , Watson Marc J. , McKenzie Litza M. , Chalmers David P. , Whitaker Gareth , Bilmen Jonathan G. 
Published: March 2024

BACKGROUND
Delays in treating anaesthesia-induced malignant hyperthermia increase risks of complications and death. NPJ5008 is a novel formulation of the indicated treatment, dantrolene sodium, developed to shorten preparation and administration times compared with the reference formulation Dantrium®. The two formulations have been compared preclinically.

OBJECTIVES
Assess bioequivalence of overall dantrolene (free acid) exposure of NPJ5008 versus Dantrium® and ascertain similarities in their pharmacokinetics and safety/tolerability profiles. Evaluate preparation/administration time savings for the new formulation.

DESIGN
Part 1 of this open-label trial in humans was a 1 : 1 randomised crossover study; part 2 was a single-arm study. Trial pharmacy data and laboratory simulations assessed preparation/administration step timings.

SETTING
Single clinical centre in the UK, April to July 2021.

PARTICIPANTS
Twenty-one healthy male and female individuals.

INTERVENTIONS
Part 1: single intravenous 60 mg dose of NPJ5008 or Dantrium®, sequentially. Part 2: single intravenous 120 mg dose of NPJ5008. Simulation: five vials per formulation using paediatric and adult cannulas.

MAIN OUTCOME MEASURES
Overall drug exposure to last measurable concentration (AUC0 to last) and extrapolated to infinity (AUC0 to ∞) were primary endpoints. Other pharmacokinetic, clinical and muscle-function parameters, and adverse events, were monitored.

RESULTS
Adjusted geometric mean ratios of NPJ5008 versus Dantrium® were 90.24 and 90.44% for AUC0 to last and AUC0 to ∞, respectively, with the 90% confidence intervals (CI) within the 80 to 125% acceptance interval, establishing bioequivalence. No new safety issues emerged: any adverse events were of a similar magnitude across treatments and related to pharmacological properties of dantrolene. Pharmacy and simulation data revealed that every step in preparation and administration was 26 to 69% faster for NPJ5008 than Dantrium®.

CONCLUSION
NPJ5008 showed comparable pharmacokinetic and safety profiles to Dantrium®, while reducing dantrolene dose preparation/administration times, potentially reducing patient complications/healthcare resourcing in malignant hyperthermia.

TRIAL REGISTRATION
EudraCT Number: 2020-005719-35, MHRA approval.