bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hypomyelination, hypodontia and craniofacial abnormalities in a Polr3b mouse model of leukodystrophy
Authors: Michell-Robinson Mackenzie A , Watt Kristin E N , Grouza Vladimir , Macintosh Julia , Pinard Maxime , Tuznik Marius , Chen Xiaoru , Darbelli Lama , Wu Chia-Lun , Perrier Stefanie , Chitsaz Daryan , Uccelli Nonthué A , Liu Hanwen , Cox Timothy C , Müller Christoph W , Kennedy Timothy E , Coulombe Benoit , Rudko David A , Trainor Paul A , Bernard Geneviève 
Published: August 2023

Abstract
RNA polymerase III (Pol III)-related hypomyelinating leukodystrophy (POLR3-HLD), also known as 4H leukodystrophy, is a severe neurodegenerative disease characterized by the cardinal features of hypomyelination, hypodontia and hypogonadotropic hypogonadism. POLR3-HLD is caused by biallelic pathogenic variants in genes encoding Pol III subunits. While approximately half of all patients carry mutations in POLR3B encoding the RNA polymerase III subunit B, there is no in vivo model of leukodystrophy based on mutation of this Pol III subunit.
Here, we determined the impact of POLR3BΔ10 (Δ10) on Pol III in human cells and developed and characterized an inducible/conditional mouse model of leukodystrophy using the orthologous Δ10 mutation in mice. The molecular mechanism of Pol III dysfunction was determined in human cells by affinity purification-mass spectrometry and western blot. Postnatal induction with tamoxifen induced expression of the orthologous Δ10 hypomorph in triple transgenic Pdgfrα-Cre/ERT; R26-Stopfl-EYFP; Polr3bfl mice. CNS and non-CNS features were characterized using a variety of techniques including microCT, ex vivo MRI, immunofluorescence, immunohistochemistry, spectral confocal reflectance microscopy and western blot. Lineage tracing and time series analysis of oligodendrocyte subpopulation dynamics based on co-labelling with lineage-specific and/or proliferation markers were performed.
Proteomics suggested that Δ10 causes a Pol III assembly defect, while western blots demonstrated reduced POLR3BΔ10 expression in the cytoplasm and nucleus in human cells. In mice, postnatal Pdgfrα-dependent expression of the orthologous murine mutant protein resulted in recessive phenotypes including severe hypomyelination leading to ataxia, tremor, seizures and limited survival, as well as hypodontia and craniofacial abnormalities. Hypomyelination was confirmed and characterized using classic methods to quantify myelin components such as myelin basic protein and lipids, results which agreed with those produced using modern methods to quantify myelin based on the physical properties of myelin membranes. Lineage tracing uncovered the underlying mechanism for the hypomyelinating phenotype: defective oligodendrocyte precursor proliferation and differentiation resulted in a failure to produce an adequate number of mature oligodendrocytes during postnatal myelinogenesis.
In summary, we characterized the Polr3bΔ10 mutation and developed an animal model that recapitulates features of POLR3-HLD caused by POLR3B mutations, shedding light on disease pathogenesis, and opening the door to the development of therapeutic interventions.
Effect of chilling on the spring emergence of overwintering Eurytoma maslovskii (Eurytomidae: Hymenoptera)
Authors: Nguyen Hai Nam , Hong Ki-Jeong 
Published: August 2023

Abstract
This study investigated the effect of chilling temperature and duration on diapause termination in Eurytoma maslovskii, a major apricot pest in Korea and China. The experimental insects were sampled in mid-autumn. Overwintering larvae were subjected to a temperature range at −16, −4, 2, 9, 13 °C for 12 wk (a temperature of 19 °C was used for nonchilled control), and then exposed to cold temperature (2 °C) for different durations (from 1 to 16, 19, and 22 wk) at different times (20 September and 30 November) to determine adult emergence, prolonged larval diapause, and development rate postchilling. The results demonstrated a strong association between chilling temperature and duration with the emergence of E. maslovskii. It was observed that diapause may be terminated after at least 6 wk in the cold. However, the rate only reached a higher significance after 10 wk or longer duration of chilling. The optimal chilling temperature ranged from 2 to 9 °C. Late autumn chilling (mid-September) did not differ from winter chilling (late November). The postdiapause development rate of E. maslovskii was determined to be affected by the chilling duration and could be described by a 3-parameter probability density Weibull function. These results suggest that winter conditions play a crucial role in the phenology of E. maslovskii in spring.
Recommendations for statin management in primary prevention: disparities among international risk scores
Authors: Mancini G B John , Ryomoto Arnold , Yeoh Eunice , Brunham Liam R , Hegele Robert A 
Published: August 2023

Abstract

Background and Aims
Statin recommendations in primary prevention depend upon risk algorithms. Moreover, with intermediate risk, risk enhancers and de-enhancers are advocated to aid decisions. The aim of this study was to compare algorithms used in North America and Europe for the identification of patients warranting statin or consideration of risk enhancers and de-enhancers.

Methods
A simulated population (n = 7680) equal in males and females, with/without smoking, aged 45–70 years, total cholesterol 3.5–7.0 mmol/L, high-density lipoprotein cholesterol 0.6–2.2 mmol/L, and systolic blood pressure 100–170 mmHg, was evaluated. High, intermediate, and low risks were determined using the Framingham Risk Score (FRS), Pooled Cohort Equation (PCE), four versions of Systematic Coronary Risk Evaluation 2 (SCORE2), and Multi-Ethnic Study of Atherosclerosis (MESA) algorithm (0–1000 Agatston Units).

Results
Concordance for the three levels of risk varied from 19% to 85%. Both sexes might be considered to have low, intermediate, or high risk depending on the algorithm applied, even with the same burden of risk factors. Only SCORE2 (High Risk and Very High Risk versions) identified equal proportions of males and females with high risk. Excluding MESA, the proportion with moderate risk was 25% (SCORE2, Very High Risk Region), 32% (FRS), 39% (PCE), and 45% (SCORE2, Low Risk Region).

Conclusion
Risk algorithms differ substantially in their estimation of risk, recommendations for statin treatment, and use of ancillary testing, even in identical patients. These results highlight the limitations of currently used risk-based approaches for addressing lipid-specific risk in primary prevention.
Frailty and outcomes in heart failure patients from high-, middle-, and low-income countries
Authors: Leong Darryl P , Joseph Philip , McMurray John J V , Rouleau Jean , Maggioni Aldo P , Lanas Fernando , Sharma Sanjib K , Núñez Julio , Mohan Bishav , Celik Ahmet , Abdullakutty Jabir , Ogah Okechukwu S , Mielniczuk Lisa M , Balasubramanian Kumar , McCready Tara , Grinvalds Alex , Yusuf Salim 
Published: August 2023

Abstract

Background and Aims
There is little information on the incremental prognostic importance of frailty beyond conventional prognostic variables in heart failure (HF) populations from different country income levels.

Methods
A total of 3429 adults with HF (age 61 ± 14 years, 33% women) from 27 high-, middle- and low-income countries were prospectively studied. Baseline frailty was evaluated by the Fried index, incorporating handgrip strength, gait speed, physical activity, unintended weight loss, and self-reported exhaustion. Mean left ventricular ejection fraction was 39 ± 14% and 26% had New York Heart Association Class III/IV symptoms. Participants were followed for a median (25th to 75th percentile) of 3.1 (2.0–4.3) years. Cox proportional hazard models for death and HF hospitalization adjusted for country income level; age; sex; education; HF aetiology; left ventricular ejection fraction; diabetes; tobacco and alcohol use; New York Heart Association functional class; HF medication use; blood pressure; and haemoglobin, sodium, and creatinine concentrations were performed. The incremental discriminatory value of frailty over and above the MAGGIC risk score was evaluated by the area under the receiver-operating characteristic curve.

Results
At baseline, 18% of participants were robust, 61% pre-frail, and 21% frail. During follow-up, 565 (16%) participants died and 471 (14%) were hospitalized for HF. Respective adjusted hazard ratios (95% confidence interval) for death among the pre-frail and frail were 1.59 (1.12–2.26) and 2.92 (1.99–4.27). Respective adjusted hazard ratios (95% confidence interval) for HF hospitalization were 1.32 (0.93–1.87) and 1.97 (1.33–2.91). Findings were consistent among different country income levels and by most subgroups. Adding frailty to the MAGGIC risk score improved the discrimination of future death and HF hospitalization.

Conclusions
Frailty confers substantial incremental prognostic information to prognostic variables for predicting death and HF hospitalization. The relationship between frailty and these outcomes is consistent across countries at all income levels.
Dramatic difference in rate of chromosome number evolution among sundew (Drosera L., Droseraceae) lineages
Authors: Mohn Rebekah A , Zenil-Ferguson Rosana , Krueger Thilo A , Fleischmann Andreas S , Cross Adam T , Yang Ya 
Published: August 2023

Abstract
Chromosome number change is a driver of speciation in eukaryotic organisms. Carnivorous sundews in the plant genus Drosera L. exhibit single chromosome number variation both among and within species, especially in the Australian Drosera subg. Ergaleium D.C., potentially linked to atypical centromeres that span much of the length of the chromosomes. We critically reviewed the literature on chromosome counts in Drosera, verified the taxonomy and quality of the original counts, and reconstructed dated phylogenies. We used the BiChrom model to test whether rates of single chromosome number increase and decrease, and chromosome number doubling differed between D. subg. Ergaleium and the other subgenera and between self-compatible and self-incompatible lineages. The best model for chromosome evolution among subgenera had equal rates of chromosome number doubling but higher rates of single chromosome number change in D. subg. Ergaleium than in the other subgenera. Contrary to expectation, self-incompatible lineages had a significantly higher rate of single chromosome loss than self-compatible lineages. We found no evidence for an association between differences in single chromosome number changes and diploidization after polyploidy or centromere type. This study presents an exemplar for critically examining published cytological data and rigorously testing factors that may impact the rates of chromosome number evolution.
Pyronaridine: a review of its clinical pharmacology in the treatment of malaria
Authors: Chu Wan-Yu , Dorlo Thomas P C 
Published: August 2023

Abstract
Pyronaridine-artesunate was recently strongly recommended in the 2022 update of the WHO Guidelines for the Treatment of Malaria, becoming the newest artemisinin-based combination therapy (ACT) for both uncomplicated Plasmodium falciparum and Plasmodium vivax malaria. Pyronaridine-artesunate, available as a tablet and paediatric granule formulations, is being adopted in regions where malaria treatment outcome is challenged by increasing chloroquine resistance. Pyronaridine is an old antimalarial agent that has been used for more than 50 years as a blood schizonticide, which exerts its antimalarial activity by interfering with the synthesis of the haemozoin pigment within the Plasmodium digestive vacuole. Pyronaridine exhibits a high blood-to-plasma distribution ratio due to its tendency to accumulate in blood cells. This feature is believed to play a crucial role in its pharmacokinetic (PK) properties and pharmacological activity. The PK characteristics of pyronaridine include rapid oral absorption, large volumes of distribution and low total body clearance, resulting in a long terminal apparent half-life. Moreover, differences in PK profiles have been observed between healthy volunteers and malaria-infected patients, indicating a potential disease-related impact on PK properties. Despite a long history, there is only limited knowledge of the clinical PK and pharmacodynamics of pyronaridine, particularly in special populations such as children and pregnant women. We here provide a comprehensive overview of the clinical pharmacology of pyronaridine in the treatment of malaria.
A method to automate the discharge summary hospital course for neurology patients
Authors: Hartman Vince C , Bapat Sanika S , Weiner Mark G , Navi Babak B , Sholle Evan T , Campion Thomas R 
Published: August 2023

Abstract

Objective
Generation of automated clinical notes has been posited as a strategy to mitigate physician burnout. In particular, an automated narrative summary of a patient’s hospital stay could supplement the hospital course section of the discharge summary that inpatient physicians document in electronic health record (EHR) systems. In the current study, we developed and evaluated an automated method for summarizing the hospital course section using encoder-decoder sequence-to-sequence transformer models.

Materials and Methods
We fine-tuned BERT and BART models and optimized for factuality through constraining beam search, which we trained and tested using EHR data from patients admitted to the neurology unit of an academic medical center.

Results
The approach demonstrated good ROUGE scores with an R-2 of 13.76. In a blind evaluation, 2 board-certified physicians rated 62% of the automated summaries as meeting the standard of care, which suggests the method may be useful clinically.

Discussion and conclusion
To our knowledge, this study is among the first to demonstrate an automated method for generating a discharge summary hospital course that approaches a quality level of what a physician would write.
GPR120 Gene expression and activity in subcutaneous and intramuscular adipose tissues of Angus crossbred steers
Authors: Westbrook Lindsay , Johnson Bradley J , Gang Gyoungok , Toyonaga Kentaro , Young Kang Eun , Smith Stephen B 
Published: August 2023

Abstract
We hypothesized that media long-chain fatty acids (LCFA) would more greatly depress cyclic adenosine monophosphate (cAMP), glycerol, and free fatty acid (FFA) concentrations in subcutaneous (s.c.) adipose tissue than in intramuscular (i.m.) adipose tissue via G protein-coupled receptor 120 (GPR120). The GPR120 receptor binds to LCFA, which reduces cAMP production, thereby causing a depression in lipolysis. Fresh ex vivo explants of s.c. and i.m. adipose tissue from the fifth to eighth longissimus thoracic rib muscle section of 8, 22-mo-old Angus crossbred steers were transferred immediately to 6-well culture plates containing 3 mL of Krebs–Henseleit buffer/Hepes/5 mM glucose. Samples were preincubated with 0.5 mM theophylline plus 10 μM forskolin for 30 min, after which increasing concentrations of acetate or propionate (volatile fatty acids, VFA) (0, 1, 5, and 10 mM) in the absence or presence of 100 µM oleate (18:1n-9) or 100 μM palmitate (16:0) (LCFA) were added to the incubation media and incubated an additional 30 min. Main effects of adipose tissue depot (i.m. vs. s.c) and VFA (acetate vs. propionate) for adipose tissue concentrations of forskolin-stimulated cAMP were P = 0.747 and P = 0.106, respectively. The addition of LCFA to the media depressed adipose tissue concentrations of cAMP (P = 0.006) (LCFA main effects). The Tissue × VFA × LCFA interaction was not significant for any dependent variable (P ≥ 0.872). Therefore, concentrations of cAMP, glycerol, and FFA were analyzed separately for i.m. and s.c. adipose tissue by split-plot analysis. Concentrations of cAMP, glycerol, or FFA in i.m. and s.c. adipose tissue were not affected by increasing concentrations of VFA (P ≥ 0.497). Media LCFA had no effect on i.m. adipose tissue cAMP (P = 0.570) or glycerol (P = 0.470) but depressed i.m. adipose tissue FFA (P &lt; 0.001). In s.c. adipose tissue, LCFA decreased concentrations of cAMP (P = 0.042) and glycerol (P = 0.038), but increased FFA concentration (P = 0.026). Expression of GPR120 (P = 0.804) and stearoyl-CoA desaturase (P = 0.538) was not different between s.c. adipose tissue and i.m. adipose tissue. The binding of VFA to the GPR43 receptor depresses cAMP production, thereby attenuating lipolysis, but GPR43 mRNA was undetectable in those adipose tissue samples. These results provide evidence for functional GPR120 receptors in s.c. adipose tissue but question the role of GPR43 in the accumulation of adipose tissue lipids in growing steers.
Differentiating Childhood Traumas in Inflammatory Bowel Disease
Authors: Gnat Lauren , Mihajlovic Valentina , Jones Krista , Tripp Dean A 
Published: August 2023

Abstract

Background
Inflammatory bowel disease is characterized by chronic inflammation of the gastrointestinal tract. Research on inflammatory bowel disease has shown a connection to childhood traumatic events. However, few studies have focused on specific types of traumatic experiences and the impact of confiding in others on disease-related outcomes. This comparative, cross-sectional study expected that: (1) patients would report higher prevalence rates of childhood traumas than healthy controls; (2) healthy controls would report fewer and less severe traumatic experiences than patients and less confiding in others compared to patients; (3) childhood trauma severity would be indirectly related to depressive symptoms through resilience and confiding in others would moderate this relationship.

Methods
Participants completed an online survey; an inflammatory bowel disease patient group (N = 195, Mage = 40.48, 76.4% female) was compared to a similarly recruited sample of healthy controls (N = 190, Mage = 31.16, 59.5% female).

Results
Patients reported a higher prevalence of experiencing sexual traumas (P = .031), major upheavals (i.e., disruptions) (P = .048), and violence (P = .050) than controls. Patients had significantly higher total trauma severity odds ratios (OR 0.89, 95% CI[0.81,0.97]) and significantly lower total confiding in other odds ratios than controls (OR 1.09, 95% CI[1.02,1.16]). Childhood trauma severity was indirectly related to depressive symptoms through resilience, b = .05, SE = 0.09, 95% CI[0.01,0.09]; however, confiding did not moderate this relationship.

Conclusions
Patients reported more sexual, disruptive, and violent traumas. Although confiding did not act as a moderator, trauma was related to depressive symptoms through resilience.
NGOs Shaping Public Participation Through Law: The Aarhus Convention and Legal Mobilisation
Authors: Abbot Carolyn , Lee Maria 
Published: August 2023

Abstract
This article explores the relative neglect by environmental NGOs—at least until recently—of the middle, public participation, pillar of the Aarhus Convention. This can be seen in litigation, as well as in political advocacy, both domestically and at the international (Aarhus) level. Interviews with some key actors in this area and analysis of published documents provide insights into NGO decision-making. The limits of law become clear—Aarhus rights are made real only through the commitment of governments and civil society. A nuanced combination of internal and external factors contributes to explaining the lack of NGO attention to Aarhus’ middle pillar. We may also see some indications that NGOs envisage participation as a process properly dominated by expertise. This is far from uniform, however, and other parts of the community clearly appreciate and value the significance of lay participation in the environmental arena.
Adolescents’ Perspectives on Skateboarding and Injury Risk: The Benefits Outweigh the Risks
Authors: Seasons Mackenzie , Morrongiello Barbara A 
Published: August 2023

Abstract

Objective
Skateboarding is an increasingly popular sport among youth, despite the fact that children and adolescents are the age groups most frequently injured when skateboarding. A greater understanding of the psycho-social factors that motivate participation in skateboarding, including why youth return to the sport after serious injury from skateboarding, is needed to inform injury prevention efforts. This study addressed that gap in knowledge.

Methods
Twenty-six Canadian adolescent skateboarders 14–17 years of age (20 males and 6 females) who had previously sustained medically attended injuries while skateboarding participated in individual interviews to explore their perspectives on skateboarding and injury risk, including reasons for returning to the sport after injury.

Results
Thematic analyses revealed that participants perceived many unique benefits from skateboarding, including interpersonal benefits, mental and physical health benefits, pleasure, personal growth, and identity development. Participants uniformly identified that a major drawback was the risk of injury, with trickle-down effects of injury including a loss of social contacts (e.g., missing friends), challenges to individual identity from not participating, and injury-specific negative outcomes (e.g., pain, physical limitations). When exploring reasons participants returned to the sport and to the trick or activity that precipitated their injury, the primary theme identified was that the benefits of skateboarding significantly outweighed the costs associated with potential re-injury.

Conclusion
Results paint a nuanced picture of psycho-social factors that impact youths’ skateboarding and decisions to return to the sport after injury. Implications for injury prevention are discussed.
Frequency of antithyroid antibodies in patients with primary biliary cholangitis
Authors: Ghozzi Mariam , Mankai Amani , Chedly Zeineb , Mlika Ikram , Manoubi Wiem , Melayah Sarra , Ghedira Ibtissem 
Published: August 2023

Abstract

Objective
Primary biliary cholangitis (PBC) is an autoimmune disease of liver that may be associated with other conditions, including autoimmune thyroid diseases. We aimed to investigate the frequency of anti-thyroperoxidase antibodies (TPO-Ab), antithyroglobulin antibodies (TG-Ab), and anti–thyrotropin receptor antibodies (TSHR-Ab) in Tunisian patients with PBC.

Methods
Sera of 80 patients with PBC were collected over a 9-year period. A total of 189 healthy blood donors (HBD) were included in the control group. Measurements of TPO-Ab and TG-Ab were performed using indirect enzyme-linked immunosorbent assay (ELISA). Competitive ELISA was used to assess TSHR-Ab.

Results
Antithyroid antibodies (ATA) were significantly more frequent in PBC patients than in the control group (13.7% vs 1.6%; P &lt; 10−3). Out of 11 patients with ATA, 10 (90.9%) were female. Nine patients and 2 HBD had TPO-Ab (11.2% vs 1%; P &lt; 10−3). TG-Ab were more frequent in patients than in healthy subjects but the difference was not statistically significant (6.2% vs 1.6%; P = .1). TPO-Ab and TG-Ab were present together in 3 patients (3.7%). TSHR-Ab were absent in patients and controls.

Conclusion
This study shows that PBC is associated with a high frequency of ATA but not TG-Ab or TSHR-Ab.