bluuebunny/crossref_metadata_2025_split huggingface dataset:
Microphysical Evolution in Mixed-Phase Midlatitude Marine Cold-Air Outbreaks
Authors: Chellappan Seethala , Zuidema Paquita , Kirschler Simon , Voigt Christiane , Cairns Brian , Crosbie Ewan C. , Ferrare Richard , Hair Johnathan , Painemal David , Shingler Taylor , Shook Michael , Thornhill Kenneth L. , Tornow Florian , Sorooshian Armin 
Published: September 2024

Abstract
Five cold-air outbreaks are investigated with aircraft offshore of continental northeast America. Flight paths aligned with the cloud-layer flow from January through March span cloud-top temperatures from −5° to −12°C, in situ liquid water paths of up to 500 g m−2, while in situ cloud droplet number concentrations exceeding 500 cm−3 maintain effective radii below 10 μm. Rimed ice is detected in the four colder cases within the first cloud pass. After further fetch, ice particle number concentrations reaching 2.5 L−1 support an interpretation that secondary ice production is occurring. Rime splintering is clearly evident, with dendritic growth increasing ice water contents within deeper clouds with colder cloud-top temperatures. Buoyancy fluxes reach 400–600 W m−2 near the Gulf Stream’s western edge, with 1-s updrafts reaching 5 m s−1 supporting closely spaced convective cells. Near-surface rainfall rates of the three more intense cold-air outbreaks are a maximum near the Gulf Stream’s eastern edge, just before the clouds transition to more open-celled structures. The milder two cold-air outbreaks transition to lower-albedo cumulus with little or no precipitation. The clouds thin through cloud-top entrainment.

Significance Statement
Cold-air outbreaks off of the eastern U.S. seaboard are visually spectacular in satellite imagery, with overcast, high-albedo clouds transitioning to more broken cloud fields. We use data from the recent NASA Aerosol Cloud Meteorology Interactions over the Western Atlantic Experiment (ACTIVATE) aircraft campaign to examine the microphysics and environmental context of five such outbreaks. We find the clouds are not ice-deprived, but updrafts still supply significant liquid water. Cloud transitions are encouraged through near-surface rain for the deeper clouds, and otherwise, clouds thin and break through mixing in drier air from above. These observations support understanding and further modeling examining how mixed-phase cloud microphysics affect cloud reflectivity and surface rainfall rates, important for both weather and climate forecasting.
Advanced glycation end products and reactive oxygen species: uncovering the potential role of ferroptosis in diabetic complications
Authors: Chen Yanchi , Meng Zihan , Li Yong , Liu Shibo , Hu Pei , Luo En 
Published: September 2024

AbstractAdvanced glycation end products (AGEs) are a diverse range of compounds that are formed when free amino groups of proteins, lipids, and nucleic acids are carbonylated by reactive carbonyl species or glycosylated by reducing sugars. Hyperglycemia in patients with diabetes can cause an overabundance of AGEs. Excess AGEs are generally acknowledged as major contributing factors to the development of diabetic complications because of their ability to break down the extracellular matrix directly and initiate intracellular signaling pathways by binding to the receptor for advanced glycation end products (RAGE). Inflammation and oxidative stress are the two most well-defined pathophysiological states induced by the AGE–RAGE interaction. In addition to oxidative stress, AGEs can also inhibit antioxidative systems and disturb iron homeostasis, all of which may induce ferroptosis. Ferroptosis is a newly identified contributor to diabetic complications. This review outlines the formation of AGEs in individuals with diabetes, explores the oxidative damage resulting from downstream reactions of the AGE-RAGE axis, and proposes a novel connection between AGEs and the ferroptosis pathway. This study introduces the concept of a vicious cycle involving AGEs, oxidative stress, and ferroptosis in the development of diabetic complications.
NAT10-mediated ac4C acetylation of TFRC promotes sepsis-induced pulmonary injury through regulating ferroptosis
Authors: Xing Pengcheng , Zhou Minjie , Sun Jian , Wang Donglian , Huang Weipeng , An Peng 
Published: September 2024

Abstract
Background
Sepsis-induced pulmonary injury (SPI) is a common complication of sepsis with a high rate of mortality. N4-acetylcytidine (ac4C) is mediated by the ac4C “writer”, N-acetyltransferase (NAT)10, to regulate the stabilization of mRNA. This study aimed to investigate the role of NAT10 in SPI and the underlying mechanism.

Methods
Twenty-three acute respiratory distress syndrome (ARDS) patients and 27 non-ARDS volunteers were recruited. A sepsis rat model was established. Reverse transcription-quantitative polymerase chain reaction was used to detect the expression of NAT10 and transferrin receptor (TFRC). Cell viability was detected by cell counting kit-8. The levels of Fe2+, glutathione, and malondialdehyde were assessed by commercial kits. Lipid reactive oxygen species production was measured by flow cytometric analysis. Western blot was used to detect ferroptosis-related protein levels. Haematoxylin & eosin staining was performed to observe the pulmonary pathological symptoms.

Results
The results showed that NAT10 was increased in ARDS patients and lipopolysaccharide-treated human lung microvascular endothelial cell line-5a (HULEC-5a) cells. NAT10 inhibition increased cell viability and decreased ferroptosis in HULEC-5a cells. TFRC was a downstream regulatory target of NAT10-mediated ac4C acetylation. Overexpression of TFRC decreased cell viability and promoted ferroptosis. In in vivo study, NAT10 inhibition alleviated SPI.

Conclusion
NAT10-mediated ac4C acetylation of TFRC aggravated SPI through promoting ferroptosis.

Graphical Abstract
Biallelic TYR and TKFC variants in Egyptian patients with OCA1 and new expanded TKFC features
Authors: Ashaat Engy A. , Esmaiel Nora N. , El-Saiedi Sonia A. , Ashaat Neveen A. , Hussen Dalia Farouk , Ramadan Abeer , Al Kersh Mohamed Ahmed , AbdelHakim Nirvana S. , Said Ibrahim , Metwally Ammal M. , Fayez Alaaeldin 
Published: September 2024

Abstract
Background
Oculocutaneous albinism type1 (OCA1) is caused by the TYR gene's homozygous and compound heterozygous variants. TKFC gene variants cause triokinase & FMN cyclase deficiency syndrome with variable multisystemic disorders.

Objectives
To determine the potential disease-causing variants in two deceased patients presenting atypical OCA1 features by demonstrating three generations for a single family. The two deceased neonates had severe skeletal abnormalities and fatal hypertrophic cardiomyopathy. We also explored the potential mechanisms for the causative relationship between TKFC and multisystem disorders.

Patients and methods
Due to the new emerging symptoms that weren’t reported before with the TYR gene, the following methods were performed: Sanger sequencing for the TYR gene, followed by whole exome sequencing, co-segregation, and computational analyses.

Results
Extensive parental consanguinity was found, and consequently an autosomal recessive mode of inheritance was prioritized. Upon performing sequencing and segregation data, the following has been confirmed: positive co-segregation of nonsense homozygous NM_000372.5:c.346C > T p.(Arg116*) variant in TYR gene and multisystem disease-missense homozygous NM_015533.4:c.598G > A p.(Val200Ile) variant in TKFC gene in the two affected index patients who deceased due to hypertrophic cardiomyopathy. Using computational analysis, we found that c.598G > A p.(Val200Ile) pathogenicity has led to the failure of L2-K1 active site closure due to the potential differential fluctuation between valine and isoleucine residues. Subsequently, disruption of endogenous DHA phosphorylation was found. Two potential mechanisms exploring the causative relationship between TKFC gene and multisystem disorders have been suggested.

Conclusions
This study presented a first family with the co-existence of biallelic variants in TYR and TKFC genes associating severe skeletal abnormalities and lethal hypertrophic cardiomyopathy. Neither of these genes would have been pursued in the standard genetic counseling. Such discovery is paving the way for more efficient genetic counseling. Comparing TKFC results with literature data showed that our relevant expanded TKFC variant is the 3rd worldwide.
Multi-omics analysis revealed the mechanism underlying flavonol biosynthesis during petal color formation in Camellia Nitidissima
Authors: Feng Yi , Li Jiyuan , Yin Hengfu , Shen Jian , Liu Weixin 
Published: September 2024

Abstract
Background
Camellia nitidissima is a rare, prized camellia species with golden-yellow flowers. It has a high ornamental, medicinal, and economic value. Previous studies have shown substantial flavonol accumulation in C. nitidissima petals during flower formation. However, the mechanisms underlying the golden flower formation in C. nitidissima remain largely unknown.

Results
We performed an integrative analysis of the transcriptome, proteome, and metabolome of the petals at five flower developmental stages to construct the regulatory network underlying golden flower formation in C. nitidissima. Metabolome analysis revealed the presence of 323 flavonoids, and two flavonols, quercetin glycosides and kaempferol glycosides, were highly accumulated in the golden petals. Transcriptome and proteome sequencing suggested that the flavonol biosynthesis-related genes and proteins upregulated and the anthocyanin and proanthocyanidin biosynthesis-related genes and proteins downregulated in the golden petal stage. Further investigation revealed the involvement of MYBs and bHLHs in flavonoid biosynthesis. Expression analysis showed that flavonol synthase 2 (CnFLS2) was highly expressed in the petals, and its expression positively correlated with flavonol content at all flower developmental stages. Transient overexpression of CnFLS2 in the petals increased flavonol content. Furthermore, correlation analysis showed that the jasmonate (JA) pathways positively correlated with flavonol biosynthesis, and exogenous methyl jasmonate (MeJA) treatment promoted CnFLS2 expression and flavonol accumulation.

Conclusions
Our findings showed that the JA-CnFLS2 module regulates flavonol biosynthesis during golden petal formation in C. nitidissima.
Evaluation of the Fill-it-up-design to use historical control data in randomized clinical trials with two arm parallel group design
Authors: Wied Stephanie , Posch Martin , Hilgers Ralf-Dieter 
Published: September 2024

Abstract
Purpose
In the context of clinical research, there is an increasing need for new study designs that help to incorporate already available data. With the help of historical controls, the existing information can be utilized to support the new study design, but of course, inclusion also carries the risk of bias in the study results.

Methods
To combine historical and randomized controls we investigate the Fill-it-up-design, which in the first step checks the comparability of the historical and randomized controls performing an equivalence pre-test. If equivalence is confirmed, the historical control data will be included in the new RCT. If equivalence cannot be confirmed, the historical controls will not be considered at all and the randomization of the original study will be extended. We are investigating the performance of this study design in terms of type I error rate and power.

Results
We demonstrate how many patients need to be recruited in each of the two steps in the Fill-it-up-design and show that the family wise error rate of the design is kept at 5$$\%$$
%
. The maximum sample size of the Fill-it-up-design is larger than that of the single-stage design without historical controls and increases as the heterogeneity between the historical controls and the concurrent controls increases.

Conclusion
The two-stage Fill-it-up-design represents a frequentist method for including historical control data for various study designs. As the maximum sample size of the design is larger, a robust prior belief is essential for its use. The design should therefore be seen as a way out in exceptional situations where a hybrid design is considered necessary.
Major mistakes or errors in the use of trial sequential analysis in systematic reviews or meta-analyses – the METSA systematic review
Authors: Riberholt Christian Gunge , Olsen Markus Harboe , Milan Joachim Birch , Hafliðadóttir Sigurlaug Hanna , Svanholm Jeppe Houmann , Pedersen Elisabeth Buck , Lew Charles Chin Han , Asante Mark Aninakwah , Pereira Ribeiro Johanne , Wagner Vibeke , Kumburegama Buddheera W. M. B. , Lee Zheng-Yii , Schaug Julie Perrine , Madsen Christina , Gluud Christian 
Published: September 2024

Abstract
Background
Systematic reviews and data synthesis of randomised clinical trials play a crucial role in clinical practice, research, and health policy. Trial sequential analysis can be used in systematic reviews to control type I and type II errors, but methodological errors including lack of protocols and transparency are cause for concern. We assessed the reporting of trial sequential analysis.

Methods
We searched Medline and the Cochrane Database of Systematic Reviews from 1 January 2018 to 31 December 2021 for systematic reviews and meta-analysis reports that include a trial sequential analysis. Only studies with at least two randomised clinical trials analysed in a forest plot and a trial sequential analysis were included. Two independent investigators assessed the studies. We evaluated protocolisation, reporting, and interpretation of the analyses, including their effect on any GRADE evaluation of imprecision.

Results
We included 270 systematic reviews and 274 meta-analysis reports and extracted data from 624 trial sequential analyses. Only 134/270 (50%) systematic reviews planned the trial sequential analysis in the protocol. For analyses on dichotomous outcomes, the proportion of events in the control group was missing in 181/439 (41%), relative risk reduction in 105/439 (24%), alpha in 30/439 (7%), beta in 128/439 (29%), and heterogeneity in 232/439 (53%). For analyses on continuous outcomes, the minimally relevant difference was missing in 125/185 (68%), variance (or standard deviation) in 144/185 (78%), alpha in 23/185 (12%), beta in 63/185 (34%), and heterogeneity in 105/185 (57%). Graphical illustration of the trial sequential analysis was present in 93% of the analyses, however, the Z-curve was wrongly displayed in 135/624 (22%) and 227/624 (36%) did not include futility boundaries. The overall transparency of all 624 analyses was very poor in 236 (38%) and poor in 173 (28%).

Conclusions
The majority of trial sequential analyses are not transparent when preparing or presenting the required parameters, partly due to missing or poorly conducted protocols. This hampers interpretation, reproducibility, and validity.

Study registration
PROSPERO CRD42021273811
Combining propensity score methods with variational autoencoders for generating synthetic data in presence of latent sub-groups
Authors: Farhadyar Kiana , Bonofiglio Federico , Hackenberg Maren , Behrens Max , Zöller Daniela , Binder Harald 
Published: September 2024

AbstractIn settings requiring synthetic data generation based on a clinical cohort, e.g., due to data protection regulations, heterogeneity across individuals might be a nuisance that we need to control or faithfully preserve. The sources of such heterogeneity might be known, e.g., as indicated by sub-groups labels, or might be unknown and thus reflected only in properties of distributions, such as bimodality or skewness. We investigate how such heterogeneity can be preserved and controlled when obtaining synthetic data from variational autoencoders (VAEs), i.e., a generative deep learning technique that utilizes a low-dimensional latent representation. To faithfully reproduce unknown heterogeneity reflected in marginal distributions, we propose to combine VAEs with pre-transformations. For dealing with known heterogeneity due to sub-groups, we complement VAEs with models for group membership, specifically from propensity score regression. The evaluation is performed with a realistic simulation design that features sub-groups and challenging marginal distributions. The proposed approach faithfully recovers the latter, compared to synthetic data approaches that focus purely on marginal distributions. Propensity scores add complementary information, e.g., when visualized in the latent space, and enable sampling of synthetic data with or without sub-group specific characteristics. We also illustrate the proposed approach with real data from an international stroke trial that exhibits considerable distribution differences between study sites, in addition to bimodality. These results indicate that describing heterogeneity by statistical approaches, such as propensity score regression, might be more generally useful for complementing generative deep learning for obtaining synthetic data that faithfully reflects structure from clinical cohorts.
The evolution of envelope function during coinfection with phylogenetically distinct human immunodeficiency virus
Authors: Omar Shatha , Woodman Zenda L. 
Published: September 2024

Abstract
Background
Coinfection with two phylogenetically distinct Human Immunodeficiency Virus-1 (HIV-1) variants might provide an opportunity for rapid viral expansion and the emergence of fit variants that drive disease progression. However, autologous neutralising immune responses are known to drive Envelope (Env) diversity which can either enhance replicative capacity, have no effect, or reduce viral fitness. This study investigated whether in vivo outgrowth of coinfecting variants was linked to pseudovirus and infectious molecular clones’ infectivity to determine whether diversification resulted in more fit virus with the potential to increase disease progression.

Results
For most participants, emergent recombinants displaced the co-transmitted variants and comprised the major population at 52 weeks postinfection with significantly higher entry efficiency than other co-circulating viruses. Our findings suggest that recombination within gp41 might have enhanced Env fusogenicity which contributed to the increase in pseudovirus entry efficiency. Finally, there was a significant correlation between pseudovirus entry efficiency and CD4 + T cell count, suggesting that the enhanced replicative capacity of recombinant variants could result in more virulent viruses.

Conclusion
Coinfection provides variants with the opportunity to undergo rapid recombination that results in more infectious virus. This highlights the importance of monitoring the replicative fitness of emergent viruses.
Association of life’s essential 8 with chronic cardiovascular-kidney disorder: a prospective cohort study
Authors: Huang Xinghe , Liang Jie , Zhang Junyu , Fu Jiayi , Deng Sicheng , Xie Wuxiang , Zheng Fanfan 
Published: September 2024

Abstract
Background
The coexistence of cardiovascular disease and chronic kidney disease, termed chronic cardiovascular-kidney disorder (CCV-KD), is increasingly prevalent. However, limited studies have assessed the association between cardiovascular health (CVH), assessed by the American Heart Association’s Life’s Essential 8 (LE8), and CCV-KD.

Methods
We conducted a prospective cohort study using data from UK Biobank. Participants without cardiovascular disease and chronic kidney disease at baseline and having complete data on metrics of LE8 were included (N = 125,986). LE8 included eight metrics, and the aggregate score was categorized as low (< 50 points), intermediate (50 to < 80 points), and high (≥ 80 points), with a higher score indicating better CVH health. Adjusted Cox proportional hazard models were conducted to explore the association of CVH with the risk of CCV-KD. The adjusted proportion of population attributable risk (PAR%) was used to calculate the population-level risk caused by low or intermediate CVH.

Results
During a median follow-up of 12.5 years, 1,054 participants (0.8%) had incident CCV-KD. Participants with intermediate and high CVH had 54% (HR = 0.46, 95% CI: 0.40–0.54, P < 0.001) and 75% (HR = 0.25, 95% CI: 0.18–0.34, P < 0.001) lower risks of incident CCV-KD compared with those in low CVH group. There was an approximately dose–response linear relationship between the overall LE8 score and incident CCV-KD. The risk of incident CCV-KD decreased by 30% (HR = 0.70, 95% CI: 0.67–0.74, P < 0.001) for a 10-point increment of LE8 score. The adjusted PAR% of lower overall CVH was 47.4% (95% CI: 31.6%-59.8%).

Conclusions
Better CVH, assessed by using LE8 score, was strongly associated with decreased risk of incident CCV-KD. These findings imply optimizing CVH may be a preventive strategy to reduce the burden of CCV-KD.
Exploring the impact of housing insecurity on the health and wellbeing of children and young people in the United Kingdom: a qualitative systematic review
Authors: Hock Emma S. , Blank Lindsay , Fairbrother Hannah , Clowes Mark , Cuevas Diana Castelblanco , Booth Andrew , Clair Amy , Goyder Elizabeth 
Published: September 2024

Abstract
Background
Housing insecurity can be understood as experiencing or being at risk of multiple house moves that are not through choice and related to poverty. Many aspects of housing have all been shown to impact children/young people’s health and wellbeing. However, the pathways linking housing and childhood health and wellbeing are complex and poorly understood.

Methods
We undertook a systematic review synthesising qualitative data on the perspectives of children/young people and those close to them, from the United Kingdom (UK). We searched databases, reference lists, and UK grey literature. We extracted and tabulated key data from the included papers, and appraised study quality. We used best fit framework synthesis combined with thematic synthesis, and generated diagrams to illustrate hypothesised causal pathways.

Results
We included 59 studies and identified four populations: those experiencing housing insecurity in general (40 papers); associated with domestic violence (nine papers); associated with migration status (13 papers); and due to demolition-related forced relocation (two papers). Housing insecurity took many forms and resulted from several interrelated situations, including eviction or a forced move, temporary accommodation, exposure to problematic behaviour, overcrowded/poor-condition/unsuitable property, and making multiple moves. Impacts included school-related, psychological, financial and family wellbeing impacts, daily long-distance travel, and poor living conditions, all of which could further exacerbate housing insecurity. People perceived that these experiences led to mental and physical health problems, tiredness and delayed development. The impact of housing insecurity was lessened by friendship and support, staying at the same school, having hope for the future, and parenting practices. The negative impacts of housing insecurity on child/adolescent health and wellbeing may be compounded by specific life circumstances, such as escaping domestic violence, migration status, or demolition-related relocation.

Conclusion
Housing insecurity has a profound impact on children and young people. Policies should focus on reducing housing insecurity among families, particularly in relation to reducing eviction; improving, and reducing the need for, temporary accommodation; minimum requirements for property condition; and support to reduce multiple and long-distance moves. Those working with children/young people and families experiencing housing insecurity should prioritise giving them optimal choice and control over situations that affect them.