bluuebunny/crossref_metadata_2025_split huggingface dataset:
Engineering an Escherichia coli strain for enhanced production of flavonoids derived from pinocembrin
Authors: Hanko Erik K. R. , Robinson Christopher J. , Bhanot Sahara , Jervis Adrian J. , Scrutton Nigel S. 
Published: November 2024

Abstract
Background
Flavonoids are a structurally diverse group of secondary metabolites, predominantly produced by plants, which include a range of compounds with pharmacological importance. Pinocembrin is a key branch point intermediate in the biosynthesis of a wide range of flavonoid subclasses. However, replicating the biosynthesis of these structurally diverse molecules in heterologous microbial cell factories has encountered challenges, in particular the modest pinocembrin titres achieved to date. In this study, we combined genome engineering and enzyme candidate screening to significantly enhance the production of pinocembrin and its derivatives, including chrysin, pinostrobin, pinobanksin, and galangin, in Escherichia coli.

Results
By implementing a combination of established strain engineering strategies aimed at enhancing the supply of the building blocks phenylalanine and malonyl-CoA, we constructed an E. coli chassis capable of accumulating 353 ± 19 mg/L pinocembrin from glycerol, without the need for precursor supplementation or the fatty acid biosynthesis inhibitor cerulenin. This chassis was subsequently employed for the production of chrysin, pinostrobin, pinobanksin, and galangin. Through an enzyme candidate screening process involving eight type-1 and five type-2 flavone synthases (FNS), we identified Petroselinum crispum FNSI as the top candidate, producing 82 ± 5 mg/L chrysin. Similarly, from a panel of five flavonoid 7-O-methyltransferases (7-OMT), we found pinocembrin 7-OMT from Eucalyptus nitida to yield 153 ± 10 mg/L pinostrobin. To produce pinobanksin, we screened seven enzyme candidates exhibiting flavanone 3-hydroxylase (F3H) or F3H/flavonol synthase (FLS) activity, with the bifunctional F3H/FLS enzyme from Glycine max being the top performer, achieving a pinobanksin titre of 12.6 ± 1.8 mg/L. Lastly, by utilising a combinatorial library of plasmids encoding G. max F3H and Citrus unshiu FLS, we obtained a maximum galangin titre of 18.2 ± 5.3 mg/L.

Conclusion
Through the integration of microbial chassis engineering and screening of enzyme candidates, we considerably increased the production levels of microbially synthesised pinocembrin, chrysin, pinostrobin, pinobanksin, and galangin. With the introduction of additional chassis modifications geared towards improving cofactor supply and regeneration, as well as alleviating potential toxic effects of intermediates and end products, we anticipate further enhancements in the yields of these pinocembrin derivatives, potentially enabling greater diversification in microbial hosts.
Phylogenetic reconstruction of Tuberolachnini and Lachninae (Insecta, Hemiptera): Morphological and molecular analyses revealed a new tribe
Authors: Kanturski Mariusz , Lee Yerim , Kim Hyojoong 
Published: November 2024

Abstract
Background
Lachninae (Insecta: Aphididae) represent a fascinating group of aphids that are traditionally divided into five tribes. Among these, members of the tribe Tuberolachnini exhibit remarkable morphological and biological diversity. One genus of this group, Miyalachnus, known from Japan, is characterized by unique features. Our study aimed to re-examine the tribal classification within Lachninae, with a focus on the diverse Tuberolachnini and the previously understudied genera Miyalachnus and Sinolachnus.

Results
We conducted a comprehensive phylogenetic analysis using four genes (COI, COII, CytB, and EF1α), employing both maximum likelihood (ML) and Bayesian inference (BI) methods on a combined dataset. Our findings challenge the monophyly of Tuberolachnini. The analyses revealed that Miyalachnus and Sinolachnus are phylogenetically distinct from the core Tuberolachnini genera (Nippolachnus, Pyrolachnus, and Tuberolachnus), instead showing a closer relationship with Tramini. Specifically, the Miyalachnus clade forms a sister clade to the clade containing Sinolachnus and Tramini.

Conclusions
On the basis of these molecular results, corroborated by morphological evidence, we propose to erect a new tribe within the Lachninae-Miyalachnini trib. nov. with Miyalachnus as the type genus. We also provide updated taxonomic diagnoses for the remaining tribes and discuss their relationships as well as distinguishing features.
Recurrent BMP4 variants in exon 4 cause non-HFE-associated hemochromatosis via the BMP/SMAD signaling pathway
Authors: Ouyang Qin , Li Yanmeng , Xu Anjian , Zhang Ning , Chen Sisi , Zhou Donghu , Zhang Bei , Ou Xiaojuan , Jia Jidong , Huang Jian , Zhang Wei 
Published: November 2024

Abstract
Background
Hereditary hemochromatosis (HH) is an iron overload disorder and can be caused by variants in non-HFE genes in Chinese patients. However, there is still a considerable proportion of patients suffering from unexplained iron overload. In our previous study, we had identified the p.R269Q variant in exon 4 of the Bone morphogenetic protein 4 (BMP4) gene in Chinese patients with unexplained primary iron overload by Whole Exome sequencing, and then the BMP4 p.H251Y variant was identified by Sanger sequencing in a Chinese patient with secondary iron overload. Our study aimed to explore the pathogenicity and underlying mechanism of BMP4 p.H251Y and BMP4 p.R269Q variants in patients with iron overload.

Methods
Sanger sequencing was conducted to identify the novel variants in the BMP4 gene of patients with unexplained iron overload. MRI and liver biopsy were used to display iron overload in the liver of the patient harboring the BMP4 p.H251Y variant. The BMP4 and hepcidin levels in BMP4 knockdown and BMP4 variant cells were examined by enzyme-linked immunosorbent assay. The effects of BMP4 p.H251Y and BMP4 p.R269Q variants on the hepcidin-regulation pathway were studied.

Results
One of 54 HH patients (1.85%) harbored the BMP4 p.R269Q variant. One of 148 patients (0.68%) with secondary hemochromatosis harbored the BMP4 p.H251Y variant, and these two variants were not found in 100 Chinese general population. For the patient harboring the BMP4 p.H251Y variant, abdominal MRI and Perl's staining of liver tissue displayed iron overload in the liver. Cells transfected with the BMP4 p.H251Y and p.R269Q variants showed down-regulation of hepcidin level and BMP/SMAD pathway compared with cells transfected with the wild-type BMP4 vector.

Conclusion
The BMP4 p.H251Y and p.R269Q variants can downregulate hepcidin levels by inhibiting the BMP/SMAD axis, suggesting they may play pathogenic roles in iron overload.
Associations of epigenetic age acceleration at birth and age 12 years with adolescent cardiometabolic risk: the HOME study
Authors: Arzu Jennifer L. , Kelsey Karl T. , Papandonatos George D. , Cecil Kim M. , Chen Aimin , Langevin Scott M. , Lanphear Bruce P. , Yolton Kimberly , Buckley Jessie P. , Braun Joseph M. 
Published: November 2024

Abstract
Background
Cardiometabolic risk factors among youth are rising. Epigenetic age acceleration, a biomarker for aging and disease-risk, has been associated with adiposity in children, but its association with other cardiometabolic risk markers remains understudied. We employed data from the Health Outcomes and Measures of the Environment (HOME) study, a prospective pregnancy and birth cohort in the greater Cincinnati metropolitan area, to examine whether accelerated epigenetic age at birth as well as accelerated epigenetic age and faster pace of biological aging at age 12 years were associated with higher cardiometabolic risk in adolescents.

Results
After adjusting for potential confounders, including estimated cell type proportions, epigenetic gestational age acceleration at birth, derived from the Bohlin, Knight, and Haftorn clocks using cord blood DNA methylation data, was not associated with cardiometabolic risk z-scores or individual cardiometabolic risk score components (visceral fat, leptin to adiponectin ratio, HOMA-IR, triglycerides to HDL-C ratio, HbA1c, or systolic blood pressure) at age 12 years. We also did not observe any associations of epigenetic age acceleration, calculated with Horvath’s skin and blood, Hannum’s, and Wu’s epigenetic clocks using peripheral blood at age 12 years, with these same cardiometabolic risk markers. In contrast, faster pace of biological aging was associated with higher cardiometabolic risk [βs (95% CIs)] cardiometabolic risk score 0.25 (0.07, 0.42); visceral fat 0.21 (0.05, 0.38); and hemoglobin A1c 0.23 (0.05, 0.41) per standard deviation increase in pace of biological aging. Faster pace of biological aging was also positively associated with systolic blood pressure, triglycerides to HDL-C ratio, HOMA-IR, and leptin to adiponectin ratio, although these associations were not statistically significant.

Conclusions
Our findings provide evidence that faster pace of biological aging was associated with higher cardiometabolic risk score, visceral fat, and HbA1c at age 12 years. Further research is needed to determine whether these associations persist from adolescence through adulthood.
A comparative study on bone density before and after implant placement using osseodensification technique: a clinical evaluation
Authors: Vaddamanu Sunil Kumar , Saini Ravinder S. , Vyas Rajesh , Kanji Masroor Ahmed , Alshadidi Abdulkhaliq Ali F. , Hafedh Salah , Cicciù Marco , Minervini Giuseppe 
Published: November 2024

Abstract
Background
Dental implant success critically depends on the primary stability of the implant, which is significantly influenced by the bone density at the osteotomy site. Traditional drilling techniques for osteotomy preparation often compromise bone volume and quality. This study aimed to evaluate the impact of osseodensification, a novel osteotomy preparation technique, on bone density and implant stability. The technique utilizes specialized drills that operate in a counter-clockwise direction to compact autografted bone laterally and apically, preserving and enhancing bone density.

Methods
A total of 32 patients undergoing dental implant surgery were included in this study. Pre-operative and post-operative bone densities at the apical, mesial, and distal regions of the osteotomy sites were measured using Dentascan (CT) and analyzed with Radiant DICOM software. The study utilized osseodensification drills for osteotomy preparation, comparing pre-operative and post-operative bone densities to assess the technique’s efficacy.

Results
The study found a statistically significant increase in bone density post-operatively (p < 0.001), with the greatest improvement observed in the distal region, followed by the mesial and apical regions. The findings underscore osseodensification’s effectiveness in enhancing bone density and primary stability, with the distal region exhibiting the highest bone density.

Conclusion
Osseodensification represents a significant advancement in implant dentistry for osteotomy preparation. By preserving and increasing bone density through compact autografting, this technique not only improves primary stability but also offers potential benefits in indirect sinus lifting and alveolar ridge expansion. The study advocates for the broader adoption of osseodensification drills in clinical practice to achieve better outcomes in dental implantology.

Trial Registration
This study received ethical approval from The Research Ethics Committee at King Khalid University’s under Approval no. ECM#2024 − 216. Additionally, it was registered with ClinicalTrials.gov, identifier no: NCT06268639.

Graphical Abstract
Computational analysis of variability and uncertainty in the clinical reference on magnetic resonance imaging radiomics: modelling and performance
Authors: Xue Cindy , Yuan Jing , Lo Gladys G. , Poon Darren M.C. , Chu Winnie CW 
Published: November 2024

AbstractTo conduct a computational investigation to explore the influence of clinical reference uncertainty on magnetic resonance imaging (MRI) radiomics feature selection, modelling, and performance. This study used two sets of publicly available prostate cancer MRI = radiomics data (Dataset 1: n = 260; Dataset 2: n = 100) with Gleason score clinical references. Each dataset was divided into training and holdout testing datasets at a ratio of 7:3 and analysed independently. The clinical references of the training set were permuted at different levels (increments of 5%) and repeated 20 times. Four feature selection algorithms and two classifiers were used to construct the models. Cross-validation was employed for training, while a separate hold-out testing set was used for evaluation. The Jaccard similarity coefficient was used to evaluate feature selection, while the area under the curve (AUC) and accuracy were used to assess model performance. An analysis of variance test with Bonferroni correction was conducted to compare the metrics of each model. The consistency of the feature selection performance decreased substantially with the clinical reference permutation. AUCs of the trained models with permutation particularly after 20% were significantly lower (Dataset 1 (with ≥ 20% permutation): 0.67, and Dataset 2 (≥ 20% permutation): 0.74), compared to the AUC of models without permutation (Dataset 1: 0.94, Dataset 2: 0.97). The performances of the models were also associated with larger uncertainties and an increasing number of permuted clinical references. Clinical reference uncertainty can substantially influence MRI radiomic feature selection and modelling. The high accuracy of clinical references should be helpful in building reliable and robust radiomic models. Careful interpretation of the model performance is necessary, particularly for high-dimensional data.
Comparative analysis of primary versus secondary paranasal sinus mucoceles: a case control study
Authors: Minh Le Tran Quang , Tuan Nguyen Thanh , Hon Nguyen Minh Hao 
Published: November 2024

Abstract
Background
Paranasal sinus mucoceles are benign cystic lesions characterized by mucous accumulation that can lead to significant complications due to erosion of sinus walls and compression of adjacent structures. This retrospective study aims to compare the clinical characteristics and treatment outcomes of primary and secondary mucoceles.

Methods
We reviewed medical records of 68 patients treated for mucoceles at the Ear, Nose, and Throat Hospital in Ho Chi Minh City, Vietnam, from June 2022 to June 2024. Advanced diagnostic imaging techniques, such as computed tomography (CT) and magnetic resonance imaging (MRI), were utilized in the management of these lesions. Statistical analysis was conducted using chi-square and t-tests to compare the characteristics and outcomes between the two groups.

Results
The study found that primary mucoceles often presented with less severe symptoms compared to secondary mucoceles, which occur post-surgery or post-trauma and are associated with more severe symptoms and complications. Primary mucoceles were most frequently located in the frontal-ethmoid region (47.4%), while secondary mucoceles had a similar distribution but were more prevalent following previous surgical interventions. Endoscopic sinus surgery was the primary treatment for both groups, with secondary mucoceles frequently requiring more complex surgical interventions. Postoperative improvement was significant in both groups, though secondary mucoceles exhibited slower recovery and higher rates of residual minor visual impairments.

Conclusion
The comparison between primary and secondary paranasal sinus mucoceles reveals critical differences in clinical profiles and treatment outcomes. Understanding these differences is essential for optimizing management strategies and improving prognosis for patients with these challenging conditions. Further research is needed to explore long-term treatment effects and the efficacy of different surgical approaches.
Characterization of desi cotton (
Gossypium arboreum
) germplasm through morpho-biochemical and fiber traits and exploring molecular marker based diversity along with allied (un)cultivated Gossypium species
Authors: Vadodaria Hrushik , Patidar Dhramendra , Kumar Sushil , Patel Dipak A. , Patel Hardik 
Published: November 2024

Abstract

Desi
cotton (
Gossypium arboreum
) or the Asian tree cotton occupies the least area amongst all the cultivated
Gossypium
species, but it is of paramount importance as a vital source of high-quality lint and stress resistance for commercially cultivated cotton species. Hence, it is essential to analyze the genetic diversity of this crop for future advancements in cotton breeding. An study comprising of 30
G. arboreum
accessions was undertaken to estimate the genetic variability using morphological traits, fibre quality parameters and oil quality. Likewise, molecular diversity analysis using 24 SSR markers was carried out for the 30
G. arboreum
genotypes and 11 additional cotton species. Presence of substantial genetic variability was revealed by analysis of variance (ANOVA) amongst all genotypes for all the traits. Morphological studies indicated that genotype PA 255 had higher seed cotton yield (80.07 g/plant). Examination of fibre and oil quality suggested that genotype Cernuum had the highest fibre fineness (7.27 µg/inch) and oil (17.68%), while genotypes 824 (29.57 mm) and PA 812 (29.30 g/tex) had the maximum UHML and fibre strength, respectively. 30 genotypes were classified into 3 classes based on the seed cotton yield, which is considered a very important trait. Manhattan dissimilarity co-efficient based phenotypic diversity divided the 30 genotypes into four main clusters, with an average dissimilarity value of 0.17, indicating low phenotypic variability. The dendrogram generated using SSR marker data based on Nei’s genetic distance grouped 41 genotypes into three clusters, with average distance of 0.47. Based upon the placement of the number of genotypes in same clusters in both matrices, it can be inferred that there is considerable correlation between morphological and molecular analysis as the value for Mantel statistic R was 0.42 (
p
value 0.0003). Fatty acid profiles of 30
desi
cotton genotypes revealed the presence of nine different fatty acids of which linoleic, palmitic and oleic acid were found to be in highest amount, with an average of 43.22%, 25.13% and 24.97%, respectively. Overall, the study suggested that the variability available in diploid cotton can be exploited through hybridization, mapping population development and polyploidization based pre-breeding.
Effects of rainfall on parasitism and survival of
Telenomus remus
, an egg parasitoid of fall armyworm
Authors: Yan Sanqiang , Lyu Baoqian , Lu Hui , Tang Jihong , Zhang Qikai , Jiao Bin , Zang Liansheng , He Xing 
Published: November 2024

Abstract

Telenomus remus
is an egg parasitoid of
Spodoptera
species, including the major agricultural pest
Spodoptera frugiperda
. Climatic factors are closely related to the development and population dynamics of such parasitoids. However, the effects of rainfall on the biological performance of this wasp have not be studied. Here, we modeled the effects of different intensities of rainfall (control: 0, light rain: 5.0, moderate rain: 10.2, and torrential rain: 42.8 mm/h; falling over a 30 min period) on the parasitism rate, developmental time, and survival of
T. remus
on eggs of
S. frugiperda
. We assessed the effect of rainfall exposure on both
T. remus
adults and on parasitized
S. frugiperda
eggs. Simulated rainfall resulted in a notable decline in the number of hosts parasitized by
T. remus
adults for up to 12 h following rainfall, but the parasitism rate returned to normal within one day after rain ceased. Torrential rain reduced immediate (within 24 h) survival of adults of
T. remus
females, but there was no subsequent effect on adult survival after rain ceased. When parasitized host eggs were exposed to rain events, some eggs were dislodged. Moderate or torrential intensity rainfall dislodged 12 and 44% of
S. frugiperda
eggs from maize leaves. For
T. remus
eggs exposed to rain that were not dislodged, the probability of reaching adulthood and successfully emerging was negatively correlated with rainfall intensity. However, for all levels of rainfall intensity, the survival of eggs that were not dislodged was greater than those that were dislodged. These findings suggest farmers should avoid releasing natural enemies when rainfall occurs or is forecast, and they should make supplemental releases after unanticipated rainfall occurs immediately after releases.
Postoperative Nausea and Vomiting in Pediatrics: Incidence and Guideline Adherence—a Retrospective Cohort Study
Authors: Portnoy Yotam , Glebov Maxim , Orkin Dina , Katsin Maxim , Berkenstadt Haim 
Published: November 2024

BACKGROUND:
Postoperative nausea and vomiting (PONV) in pediatric patients is a common and clinically significant postoperative complication. The incidence of PONV has not been extensively studied in large pediatric cohorts. Furthermore, in 2020, the Fourth Consensus Guidelines for the management of PONV were published. However, the association between perioperative factors and adherence to these guidelines remains unclear. This study aims to assess both the incidence of PONV and guideline adherence within a large and diverse pediatric population.

METHODS:
We conducted a retrospective observational study at a large tertiary medical center, including pediatric patients (≤18 years) who underwent surgery between September 2020 and March 2023. We conducted a retrospective analysis of data from our electronic health records, focusing on patient demographics, surgical details, anesthesia details, and prophylaxis for PONV. We calculated the incidence of PONV and used multivariable logistic regression to identify the predictors of guideline adherence.

RESULTS:
The cohort included 3772 patients with a median (interquartile range [IQR]) age of 9.21 (3.55–14.68) years. The incidence (95% confidence intervals) of early PONV was 1.0% (0.7–1.4) and 3.8% (3.2–4.5) for delayed PONV. Adherence to the fourth consensus guidelines for PONV management was observed in 32.5% (31.0–34.0) of cases. A high risk of PONV was identified in 55.9% (54.3–57.5) of the patients. The most common number of PONV risk factors was 3, observed in 1151 patients (30.5% [29.1–32.0]). Significant predictors of guideline adherence included the intraoperative use of long-acting opioids (odds ratio [OR], 2.711, P < .001) and age ≥3 years (OR, 2.074, P < .001). Nonadherence was associated with a higher incidence of PONV at 24 hours postsurgery (4.4% (3.6–5.2) vs 2.7% (1.9–3.8), P = .012). Factors such as specific high PONV risk surgeries (P = .001), maintenance with inhalational agents solely (P = .017), and neostigmine use (P < .001) were also all statistically significant.

CONCLUSIONS:
Our study revealed a lower-than-expected incidence of PONV in pediatric patients, highlighting the need for standardized definitions and improved reporting. Adherence to PONV guidelines was suboptimal, emphasizing the need for better implementation strategies.