bluuebunny/crossref_metadata_2025 huggingface dataset:
Cannabinoids detected in exhaled breath condensate after cannabis use
Authors: Berry Jennifer L , Brooks-Russell Ashley , Beuning Cheryle N , Limbacher Sarah A , Lovestead Tara M , Jeerage Kavita M
Published: July 2024

Cannabinoids can be detected in breath after cannabis use, but different breath matrices need to be explored as studies to date with filter-based devices that collect breath aerosols have not demonstrated that breath-based measurements can reliably identify recent cannabis use. Exhaled breath condensate (EBC) is an unexplored aqueous breath matrix that contains condensed volatile compounds and water vapor in addition to aerosols. EBC was collected from participants both before and at two time points (0.7 ± 0.2 h and 1.7 ± 0.3 h) after observed cannabis use. Eleven different cannabinoids were monitored with liquid chromatography tandem mass spectrometry. Five different cannabinoids, including Δ9-tetrahydrocannabinol (THC), were detected in EBC collected from cannabis users. THC was detected in some EBC samples before cannabis use, despite the requested abstinence period. THC was detected in all EBC samples collected at 0.7 h post use and decreased for all participants at 1.7 h. Non-THC cannabinoids were only detected after cannabis use. THC concentrations in EBC samples collected at 0.7 h showed no trend with sample metrics like mass or number of breaths. EBC sampling devices deserve further investigation with respect to modes of cannabis use (e.g, edibles), post use time points, and optimization of cannabinoid recovery.
A practical machine learning approach for predicting the quality of 3D (bio)printed scaffolds
Authors: Rafieyan Saeed , Ansari Elham , Vasheghani-Farahani Ebrahim
Published: July 2024

3D (Bio)printing is a highly effective method for fabricating tissue engineering scaffolds, renowned for their exceptional precision and control. Artificial intelligence (AI) has become a crucial technology in this field, capable of learning and replicating complex patterns that surpass human capabilities. However, the integration of AI in tissue engineering is often hampered by the lack of comprehensive and reliable data. This study addresses these challenges by providing one of the most extensive datasets on 3D-printed scaffolds. It provides the most comprehensive open-source dataset and employs various AI techniques, from unsupervised to supervised learning. This dataset includes detailed information on 1171 scaffolds, featuring a variety of biomaterials and concentrations—including 60 biomaterials such as natural and synthesized biomaterials, crosslinkers, enzymes, etc.—along with 49 cell lines, cell densities, and different printing conditions. We used over 40 machine learning and deep learning algorithms, tuning their hyperparameters to reveal hidden patterns and predict cell response, printability, and scaffold quality. The clustering analysis using KMeans identified five distinct ones. In classification tasks, algorithms such as XGBoost, Gradient Boosting, Extra Trees Classifier, Random Forest Classifier, and LightGBM demonstrated superior performance, achieving higher accuracy and F1 scores. A fully connected neural network with six hidden layers from scratch was developed, precisely tuning its hyperparameters for accurate predictions. The developed dataset and the associated code are publicly available on https://github.com/saeedrafieyan/MLATE to promote future research.
Production of paver blocks from polyethylene terephthalate solid waste as partial replacement of sand
Authors: Worku Getahun Demeke , Ejigu Assamen Ayalew
Published: July 2024

Plastic waste management is an international concern. Polyethylene terephthalate (PET) plastic waste is present everywhere in Addis Ababa relative to other types of plastic waste and it is an international concern regarding environmental problems. The amount of plastic trash produced globally is increasing at a rapid rate, and this pollution is caused by improper disposal, the waste’s non-biodegradability, and the harmful gases released during incineration pose a hazard to human health. Because it’s used in so many commonplace items, such as bottles and containers for the food and beverage sectors, polyethylene terephthalate, or PET, is one of the most widely used consumer polymers. Because of its many characteristics, including its inability to biodegrade and the gasses it releases when burned, it has grown to be a significant environmental problem. Waste made of polyethylene terephthalate (PET) must therefore be recycled and used efficiently. The purpose of this study was to produce paver blocks by partially replacing sand with waste Polyethylene Terephthalate (PET) material. Preparing the raw materials, mixing, vibrating, molding, curing, testing the flexural and compressive strengths, and curing are the steps in the production process. . The mixing proportion of paver blocks implemented for this study was 1:2:3, which is a predictable volume basis-mixing ratio of cement, aggregate, and sand correspondingly. Design-Expert 13.0.0 Three-level three factor Box–Behnken design was used for experimental design and statistical analysis of results based on the outcome and discussion. A total of 17 trials were carried out with the following parameters: 10, 20, and 30% of polyethylene terephthalate; 0.52, 0.55, and 0.58 as the water-to-cement ratio; and 7, 14, and 28 days for the curing period. The interaction effects were examined based on the examination of the experimental data. The physio-mechanical properties of Paver Blocks, including water absorption, compressive strength, and flexural strength, were examined. At a water-to-cement ratio of 0.55, obtained maximum flexural and compressive strength which is 4.92 MPa, and 29.74 MP respectively, and when PET plastic waste percentage increased, both flexural and compressive strength decreased but we got a good flexural and compressive strength value at 10% PET. And also water absorption rates were increased as PET plastic waste increased. The ideal process variables for polyethylene terephthalate percentage were 10 and 28. The paver blocks average and maximum water absorption rates were 3.39% and 3.95%, respectively. Compared to regular blocks, the resultant Paver Blocks are lighter and have superior physical and mechanical qualities. These are excellent illustrations of planned paver applications that can make use of prefabricated paver blocks.
Enhancing the functionality of sugar palm (Arenga Pinnata) fibre reinforced polylactic acid composite filament of fused deposition modelling through Taguchi method
Authors: C H Hazliza Aida , Mastura M T , Abdul Kudus S I , Muhd Mufqi A
Published: July 2024

Constructing functional components using Fused Deposition Modelling (FDM) is challenging due to various processing factors that influence the quality of the final product. The main reason for this is the many processing parameters involved, which have the ability to impact the quality of the produced components. The aim of this research is to use the Taguchi technique in attempt to improve the printing variables for attaining the best possible mechanical and physical qualities in the three-dimensional (3D) printed product made from sugar palm fibre reinforced polylactic acid (SPF/PLA). The layer thickness, infill density, and printing speed are characteristics that directly affect the mechanical qualities, surface roughness, and dimensional accuracy of FDM products. The research applied Taguchi’s L9 array, consisting of 9 experimental trials, with each trial including 5 duplicated specimens. Thus, a total of 45 specimens were generated by altering various processing settings. The most effective printing settings for FDM using SPF and PLA were found to be a layer thickness of 0.1 mm, infill density set to 100%, and a printing speed of 25 mm s−1. The microscopic images reveal a significant rise in the number of voids as the layer thickness is raised. Additionally, the printing speed has a substantial impact on the nead structure, making it more resilient. Overall, the results will provide a significant collection of data in the area of 3D printing, improving the utilization of indigenous plant fibres in additive manufacturing technology.
A comprehensive analysis of SOX17 expression by immunohistochemistry in human epithelial tumors, with an emphasis on gynecologic tumors
Authors: Clark Beth Z , Soong T Rinda , Goel Kanika , Elishaev Esther , Zhao Chengquan , Jones Terri E , Jones Mirka W , Skvarca Lauren B , Motanagh Samaneh A , Carter Gloria J , Fine Jeffrey L , Harinath Lakshmi , Villatoro Tatiana M , Yu Jing , Bhargava Rohit
Published: July 2024

Objectives

The objective of this study was to evaluate SOX17, a transcription factor from the Sry high-mobility group–related box superfamily, as a diagnostic marker to determine site of origin using both whole-tissue sections and tissue microarrays (TMAs).

Methods

SOX17 immunohistochemistry was performed on gynecologic and nongynecologic tissues (N = 1004) using whole-tissue sections and both internally constructed and commercially available TMAs. SOX17 nuclear reactivity was scored as positive or negative on the whole-tissue sections and using the semiquantitative H score method on TMAs.

Results

Using both whole-tissue sections and TMAs, SOX17 was positive in 94% (n = 155) of endometrial tumors and 96% (n = 242) of ovarian tumors. All breast cases (n = 241) and vulvar/cervical squamous cell carcinomas (n = 150) were negative. Among 1004 tumors from 20 sites, the only organs with positive tumors were ovary, uterus, and testis.

Conclusions

SOX17 is a sensitive and specific marker for gynecologic origin in the tissues tested and may be a valuable adjunct to PAX8 and other commonly used markers to confirm endometrial or ovarian origin. SOX17 expression is lower in mucinous tumors, endocervical adenocarcinoma, high-grade neuroendocrine tumors, and undifferentiated/dedifferentiated endometrial carcinoma.
State-of-the-Art-Review: Mechanisms of Action of SGLT2 Inhibitors and Clinical Implications
Authors: Vallon Volker
Published: July 2024

BACKGROUND

Inhibitors of the Na+-coupled glucose transporter SGLT2 (SGLT2i) primarily shift the reabsorption of large amounts of glucose from the kidney’s early proximal tubule to downstream tubular segments expressing SGLT1, and the non-reabsorbed glucose is spilled into the urine together with some osmotic diuresis. How can this protect the kidneys and heart from failing as observed in individuals with and without type 2 diabetes?

GOAL

Mediation analyses identified clinical phenotypes of SGLT2i associated with improved kidney and heart outcome, including a reduction of plasma volume or increase in hematocrit, and lowering of serum urate levels and albuminuria. This review outlines how primary effects of SGLT2i on the early proximal tubule can explain these phenotypes.

RESULTS

The physiology of tubule-glomerular communication provides the basis for acute lowering of GFR and glomerular capillary pressure, which contributes to lowering of albuminuria but also to long term preservation of GFR, at least in part by reducing kidney cortex oxygen demand. Functional co-regulation of SGLT2 with other sodium and metabolite transporters in the early proximal tubule explains why SGLT2i initially excrete more sodium than expected and are uricosuric, thereby reducing plasma volume and serum urate. Inhibition of SGLT2 reduces early proximal tubule gluco-toxicity and by shifting transport downstream may simulate “systemic hypoxia”, and the resulting increase in erythropoiesis, together with the osmotic diuresis, enhances hematocrit and improves blood oxygen delivery. Cardio-renal protection by SGLT2i is also provided by a fasting-like and insulin-sparing metabolic phenotype and, potentially, by off-target effects on the heart and microbiotic formation of uremic toxins.
Impact of a pharmacist-led intervention on prostate cancer illness perception
Authors: Iheanacho Chinonyerem O , Odili Valentine U
Published: July 2024

Purpose

Illness perception (IP) significantly determines illness outcomes. This study determined the impact of a pharmacist educational intervention on IP and the predictors of IP in patients with prostate cancer (PCa).

Methods

Using a brief IP questionnaire, an interventional study of patients with PCa was conducted in all cancer reference hospitals in one Nigerian state. After a pre-post assessment of patients’ IP, descriptive and inferential statistical analyses were performed. The impact of pharmacists’ intervention on IP was determined by paired-sample statistics and correlation analysis at the 95% CI. Relationships and predictors of IP were determined using Kendall’s tau-b (τb), likelihood ratio, and F tests of equality of means, respectively. P < 0.05 was considered statistically significant.

Results

Pharmacists’ educational intervention significantly improved IP (SEM, 0.13; r = 0.875; P < 0.0001) among the 200 participants. The analyses also showed a significant paired sample difference (2.662; SEM, 0.06; 95%CI, 2.536-2.788; t = 41.69; df = 199; P < 0.0001). All subscales of patients’ IP significantly improved except for illness consequences (P = 0.173) and identity (mean [SD], 4.40 [3.730] in both pre- and postintervention assessments). Pre- and postintervention assessments showed a significant negative relationship of IP with age (τb = –110 [P = 0.040] and τb = –14 [P = 0.021], respectively), Gleason score (τb = –0.125 [P = 0.021] and τb = –0.124 [P=0.012], respectively), and age at diagnosis (τb = –0.103 [P = 0.036] post intervention). IP was significantly dependent on the drug therapy (df = 8; mean square [M] = 6.292; F = 2.825; P = 0.006), alcohol intake (df = 1; M = 9.608; F = 4.082; P = 0.045) and Gleason score (df = 9; M = 6.706; F = 3.068; P = 0.002).

Conclusion

Patients’ IP significantly improved after pharmacists’ educational intervention. Predictors of IP were drug therapies, alcohol use and Gleason score. Findings can be extrapolated in clinical settings to improve treatment outcomes.
DeepIDA-GRU: a deep learning pipeline for integrative discriminant analysis of cross-sectional and longitudinal multiview data with applications to inflammatory bowel disease classification
Authors: Jain Sarthak , Safo Sandra E
Published: July 2024

Biomedical research now commonly integrates diverse data types or views from the same individuals to better understand the pathobiology of complex diseases, but the challenge lies in meaningfully integrating these diverse views. Existing methods often require the same type of data from all views (cross-sectional data only or longitudinal data only) or do not consider any class outcome in the integration method, which presents limitations. To overcome these limitations, we have developed a pipeline that harnesses the power of statistical and deep learning methods to integrate cross-sectional and longitudinal data from multiple sources. In addition, it identifies key variables that contribute to the association between views and the separation between classes, providing deeper biological insights. This pipeline includes variable selection/ranking using linear and nonlinear methods, feature extraction using functional principal component analysis and Euler characteristics, and joint integration and classification using dense feed-forward networks for cross-sectional data and recurrent neural networks for longitudinal data. We applied this pipeline to cross-sectional and longitudinal multiomics data (metagenomics, transcriptomics and metabolomics) from an inflammatory bowel disease (IBD) study and identified microbial pathways, metabolites and genes that discriminate by IBD status, providing information on the etiology of IBD. We conducted simulations to compare the two feature extraction methods.
Biclustering data analysis: a comprehensive survey
Authors: Castanho Eduardo N , Aidos Helena , Madeira Sara C
Published: July 2024

Biclustering, the simultaneous clustering of rows and columns of a data matrix, has proved its effectiveness in bioinformatics due to its capacity to produce local instead of global models, evolving from a key technique used in gene expression data analysis into one of the most used approaches for pattern discovery and identification of biological modules, used in both descriptive and predictive learning tasks. This survey presents a comprehensive overview of biclustering. It proposes an updated taxonomy for its fundamental components (bicluster, biclustering solution, biclustering algorithms, and evaluation measures) and applications. We unify scattered concepts in the literature with new definitions to accommodate the diversity of data types (such as tabular, network, and time series data) and the specificities of biological and biomedical data domains. We further propose a pipeline for biclustering data analysis and discuss practical aspects of incorporating biclustering in real-world applications. We highlight prominent application domains, particularly in bioinformatics, and identify typical biclusters to illustrate the analysis output. Moreover, we discuss important aspects to consider when choosing, applying, and evaluating a biclustering algorithm. We also relate biclustering with other data mining tasks (clustering, pattern mining, classification, triclustering, N-way clustering, and graph mining). Thus, it provides theoretical and practical guidance on biclustering data analysis, demonstrating its potential to uncover actionable insights from complex datasets.
A novel deep machine learning algorithm with dimensionality and size reduction approaches for feature elimination: thyroid cancer diagnoses with randomly missing data
Authors: Tutsoy Onder , Sumbul Hilmi Erdem
Published: July 2024

Thyroid cancer incidences endure to increase even though a large number of inspection tools have been developed recently. Since there is no standard and certain procedure to follow for the thyroid cancer diagnoses, clinicians require conducting various tests. This scrutiny process yields multi-dimensional big data and lack of a common approach leads to randomly distributed missing (sparse) data, which are both formidable challenges for the machine learning algorithms. This paper aims to develop an accurate and computationally efficient deep learning algorithm to diagnose the thyroid cancer. In this respect, randomly distributed missing data stemmed singularity in learning problems is treated and dimensionality reduction with inner and target similarity approaches are developed to select the most informative input datasets. In addition, size reduction with the hierarchical clustering algorithm is performed to eliminate the considerably similar data samples. Four machine learning algorithms are trained and also tested with the unseen data to validate their generalization and robustness abilities. The results yield 100% training and 83% testing preciseness for the unseen data. Computational time efficiencies of the algorithms are also examined under the equal conditions.
TWCOM: an R package for inference of cell–cell communication on spatially resolved transcriptomics data
Authors: Wu Dongyuan , Datta Susmita
Published: July 2024

The inference of cell–cell communication is important, as it unveils the intricate cellular behaviors at the molecular level, providing crucial insights essential for understanding complex biological processes and informing targeted interventions in various pathological contexts. Here, we present TWCOM, an R package that implements a Tweedie distribution-based model for accurate cell–cell communication inference. Operating under a generalized additive model framework, TWCOM adeptly handles both single-cell resolution and spot-based spatially resolved transcriptomics data, providing a versatile tool for robust biological sample analysis.

Availability and implementation

The R package TWCOM is available at https://github.com/dongyuanwu/TWCOM. Comprehensive documentation is included with the package.
Increased EHD1 in trophoblasts causes RSM by activating TGFβ signaling
Authors: Wu Xing , Shen Jiayan , Liu Jinjin , Kang Nannan , Zhang Mingshun , Cai Xinyu , Zhen Xin , Yan Guijun , Liu Yang , Sun Haixiang
Published: July 2024

Background

Recurrent spontaneous miscarriage is one of the complications during pregnancy. However, the pathogenesis of recurrent spontaneous miscarriage is far from fully elucidated.

Objective

Since the endocytic pathway is crucial for cellular homeostasis, our study aimed to explore the roles of endocytic recycling, especially EH domain containing 1, a member of the endocytic recycling compartment, in recurrent spontaneous miscarriage.

Study Design

We first investigated the expression of the endocytic pathway member EH domain containing 1 in villi from the normal and recurrent spontaneous miscarriage groups. Then, we performed ribonucleic acid sequencing and experiments in villi, HTR8 cells and BeWo cells to determine the mechanisms by which EH domain containing 1–induced recurrent spontaneous miscarriage. Finally, placenta–specific EH domain containing 1–overexpressing mice were generated to investigate the recurrent spontaneous miscarriage phenotype in vivo.

Results

EH domain containing 1 was expressed in extravillous trophoblasts and syncytiotrophoblast in the villi. Compared with the control group, recurrent spontaneous miscarriage patients expressed higher EH domain containing 1. A high level of EH domain containing 1 decreased proliferation, promoted apoptosis, and reduced the migration and invasion of HTR8 cells by activating the TGFβ receptor 1-SMAD2/3 signaling pathway. The TGFβ receptor 1 antagonist LY3200882 partially reversed the EH domain containing 1 overexpression-induced changes in the cell phenotype. Besides, a high level of EH domain containing 1 also induced abnormal syncytialization, which disturbed maternal–fetal material exchanges. In a mouse model, placenta-specific overexpression of EH domain containing 1 led to the failure of spiral artery remodeling, excessive syncytialization, and miscarriage.

Conclusions

Increased expression of EH domain containing 1 impaired the invasion of extravillous trophoblasts mediated by the TGFβ receptor 1-SMAD2/3 signaling pathway and induced abnormal syncytialization of syncytiotrophoblast, which is at least partially responsible for recurrent spontaneous miscarriage.
PathGPS: discover shared genetic architecture using GWAS summary data
Authors: Gao Zijun , Zhao Qingyuan , Hastie Trevor
Published: July 2024

The increasing availability and scale of biobanks and “omic” datasets bring new horizons for understanding biological mechanisms. PathGPS is an exploratory data analysis tool to discover genetic architectures using Genome Wide Association Studies (GWAS) summary data. PathGPS is based on a linear structural equation model where traits are regulated by both genetic and environmental pathways. PathGPS decouples the genetic and environmental components by contrasting the GWAS associations of “signal” genes with those of “noise” genes. From the estimated genetic component, PathGPS then extracts genetic pathways via principal component and factor analysis, leveraging the low-rank and sparse properties. In addition, we provide a bootstrap aggregating (“bagging”) algorithm to improve stability under data perturbation and hyperparameter tuning. When applied to a metabolomics dataset and the UK Biobank, PathGPS confirms several known gene–trait clusters and suggests multiple new hypotheses for future investigations.
Identification of gaps in the delivery of high-quality care of patients with eosinophilic esophagitis
Authors: Njie Cheikh , Richman Courtney , Rebhun Jeffrey , Achalu Sudharshan , Kamal Afrin N , Otaki Fouad , Leiman David A , Kathpalia Priya
Published: July 2024

Quality indicators (QIs) are standardized metrics that can be used to quantify health care delivery and identify important areas for practice improvement. Nine QIs pertaining to the diagnosis and management of eosinophilic esophagitis (EoE) were recently established. We therefore aimed to identify existing gaps in care using these QIs. This is a retrospective, multicenter study utilizing recently established EoE QIs to evaluate practice patterns among adult gastroenterologists in the diagnosis and management of EoE. Three patient cohorts of 30 patients each presenting with dysphagia, food impaction, and new diagnosis of EoE, respectively, were obtained, yielding 120 patients per site to assess for every QI. Summary statistics were reported across two main themes: diagnosis and management. Subsequent analysis of gaps in care was then performed. The domain of diagnosis of EoE (QI 1 and 2) had the most notable gap in care with only 55% of the presenting patients undergoing appropriate evaluation for EoE. The domain of management of EoE had overall higher QI fulfillment—however it also contained significant intra-category variation in care. Notably, while 79% of patients had clinical follow-up within 1 year from remission, only 54% underwent surveillance endoscopy within 2 years of remission. In contrast, 100% of patients with symptomatic strictures independent of histologic response underwent endoscopic dilation (QI 4). Management approaches for EoE are evolving and variation in care delivery exists. We identified significant gaps in both diagnosis of EoE especially amongst patients presenting with index food impaction and long term management of EoE, when retrospectively evaluating care patterns using newly established QIs. This is the first study of its kind to utilize these previously established QIs to objectively identify care gaps that exist in EoE amongst several institutions. These findings also highlight the importance of QIs and standardization of management of complex chronic diseases like EoE to help bridge these gaps and provide a framework to measure adherence to these best practices.
Catheter ablation for atrial fibrillation and impact on clinical outcomes
Authors: Providencia Rui , Ali Hussam , Creta Antonio , Barra Sérgio , Kanagaratnam Prapa , Schilling Richard J , Farkowski Michal , Cappato Riccardo
Published: July 2024

Aims

Catheter ablation is the most effective rhythm-control option in patients with atrial fibrillation (AF) and is currently considered an option mainly for improving symptoms. We aimed to assess the impact of catheter ablation on hard clinical outcomes.

Methods and results

We performed a systematic review of randomized controlled trials (RCTs) comparing catheter ablation vs. optimized medical treatment. We searched MEDLINE, EMBASE, and CENTRAL on 8 January 2024, for trials published ≤10 years. We pooled data through risk ratio (RR) and mean differences (MDs), with 95% confidence interval (CI), and calculated the number needed to treat (NNT). Sub-group and sensitivity analyses were performed for the presence/absence of heart failure (HF), paroxysmal/persistent AF, early ablation, higher/lower quality, and published ≤5 vs. >5 years. Twenty-two RCTs were identified, including 6400 patients followed for 6–52 months. All primary endpoints were significantly reduced by catheter ablation vs. medical management: all-cause hospitalization (RR = 0.57, 95% CI 0.39–0.85, P = 0.006), AF relapse (RR = 0.48, 95% CI 0.39–0.58, P < 0.00001), and all-cause mortality (RR = 0.69, 95% CI 0.56–0.86, P = 0.0007, NNT = 44.7, driven by trials with HF patients). A benefit was also demonstrated for all secondary endpoints: cardiovascular mortality (RR = 0.55, 95% CI 0.34–0.87), cardiovascular (RR = 0.83, 95% CI 0.71–0.96), and HF hospitalizations (RR = 0.71, 95% CI 0.56–0.89), AF burden (MD = 20.6%, 95% CI 5.6–35.5), left ventricular ejection fraction (LVEF) recovery (MD = 5.7%, 95% CI 3.5–7.9), and quality of life (MLHFQ, AFEQT, and SF-36 scales).

Conclusion

Catheter ablation significantly reduced hospitalizations, AF burden, and relapse, and improved quality of life. An impact on hard clinical outcomes, with an important mortality reduction and improvement in LVEF, was seen for patients with AF and HF.
‘JOY to great Caesar’: popular songs on Farinel’s Ground in late 17th-century England
Authors: Schönlau Stephan
Published: July 2024

This article represents a follow-up to a previous article on ‘Farinel’s Ground’, published in the May 2021 issue of this journal. There, I had focused on the numerous instrumental versions of this extremely popular ground bass, not least because the late 17th- and early 18th-century folia—as it was known more widely across Europe—seems to have been primarily an instrumental genre. Nevertheless, the popularity of this ground in the 1680s—and of some of the divisions associated with it—gave rise to a number of vocal versions or ballads, some of which may have been at least comparable in popularity to the instrumental versions printed in The Genteel Companion (1683) and The Division-Violin (1684). Sharing the same melody and bass (whether notated or implied), these ballads were written and published during some of the most turbulent years in British history (1682–1702). While the origins of the first of these, Thomas D’Urfey’s The King’s Health or ‘JOY to great Caesar’, can be traced to the violin and recorder divisions on Farinel’s Ground published at more or less the same time as D’Urfey’s song, the song itself seems to have spawned a number of offshoots, including later instrumental versions referring to its textual incipit. Resulting from a study of the music, text and context of songs on ‘Farinel’s Ground, this article also discusses issues applicable to English broadside ballads of the 17th century more generally, such as changes in the political environment and the at times almost decorative function of musical notation on broadsides.
Riboflavin overproduction on lignocellulose hydrolysate by the engineered yeast Candida famata
Authors: Dzanaeva Ljubov S , Wojdyła Dominik , Fedorovych Dariya V , Ruchala Justyna , Dmytruk Kostyantyn V , Sibirny Andriy A
Published: July 2024

Lignocellulose (dry plant biomass) is an abundant cheap inedible residue of agriculture and wood industry with great potential as a feedstock for biotechnological processes. Lignocellulosic substrates can serve as valuable resources in fermentation processes, allowing the production of a wide array of chemicals, fuels, and food additives. The main obstacle for cost-effective conversion of lignocellulosic hydrolysates to target products is poor metabolism of the major pentoses, xylose and L-arabinose, which are the second and third most abundant sugars of lignocellulose after glucose. We study the oversynthesis of riboflavin in the flavinogenic yeast Candida famata and found that all major lignocellulosic sugars, including xylose and L-arabinose, support robust growth and riboflavin synthesis in the available strains of C. famata. To further increase riboflavin production from xylose and lignocellulose hydrolysate, genes XYL1 and XYL2 coding for xylose reductase and xylitol dehydrogenase were overexpressed. The resulting strains exhibited increased riboflavin production in both shake flasks and bioreactors using diluted hydrolysate, reaching 1.5 g L−1.
Piece by piece—a computer-aided method for virtual re-association of commingled fragmented remains
Authors: Camine Lise Malfroy , Magnin Virginie , Soto Ruben , Bruguier Christine , Grabherr Silke , Varlet Vincent , Moghaddam Negahnaz
Published: July 2024

Air crashes or explosions with numerous victims may result in thousands of fragmented human remains that present a massive challenge for disaster victim identification teams. Genetic identification may present important financial and technical limits, and the physical re-association of fractured bones by forensic anthropologists may require a time-consuming phase of cleaning and drying. A virtual re-association (VRA) of fragmented human remains using postmortem computed tomography (CT)-scan images could enhance the identification process and reduce the number of genetic analyses required. Therefore, this study investigated the advantages and limitations of a VRA protocol in comparison with physical re-association (PRA) in a laboratory setting and in a real case scenario. As a first step, six porcine femurs were scanned by multi-detector CT before and after physical fragmentation. PRA of the dry bones and VRA of the 3D models of the fragments were then performed. The physically reconstructed dry bones were then once more scanned with CT. The mean distance between intact and reconstructed models, the number of re-associated fragments, and the time needed for the reconstruction were evaluated. In a second step, 87 fragmented remains resulting from a controlled pig bombing were collected, scanned, and virtually re-associated to test the feasibility of the protocol in a real context. The reconstruction of the femurs showed no difference in accuracy between PRA and VRA. Although the VRA was faster than PRA, the preparation of the material still needs to be taken into consideration. The VRA after the controlled pig bombing was limited to 8% of the total fragments. Differences in alveolar and cortical osseous structure and the presence of cartilage resulted in segmentation approximations and difficulties in the re-association itself. The explosion produced an important loss of intermediate bone elements. The VRA method still needs further evaluations with a larger sample size and different fragmentation mechanisms. However, the presented research shows promising results towards enhancing the efficiency of identifying individuals after a mass disaster.

Key points
The Psathyrostachys juncea DWARF27 gene encodes an all-trans-/9-cis-beta-carotene isomerase in the control of plant branches in Arabidopsis thaliana by strigolactones
Authors: Ren Xiaomin , Ai Qian , Li Zhen , Zhao Qiao , Yun Lan
Published: July 2024

Strigolactones (SLs), carotenoid-derived plant hormones, govern the growth and development of both monocotyledonous and dicotyledonous plants. DWARF27 (D27), a plastid-targeted protein located at the initiation site of the core pathway in SL synthesis, plays a crucial role in regulating plant tillering (branching). In rice (Oryza sativa) and wheat (Triticum aestivum), OsD27 and TaD27-B proteins modulate the number of plant tillers by participating in SL biosynthesis. Similarly, AtD27 in Arabidopsis thaliana is required for SL production and has a significant impact on phenotypic changes related to branching. At the same time, TaD27 in wheat has been confirmed as a functional orthologue of AtD27 in Arabidopsis, and both Psathyrostachys juncea and wheat belong to the Triticeae, so we speculate that PjD27 gene may also have the same function as AtD27 in Arabidopsis. In this study, we initially screened the PjD27 gene significantly associated with tillering regulation through transcriptome data analysis and subsequently validated its expression levels using qRT-PCR analysis. Furthermore, we conducted phylogenetic analysis using amino acid sequences from 41 species, including P. juncea, to identify closely related species of P. juncea. Here, we analyze the conservation of D27 protein among P. juncea, rice, wheat, and Arabidopsis and provide preliminary evidence suggesting that PjD27 protein is an orthologue of D27 protein in Arabidopsis. Through reverse genetics, we demonstrate the crucial role of PjD27 in regulating plant branching, establishing it as a functional orthologue of D27 in Arabidopsis. Furthermore, following transient expression in tobacco (Nicotiana tabacum), we demonstrate that the subcellular location of the PjD27 protein is consistent with the cellular location of TaD27-B in wheat. Quantitative analysis of SLs shows that PjD27 is a key gene regulating tillering (branching) by participating in SL biosynthesis. By elucidating the function of the PjD27 gene, our findings provide valuable genetic resources for new germplasm creation and improving grain yield in P. juncea.
Ancestral Sequence Reconstruction as a Tool to Detect and Study De Novo Gene Emergence
Authors: Vakirlis Nikolaos , Acar Omer , Cherupally Vijay , Carvunis Anne-Ruxandra
Published: July 2024

New protein-coding genes can evolve from previously noncoding genomic regions through a process known as de novo gene emergence. Evidence suggests that this process has likely occurred throughout evolution and across the tree of life. Yet, confidently identifying de novo emerged genes remains challenging. Ancestral sequence reconstruction is a promising approach for inferring whether a gene has emerged de novo or not, as it allows us to inspect whether a given genomic locus ancestrally harbored protein-coding capacity. However, the use of ancestral sequence reconstruction in the context of de novo emergence is still in its infancy and its capabilities, limitations, and overall potential are largely unknown. Notably, it is difficult to formally evaluate the protein-coding capacity of ancestral sequences, particularly when new gene candidates are short. How well-suited is ancestral sequence reconstruction as a tool for the detection and study of de novo genes? Here, we address this question by designing an ancestral sequence reconstruction workflow incorporating different tools and sets of parameters and by introducing a formal criterion that allows to estimate, within a desired level of confidence, when protein-coding capacity originated at a particular locus. Applying this workflow on ∼2,600 short, annotated budding yeast genes (<1,000 nucleotides), we found that ancestral sequence reconstruction robustly predicts an ancient origin for the most widely conserved genes, which constitute “easy” cases. For less robust cases, we calculated a randomization-based empirical P-value estimating whether the observed conservation between the extant and ancestral reading frame could be attributed to chance. This formal criterion allowed us to pinpoint a branch of origin for most of the less robust cases, identifying 49 genes that can unequivocally be considered de novo originated since the split of the Saccharomyces genus, including 37 Saccharomyces cerevisiae-specific genes. We find that for the remaining equivocal cases we cannot rule out different evolutionary scenarios including rapid evolution, multiple gene losses, or a recent de novo origin. Overall, our findings suggest that ancestral sequence reconstruction is a valuable tool to study de novo gene emergence but should be applied with caution and awareness of its limitations.
Adult Physical Function Has Roots in Early Childhood Brain Function: A Five-Decade Cohort Study
Authors: Xie J Kathy , Caspi Avshalom , Harrington HonaLee , Houts Renate , Pietrosimone Laura , Whitman Ethan T , McKinney Lauren W , Moffitt Terrie E
Published: July 2024

Objectives

Tests of physical function are often thought to measure functioning that is (1) musculoskeletal, and (2) newly declining in adult life. In contrast, this study aimed to: (1) add to evidence that physical-function tests also measure brain function, and (2) test the novel hypothesis that adult physical function is associated with brain function beginning in early childhood. We investigated early childhood brain function and midlife physical function in the Dunedin Study, a 5-decade longitudinal birth cohort (n = 1,037).

Methods

Brain function was measured at age 3 using 5 measures which formed a reliable composite (neurological examination, cognitive and motor tests, and temperament ratings). Physical function was measured at age 45 using 5 measures which formed a reliable composite (gait speed, step-in-place, chair stands, balance, and grip strength).

Results

Children with worse age-3 brain function had worse midlife physical function as measured by the age-45 composite, even after controlling for childhood socioeconomic status (β: 0.23; 95% CI: 0.16 to 0.30; p < .001). Worse age-3 brain function significantly predicted slower gait speed, fewer steps-in-place and chair-stands, worse balance, and weaker grip strength.

Discussion

Children with poorer brain function were more likely to have poorer physical-function scores as adults. In addition to indicating recent musculoskeletal decline, physical-function tests may also provide indications of lifelong, integrated brain–body health. By reconceptualizing the meaning of physical-function scores, clinicians can orient the use of physical-function tests in a more holistic approach to health care.
National Institute on Aging’s 50th Anniversary: Advancing Cognitive Aging Research and the Cognitive Health of Older Adults
Authors: Harrell Erin R , King Jonathan W , Stoeckel Luke E , Treviño Melissa
Published: July 2024

In celebration of the National Institute on Aging’s (NIA) 50th anniversary, this paper highlights the significant advances in cognitive aging research and the promotion of cognitive health among older adults. Since its inception in 1974, the NIA has played a pivotal role in understanding cognitive aging, including cognitive epidemiology, interventions, and methods, for measuring cognitive change. Key milestones include the shift toward understanding cognitive impairment and Alzheimer’s disease and Alzheimer’s disease-related dementias (AD/ADRD), the development of large-scale longitudinal studies, and the incorporation of AD/ADRD-related biomarkers in cognitive aging cohorts. Additionally, NIA has championed diversifying the scientific workforce through initiatives, such as the Resource Centers for Minority Aging Research and the Butler-Williams Scholars Program. The next 50 years will continue to emphasize the importance of inclusion, innovation, and impactful research to enhance the cognitive health and well-being of older adults.
Introducing biosimilar competition for cell and gene therapy products
Authors: Canter Brian , Sussman Sabine , Colvill Stephen , Arad Nitzan , Staton Elizabeth , Rai Arti
Published: July 2024

This article provides an early analysis of the potential for creating future biosimilar competition for cell and gene therapies (CGTs) to lower prices and improve patient access, building on a unique set of interviews with relevant experts. Our discussion addressed regulatory, manufacturing, intellectual property, and market size challenges. Due to CGTs' complexity, meeting the regulatory requirement of ‘high similarity with no clinically meaningful differences’ will be difficult. Gene therapies are likely better candidates for biosimilar development than cell therapies. Biosimilarity should be met when gene therapy biosimilars contain the same genetic sequence as a reference product, and the variability in the vector meets the high similarity standard. Manufacturing challenges, including the lack of standardized platforms, high production costs, and complexity, pose significant obstacles. It may also be important to demonstrate biosimilarity within the manufacturing process. Intellectual property barriers, specifically patenting, trade secrecy, and regulatory exclusivity, could hinder biosimilars' ability to gain market share, although recent Supreme Court decisions limiting the breadth of patent claims could ease barriers to future CGT competition, including from biosimilars. Finally, inadequate market sizes might create hurdles, especially for curative treatments, as patient pools shrink following treatment by the reference CGT.
Japanese fathers’ work-related factors associated with involvement in childcare
Authors: Ochi Manami , Kato Tsuguhiko , Kachi Yuko , Dhungel Bibha , Nagayoshi Mako , Ichinose Yuichi , Takehara Kenji
Published: July 2024

Objectives

Existing studies of fathers’ involvement in childcare have focused on its impact on children’s psychosocial development and the facilitation of family functions, like marital relationships. In this study, we investigated the factors that determine paternal childcare in Japan, particularly focusing on work-related hours and environment, separately, according to mothers’ employment status.

Methods

We used data from the Longitudinal Survey of Newborns in the 21st Century (2010 cohort) conducted in Japan. We restricted the sample to 27 783 participants with working fathers and analyzed how paternal work-related factors affect fathers’ childcare involvement by mothers’ employment status using an ordered logistic regression model.

Results

In the model adjusting for all covariates, the odds ratio (OR) of spending less time with children on weekdays was higher: for fathers who worked 50 and more hours per week compared with those who worked 40-49 hours per week (OR = 1.95, 95% CI: 1.72-2.20 for 50-59 hours), for fathers whose commuting hours were longer than those commuting less than 0.5 hours per day (OR = 2.93, 95% CI: 2.34-3.69 for 1.5 or more hours), for larger workplace employee sizes than for 5-99 employee sizes (OR = 1.56, 95% CI: 1.38-1.77 for 500 or more employees). The associations between these paternal work-related variables and paternal hours spent with the children on weekdays were almost the same if the mothers were working or not working.

Conclusions

Regardless of whether the mother is working, fathers’ work environment factors, such as working hours, play a key role in their involvement in childcare.
‘Don’t educate me—move me!’ Why we need art and artists (especially films and filmmakers) to love education into existence
Authors: Frimberger Katja
Published: July 2024

This paper explores the anthropological and ontological conditions of our ‘educational movement’ in aesthetic experience and illustrates these through a range of examples from popular cinema/film (the Empire Strikes Back; Memento; David Lynch’s musings). For the anthropological framing of education, I enlist the help of German philosopher Hans-Georg Gadamer and his notion of ‘formation’ as it unfolds in the aesthetic appearance of the cultural world—with film’s moving images’ coming-into-form-and-meaning as my key example. For Gadamer, the artwork’s formative potential is bound up in its capacity to move our senses and intellect into an encounter with what is other to our subjectivity. Drawn into a mode of paying attention to what appears (e.g. in film’s moving images), we are called to lose ourselves and be present in a new way to familiar world objects and relations. The second part of the paper imagines the ontological conditions that make possible our formative movement in the cultural world: the mode of the beautiful. Why do certain artworks shine forth and summon us to be present to them? To pursue this question, I turn to French Catholic philosopher Jacques Maritain’s notion of Beauty and craftsmanship. He turns us (like Gadamer) to a neo-Platonic notion of Beauty rooted in St Thomas Aquinas’ notion of the mystery of B/being (i.e. God). In Maritain’s reading, our hermeneutic aesthetic experience—and with that our movement into self-formation—is held in existence through the artist’s participation in the mode of the beautiful and their loss of self in the labour of love of craftsmanship.
Application of Weak-Beam Dark-Field STEM for Dislocation Loop Analysis
Authors: Lin Yan-Ru , Li Yao , Zinkle Steven J , Arregui-Mena Jose’ D , Burke M Grace
Published: July 2024

Nanoscale dislocation loops formed by irradiation can significantly contribute to both irradiation hardening and embrittlement of materials when subjected to extreme nuclear reactor environments. This study explores the application of weak-beam dark-field (WBDF) scanning transmission electron microscopy (STEM) methods for quantitative irradiation-induced defect analysis in crystalline materials, with a specific focus on dislocation loop imaging and analysis. A high-purity Fe-5 wt% Cr model alloy was irradiated with 8 MeV Fe2+ ions at 450°C to a fluence of 8.8 × 1019 m−2, inducing dislocation loops for analysis. While transmission electron microscopy (TEM) has traditionally been the primary tool for dislocation imaging, recent advancements in STEM technology have reignited interest in using STEM for defect imaging. This study introduces and compares three WBDF STEM methods, demonstrating their effectiveness in suppressing background contrasts, isolating defect information for dislocation loop type classification, providing finer dislocation line images for small loop analysis, and presenting inside–outside contrast for identifying loop nature. Experimental findings indicate that WBDF STEM methods surpass traditional TEM approaches, yielding clearer and more detailed images of dislocation loops. The study concludes by discussing the potential applications of WBDF STEM techniques in defect analysis, emphasizing their adaptability across various material systems beyond nuclear materials.