bluuebunny/crossref_metadata_2025_split huggingface dataset:
Automating Wood Species Detection and Classification in Microscopic Images of Fibrous Materials with Deep Learning
Authors: Nieradzik Lars , Sieburg-Rockel Jördis , Helmling Stephanie , Keuper Janis , Weibel Thomas , Olbrich Andrea , Stephani Henrike 
Published: May 2024

Abstract
We have developed a methodology for the systematic generation of a large image dataset of macerated wood references, which we used to generate image data for nine hardwood genera. This is the basis for a substantial approach to automate, for the first time, the identification of hardwood species in microscopic images of fibrous materials by deep learning. Our methodology includes a flexible pipeline for easy annotation of vessel elements. We compare the performance of different neural network architectures and hyperparameters. Our proposed method performs similarly well to human experts. In the future, this will improve controls on global wood fiber product flows to protect forests.
Structural basis of archaeal RNA polymerase transcription elongation and Spt4/5 recruitment
Authors: Tarău Daniela , Grünberger Felix , Pilsl Michael , Reichelt Robert , Heiß Florian , König Sabine , Urlaub Henning , Hausner Winfried , Engel Christoph , Grohmann Dina 
Published: May 2024

Abstract
Archaeal transcription is carried out by a multi-subunit RNA polymerase (RNAP) that is highly homologous in structure and function to eukaryotic RNAP II. Among the set of basal transcription factors, only Spt5 is found in all domains of life, but Spt5 has been shaped during evolution, which is also reflected in the heterodimerization of Spt5 with Spt4 in Archaea and Eukaryotes. To unravel the mechanistic basis of Spt4/5 function in Archaea, we performed structure-function analyses using the archaeal transcriptional machinery of Pyrococcus furiosus (Pfu). We report single-particle cryo-electron microscopy reconstructions of apo RNAP and the archaeal elongation complex (EC) in the absence and presence of Spt4/5. Surprisingly, Pfu Spt4/5 also binds the RNAP in the absence of nucleic acids in a distinct super-contracted conformation. We show that the RNAP clamp/stalk module exhibits conformational flexibility in the apo state of RNAP and that the enzyme contracts upon EC formation or Spt4/5 engagement. We furthermore identified a contact of the Spt5-NGN domain with the DNA duplex that stabilizes the upstream boundary of the transcription bubble and impacts Spt4/5 activity in vitro. This study, therefore, provides the structural basis for Spt4/5 function in archaeal transcription and reveals a potential role beyond the well-described support of elongation.
Imputation Server PGS: an automated approach to calculate polygenic risk scores on imputation servers
Authors: Forer Lukas , Taliun Daniel , LeFaive Jonathon , Smith Albert V , Boughton Andrew P , Coassin Stefan , Lamina Claudia , Kronenberg Florian , Fuchsberger Christian , Schönherr Sebastian 
Published: May 2024

Abstract
Polygenic scores (PGS) enable the prediction of genetic predisposition for a wide range of traits and diseases by calculating the weighted sum of allele dosages for genetic variants associated with the trait or disease in question. Present approaches for calculating PGS from genotypes are often inefficient and labor-intensive, limiting transferability into clinical applications. Here, we present ‘Imputation Server PGS’, an extension of the Michigan Imputation Server designed to automate a standardized calculation of polygenic scores based on imputed genotypes. This extends the widely used Michigan Imputation Server with new functionality, bringing the simplicity and efficiency of modern imputation to the PGS field. The service currently supports over 4489 published polygenic scores from publicly available repositories and provides extensive quality control, including ancestry estimation to report population stratification. An interactive report empowers users to screen and compare thousands of scores in a fast and intuitive way. Imputation Server PGS provides a user-friendly web service, facilitating the application of polygenic scores to a wide range of genetic studies and is freely available at https://imputationserver.sph.umich.edu.
Arrayed in vivo barcoding for multiplexed sequence verification of plasmid DNA and demultiplexing of pooled libraries
Authors: Li Weiyi , Miller Darach , Liu Xianan , Tosi Lorenzo , Chkaiban Lamia , Mei Han , Hung Po-Hsiang , Parekkadan Biju , Sherlock Gavin , Levy Sasha F 
Published: May 2024

Abstract
Sequence verification of plasmid DNA is critical for many cloning and molecular biology workflows. To leverage high-throughput sequencing, several methods have been developed that add a unique DNA barcode to individual samples prior to pooling and sequencing. However, these methods require an individual plasmid extraction and/or in vitro barcoding reaction for each sample processed, limiting throughput and adding cost. Here, we develop an arrayed in vivo plasmid barcoding platform that enables pooled plasmid extraction and library preparation for Oxford Nanopore sequencing. This method has a high accuracy and recovery rate, and greatly increases throughput and reduces cost relative to other plasmid barcoding methods or Sanger sequencing. We use in vivo barcoding to sequence verify &gt;45 000 plasmids and show that the method can be used to transform error-containing dispersed plasmid pools into sequence-perfect arrays or well-balanced pools. In vivo barcoding does not require any specialized equipment beyond a low-overhead Oxford Nanopore sequencer, enabling most labs to flexibly process hundreds to thousands of plasmids in parallel.
A novel regulatory interplay between atypical B12 riboswitches and uORF translation in Mycobacterium tuberculosis
Authors: Kipkorir Terry , Polgar Peter , Barker Declan , D’Halluin Alexandre , Patel Zaynah , Arnvig Kristine B 
Published: May 2024

Abstract
Vitamin B12 is an essential cofactor in all domains of life and B12-sensing riboswitches are some of the most widely distributed riboswitches. Mycobacterium tuberculosis, the causative agent of tuberculosis, harbours two B12-sensing riboswitches. One controls expression of metE, encoding a B12-independent methionine synthase, the other controls expression of ppe2 of uncertain function. Here, we analysed ligand sensing, secondary structure and gene expression control of the metE and ppe2 riboswitches. Our results provide the first evidence of B12 binding by these riboswitches and show that they exhibit different preferences for individual isoforms of B12, use distinct regulatory and structural elements and act as translational OFF switches. Based on our results, we propose that the ppe2 switch represents a new variant of Class IIb B12-sensing riboswitches. Moreover, we have identified short translated open reading frames (uORFs) upstream of metE and ppe2, which modulate the expression of their downstream genes. Translation of the metE uORF suppresses MetE expression, while translation of the ppe2 uORF is essential for PPE2 expression. Our findings reveal an unexpected regulatory interplay between B12-sensing riboswitches and the translational machinery, highlighting a new level of cis-regulatory complexity in M. tuberculosis. Attention to such mechanisms will be critical in designing next-level intervention strategies.
Unravelling genetic architecture of circulatory amino acid levels, and their effect on risk of complex disorders
Authors: Abar Leila , Zuber Verena , Otto Georg W , Tzoulaki Ioanna , Dehghan Abbas 
Published: May 2024

Abstract
Variations in serum amino acid levels are linked to a multitude of complex disorders. We report the largest genome-wide association study (GWAS) on nine serum amino acids in the UK Biobank participants (117 944, European descent). We identified 34 genomic loci for circulatory levels of alanine, 48 loci for glutamine, 44 loci for glycine, 16 loci for histidine, 11 loci for isoleucine, 19 loci for leucine, 9 loci for phenylalanine, 32 loci for tyrosine and 20 loci for valine. Our gene-based analysis mapped 46–293 genes associated with serum amino acids, including MIP, GLS2, SLC gene family, GCKR, LMO1, CPS1 and COBLL1.The gene–property analysis across 30 tissues highlighted enriched expression of the identified genes in liver tissues for all studied amino acids, except for isoleucine and valine, in muscle tissues for serum alanine and glycine, in adrenal gland tissues for serum isoleucine and leucine, and in pancreatic tissues for serum phenylalanine. Mendelian randomization (MR) phenome-wide association study analysis and subsequent two-sample MR analysis provided evidence that every standard deviation increase in valine is associated with 35% higher risk of type 2 diabetes and elevated levels of serum alanine and branched-chain amino acids with higher levels of total cholesterol, triglyceride and low-density lipoprotein, and lower levels of high-density lipoprotein. In contrast to reports by observational studies, MR analysis did not support a causal association between studied amino acids and coronary artery disease, Alzheimer’s disease, breast cancer or prostate cancer. In conclusion, we explored the genetic architecture of serum amino acids and provided evidence supporting a causal role of amino acids in cardiometabolic health.
A computational approach for deciphering the interactions between proximal and distal gene regulators in GC B-cell response
Authors: Park Sung-Joon , Nakai Kenta 
Published: May 2024

Abstract
Delineating the intricate interplay between promoter-proximal and -distal regulators is crucial for understanding the function of transcriptional mediator complexes implicated in the regulation of gene expression. The present study aimed to develop a computational method for accurately modeling the spatial proximal and distal regulatory interactions. Our method combined regression-based models to identify key regulators through gene expression prediction and a graph-embedding approach to detect coregulated genes. This approach enabled a detailed investigation of the gene regulatory mechanisms for germinal center B cells, accompanied by dramatic rearrangements of the genome structure. We found that while the promoter-proximal regulatory elements were the principal regulators of gene expression, the distal regulators fine-tuned transcription. Moreover, our approach unveiled the presence of modular regulators, such as cofactors and proximal/distal transcription factors, which were co-expressed with their target genes. Some of these modules exhibited abnormal expression patterns in lymphoma. These findings suggest that the dysregulation of interactions between transcriptional and architectural factors is associated with chromatin reorganization failure, which may increase the risk of malignancy. Therefore, our computational approach helps decipher the transcriptional cis-regulatory code spatially interacting.
CBTRUS Statistical Report: American Brain Tumor Association & NCI Neuro-Oncology Branch Adolescent and Young Adult Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2016–2020
Authors: Price Mackenzie , Neff Corey , Nagarajan Nitin , Kruchko Carol , Waite Kristin A , Cioffi Gino , Cordeiro Brittany B , Willmarth Nicole , Penas-Prado Marta , Gilbert Mark R , Armstrong Terri S , Barnholtz-Sloan Jill S , Ostrom Quinn T 
Published: May 2024

Abstract
Recent analyses have shown that, whereas cancer survival overall has been improving, it has not improved for adolescents and young adults ages 15–39 years (AYA). The clinical care of AYA with primary brain and other central nervous system (CNS) tumors (BT) is complicated by the fact that the histopathologies of such tumors in AYA differ from their histopathologies in either children (ages 0–14 years) or older adults (ages 40+ years). The present report, as an update to a 2016 publication from the Central Brain Tumor Registry of the United States and the American Brain Tumor Association, provides in-depth analyses of the epidemiology of primary BT in AYA in the United States and is the first to provide biomolecular marker-specific statistics and prevalence by histopathology for both primary malignant and non-malignant BT in AYA. Between 2016 and 2020, the annual average age-specific incidence rate (AASIR) of primary malignant and non-malignant BT in AYA was 12.00 per 100,000 population, an average of 12,848 newly diagnosed cases per year. During the same period, an average of 1,018 AYA deaths per year were caused by primary malignant BT, representing an annual average age-specific mortality rate of 0.96 per 100,000 population. When primary BT were categorized by histopathology, pituitary tumors were the most common (36.6%), with an AASIR of 4.34 per 100,000 population. Total incidence increased with age overall; when stratified by sex, the incidence was higher in females than males at all ages. Incidence rates for all primary BT combined and for non-malignant tumors only were highest for non-Hispanic American Indian/Alaska Native individuals, whereas malignant tumors were more frequent in non-Hispanic White individuals, compared with other racial/ethnic groups. On the basis of histopathology, the most common molecularly defined tumor was diffuse glioma (an AASIR of 1.51 per 100,000). Primary malignant BT are the second most common cause of cancer death in the AYA population. Incidence rates of primary BT overall, as well as specific histopathologies, vary significantly by age. Accordingly, an accurate statistical assessment of primary BT in the AYA population is vital for better understanding the impact of these tumors on the US population and to serve as a reference for afflicted individuals, for researchers investigating new therapies, and for clinicians treating these patients.
Molecular and Epidemiological Investigation of Fluconazole-resistant Candida parapsilosis—Georgia, United States, 2021
Authors: Misas Elizabeth , Witt Lucy S , Farley Monica M , Thomas Stepy , Jenkins Emily N , Gade Lalitha , Peterson Joyce G , Mesa Restrepo Ana , Fridkin Scott , Lockhart Shawn R , Chow Nancy A , Lyman Meghan 
Published: May 2024

Abstract

Background
Reports of fluconazole-resistant Candida parapsilosis bloodstream infections are increasing. We describe a cluster of fluconazole-resistant C parapsilosis bloodstream infections identified in 2021 on routine surveillance by the Georgia Emerging Infections Program in conjunction with the Centers for Disease Control and Prevention.

Methods
Whole-genome sequencing was used to analyze C parapsilosis bloodstream infections isolates. Epidemiological data were obtained from medical records. A social network analysis was conducted using Georgia Hospital Discharge Data.

Results
Twenty fluconazole-resistant isolates were identified in 2021, representing the largest proportion (34%) of fluconazole-resistant C parapsilosis bloodstream infections identified in Georgia since surveillance began in 2008. All resistant isolates were closely genetically related and contained the Y132F mutation in the ERG11 gene. Patients with fluconazole-resistant isolates were more likely to have resided at long-term acute care hospitals compared with patients with susceptible isolates (P = .01). There was a trend toward increased mechanical ventilation and prior azole use in patients with fluconazole-resistant isolates. Social network analysis revealed that patients with fluconazole-resistant isolates interfaced with a distinct set of healthcare facilities centered around 2 long-term acute care hospitals compared with patients with susceptible isolates.

Conclusions
Whole-genome sequencing results showing that fluconazole-resistant C parapsilosis isolates from Georgia surveillance demonstrated low genetic diversity compared with susceptible isolates and their association with a facility network centered around 2 long-term acute care hospitals suggests clonal spread of fluconazole-resistant C parapsilosis. Further studies are needed to better understand the sudden emergence and transmission of fluconazole-resistant C parapsilosis.
A New Calibration of the OPAM Thermobarometer for Anhydrous and Hydrous Mafic Systems
Authors: Higgins Oliver , Stock Michael J 
Published: May 2024

Abstract
Melt-based thermobarometers are essential tools to recover pre-eruptive magma storage conditions through their application to bulk rock and liquid chemistry. In active volcanic systems, thermobarometric results can be combined with independent geophysical data during or after an eruption to validate conceptual models. In this contribution, we revisit the thermobarometer for melts equilibrated with the mineral assemblage of olivine + plagioclase + augitic clinopyroxene (OPAM). We first demonstrate that the most widely applied OPAM thermobarometer suffers from both random and systematic uncertainty, even for anhydrous melts, and that the uncertainty increases proportionally with melt H2O. To address this issue, we use a modern compilation of anhydrous and hydrous OPAM-saturated experiments to regress a new empirical melt-based OPAM thermometer and barometer. Our new equations recover a validation dataset with a standard error estimate of ±1.14 kbar and ± 36 °C for pressure and temperature, respectively, as well as a low systematic uncertainty that does not depend on melt H2O. Additionally, we present a novel statistical approach to determine the probability that a given melt is OPAM-saturated, which can be used alongside rigorous petrographic and geochemical observations. Our thermobarometer and saturation test are presented as a user-friendly R script that reads from an input csv file to be populated with natural data. We benchmark the new calibrations on the products of the 2015 eruption of Wolf Volcano (Isabela Island, Galápagos archipelago) and the 2014–2015 Holuhraun eruption (Iceland), both of which have independent geophysical estimates of magma storage that agree well with our thermobarometric results.
Acetyl-CoA Carboxylase1 influences ECERIFERUM2 activity to mediate the synthesis of very-long-chain fatty acid past C28
Authors: Yang Xianpeng , Huang Haodong , Wang Zhen , Haslam Tegan M , Kunst Ljerka , Wang Pingping , Zhao Huayan , Lü Shiyou , Ma Changle 
Published: May 2024

Abstract
Cuticular wax is a protective layer on the aerial surfaces of land plants. In Arabidopsis (Arabidopsis thaliana), cuticular wax is mainly constituted of compounds derived from very-long-chain fatty acids (VLCFAs) with chain lengths longer than C28. CER2-LIKE (ECERIFERUM2-LIKE) proteins interact with CER6/KCS6 (ECERIFERUM6/β-Ketoacyl-CoA Synthase6), the key enzyme of the fatty acid elongase complex, to modify its substrate specificity for VLCFA elongation past C28. However, the molecular regulatory mechanism of CER2-LIKE proteins remains unclear. Arabidopsis eceriferum19 (cer19) mutants display wax-deficient stems caused by loss of waxes longer than C28, indicating that CER19 may participate in the CER2-LIKE-mediated VLCFA elongation past C28. Using positional cloning and genetic complementation, we showed that CER19 encodes Acetyl-CoA Carboxylase1 (ACC1), which catalyzes the synthesis of malonyl-CoA, the essential substrate for the CER6/KCS6-mediated condensation reaction in VLCFA synthesis. We demonstrated that ACC1 physically interacts with CER2-LIKE proteins via split-ubiquitin yeast 2-hybrid and firefly luciferase complementation imaging analysis. Additionally, heterologous expression in yeast and genetic analysis in Arabidopsis revealed that ACC1 affects CER2 activity to influence VLCFA elongation past C28. These findings imply that CER2-LIKE proteins might function as a link between ACC1 and CER6/KCS6 and subsequently enhance CER6/KCS6 binding to malonyl-CoA for further utilization in VLCFA elongation past C28. This information deepens our understanding of the complex mechanism of cuticular wax biosynthesis.
Local Financial Structure and the Pandemic’s Effect on the Distribution of Employment
Authors: Levine Ross , Lin Chen , Xie Wensi 
Published: May 2024

Abstract
Does the structure of financial systems influence the employment respo0nse to adverse shocks? Using (a) county-industry employment data differentiated by firm size and (b) high-frequency county employment data differentiated by income, we find that employment at small firms, employment of low-income workers, and overall employment fell less in counties with higher proportions of small banks in response to the pandemic. Furthermore, small banks lend more to small businesses than large banks, above and beyond government-guaranteed PPP loans. Evidence suggests that small banks cushioned small firms and low-income workers from the adverse effects of the pandemic. (JEL G21, E24, E32, J21, H12)
Received: 15 April 2021; Editorial decision: 13 December 2023 Editor: Andrew Ellul Authors have furnished an Internet Appendix,which is available on the Oxford University Press Web site next to the link to the final published paper online.
Transitioning from pediatric to adult-oriented healthcare in rheumatology: the pediatric side of the coin
Authors: Batu Ezgi Deniz , Balik Zeynep , Sener Seher , Aliyev Emil , Bayindir Yagmur , Cam Veysel , Kasap Cuceoglu Muserref , Kaya Akca Ummusen , Kilic Levent , Basaran Ozge , Bilginer Yelda , Apras Bilgen Sule , Ozen Seza 
Published: May 2024

Abstract

Objectives
The transition of adolescents and young adults (AYAs) from pediatric to adult-oriented healthcare may be affected by many factors, including the personal and cultural settings. We aimed to analyse the transition readiness and the factors affecting the transition success in rheumatology.

Methods
Patients older than 12 years were included in this prospective study. All filled out the Transition Readiness Assessment Questionnaire (TRAQ) 5.0. AYAs were phone-interviewed after their transfer to adult-oriented healthcare. Drug adherence was evaluated with 4-item Morisky Medication Adherence Scale (MMAS-4). AYAs rated their transitional care experience with visual analogue scale (VAS 0–10; 0, the worst; 10, the best).

Results
A total of 504 TRAQs were filled out by 406 patients (F/M = 1.5). The total TRAQ score was positively correlated with age and higher in the forms filled out by girls than boys (4.2 vs 4.0, respectively; P = 0.005). The transition was successful for 78 (83.9%) out of 93 patients transferred to adult-oriented healthcare. The VAS for the transition process was lower and the post-transfer MMAS-4 score was worse (8 vs 9, P = 0.030 and 3 vs 4, P = 0.020, respectively) in patients whose transition was not successful when compared with those that successfully transitioned. The best-performing TRAQ cut-off value was &gt;4.0 for predicting transfer readiness in rheumatology.

Conclusion
A TRAQ score of &gt;4 could be used while deciding about the transfer readiness of AYAs in rheumatology. Improving the AYAs’ experience of the transition process and closely monitoring medication adherence during transition are essential for a successful transition.