bluuebunny/crossref_metadata_2025_split huggingface dataset:
Changes in Hepatic Steatosis Before and After Direct-Acting Antiviral Treatment in People With HIV and Hepatitis C Coinfection
Authors: Truscello Esther , Wang Shouao , Young Jim , Sebastiani Giada , Walmsley Sharon L , Hull Mark , Cooper Curtis , Klein Marina B 
Published: October 2024

Abstract

Background
Both human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infections increase the risk of hepatic steatosis (HS), which in turn contribute to the severity and progression of liver disease. Direct-acting antivirals (DAAs) can cure HCV but whether they reduce HS is unclear.

Methods
HS was assessed using the controlled attenuation parameter (CAP) and the Hepatic Steatosis Index (HSI) in participants coinfected with HIV and HCV from the Canadian Coinfection Cohort. Changes in HS, before, during, and after successful DAA treatment were estimated using generalized additive mixed models, adjusted for covariates measured prior to treatment (age, sex, duration of HCV infection, body mass index, diabetes, prior exposure to dideoxynucleosides, and hazardous drinking).

Results
In total, 431 participants with at least 1 measure of CAP or HSI before treatment were included. CAP steadily increased over time: adjusted annual slope 3.3 dB/m (95% credible interval [CrI], 1.6–4.9) before, and 3.9 dB/m (95% CrI, 1.9–5.9) after DAA treatment, irrespective of pretreatment CAP. In contrast, HSI changed little over time: annual slope 0.2 (95% CrI, −0.1 to 0.5) before and 0.2 (95% CrI, −0.1 to 0.5) after, but demonstrated a marked reduction during treatment −4.5 (95% CrI, −5.9 to −3.1).

Conclusions
When assessed by CAP, HS was unaffected by DAA treatment and steadily increased over time. In contrast, HSI did not appear to reflect changes in HS, with the decrease during treatment likely related to resolution of hepatic inflammation. Ongoing HS may pose a risk for liver disease in coinfected people cured of HCV.
Signaling, interests, and domestic politics: What matters for US credibility in Taiwan
Authors: Fu Ronan Tse-min , Lee Elaine I-lien , Park Gene 
Published: October 2024

Abstract
There have been growing calls for a rethink of U.S. policy towards Taiwan. Some argue that the U.S. should signal stronger commitment to Taiwan to deter China and maintain peace. To do so, a growing number of commentators and policymakers advocate that the U.S. provide a clear security guarantee to Taiwan. Others have suggested deploying troops on Taiwanese soil again. These calls beg an empirical question, one central to the study of international politics: how much would such reassurance measures increase confidence that one country would defend another if attacked? We find that an alliance with the U.S. and the deployment of troops on Taiwan would meaningfully increase confidence in the U.S. even when controlling for other factors. By estimating the magnitude of the effect of other variables cited in the literature, we also contribute to the ongoing debate over their relative influence on credibility. Specifically, our evidence suggests that the perceived alignment of interests is the cornerstone of credibility. The degree of division in the domestic politics of the patron state, in this case the U.S., also is a crucial determinant of credibility.
Long-term stability of sufentanil quantified by UPLC–MS–MS in human plasma frozen for 11 years at −20°C
Authors: Wehrfritz Andreas , Schmidt Stefanie , Ihmsen Harald , Schüttler Jürgen , Jeleazcov Christian 
Published: October 2024

Abstract
The long-term stability of drug concentrations in human plasma samples, when stored under normal laboratory conditions over several years, is important for research purposes and clinical re-evaluation, and forensic toxicology. Fifty human plasma samples from a former clinical trial were re-analyzed after storage at −20°C for 11 years. Plasma samples were extracted using solid-phase extraction. Isotope labeled sufentanil-d5 was used as internal standard. Sufentanil plasma concentrations were determined by ultra-performance liquid chromatography with gradient elution, followed by tandem mass spectrometry with electrospray ionization. The linear dynamic range was 25–2500 pg/mL, the limit of detection was 10 pg/mL, and the lower limit of quantification was 25 pg/mL. Intra- and inter-assay error did not exceed 6%. The deviation of the measured sufentanil plasma concentrations between the re-analysis and the first analysis was −63 ± 14% (mean ± SD). Therefore, sufentanil concentrations in human plasma were not stable in samples frozen at −20°C over 11 years.
Dorsal agenesis of the pancreas: an incidental finding
Authors: Cauchi Daphne , Mangion Shaun , Cassar Noel 
Published: October 2024

Abstract
This case report focuses on a 29-year-old female who presented with acute abdominal pain at Mater Dei Hospital, Malta. Her clinical presentation, followed up by diagnostic imaging, led to the diagnosis of a rare congenital abnormality known as dorsal agenesis of the pancreas. This condition is characterized by the absence or underdevelopment of the dorsal portion of the pancreas, a crucial aspect of pancreatic anatomy and function. The following text details the clinical presentation, diagnostic findings, and the broader implications of dorsal pancreatic agenesis in medical practice, reflecting on the rarity of this condition and the complexity of its diagnosis and management.
State-space analysis of a continuous gravitational wave source with a pulsar timing array: inclusion of the pulsar terms
Authors: Kimpson Tom , Melatos Andrew , O’Leary Joseph , Carlin Julian B , Evans Robin J , Moran William , Cheunchitra Tong , Dong Wenhao , Dunn Liam , Greentree Julian , O’Neill Nicholas J , Suvorova Sofia , Thong Kok Hong , Vargas Andrés F 
Published: October 2024

ABSTRACT
Pulsar timing arrays (PTA) can detect continuous nanohertz gravitational waves (GW) emitted by individual supermassive black hole binaries. The data analysis procedure can be formulated within a time-domain, state-space framework, in which the radio timing observations are related to a temporal sequence of latent states, namely the intrinsic pulsar spin frequency. The achromatic wandering of the pulsar spin frequency is tracked using a Kalman filter concurrently with the pulse frequency modulation induced by a GW from a single source. The modulation is the sum of terms proportional to the GW strain at the Earth and at every pulsar in the array. Here, we generalize previous state-space formulations of the PTA problem to include the pulsar terms; that is, we copy the pulsar terms from traditional, non-state-space analyses over to the state-space framework. The performance of the generalized Kalman filter is tested using astrophysically representative software injections in Gaussian measurement noise. It is shown that including the pulsar terms corrects for previously identified biases in the parameter estimates (especially the sky position of the source) which also arise in traditional matched-filter analyses that exclude the pulsar terms. Additionally, including the pulsar terms decreases the minimum detectable strain by 14 per cent. Overall, the study verifies that the pulsar terms do not raise any special extra impediments for the state-space framework, beyond those studied in traditional analyses. The inspiral-driven evolution of the wave frequency at the Earth and at the retarded time at every pulsar in the array is also investigated.
Nexus: a framework for controlled simulations of idealized galaxies
Authors: Tepper-García Thor , Bland-Hawthorn Joss , Vasiliev Eugene , Agertz Oscar , Teyssier Romain , Federrath Christoph 
Published: October 2024

ABSTRACT
Motivated by the need for realistic, dynamically self-consistent, evolving galaxy models that avoid the complexity of full, and zoom-in, cosmological simulations, we have developed Nexus, an integral framework to create and evolve synthetic galaxies made of collisionless and gaseous components. Nexus leverages the power of publicly available, tried-and-tested packages: the stellar-dynamics, action-based library Action-based Galaxy Modelling Architecture (AGAMA); and the adaptive mesh refinement, N-body/hydrodynamical code Ramses, modified to meet our needs. In addition, we make use of a proprietary module to account for galaxy formation physics, including gas cooling and heating, star formation, stellar feedback, and chemical enrichment. Nexus’ basic functionality consists in the generation of bespoke initial conditions (ICs) for a diversity of galaxy models, which are advanced in time to simulate the galaxy’s evolution. The fully self-consistent ICs are generated with a distribution-function-based approach, as implemented in the galaxy modelling module of AGAMA – up to now restricted to collisionless components, extended in this work to treat two types of gaseous configurations: hot haloes and gas discs. Nexus allows constructing equilibrium models with disc gas fractions $0~\le ~f_{\rm {\rm gas}}~\le ~1$, appropriate to model both low- and high-redshift galaxies. Similarly, the framework is ideally suited to the study of galactic ecology, i.e. the dynamical interplay between stars and gas over billions of years. As a validation and illustration of our framework, we reproduce several isolated galaxy model setups reported in earlier studies, and present a new, ‘nested bar’ galaxy simulation. Future upgrades of Nexus will include magnetohydrodynamics and highly energetic particle (‘cosmic ray’) heating.
Predicting Phylogenetic Bootstrap Values via Machine Learning
Authors: Wiegert Julius , Höhler Dimitri , Haag Julia , Stamatakis Alexandros 
Published: October 2024

Abstract
Estimating the statistical robustness of the inferred tree(s) constitutes an integral part of most phylogenetic analyses. Commonly, one computes and assigns a branch support value to each inner branch of the inferred phylogeny. The still most widely used method for calculating branch support on trees inferred under maximum likelihood (ML) is the Standard, nonparametric Felsenstein bootstrap support (SBS). Due to the high computational cost of the SBS, a plethora of methods has been developed to approximate it, for instance, via the rapid bootstrap (RB) algorithm. There have also been attempts to devise faster, alternative support measures, such as the SH-aLRT (Shimodaira–Hasegawa-like approximate likelihood ratio test) or the UltraFast bootstrap 2 (UFBoot2) method. Those faster alternatives exhibit some limitations, such as the need to assess model violations (UFBoot2) or unstable behavior in the low support interval range (SH-aLRT). Here, we present the educated bootstrap guesser (EBG), a machine learning-based tool that predicts SBS branch support values for a given input phylogeny. EBG is on average 9.4 (σ=5.5) times faster than UFBoot2. EBG-based SBS estimates exhibit a median absolute error of 5 when predicting SBS values between 0 and 100. Furthermore, EBG also provides uncertainty measures for all per-branch SBS predictions and thereby allows for a more rigorous and careful interpretation. EBG can, for instance, predict SBS support values on a phylogeny comprising 1,654 SARS-CoV2 genome sequences within 3 h on a mid-class laptop. EBG is available under GNU GPL3.
Ancient Secretory Pathways Contributed to the Evolutionary Origin of an Ecologically Impactful Bioluminescence System
Authors: Mesrop Lisa Y , Minsky Geetanjali , Drummond Michael S , Goodheart Jessica A , Proulx Stephen R , Oakley Todd H 
Published: October 2024

Abstract
Evolutionary innovations in chemical secretion—such as the production of secondary metabolites, pheromones, and toxins—profoundly impact ecological interactions across a broad diversity of life. These secretory innovations may involve a “legacy-plus-innovation” mode of evolution, whereby new biochemical pathways are integrated with conserved secretory processes to create novel products. Among secretory innovations, bioluminescence is important because it evolved convergently many times to influence predator–prey interactions, while often producing courtship signals linked to increased rates of speciation. However, whether or not deeply conserved secretory genes are used in secretory bioluminescence remains unexplored. Here, we show that in the ostracod Vargula tsujii, the evolutionary novel c-luciferase gene is co-expressed with many conserved genes, including those related to toxin production and high-output protein secretion. Our results demonstrate that the legacy-plus-innovation mode of secretory evolution, previously applied to sensory modalities of olfaction, gustation, and nociception, also encompasses light-producing signals generated by bioluminescent secretions. This extension broadens the paradigm of secretory diversification to include not only chemical signals but also bioluminescent light as an important medium of ecological interaction and evolutionary innovation.
Development of hydrophobic tag purifying monophosphorylated RNA for chemical synthesis of capped mRNA and enzymatic synthesis of circular mRNA
Authors: Ototake Mami , Inagaki Masahito , Kimura Seigo , Onda Kaoru , Tada Mizuki , Kawaguchi Daisuke , Murase Hirotaka , Fukuchi Kosuke , Gao Yinuo , Kokubo Kengo , Acharyya Susit , Meng Zheyu , Ishida Tatsuma , Kawasaki Tairin , Abe Naoko , Hashiya Fumitaka , Kimura Yasuaki , Abe Hiroshi 
Published: October 2024

Abstract
We developed phosphorylation reagents with a nitrobenzyl hydrophobic tag and used them for 5′-phosphorylation of chemically or transcriptionally synthesized RNA. The capability of hydrophobic tags to synthesize 5′-monophosphorylated RNA was evaluated based on the yield of the desired oligonucleotides, stability of protecting groups during cleavage/deprotection, separation ability in reverse-phase HPLC (RP-HPLC), and deprotection efficiency after RP-HPLC purification. The results showed that a nitrobenzyl derivative with a tert-butyl group at the benzyl position was most suitable for RNA 5′-phosphorylation. Using the developed phosphorylation reagent, we chemically synthesized 5′-phosphorylated RNA and confirmed that it could be purified by RP-HPLC and the following deprotection. In addition, we demonstrated complete chemical synthesis of minimal mRNA by chemical capping of 5′-monophosphorylated RNA. Ribonucleoside 5′-monophosphates with hydrophobic protecting groups have also been developed and used as substrates to transcriptionally synthesize 5′-phosphorylated RNA with &gt;1000 bases. From the mixture of the by-products and the desired RNA, only 5′-monophosphorylated RNA could be effectively isolated by RP-HPLC. Furthermore, monophosphorylated RNA can be converted into circular mRNA via RNA ligase-mediated cyclization. Circular mRNA expression of nanoluciferase in cultured cells and mice. These techniques are important for the production of chemically synthesized mRNA and circular mRNA.
Structure-based discovery of first inhibitors targeting the helicase activity of human PIF1
Authors: Wever Mark J A , Scommegna Francesca R , Egea-Rodriguez Sara , Dehghani-Tafti Saba , Brandao-Neto Jose , Poisson Jean-François , Helfrich Iris , Antson Alfred A , Rodeschini Vincent , Bax Ben , Roche Didier , Sanders Cyril M 
Published: October 2024

Abstract
PIF1 is a conserved helicase and G4 DNA binding and unwinding enzyme, with roles in genome stability. Human PIF1 (hPIF1) is poorly understood, but its functions can become critical for tumour cell survival during oncogene-driven replication stress. Here we report the discovery, via an X-ray crystallographic fragment screen (XChem), of hPIF1 DNA binding and unwinding inhibitors. A structure was obtained with a 4-phenylthiazol-2-amine fragment bound in a pocket between helicase domains 2A and 2B, with additional contacts to Valine 258 from domain 1A. The compound makes specific interactions, notably through Leucine 548 and Alanine 551, that constrain conformational adjustments between domains 2A and 2B, previously linked to ATP hydrolysis and DNA unwinding. We next synthesized a range of related compounds and characterized their effects on hPIF1 DNA-binding and helicase activity in vitro, expanding the structure activity relationship (SAR) around the initial hit. A systematic analysis of clinical cancer databases is also presented here, supporting the notion that hPIF1 upregulation may represent a specific cancer cell vulnerability. The research demonstrates that hPIF1 is a tractable target through 4-phenylthiazol-2-amine derivatives as inhibitors of its helicase action, setting a foundation for creation of a novel class of anti-cancer therapeutics.
What is the real value of omics data? Enhancing research outcomes and securing long-term data excellence
Authors: Price Eva , Feyertag Felix , Evans Thomas , Miskin James , Mitrophanous Kyriacos , Dikicioglu Duygu 
Published: October 2024

Abstract
A wealth of high-throughput biological data, of which omics constitute a significant fraction, has been made publicly available in repositories over the past decades. These data come in various formats and cover a range of species and research areas providing insights into the complexities of biological systems; the public repositories hosting these data serve as multifaceted resources. The potentially greater value of these data lies in their secondary utilization as the deployment of data science and artificial intelligence in biology advances. Here, we critically evaluate challenges in secondary data use, focusing on omics data of human embryonic kidney cell lines available in public repositories. The emerging issues are obstacles faced by secondary data users across diverse domains as they concern platforms and repositories, which accept deposition of data irrespective of their species type. The evolving landscape of data-driven research in biology prompts re-evaluation of open access data curation and submission procedures to ensure that these challenges do not impede novel research opportunities through data exploitation. This paper aims to draw attention to widespread issues with data reporting and encourages data owners to meticulously curate submissions to maximize not only their immediate research impact but also the long-term legacy of datasets.
KEGG: biological systems database as a model of the real world
Authors: Kanehisa Minoru , Furumichi Miho , Sato Yoko , Matsuura Yuriko , Ishiguro-Watanabe Mari 
Published: October 2024

Abstract
KEGG (https://www.kegg.jp/) is a database resource for representation and analysis of biological systems. Pathway maps are the primary dataset in KEGG representing systemic functions of the cell and the organism in terms of molecular interaction and reaction networks. The KEGG Orthology (KO) system is a mechanism for linking genes and proteins to pathway maps and other molecular networks. Each KO is a generic gene identifier and each pathway map is created as a network of KO nodes. This architecture enables KEGG pathway mapping to uncover systemic features from KO assigned genomes and metagenomes. Additional roles of KOs include characterization of conserved genes and conserved units of genes in organism groups, which can be done by taxonomy mapping. A new tool has been developed for identifying conserved gene orders in chromosomes, in which gene orders are treated as sequences of KOs. Furthermore, a new dataset called VOG (virus ortholog group) is computationally generated from virus proteins and expanded to proteins of cellular organisms, allowing gene orders to be compared as VOG sequences as well. Together with these datasets and analysis tools, new types of pathway maps are being developed to present a global view of biological processes involving multiple organism groups.
Reference values for handgrip strength, five times sit-to-stand and gait speed in patients on hemodialysis
Authors: Duarte Marvery P , Nóbrega Otávio T , Vogt Barbara P , Pereira Marina S , Silva Maryanne Z C , Mondini Dario R , Disessa Henrique S , Adamoli Angélica N , Bündchen Daiana C , Sant'Helena Bruna R M , Krug Rodrigo R , Bohlke Maristela , Inda-Filho Antônio J , Lima Ricardo M , Avesani Carla M , Nakamura Luiz R , Reboredo Maycon M , Ribeiro Heitor S ,   the SARC-HD Study Group, Baião Victor M , Rocha João M , Silva João P , Varela Priscila M , Monteiro Jacqueline S , Bainha Ana C , Gravina Emanuele P , Castro Abner R , Costa Fabiana L , Rosa Clara C , Monteiro Henrique L , Medina Luiz R , Nishimaru Flávio I , Rosa Maria G , Picinato Ana C , Uchida Marco C , Moreira Paulo R , Vignali Camila R , de Oliveira Luane B , Mendez Samy , Mansur Augusto H , Colling Catiussa , Thomé Fernando S , Ferreira Aparecido P 
Published: October 2024

ABSTRACT

Background
Low levels of muscle strength and physical performance predict adverse clinical outcomes in patients on hemodialysis; however, reference values remain lacking. We described reference values for handgrip strength, five times sit-to-stand (STS-5) and 4-m gait speed in a large-scale sample of patients on hemodialysis.

Methods
Baseline data from the SARCopenia trajectories and associations with adverse clinical outcomes in patients on HemoDialysis (SARC-HD) study were analyzed. Muscle strength was evaluated using handgrip strength and the STS-5, whereas physical performance was evaluated using usual 4-m gait speed before a midweek dialysis session. Sex- and age-specific smoothed reference curves for each test at the 3rd, 15th, 50th, 85th and 97th percentiles were constructed using generalized additive models for location shape and scale. Comparisons between sex and age were also performed.

Results
Data from 1004 patients (39% female; 19–96 years; 49% ≥60 years) were analyzed. Declines in muscle strength and physical performance were observed with advancing age in both sexes. However, among males, muscle strength and performance were similar between 18 and 49 years of age. Males exhibited substantially greater performance in handgrip strength [10.3 kg, 95% confidence interval (CI) 9.1 to 11.4] and 4-m gait speed (0.10 s, 95% CI 0.05 to 0.14) compared with females. Older patients, independent of sex, exhibited poorer performance on most tests. Lower handgrip strength in the arm with arteriovenous fistula was observed in both sexes (males –2.3 kg, 95% CI –2.8 to –1.7; and females –2.1 kg, 95% CI –2.6 to –1.6).

Conclusion
Reference values obtained in this study may be used in clinical and research settings to identify patients on hemodialysis with low physical function according to sex and age. Future studies should test these reference values as potential predictors of adverse clinical outcomes.