bluuebunny/crossref_metadata_2025_split huggingface dataset:
Serum and Plasma Sphingolipids as Biomarkers of Anthracycline-Induced Cardiotoxicity
Authors: Mohammed Samia , Kalogeropoulos Andreas P. , Alvarado Victoria , Weisfelner-Bloom Michelle , Clarke Christopher J. 
Published: January 2025

ABSTRACTAlthough effective as a chemotherapy, the utility of Doxorubicin (Dox) is hampered by cardiotoxicity. Despite this, the ability to predict and guide monitoring of patients receiving Dox or other anthracyclines is hampered by a lack of effective biomarkers to identify susceptible patients, and to detect early signs of subclinical cardiotoxicity. Based on their well-established roles in the response to Dox and other chemotherapies, we performed a retrospective analysis of serum and plasma sphingolipids (SLs) from patients undergoing anthracycline-containing therapy, correlating with cardiac parameters assessed by echocardiography. Results showed there were substantial changes in both plasma and serum SL species during therapy including ceramide (Cer), deoxydihydroCer, and dihydrosphingosine with reversion towards baseline following treatment. Linear mixed-effects model analysis revealed that at baseline, a number of SLs correlated with adverse cardiac outcomes with serum sphingosine-1-phosphate (S1P) and dihydroS1P, and plasma Cer performing comparably to the prognostic value of pro-NT-BNP, an established biomarker of cardiotoxicity. Intriguingly, while pro-NT-BNP had no predictive value at mid- and post-therapy timepoints, serum S1P and dhS1P and plasma Cer levels showed correlation with adverse outcomes, particularly at the post-therapy timepoint. Finally, analysis of plasma and serum C16:C24- Cer ratios – previously reported as predictive of adverse cardiac outcomes – showed no correlation in the context of anthracycline treatment. Taken together, this pilot study provides supporting evidence that plasma and serum SLs may have benefit as both prognostic and diagnostic biomarkers for patients undergoing anthracycline-containing therapy. This suggests that diagnostic SL measurements – recently implemented for metabolic-associated cardiac disorders – could have wider utility.
Characterization and automated classification of sentences in the biomedical literature: a case study for biocuration of gene expression and protein kinase activity
Authors: Raciti Daniela , Van Auken Kimberly M. , Arnaboldi Valerio , Tabone Christopher J. , Muller Hans-Michael , Sternberg Paul W. 
Published: January 2025

AbstractBiological knowledgebases are essential resources for biomedical researchers, providing ready access to gene function and genomic data. Professional, manual curation of knowledgebases, however, is labor-intensive and thus high-performing machine learning methods that improve biocuration efficiency are needed. Here we report on sentence-level classification to identify biocuration-relevant sentences in the full text of published references for two gene function data types: gene expression and protein kinase activity. We performed a detailed characterization of sentences from references in the WormBase bibliography and used this characterization to define three tasks for classifying sentences as either 1) fully curatable, 2) fully and partially curatable, or 3) all language-related. We evaluated various machine learning (ML) models applied to these tasks and found that GPT and BioBERT achieve the highest average performance, resulting in F1 performance scores ranging from 0.89 to 0.99 depending upon the task. Our findings demonstrate the feasibility of extracting biocuration-relevant sentences from full text. Integrating these models into professional biocuration workflows, such as those used by the Alliance of Genome Resources and the ACKnowledge community curation platform, might well facilitate efficient and accurate annotation of the biomedical literature.
TheRalstonia solanacearumeffector RipAV targets Plant U-box proteins and induces proteasomal-dependent degradation of BIK1
Authors: Rufian Jose S. , Liu Xin , Wang Yaru , Rueda-Blanco Javier , Yu Gang , Ruiz-Albert Javier , Macho Alberto P. 
Published: January 2025

SummaryPlants have developed a complex immune system to detect and respond to invading pathogens. A critical aspect of this defence relies on regulatory mechanisms that control the activation of immune responses, ensuring these are efficient yet do not compromise overall plant performance. Many pathogens secrete proteins called effectors to manipulate plant cellular functions, suppressing plant immunity and promoting infection. Here, we show that the bacterial effector RipAV, secreted by the soil-borne bacterial pathogenRalstonia solanacearum, hijacks a major immune signalling hub to suppress immune responses. RipAV targets members of the plant-specific ubiquitin ligase (PUB) family and calcium-dependent protein kinase 28 (CPK28), which has been shown to phosphorylate a set of PUBs to enhance their activity and regulate the stability of the key immune regulator BIK1. RipAV association enhances the CPK28-mediated phosphorylation of PUBs, inducing the proteasome-mediated degradation of BIK1 and the suppression of immunity. Importantly, we found that RipAV is required for maintaining a low accumulation of BIK1 during aR. solanacearuminfection. These findings provide new insights into the sophisticated strategies employed by pathogens to subvert plant immunity.
DNALongBench: A Benchmark Suite for Long-Range DNA Prediction Tasks
Authors: Cheng Wenduo , Song Zhenqiao , Zhang Yang , Wang Shike , Wang Danqing , Yang Muyu , Li Lei , Ma Jian 
Published: January 2025

AbstractModeling long-range DNA dependencies is crucial for understanding genome structure and function across a wide range of biological contexts. However, effectively capturing these extensive dependencies, which may span millions of base pairs in tasks such as three-dimensional (3D) chromatin folding prediction, remains a significant challenge. Furthermore, a comprehensive benchmark suite for evaluating tasks that rely on long-range dependencies is notably absent. To address this gap, we introduce DNALongBench, a benchmark dataset encompassing five important genomics tasks that consider long-range dependencies up to 1 million base pairs: enhancer-target gene interaction, expression quantitative trait loci, 3D genome organization, regulatory sequence activity, and transcription initiation signals. To comprehensively assess DNALongBench, we evaluate the performance of five methods: a task-specific expert model, a convolutional neural network (CNN)-based model, and three fine-tuned DNA foundation models – HyenaDNA, Caduceus-Ph, and Caduceus-PS. We envision DNALongBenchas a standardized resource with the potential to facilitate comprehensive comparisons and rigorous evaluations of emerging DNA sequence-based deep learning models that account for long-range dependencies.
Growth Hormone Excess Drives Liver Aging via increased Glycation stress
Authors: Singh Parminder , Gautam Anil , Trujillo Marissa , Galligan James , Hensley Lisa , Kapahi Pankaj , Bartke Andrzej 
Published: January 2025

AbstractGrowth hormone (GH) plays a crucial role in various physiological functions, with its secretion tightly regulated by complex endocrine mechanisms. Pathological conditions such as acromegaly or pituitary tumors result in elevated circulating GH levels, which have been implicated in a spectrum of metabolic disorders, potentially by regulating liver metabolism. In this study, we focused on the liver, a key organ in metabolic regulation and a primary target of GH, to investigate the impact of high circulating GH on liver metabolism. We used bovine GH overexpressing transgenic (bGH-Tg) mice to conduct a comprehensive transcriptomic analysis of hepatic tissues. The bGH-Tg mouse livers exhibit dysregulated fatty acid metabolism and heightened inflammatory responses. Notably, the transcriptomic profile of young bGH-Tg mouse livers resembled that of aged livers and displayed markers of increased cellular senescence. Furthermore, these mice exhibited a significant accumulation of advanced glycation end products (AGEs). Intervention with glycation-lowering compounds effectively reversed the insulin resistance and aberrant transcriptomic signatures in the liver that are associated with elevated GH levels. These findings underscore the potential therapeutic value of glycation-lowering agents in mitigating the deleterious effects of chronic GH overexpression.HighlightsOverexpression of bovine growth hormone impacts transcriptional changes in liver fat metabolism and inflammatory response in mice.High circulating growth hormone leads to transcriptional changes that suggest enhanced liver aging and induce cellular senescence.Detoxification pathways in bGH-Tg mice are inhibited, leading to the accumulation of Advanced Glycation End (AGE) products.Glycation-lowering compounds can mitigate pathologies associated with high GH levels.
Radial extracorporeal shock wave therapy is more effective than a combination of physical therapy modalities for rotator cuff injury: a randomized controlled trial
Authors: Wang Zheng , Tang Lan , Wang Ni , Huang Lihua , Schmitz Christoph , Zhou Jun , Zhao Yingjie , Chen Kang , Ma Yanhong 
Published: January 2025

ABSTRACTObjectivesThis study tested the hypothesis that in treatment of rotator cuff (RC) injury, radial extracorporeal shock wave therapy (rESWT) is more effective than a combination of physical therapy modalities (PTMs; i.e., interferential current therapy, shortwave diathermy and magnetothermal therapy).MethodsA total of 60 patients with RC injury without presence of full-thickness RC tear were randomly allocated to rESWT for 6 weeks (n=30; one session per week) or treatment with PTMs for 6 weeks (n=30; five sessions per week). The primary outcome measure was the ASES shoulder score. Secondary outcome measures were the VAS pain score, patient’s satisfaction, shoulder range of motion, thickness of the supraspinatus tendon and the acromiohumeral distance. All outcome measures were assessed by blinded assessors at baseline as well as at 6 weeks post-baseline (W6) and W12.ResultsNo serious adverse events occurred during the trial. Compared to the patients in the PTMs group, the patients in the rESWT group had significantly (p<0.05) higher mean ASES total scores at W6 and W12 (power with two-sided 95% confidence interval: 65.7% at W6 and 92.8% at W12) as well as lower mean VAS pain scores, higher mean satisfaction scores and higher mean active and passive shoulder abduction values at W6 and W12. Furthermore, rESWT but not PTMs significantly reduced the mean thickness of the ST and increased the acromiohumeral distance.ConclusionIn treatment of rotator cuff injury without presence of full-thickness rotator cuff tear, rESWT is more effective than the investigated combination of PTMs.RegistrationChina Clinical Trials Registration Center (Registration number: ChiCTR2300077386; registration on 7 November 2023).
Genetic Insights from Automated Lumen Diameter Measurements in Carotid Ultrasounds of the UK Biobank
Authors: Ortín Vela Sofía , Bontempi Dennis , Mazini Bianca , Böttger Leah , Trofimova Olga , Bergmann Sven 
Published: January 2025

AbstractCarotid ultrasound is routinely used in clinical practice for non-invasive vascular anatomical and functional assessment, such as measuring carotid Intima-Media Thickness (cIMT), an important marker for quantifying atherosclerotic burden in the common carotid arteries (CCAs). Recent research suggests that several risk factors associated with higher cIMT, such as high blood pressure, can induce a compensatory increase in the carotid Lumen Diameter (cLD) of the CCAs. However, the genetic architecture of cLD and its association with other cardiovascular traits are still poorly understood. To investigate these questions, we trained a Deep Learning model to segment the carotid artery from ultrasound images and developed an algorithm to measure the cLD. We compared multiple measures of cLD corresponding to lateral and central views of the left and right carotid arteries. By applying genome-wide association studies (GWAS), we investigated the genetic architecture of cLD and the relationship between cLD and cIMT in a cohort of 18 804 individuals imaged with carotid ultrasound from the UK Biobank. We found that cLD has an estimated heritability of 31%, substantially higher than that of cIMT (23%). Furthermore, these phenotypes only have a mild phenotypic (37%) but much higher genotypic (58%) correlation.
Spinal Movement Impairments in People with Acute Low Back Pain
Authors: Krueger Kayla O. , Duncan Ryan P. , van Dillen Linda R. 
Published: January 2025

ABSTRACTObjectiveIdentify whether people with people with acute low back pain (LBP) display spinal movement impairments during clinical tests. Compare the prevalence of impairments in people with acute LBP to that of people with chronic LBP. Examine the effect on symptoms of systematically modifying impairments.DesignSecondary analysis of data from a cross-sectional study on LBP.Methods183 people with LBP were examined by a physical therapist using a standardized examination. Participants performed 9 primary tests using their preferred strategy. The clinician determined whether an impairment was present or absent. Participants reported the effect of the primary test on symptoms. If an impairment was present, it was modified during a secondary test. Participants reported the effect of the secondary test on symptoms relative to symptoms with the primary test. Chi-square tests of independence were used to test for differences in the proportion of impairments between people with acute LBP and people with chronic LBP. A McNemar-Bowker test was used to test whether there was a change in symptoms from the primary test to the secondary test.ResultsPeople with acute LBP displayed spinal movement impairments and the prevalence was similar to that of people with chronic LBP for 7 of the 9 primary tests. Most participants with symptomatic impairments reported their symptoms improved when the impairment was modified.ConclusionSpinal movement impairments are prevalent in people with acute LBP and may be modified during clinical tests to improve LBP symptoms.
Computationally optimized ctDNA surveillance for recurrence detection in HPV-positive head and neck squamous cell carcinoma
Authors: Mohammadi Narges , Rosenberg Ari J , Izumchenko Evgeny G , Pearson Alexander T , Skandari M. Reza 
Published: January 2025

ImportanceEarly detection of Head and Neck Squamous Cell Carcinoma (HNSCC) recurrence in HPV-positive patients is crucial for improving survival rates and reducing treatment costs. Integrating circulating tumor DNA (ctDNA) testing as part of post-treatment surveillance may enhance timely cancer recurrence detection, reduce false-positive rates, and lower overall costs.ObjectiveTo develop and evaluate personalized, cost-effective post-treatment surveillance strategies that integrate ctDNA testing with established, computed tomography (CT) scans, with the goal of minimizing costs and treatment delays for HPV-positive HNSCC patients.MethodsWe constructed a microsimulation model that optimizes the timing of ctDNA tests and generates testing schedules designed to achieve detection delays below specified thresholds at a minimum cost. The model was fit using n= 840 training data and validated using n= 447 external data. Six sub-populations were created based on the combination of cancer stage (AJCC 8th edition stage 1, stage 2, and stage 3) and smoking status (non-smoker and ever-smoker). The study compared the proposed ctDNA-based strategy with established clinical guidelines, as well as a strategy from the literature.ResultsOur optimization model generated cost-effecive strategies for scheduling ctDNA tests for a range of detection delay tolerances (i.e., 3, 6, and 9 months) across the six subpopulations. The optimal ctDNA-based strategy demonstrated substantial cost savings, potentially reducing annual surveillance costs in the USA by at least $200 million compared to imaging-based guidelines, while matching an equal patient outcome of treatment delay. Additionally, a hypothetical scenario of monthly ctDNA testing, incurring comparable total cost to the existing guidelines’, offers a 32% reduction in treatment delay. The study also highlighted the growing importance of HPV-positive HNSCC surveillance, with the annual incidence projected to rise, further emphasizing the cost-saving potential of ctDNA integration.ConclusionIntegrating ctDNA testing with traditional imaging methods for post-treatment surveillance of HPV-positive HNSCC patients offers a cost-effective strategy that minimizes surveillance costs and treatment delays. As the HPV-positive HNSCC population grows, the significance of the cost savings will increase. Future research should focus on the applicability of the developed strategy and their impact on patient survival and quality of life.
Evaluation of Flow Control Using PID versus Fuzzy Logic in an Electropneumatic Circuit for Pulmonary Ventilation Applications
Authors: Lescher Alfredo , González Lina , Griffith Issa , Molino Jay , Rojas Asdrúal , Quijano Damián 
Published: January 2025

AbstractHigh-tech commercial mechanical ventilators are designed to provide a constant and accurate flow, thus ensuring the precision of ventilatory treatment. Therefore, this research aims to evaluate the flow control in a prototype electro-pneumatic unit for mechanical ventilator applications using a PID versus a Fuzzy Logic method.Specifically, the intention is to determine if there is evidence of superior performance of fuzzy logic control over PID in this application. For this reason, the methodology is based on measurement and numerical analysis. The design of this research is quasi-experimental and conducted in a laboratory. Thus, samples of the data of the variables were taken at convenience under a pre-established scheme and conditions. In terms of the type of study, it is considered quantitative, experimental, and applied.The main results show that according, the Bland-Altman analysis both controllers meet the accuracy limits of commercial equipment. However, the fuzzy logic controller presented better standard deviation and difference limits, demonstrating greater reliability in the accuracy of results. Additionally, the PID control demonstrated quicker response times with a shorter settling time (between 0.32 and 0.43 seconds) than in the fuzzy logic control (between 0.43 and 0.77 seconds); moreover, the fuzzy control presents an improvement in the volume of 900 mL, highlighting the efficiency of this controller in conditions of higher demand. The results show that both the PID and Fuzzy Logic controllers meet the stability conditions of the Jury Test. The system’s poles are within the unit circle of the Z plane, confirming the controllers’ stability. Also, the curve of the fuzzy control in the Nyquist analysis is farther away from the origin and from the point (−1, 0j) than the curve of the PID control, indicating better stability and a more robust system against variations or disturbances.
Investigating the Role of Vitamin D in the Prevention and Control of Dengue Virus Vectors and Related Diseases: A Systematic Review Study
Authors: Abbasi Ebrahim 
Published: January 2025

ABSTRACTIntroductionDengue fever is one of the most common vector-borne diseases in the world, affecting many people annually and causing many deaths. Besides, treating this disease is difficult, and there is no effective vaccine for it. In recent years, attention has been paid to the role of micronutrients, including vitamin D, in the control and treatment of viral diseases, including dengue fever. Accordingly, this study aimed to investigate the role of vitamin D in the treatment and control of dengue fever worldwide using a systematic review method.MethodsThis study was conducted as a systematic review of the role of vitamin D in the prevention and control of dengue fever globally using a systematic review method. Therefore, all relevant articles were extracted and reviewed through a search in the international scientific databases, including PubMed/MEDLINE, WEB OF Science (ISI), and SCOPUS, without a time limit until the end of 2024. The quality of the articles was assessed using the STROB checklist.ResultsSix articles published between 2018 and 2023 were included in the systematic review process. According to the findings, vitamin D affects macrophages that are differentiated from monocytes and increases resistance to dengue virus. Vitamin D also reduces pro-inflammatory cytokines, transcription, and reduction of mRNA receptors, increases the production of interleukins, especially IL-10, and plays a role in reducing viral load, severity of clinical symptoms, and infection control.ConclusionVitamin D3 can control the disease and decrease viral load and the severity of dengue fever in patients by inhibiting the inflammatory response and enhancing the immune response. However, given the limited number of studies, it is recommended that more studies be conducted in this field so that this can be discussed with more evidence and accuracy.
Regional Variations in Burden of Chronic Obstructive Pulmonary Disease
Authors: Mehareen Jeenat , Choy Kayly , Yin Yiwei , Sin Don D. , Sadatsafavi Mohsen 
Published: January 2025

AbstractBackgroundChronic Obstructive Pulmonary Disease (COPD) imposes a significant burden on individuals and communities. While differences in such burden are often studied across countries and healthcare systems, differences within jurisdictions have not been well evaluated. The aim of this study was to assess the trends of, and factors explaining, regional variability in the burden of COPD within a well-defined population with publicly funded healthcare system.MethodologyWe used population-based health records of people aged 35 years or older diagnosed with COPD across the 16 health regions of British Columbia, Canada (2010–2020). The primary outcomes were prevalence, incidence, all-cause hospital admissions, and all-cause mortality, while secondary outcomes were COPD- and cardiovascular disease (CVD)-specific hospitalization and mortality. We used generalized linear models to examine how outcomes varied by regions and changed over time, controlling for sex, age, socioeconomic status, and rural/urban residence.ResultsOver the 11-year study period, there were 312,014 individuals diagnosed with COPD (48.1% female, mean baseline age: 68.2 years). Across the province, standardized prevalence and all-cause mortality remained relatively stable during the study period, whereas incidence and all-cause hospitalization declined. There were up to a three-fold difference in standardized incidence and prevalence, and up to a two-fold difference in standardized all-cause hospitalization and mortality across regions (all p<0.05). These differences remained significant after controlling for case mix. Among COPD patients, both CVD-specific hospitalization and mortality were higher compared to COPD-specific hospitalization and mortality.ConclusionDespite being governed by the same universal healthcare system, difference in burden of COPD across geographic regions in this Canadian province was significant. Heterogeneity was more prominent in incidence and prevalence, compared with hospitalization and mortality, suggesting that the variation in the process of care leading to diagnosis is more substantial than variation in COPD outcomes.