bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identify potential drug candidates within a high-quality compound search space
Authors: Ru Xiaoqing , Zhao Shulin , Zou Quan , Xu Lifeng 
Published: January 2025

Abstract
The identification of potential effective drug candidates is a fundamental step in new drug discovery, with profound implications for pharmaceutical research and the healthcare sector. While many computational methods have been developed for such predictions and have yielded promising results, two challenges persist: (i) The cold start problem of new drugs, which increases the difficulty of prediction due to lack of historical data or prior knowledge. (ii) The vastness of the compound search space for potential drug candidates. In this study, we present a promising method that not only enhances the accuracy of identifying potential novel drug candidates but also refines the search space. Drawing inspiration from solutions to the cold start problem in recommender systems, we apply ‘learning to rank’ techniques to the field of new drug discovery. Furthermore, we propose using three similarity metrics to condense the compound search space into compact yet high-quality spaces, allowing for more efficient screening of potential drug candidates. Experimental results from two widely used datasets demonstrate that our method outperforms other state-of-the-art approaches in the new drug cold-start scenario. Additionally, we have verified that it is feasible to identify potential drug candidates within these high-quality compound search spaces. To our knowledge, this study is the first to address drug cold-start problem in such a confined space, potentially providing valuable insights and guidance for drug screening.
Review: D. Furley, ‘Variations on themes from Empedocles in Lucretius’ proem’, BICS 17 (1970), 55–64
Authors: Garani Myrto 
Published: January 2025

ABSTRACT
The article discusses the scholarly impact of Furley’s study that argues in favour of Empedocles’ twofold presence in Lucretius’ DRN, both poetic and philosophical. As it concludes, in vast majority of cases the discussion of Empedocleo-Lucretian presence in Latin poetry heavily relies on it.
The end of latifundia: development in scholarship on landholding patterns in the late Roman Republic
Authors: Roselaar Saskia T 
Published: January 2025

ABSTRACT
This article starts with a review of a K. D. White’s article on latifundia, long considered an essential work on landholding patterns in the late Roman Republic and early Roman Empire. It then traces developments of the research topic in literature that has been published since. Finally, it explores present and potential future trends and the direction the research field is taking.
MetAssimulo 2.0: a web app for simulating realistic 1D & 2D Metabolomic 1H NMR spectra
Authors: Yan Yan , Jiménez Beatriz , Judge Michael T , Athersuch Toby , De Iorio Maria , Ebbels Timothy M D 
Published: January 2025

Abstract

Metabolomics extensively utilizes Nuclear Magnetic Resonance (NMR) spectroscopy due to its excellent reproducibility and high throughput. Both one-dimensional (1D) and two-dimensional (2D) NMR spectra provide crucial information for metabolite annotation and quantification, yet present complex overlapping patterns which may require sophisticated machine learning algorithms to decipher. Unfortunately, the limited availability of labeled spectra can hamper application of machine learning, especially deep learning algorithms which require large amounts of labelled data. In this context, simulation of spectral data becomes a tractable solution for algorithm development.
Here, we introduce MetAssimulo 2.0, a comprehensive upgrade of the MetAssimulo 1.0 metabolomic 1H NMR simulation tool, reimplemented as a Python-based web application. Where MetAssimulo 1.0 only simulated 1D 1H spectra of human urine, MetAssimulo 2.0 expands functionality to urine, blood, and cerebral spinal fluid (CSF), enhancing the realism of blood spectra by incorporating a broad protein background. This enhancement enables a closer approximation to real blood spectra, achieving a Pearson correlation of approximately 0.82. Moreover, this tool now includes simulation capabilities for 2D J-resolved (J-Res) and Correlation Spectroscopy (COSY) spectra, significantly broadening its utility in complex mixture analysis. MetAssimulo 2.0 simulates both single, and groups, of spectra with both discrete (case-control, e.g. heart transplant vs healthy) and continuous (e.g. BMI) outcomes and includes inter-metabolite correlations. It thus supports a range of experimental designs and demonstrating associations between metabolite profiles and biomedical responses.
By enhancing NMR spectral simulations, MetAssimulo 2.0 is well positioned to support and enhance research at the intersection of deep learning and metabolomics.

Availability and Implementation
The code and the detailed instruction/tutorial for MetAssimulo 2.0 is available at https://github.com/yanyan5420/MetAssimulo_2.git The relevant NMR spectra for metabolites are deposited in MetaboLights with accession number MTBLS12081.

Supplementary information
Supplementary data are available at Bioinformatics online.
Genetic diversity and environmental adaptation in Ethiopian tef
Authors: Hein Kirsten , Girma Dejene , McKay John 
Published: January 2025

Abstract
Orphan crops serve as essential resources for both nutrition and income in local communities and offer potential solutions to the challenges of food security and climate vulnerability. Tef [Eragrostis tef (Zucc.)], a small-grained allotetraploid, C4 cereal mainly cultivated in Ethiopia, stands out for its adaptability to marginal conditions and high nutritional value, which holds both local and global promise. Despite its significance, tef is considered an orphan crop due to limited genetic improvement efforts, reliance on subsistence farming, and its nutritional, economic, and cultural importance. Although pre-Semitic inhabitants of Ethiopia have cultivated tef for millennia (4000–1000 BCE), the genetic and environmental drivers of local adaptation remain poorly understood. To address this, we resequenced a diverse collection of traditional tef varieties to investigate their genetic structure and identify genomic regions under environmental selection using redundancy analysis, complemented by differentiation-based methods. We identified 145 loci associated with abiotic environmental factors, with minimal geographic influence observed in the genetic structure of the sample population. Overall, this work contributes to the broader understanding of local adaptation and its genetic basis in tef, providing insights that support efforts to develop elite germplasms with improved environmental resilience.
Deregulated ion channels contribute to RHOBTB2-associated developmental and epileptic encephalopathy
Authors: Langhammer Franziska , Gregor Anne , Ntamati Niels R , Ekici Arif B , Winner Beate , Nevian Thomas , Zweier Christiane 
Published: January 2025

Abstract
While de novo missense variants in the BTB domains of atypical RhoGTPase RHOBTB2 cause a severe developmental and epileptic encephalopathy, de novo missense variants in the GTPase domain or bi-allelic truncating variants are associated with more variable neurodevelopmental and seizure phenotypes. Apart from the observation of RHOBTB2 abundance resulting from BTB-domain variants and increased seizure susceptibility in Drosophila overexpressing RhoBTB, our knowledge on RHOBTB2-related pathomechanisms is limited. We now found enrichment for ion channels among the differentially expressed genes from RNA-Seq on fly heads overexpressing RhoBTB. Subsequent genetic interaction experiments confirmed a functional link between RhoBTB and paralytic, the orthologue of human sodium channels, including epilepsy associated SCN1A, in vivo. We then performed patch-clamp recordings on mature neurons differentiated from human induced pluripotent stem cells with either homozygous frameshifts or patient-specific heterozygous missense variants in the GTPase or the BTB domains. This revealed significantly altered neuronal activity and excitability resulting from BTB domain variants but not from GTPase domain variants or upon complete loss of RHOBTB2. Our study indicates a role of deregulated ion channels in the pathogenesis of RHOBTB2-related developmental and epileptic encephalopathy and points to specific pathomechanisms underlying the observed genotype–phenotype correlations regarding variant zygosity, location and nature.
A novel frameshift mutation of SOX10 identified in Waardenburg syndrome type 2
Authors: Han Wenqing , Yang Run , Chen Xin , Chen Ying , Zhang Tianyu , Ma Jing 
Published: January 2025

Abstract
Waardenburg syndrome type 2 (WS2) is an autosomal dominant disorder characterized by congenital sensorineural hearing loss, blue iris, and abnormal pigmentation of the hair and skin. WS2 is genetically heterogeneous, often resulting from pathogenic mutations in SOX10 gene. We identified a novel heterozygous frameshift mutation in SOX10 (NM_006941.4: c.22delT, p.S8Rfs*5) in a two-generation Chinese family with WS2 through whole exome sequencing. This mutation was present in both the proband, who exhibited typical features of hearing loss and pigmentation abnormalities, and his father, who showed only mild facial features. Quantitative real-time PCR revealed that the frameshift mutation leads to a reduced expression levels of SOX10 in the peripheral blood of mutation carriers. Our findings expand the spectrum of pathogenic mutations in SOX10 associated with WS2, providing valuable information for prenatal diagnosis and preimplantation screening, and underscore the role of genetic diagnosis in identifying atypical patients.
Inflammation-Induced Th17 Cells Synergize with the Inflammation-Trained Microbiota to Mediate Host Resiliency Against Intestinal Injury
Authors: Golob Jonathan L , Hou Guoqing , Swanson Benjamin J , Berinstein Jeffrey A , Bishu Shreenath , Grasberger Helmut , Zataari Mohamed El , Lee Allen , Kao John Y , Kamada Nobuhiko , Bishu Shrinivas 
Published: January 2025

Abstract

Background and Aims
Inflammation can generate pathogenic Th17 cells and cause an inflammatory dysbiosis. In the context of inflammatory bowel disease (IBD), these inflammatory Th17 cells and dysbiotic microbiota may perpetuate injury to intestinal epithelial cells. However, many models of IBD like T-cell transfer colitis and IL-10−/− mice rely on the absence of regulatory pathways, so it is difficult to tell if inflammation can also induce protective Th17 cells.

Methods
We subjected C57BL6, RAG1−/−, or JH−/− mice to systemic or gastrointestinal (GI) Citrobacter rodentium (Cr). Mice were then subjected to 2.5% dextran sodium sulfate (DSS) to cause epithelial injury. Fecal microbiota transfer was performed by bedding transfer and co-housing. Flow cytometry, qPCR, and histology were used to assess mucosal and systemic immune responses, cytokines, and tissue inflammation. 16s sequencing was used to assess gut bacterial taxonomy.

Results
Transient inflammation with GI but not systemic Cr was protective against subsequent intestinal injury. This was replicated with sequential DSS collectively indicating that transient inflammation provides tissue-specific protection. Inflammatory Th17 cells that have a tissue-resident memory (TRM) signature expanded in the intestine. Experiments with reconstituted RAG1−/−, JH−/− mice, and cell trafficking inhibitors showed that inflammation-induced Th17 cells were required for protection. Fecal microbiota transfer showed that the inflammation-trained microbiota was necessary for protection, likely by maintaining protective Th17 cells in situ.

Conclusion
Inflammation can generate protective Th17 cells that synergize with the inflammation-trained microbiota to provide host resiliency against subsequent injury, indicating that inflammation-induced Th17 TRM T cells are heterogenous and contain protective subsets.
Assessing the physicochemical and bioactivity properties of vinegar derived from ‘Phulae’ pineapple fruitlets during inoculated fermentation: A comparative study
Authors: Konsue Nattaya , Suthiluk Phunsiri 
Published: January 2025

Abstract
This study investigated the changes in physicochemical properties and bioactive compounds of vinegar produced from 'Phulae' pineapple waste, a byproduct of fresh-cut pineapple processing in Thailand. A two-stage fermentation process incorporating both alcoholic and acetic acid fermentation was employed. The results showed that acetic acid concentration increased along with the fermentation period to its maximum at 7.84 ± 0.09 g/100 mL over a 16-day period. On the other hand, phenolic acid compositions determined by liquid chromatography quadrupole time-of-flight mass spectrometry (LC-Q-TOF-MS) were highest after 40 days of fermentation. These were in agreement with the highest antioxidant activity. The fermentation duration significantly influenced the concentrations of flavonoids, fructose, and glucose, while phenolic acids remained consistently abundant throughout the fermentation process. The bioactivities of pineapple vinegar (PAV) were comparable to those of commercial apple cider vinegar (AV) and demonstrated superior activity relative to pineapple juice (PAJ), particularly in inhibiting enzymes, namely α-amylase, α-glucosidase, cholesterol esterase, and pancreatic lipase. Besides, PAV exhibited lower cytotoxicity than AV and displayed significant antibacterial activity against a range of pathogenic microorganisms. This study suggests that acetic acid fermentation of pineapple waste may serve as a promising functional beverage with potential health benefits for diabetes and cholesterol regulation.
Analysis on dynamic characteristics and control strategy of medium structure network converter in new energy medium voltage flexible interconnection project
Authors: Shang Jiaohui , Yang Jian , Xin Shijin , Xu Qing , Guo Mingqiang , Niu Haitao 
Published: January 2025

Abstract
In view of the possible voltage and current overshoot problems in the process of new energy grid connection, the dynamic characteristics analysis and control strategy of the network converter in the new medium voltage flexible interconnection project are proposed. Firstly, a synchronous control strategy based on voltage phase and amplitude compensation is proposed. Then, based on the characteristics of new AC-DC hybrid distribution network, the new energy medium voltage flexible interconnection network is analyzed. The simulation experiment reveals the dynamic response characteristics of the new energy grid converter under frequency interference and load change.
Comparison of immune responses to respiratory syncytial virus in infancy, childhood, and adulthood using an in vitro model of human respiratory infection
Authors: Smith Christiana , Curtis Kaili , Bonham Adrianne , Boyer Shea , Lenz Laurel , Weinberg Adriana 
Published: January 2025

Abstract
Respiratory syncytial virus (RSV) is a major contributor to morbidity and mortality in infants. We developed an in vitro model of human respiratory infection to study cellular immune responses to RSV in infants, children, and adults. The model includes human lung epithelial A549 cells or human fetal lung fibroblasts infected with a clinical strain of RSV at a multiplicity of infection of 0.3, cocultured with human cord blood mononuclear cells (CBMCs) or peripheral blood mononuclear cells (PBMCs). Mononuclear cells were collected at multiple ages ranging from birth to adulthood. After 20 h of incubation, flow cytometry was used to measure CBMC/PBMC responses to RSV. A549s were more permissive to RSV and when infected produced more CCL5, CCL11, and CXCL9; less CSF-3, CXCL10, interleukin (IL)-1α, IL-1RA, and IL-6; and similar CCL2, CCL3, CCL4, CCL7, CXCL1, CXCL11, IL-1β, IL-7, IL-8, and tumor necrosis factor α compared with fibroblasts; A594s were used for subsequent experiments. CBMCs/PBMCs upregulated multiple markers of activation, maturation, and degranulation upon exposure to RSV-infected A549s. Interferon γ expression in natural killer, CD4, and CD8 cells and CD107a expression in natural killer cells showed a gradual increase from infancy to adulthood. IL-12 expression in dendritic cells and monocytes was highest in adult PBMCs. Our in vitro model of human RSV infection recapitulated the expected bias away from T helper 1 and effector responses to RSV infection in infancy and revealed changes in innate and adaptive RSV-specific cellular immune responses over time.
Global prevalence of human intestinal carriage of ESBL-producing E. coli during and after the COVID-19 pandemic
Authors: Ng Rita W Y , Yang Liuyue , Lau Sai Hung , Hawkey Peter , Ip Margaret 
Published: January 2025

Abstract

Background
There is a pressing need for global surveillance of ESBL-producing Escherichia coli due to its health impacts, travel and increased antibiotic use during the COVID-19 pandemic. This systematic review and meta-analysis aimed to summarize evidence investigating the global prevalence of ESBL E. coli.

Methods
Four databases, including Embase, MEDLINE, PubMed and Web of Science, were searched for quantitative studies that reported prevalence data of faecal carriage of ESBL-producing E. coli published between 23 April 2021 and 22 April 2024. Meta-analysis was performed using the inverse variance heterogeneity model.

Results
Of the 25 studies (13 901 unique participants) included for final analysis, the overall pooled prevalence of ESBL E. coli was 25.4% (95% CI, 19.7%–31.2%). The pooled prevalences of ESBL E. coli in healthy individuals in community settings and inpatients in healthcare settings were 23.4% (95% CI, 14.7%–32.2%) and 27.7% (95% CI, 18.8%–36.7%), respectively. Nearly one-third of the included studies (32%) were from the Western Pacific Region. There was a significant between-group difference for studies with different WHO regions and healthcare contact.

Conclusions
The pooled prevalence of ESBL E. coli remains high and there was a significant between-group difference for different WHO regions, with the highest being in Asian regions. Standardized surveillance of antimicrobial resistance and antibiotic stewardship especially in these regions are needed to enhance the control of this global emergency.
Effects of femoral neck width and hip Axis length on incident hip fracture risk: a registry-based cohort study
Authors: Zarzour Fatima , Aftabi Sajjad , Leslie William D 
Published: January 2025

Abstract
Bone mineral density (BMD) measured with dual-energy X-ray absorptiometry (DXA) is widely used in clinical practice to assess fracture risk and guide management. DXA can also assess hip geometry, including femoral neck width (FNW) and hip axis length (HAL), which have both been associated with increased risk for hip fracture independently from BMD. Our objective was to assess if FNW predicts hip fracture independently from other factors including HAL. We performed a retrospective cohort study using the Province of Manitoba BMD registry. The study population comprised 75 095 individuals (90.8% women), mean age 64.7 years, with baseline hip BMD and hip geometry parameters. Linked health records were used to ascertain subsequent hospitalization with hip fracture as a primary diagnosis. During a mean follow up of 8.3 (SD 5.1) years, 2341 incident hip fractures were recorded. Each SD increase in age- and sex-adjusted FNW was associated with incident hip fracture (HR 1.15, 95% CI 1.10-1.19) which was unchanged after adjustment for height, weight, femoral neck BMD and clinical risk factors. However, FNW showed a significant positive correlation with HAL (r = 0.68). When further adjusted for HAL, FNW was no longer associated with increased risk for hip fracture (HR 0.98, 95% CI 0.94-1.03). A similar pattern was seen for femoral neck, intertrochanteric and non hip fractures. In contrast, increased risk of hip fracture was consistently seen with each SD increase in HAL even after adjustment for all covariates including FNW (HR 1.35, 95% CI 1.28-1.42). In conclusion, FNW is a risk factor for hip fracture before but not after adjustment for HAL. HAL, on the other hand, robustly and independently predicts hip fracture, including both femoral neck and trochanteric fractures.
A multivariable prediction model to stratify risk of 90-day rehospitalization among adults with ulcerative colitis
Authors: Dziegielewski Claudia , Gupta Sarang , Lombardi Julia , Kelly Erin , McCurdy Jeffrey D , Sy Richmond , Saloojee Nav , Ramsay Tim , Pugliese Michael , Begum Jahanara , Benchimol Eric I , Murthy Sanjay K 
Published: January 2025

Abstract

Background
Individuals with ulcerative colitis (UC) are frequently re-hospitalized for persistent or recurrent severe disease flares. Accurate prediction of the risk of early re-hospitalization at the time of discharge could promote targeted outpatient interventions to reduce this risk.

Methods
We conducted a retrospective study in adults with UC admitted to The Ottawa Hospital between 2009 and 2016 for an acute UC-related indication. We ascertained candidate demographic, clinical, and health services predictors through medical records and administrative health databases. We derived and bootstrap validated a multivariable logistic regression model of 90-day UC-related re-hospitalization risk. We chose a probability cut point that maximized Youden’s index to differentiate high-risk from low-risk individuals and assessed model performance.

Results
Among 248 UC-related hospitalizations, there were 27 (10.9%) re-hospitalizations within 90 days of discharge. Our multivariable model identified gastroenterologist consultation within the prior year (adjusted odds ratio [aOR] 0.11, 95% confidence interval [CI], 0.04-0.39), male sex (aOR 3.27, 95% CI, 1.33-8.05), length of stay (OR 0.94, 95% CI, 0.88-1.01), and narcotic prescription at discharge (OR 1.96, 95% CI, 0.73-5.27) as significant predictors of 90-day re-hospitalization. The optimism-corrected c-statistic value was 0.78, and the goodness-of-fit test P-value was .09. The chosen probability cut point produced a sensitivity of 77.8%, specificity of 80.9%, positive predictive value (PPV) of 33.0%, and negative predictive value (NPV) of 96.7% in the derivation cohort.

Conclusions
A limited set of variables accessible at the point of hospital discharge can reasonably discriminate re-hospitalization risk among individuals with UC. Future studies are required to validate our findings.
The Colombian Catholic Church’s Quest for Legitimacy in the Colombian Armed Conflict
Authors: Parisi Piergiuseppe , Ibarra Padilla Adelaida Maria 
Published: January 2025

Abstract
Since the 1960s, Colombia has been the theatre of multiple armed conflicts that, one way or another, have involved all sectors of society. Colombian religious actors, including the Catholic Church, in particular, have historically played an ambivalent role in the conflict. While some Catholic clerics have ideologically supported, aided and abetted, or even joined state and non-state armed actors especially during the first decades of the conflict, since the 1980s the Colombian Catholic Church has progressively been assuming a posture in favour of peace either through action or discourse. Most recently, these praxes have culminated in the participation of the Catholic Church in most of the high-level negotiations between the Colombian state and non-state armed groups (NSAGs). The scholarship exploring the Church’s influential role in these peacebuilding and mediation efforts in Colombia has begun to burgeon only in the past twenty-five years. However, this literature has left largely unaddressed questions around the influence that the Catholic Church has had on the parties to the conflict. Such questions may help explain how the Church, as an institution, was able to garner the legitimacy necessary to become a key mediator between the state and NSAGs. Building on the data gathered and the framework elaborated as part of the Generating Respect Project (GRP), this article explores how the Church’s legitimacy was constructed from the bottom, by both leveraging affinities with armed groups’ ideologies and the impact of local initiatives aimed at protecting the civilian population in the midst of the armed conflict.