bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improved protein binder design using beta-pairing targeted RFdiffusion
Authors: Baker David , Sappington Isaac , Toul Martin , Lee David , Robinson Stephanie , Goreshnik Inna , McCurdy Clara , Chan Tung Ching , Buccholz Nic , Huang Buwei , Vafeados Dionne , Garcia-Sanchez Mariana , Roullier Nicole , Glögl Matthias , Kim Christopher , Watson Joseph , Torres Susana Vázquez , Verschueren Koen , Verstraete Kenneth , Hinck Cynthia , Valle Melisa Benard , Coventry Brian , Sims Jeremiah , Ahn Green , Wang Xinru , Hinck Andrew , Jenkins Timothy , Ruohola-Baker Hannele , Banik Steven , Savvides Savvas 
Published: January 2025

Abstract

Despite recent advances in the computational design of protein binders, designing proteins that bind with high affinity to polar protein targets remains an outstanding problem. Here we show that RFdiffusion can be conditioned to efficiently generate protein scaffolds that form geometrically matched extended beta-sheets with target protein edge beta-strands in which polar groups on the target are nearly perfectly complemented with hydrogen bonding groups on the design. We use this approach to design binders against a set of therapeutically relevant polar targets (KIT, PDGFRɑ, ALK-2, ALK-3, FCRL5, and NRP1) and find that beta-strand-targeted design yields higher affinities and success rates than unconditioned RFdiffusion. All by all binding experiments show that the designs have affinities ranging from 137 pM to mid nM for their targets and essentially no off target binding despite the sharing of beta-strand interactions, likely reflecting the precise customization of interacting beta-strand geometry and additional designed binder-target interactions. A co-crystal structure of one such design in complex with the KIT receptor is nearly identical to the computational design model confirming the accuracy of the design approach. The ability to robustly generate binders displaying high affinity and specificity to polar interaction surfaces with exposed beta-strands considerably increases the range and capabilities of computational binder design.
Molecular Diversity of Dissolved Organic Matter Reflects Macroecological Patterns in River Networks
Authors: Freeman Erika C. , Mudunuru Maruti K. , Feeser Kelli L. , McClure Emily Ann , González-Pinzón Ricardo , Ward Christopher S. , Bottos Eric M. , Krause Stefan , Peña Jasquelin , Newcomer Michelle E. 
Published: January 2025

Abstract

Understanding the molecular complexity of dissolved organic matter (DOM) is crucial for deciphering ecosystem function and predicting responses to environmental change. Using a continental-scale dataset of molecular formulae generated by Fourier-transform ion cyclotron resonance mass spectrometry through the WHONDRS Project, we reveal fundamental scaling patterns of DOM diversity across watershed characteristics. We show that both local and regional watershed features across latitude reveal universal scaling patterns across compound classes. Our analysis demonstrates that local and regional watershed features—including drainage area, land use, land cover, and water temperature—significantly influence DOM diversity, quantified through DOM richness and chemodiversity. Notably, we document one of the first observed latitudinal gradients in freshwater chemodiversity, suggesting that macroecological factors orchestrate molecular diversity similarly to organismal distributions. These findings offer more than descriptive insights. By identifying universal scaling laws, we propose that simple predictive models can forecast compound responses to climate change, providing critical understanding of watershed functional dynamics under emerging environmental conditions. The research contributes a novel perspective on ecosystem molecular complexity, bridging biogeochemical processes with broader ecological principles and offering a quantitative framework for anticipating ecosystem molecular transformations across scales.
Unveiling microbial complexity within Astragalus propinquus and Glycyrrhiza uralensis roots
Authors: KIM Zerrin KOZMA , Park Young Sang , Yang Tae-Jin , Kim Hyun , Lee Yong-Hwan 
Published: January 2025

Abstract

Background
Astragalus propinquus (AP) and Glycyrrhiza uralensis (GU), members of the Fabaceae family, are widely used for their therapeutic properties. However, the endophytic microbial communities in their roots remain largely unknown. Herein, we compared the structure and properties of root-associated bacterial and fungal communities of AP and GU, specifically excluding the microbial communities thriving in the rhizosphere, using both culture-dependent and -independent methods.
Results
A metabarcoding-based approach revealed a higher abundance of Proteobacteria in the root microbiome of GU than in that of AP. Fungal communities showed similar distinctions, with AP and GU predominantly harboring Ascomycota and Basidiomycota, respectively. The bacterial community in AP exhibited significantly higher diversity than in GU and included unique taxa, e.g., Steroidobacterales and Micromonosporales. However, the bacterial community in GU was relatively less diverse and dominated by Xanthomonadales. Differential abundance analysis revealed that the plant species significantly impacted 301 bacterial and 228 fungal amplicon sequence variants (ASVs) in AP and GU. Among these, B5_f_Comamonadaceae was markedly more enriched in AP than in GU. A random forest model analyzing bacterial ASVs with significant differences in abundance indicated that most bacterial ASVs were enriched in AP. A pan-microbial community of 1,243 ASVs was identified, including 96 co-detected ASVs between AP and GU, with 3 core ASVs (B2_f_Pseudomonas, B5_Comamonadaceae, and B70_Cutibacterium). The fungal community comprised 435 ASVs, with 98 shared ASVs and 8 core ASVs (F5_Paraphoma, F6_f_Lysurus, F22_Alternaria, F30_Phaeosphaeria, F53_Cladosporium, F36_Moesziomyces, F55_f_Neocucurbitaria, and F56_Malassezia). Hub nodes were identified to elucidate the roles of microorganisms within microbial networks. In AP, B152_o_Burkholderiales, F14_Exophiala, and F33_Fusarium were the key hub nodes, whereas, in GU, B36_Paenibacillus was the central hub node. The comparative analyses of in vitro culture data and molecular sequencing results showed overlapping patterns, with Pseudomonas dominant in AP and Bacillus in GU.
Conclusions
These findings highlight distinct microbial communities between AP and GU, with each species exhibiting unique bacterial and fungal orders and differences in microbial network complexity and diversity. These differences suggest the potential functional contributions, e.g., nutrient cycling and secondary metabolite production, of root-associated microbial communities, likely impacting the therapeutic properties of these plants.
Fault Detection in IEEE 9 Bus System Using Matlab &amp; Simulink
Authors: Kiruthika K , Vishal G , Vivek N , Mature Jyoti 
Published: January 2025

Abstract

This project presents a fault detection methodology for the IEEE 9-bus system using MATLAB and Simulink. The IEEE 9-bus system is a well-established testbed for studying power system stability and fault analysis due to its complexity and interconnectivity. In this study, various types of faults, including single-line-to-ground (SLG), line-to-line (LL), double-line-to-ground (DLG), and three-phase faults, are simulated and analyzed. The primary objective is to develop a fault detection mechanism that accurately identifies and classifies fault types, location, and severity within the network. The system dynamics are modeled using MATLAB’s Simulink environment, leveraging the capabilities of the Sim Power Systems toolbox for power systems simulation. The proposed fault detection algorithm employs wavelet transforms and signal processing techniques to analyze the transient response during fault conditions. By examining voltage and current waveforms at critical nodes, the algorithm pinpoint’s fault locations and classify fault types based on characteristic transient features. The findings of this research are essential for advancing the reliability of protection systems, as the early detection of faults minimizes system downtime and ensures stable power delivery. The project concludes with a performance analysis of the fault detection approach, illustrating its effectiveness and accuracy across different fault scenarios in the IEEE 9-bus model.
OR7E47P regulates TGF-β secretion of fibroblast via ROBO2 pathway to modulate the TME in NSCLC
Authors: Zhang Haohan , Wu Jie , Li Lan , Li Jing , Zhao Xinyi , Zhong Hao , Dan Yuchao , Mao Zhangfan , Song Qibin , Xu Bin 
Published: January 2025

Abstract

Whereas the role of OR7E47P in NSCLC is not clear, we explored the impact of OR7E47P on the prognosis of NSCLC patients and possible mechanisms through bioinformatics and experi-mental approaches. OR7E47P, underexpressed in NSCLC tumor tissues, is associated with better prognosis and enhanced immune benefits. Localization analyses showed OR7E47P may func-tions as a cytoplasmic processing pseudogene, regulating ROBO2 expression via the OR7E47P/miR-183-5p/ROBO2 pathway at the post-transcriptional level. Single-cell analyses re-vealed that ROBO2 reduces the tumor-supportive role of cancer-associated fibroblasts (CAFs) by promoting programmed cell death of FAP/TGFB1 + CAFs, enhancing immune infiltration, and suppressing the TGF-β/Smad signaling pathway in fibroblasts and NSCLC cells. Finally, we con-firmed our findings through experiments, where OR7E47P directly binds to miR-183-5p, with a binding site that allows for endogenous competition, leading to the upregulation of ROBO2 ex-pression and potentially regulate TGF-β secretion of fibroblast, thereby regulating the TME in NSCLC.
Developing and Assessing a Scalable Digital Health Tool for Pretest Genetic Education in Patients With Early-Onset Colorectal Cancer: Mixed Methods Design
Authors: Rivera Rivera Jessica N , Snir Moran , Simmons Emilie , Schmidlen Tara , Sholeh Misha , Maconi Melinda Leigh , Geiss Carley , Fulton Hayden , Barton Laura , Gonzalez Brian D , Permuth Jennifer , Vadaparampil Susan 
Published: January 2025

Background
National guidelines recommend germline genetic testing (GT) for all patients with early-onset colorectal cancer. With recent advances in targeted therapies and GT, these guidelines are expected to expand to include broader groups of patients with colorectal cancer. However, there is a shortage of genetic professionals to provide the necessary education and support for informed consent. As such, there is a pressing need to identify alternative approaches to facilitate and expedite access to GT.

Objective
This study describes the development of a pretest education intervention, Nest-CRC, to facilitate the uptake of germline GT among patients with early-onset colorectal cancer. Patients with early-onset colorectal cancer and health care providers reviewed Nest-CRC, and their reactions and recommendations were captured using a nested mixed methods approach.

Methods
Using the learner verification approach, we conducted 2 sequential phases of surveys and interviews with English- and Spanish-speaking patients with early-onset colorectal cancer and health care providers. The surveys assessed participants’ experiences with genetic services and provided immediate feedback on the Nest-CRC genetic education modules. Semistructured interviews evaluated participants’ perceptions of self-efficacy, attraction, comprehension, cultural acceptability, and usability of Nest-CRC. Survey data were analyzed using descriptive statistics (mean, median, and proportions), while interview data were analyzed through line-by-line coding of the transcribed interviews. After each phase, Nest-CRC was refined based on participants’ recommendations.

Results
A total of 52 participants, including 39 patients with early-onset colorectal cancer and 13 providers, participated in the study. Of these, 19 patients and 6 providers participated in phase 1 (N=25), and 20 patients and 7 providers participated in phase 2 (N=27). Most participants (phase 1: 23/25, 92%, to 25/25, 100%; phase 2: 24/27, 89%, to 27/27, 100%) agreed that each of the 5 education modules was easy to understand and helpful; 13 patients reported no history of GT, with 11 (85%) expressing interest in GT and 2 (15%) remaining unsure after completing Nest-CRC. Participants reported that Nest-CRC provided sufficient information to help them decide about GT. The tool was deemed acceptable by individuals from diverse backgrounds, and participants found it visually attractive, easy to comprehend, and user-friendly.

Conclusions
The findings revealed that Nest-CRC is a promising strategy for facilitating pretest education and promoting GT. Nest-CRC has been refined based on participant recommendations and will be re-evaluated.
Design, Characterisation and Evaluation of Sustained Release Formulation of Remogliflozin Etabonate
Authors: Aveek Datta  , Dr. Subhasis Maity  , Dr. Miltu Kr. Ghosh  , Dr. Kuntal Hazra  
Published: January 2025

Now-a-days Type 2 diabetes mellitus is a very crucial common disease and emerging condition that glucose level of Human body cannot be controlled. In case of Type-2 diabetes mellitus, pancreas does not produce enough insulin. In such a condition, we have to thing for a medicament for treating the disease; Remogliflozin Etabonate is such type of drug that efficacious and safe agent that we can administer in our body. The Half-Life of the drug is 120 minutes.This research has taken into consideration on improving the release pattern of the drug by sustaining its action at maximum level of time, using the different ratios of Polymer and discusses the individual studies performed during its development for design, characterization and evaluation of analytical and formulative profile, as well as in-vitro Characterization. In that case, this research work is hopefully very much useful for further proceeding and for large scale aspect in industrial point of view.
Immunological criteria for the diagnosis of multisystem inflammatory syndrome associated with MERS-COV-2 and infectious diseases with sepsis in children
Authors: Konstantinovа Yu. E. , Zhirkov A. A. , Alekseeva L. A. , Vilnits A. A. , Bessonov T. V. , Zhdanov K. V. 
Published: January 2025

Multisystem inflammatory syndrome associated with SARS­CoV­2 in children is a potentially life–threatening condition that develops several weeks after COVID­19 and is characterized by a hyperinflammatory response with damage to ≥2 organs and systems. At the moment, there is no understanding of how the mechanisms of development and course of this disease differ from other more studied similar conditions, for example, sepsis in infectious diseases.The aim is to compare immunological parameters in multisystem inflammatory syndrome associated with SARSCoV­2 and infectious diseases with sepsis in children.Materials and methods. The concentration of cytokines, chemokines and growth factors in serum was determined in 14 children with multisystem inflammatory syndrome associated with SARS­CoV­2, 19 children and 16 healthy children (control group) with IHS.Results. Both common and distinctive signs of inflammation were found in patients with MVS­D and IHS. Patients with MVS­D, unlike healthy children, were characterized by a decrease in Basic FGF, IFN­a2, IL­1a, IL­1b, IL­2, IL­3, IL­4, IL­5, IL­9, IL­12(p40), IL­13, IL­18, PDGF­BB, RANTES, TRAIL and Boost G­CSF, HGF, IL­1ra, IL­2Ra, IL­6, IL­10, IL­16, IP­10, MCP­1, M­CSF, MIG. Statistically significant in MVS­D was a decrease in IL­2 and IL­5 levels compared with the control group, but significantly less pronounced than in IS (8.0 times and 3.5 times, respectively), a pronounced increase in MIG levels (12.0 times compared with children with IS). The RANTES index (a proinflammatory chemokine that attracts leukocytes to the focus of inflammation) decreased with MVS­D, while it increased with IS compared with the control group.Conclusions. Immunological features of MISC have been found that distinguish the pathogenesis of the syndrome from infectious diseases occurring with sepsis. The identified markers can be used as criteria for the differential diagnosis of these diseases.
Influenza vaccination and cytokine profile dynamics in young men in Primorsky krai
Authors: Li Yu. A. , Dmitrachenko M. N. , Kostinov M. P. , Markelova E. V. , Korolev I. V. , Saprykin S. L. 
Published: January 2025

Seasonal vaccination against influenza is considered the most effective method of specific prevention of this infection. However, in recent years, the issue of non­specific, training effects of vaccines on the immune system has been widely studied. One of the mechanisms of implementation may be a change in the production of cytokines in vaccinated people.Purpose of the study: to study the dynamics of pro­inflammatory and anti­inflammatory cytokines before and after vaccination against influenza.Materials and methods: The study involved 75 young men, the average age was 18.7±0.8 years, who were vaccinated with the Sovigripp vaccine. Those included in the study had two blood samples: (1) – before the flu vaccination; (2) – one month after the flu vaccination. Serum levels of proand anti­inflammatory cytokines were determined by solid­phase enzyme immunoassay: IL1β, IL4, IL6, IL8, IL10, IL17, IFNγ, TNFα. The results were recorded using an automatic enzyme immunoassay analyzer. Statistical processing of the obtained results was carried out using the STATISTICA 10 software package.Results: In the analysis of cytokines before vaccination, an increase in IL8, IL17 and IL6 levels was detected in 100% of cases – in 76% of cases. Within the generally accepted norms, only TNFa was determined in 92% of the surveyed population. The remaining indicators were reduced: IFNγ – in 100%, IL1β and IL4 – in more than 80% and IL10 – in 50% of cases. After influenza vaccination, there was a noticeable tendency to decrease the levels of all cytokines compared to baseline values.Conclusion: The results of the study revealed features in cytokine levels before and after influenza vaccination in healthy young people, which were characterized by deviations from the norm in both directions.
Possibilities of rational application of bacteriophages in the therapy of infections caused by polyresistant strains of Klebsiella pneumoniae
Authors: Gumbatova L. A. , Lebedeva E. V. , Sergeeva T. A. , Aslanov B. I. , Gordeeva S. A. , Gusev D. A. 
Published: January 2025

The issue of combating antimicrobial resistance has been relevant for several decades, since the arsenal of effective antibiotics used in infectious diseases is significantly reduced, and the development of new antibacterial drugs is significantly difficult and expensive. At the same time, the possibility of widespread use of bacteriophages in hospital settings is being discussed.Goal. Evaluation of the sensitivity to bacteriophages of hospital strains of K.pneumoniae isolated from patients in the departments of surgery and intensive care and intensive care of the Structure Clinical Infectious Disease Hospital named after S.P.Botkin.Materials and methods. The activity of bacteriophage preparations “Sextafag” (series p158, p220, p242), “Klebsiell polyvalent bacteriophage” (series y04, y07, y10, y16), “Polyvalent Pyobacteriophage purified” (series y10, y291022) (Manufacturer: NPO Microgen JSC, Moscow) was determined by preparing suspensions of microorganisms, their sowing on nutrient media with subsequent application of bacteriophages, taking into account and interpreting the results.Results. The majority of polyresistant K.pneumoniae strains showed sensitivity to the presented bacteriophage preparations, which allows them to be considered as additional antibacterial agents for the treatment of these groups of patients.Conclusion. The presented results of the study showed that hospital polyand pan­resistant strains of K.pneumoniae are sensitive to preparations of monoand polyvalent bacteriophages, which can be considered as a potential alternative in conditions of antibiotic resistance. The study did not reveal a link between the antibiotic resistance profile of the culture and sensitivity to bacteriophages.
Heparinized venous blood gas syringes are associated with a significant decrease in measured packed cell volume in dogs due to hemodilution
Authors: Hopey Coyne M. , Caldwell Dana , Binagia Erin , Keys Deborah A. , Stastny Tereza 
Published: January 2025

Abstract

OBJECTIVE
To assess the effect of hemodilution on PCV when commercial preheparinized venous blood gas (PH-VBG) syringes are used compared to directly filled Hct tubes, and to evaluate the impact of delayed centrifugation on PCV.

METHODS
A prospective study of 102 dogs presenting to a private emergency department between November 1, 2023, and February 29, 2024, with 306 corresponding blood samples. Samples were collected by direct venipuncture. Samples were analyzed with the use of 3 methods: directly filled microhematocrit tubes (direct), PH-VBG syringe (PH-VBG), and PH-VBG syringe with a 15-minute delay before centrifugation (delayed PH-VBG).

RESULTS
Mean PCV of the direct method was 43.9%, the PH-VBG method was 41.7% (range, 11.0% to 60.0%; SD, 9.8%), and the delayed PH-VBG method was 40.1% (range, 7.0% to 60.0%; SD, 11.2%). When the direct and PH-VBG methods were compared, the direct method was biased on average 2.2% higher than the PH-VBG method, with limits of agreement (LOAs) of –0.9 to 5.3. The direct method was biased on average 3.8% higher than the delayed PH-VBG method, with LOAs of –4.3 to 11.9. In anemic dogs (n = 14), the direct method was biased on average 6.1% higher than the delayed PH-VBG method, with LOAs of –0.05 to 12.2. In nonanemic dogs (n = 88), the direct method was biased on average 2.3% higher than the PH-VBG method, with LOAs of –0.9 to 5.4.

CONCLUSIONS
Use of preheparinized syringes and delayed sample processing led to hemodilution and lower PCV values.

CLINICAL RELEVANCE
Direct venipuncture and immediate sample processing are recommended to ensure accurate PCV results.
The necessity of a new approach in the legal migration policies of the EU due to discrimination in the labor market, considering the post-Covid 19 context
Authors: Arrinaj Florida 
Published: January 2025

Abstract
The global trends in the labor market and the dynamics surrounding migration for employment have become a highly debated and prominent issue within the EU. Labor migration policies within the EU have undergone significant reforms over the years. These changes aim to address the evolving needs of the labor market while managing the migration of workers for employment purposes. This article examines the impact of the EU Blue Card Directive, the Seasonal Workers Directive and the Single Permit Directive on the labor market, with a particular focus on the issues and challenges faced by third country nationals. A valuable contribution has been made in attracting qualified labor force, but on the other hand, these policies have not managed to meet all the needs of migrant workers, especially those with low and medium qualifications. The COVID-19 pandemic has further highlighted the vulnerability of migrant workers, worsening pre-existing disparities in their access to employment opportunities, social services, and labor rights. These precarious conditions have exposed the shortcomings of existing labor migration policies, emphasizing the need for comprehensive reforms that address these inequalities and offer better protection for migrant workers in the post-pandemic context. The post-pandemic period has highlighted the urgent need for comprehensive reforms that not only support economic recovery, but also promote social inclusion and fair treatment of migrant workers. This article will propose recommendations to enhance EU migration policies by focusing on the development of legal migration pathways, implementing anti-discrimination measures, and strengthening integration initiatives. These changes are essential to creating a more equitable and resilient labor market in the EU, fostering better opportunities and protections for migrant workers and promoting social inclusion.