bluuebunny/crossref_metadata_2025_split huggingface dataset:
A novel engineered strain of Methylorubrum extorquens for methylotrophic production of glycolic acid
Authors: Dietz Katharina , Sagstetter Carina , Speck Melanie , Roth Arne , Klamt Steffen , Fabarius Jonathan Thomas 
Published: December 2024

AbstractThe conversion of CO2 into methanol depicts one of the most promising emerging renewable routes for the chemical and biotech industry. Under this regard, native methylotrophs have a large potential for converting methanol into value-added products but require targeted engineering approaches to enhance their performances and to widen their product spectrum. Here we use a systems-based approach to analyze and engineer M. extorquens TK 0001 for production of glycolic acid. Application of constraint-based metabolic modeling reveals the great potential of M. extorquens for that purpose, which is not yet described in literature. In particular, a superior theoretical product yield of 1.0 C-molGlycolic acid C-molMethanol−1 is predicted by our model, surpassing theoretical yields of sugar fermentation. Following this approach, we show here that strain engineering is viable and present 1st generation strains producing glycolic acid via a heterologous NADPH-dependent glyoxylate reductase. It was found that lactic acid is a surprising by-product of glycolic acid formation in M. extorquens, most likely due to a surplus of available NADH upon glycolic acid synthesis. Finally, the best performing strain was tested in a fed-batch fermentation producing a mixture of up to total 1.2 g L−1 glycolic acid and lactic acid. Several key performance indicators of our glycolic acid producer strain are superior to state-of-the-art synthetic methylotrophs. The presented results open the door for further strain engineering of the native methylotroph M. extorquens and pave the way to produce two promising biopolymer building blocks from green methanol, i.e., glycolic acid and lactic acid.
Unlocking the potential of titanium dioxide nanoparticles: an insight into green synthesis, optimizations, characterizations, and multifunctional applications
Authors: Ghareeb Ahmed , Fouda Amr , Kishk Rania M. , El Kazzaz Waleed M. 
Published: December 2024

AbstractThis comprehensive review explores the emergence of titanium dioxide nanoparticles (TiO2-NPs) as versatile nanomaterials, particularly exploring their biogenic synthesis methods through different biological entities such as plants, bacteria, fungi, viruses, and algae. These biological entities provide eco-friendly, cost-effective, biocompatible, and rapid methods for TiO2-NP synthesis to overcome the disadvantages of traditional approaches. TiO2-NPs have distinctive properties, including high surface area, stability, UV protection, and photocatalytic activity, which enable diverse applications. Through detailed analysis, this review demonstrates significant applications of green fabricated TiO2-NPs in biomedicine, explicitly highlighting their antimicrobial, anticancer, and antioxidant activities, along with applications in targeted drug delivery, photodynamic therapy, and theragnostic cancer treatment. Additionally, the review underscores their pivotal significance in biosensors, bioimaging, and agricultural applications such as nanopesticides and nanofertilizers. Also, this review proves valuable incorporation of TiO2-NPs in the treatment of contaminated soil and water with various environmental contaminants such as dyes, heavy metals, radionuclides, agricultural effluents, and pathogens. These comprehensive findings establish the foundation for future innovations in nanotechnology, underscoring the importance of further investigating bio-based synthetic approaches and bioactivity mechanisms to enhance their efficacy and safety across healthcare, agricultural, and environmental applications.
H2-driven xylitol production in Cupriavidus necator H16
Authors: Jämsä Tytti , Claassens Nico J. , Salusjärvi Laura , Nyyssölä Antti 
Published: December 2024

Abstract

Background
Biocatalysis offers a potentially greener alternative to chemical processes. For biocatalytic systems requiring cofactor recycling, hydrogen emerges as an attractive reducing agent. Hydrogen is attractive because all the electrons can be fully transferred to the product, and it can be efficiently produced from water using renewable electricity. In this article, resting cells of Cupriavidus necator H16 harboring a NAD-dependent hydrogenase were employed for cofactor recycling to reduce d-xylose to xylitol, a commonly used sweetener. To enable this bioconversion, d-xylose reductase from Scheffersomyces stipitis was heterologously expressed in C. necator.

Results

d-xylose reductase was successfully expressed in C. necator, enabling almost complete bioconversion of 30 g/L of d-xylose into xylitol. It was found that over 90% of the energy and protons derived from hydrogen were spent for the bioconversion, demonstrating the efficiency of the system. The highest xylitol productivity reached was 0.7 g/L/h. Additionally, the same chassis efficiently produced l-arabitol and d-ribitol from l-arabinose and d-ribose, respectively.

Conclusions
This study highlights the efficient utilization of renewable hydrogen as a reducing agent to power cofactor recycling. Hydrogen-oxidizing bacteria, such as C. necator, can be promising hosts for performing hydrogen-driven biocatalysis.
Experimental and computational evaluation of knee implant wear and creep under in vivo and ISO boundary conditions
Authors: Dreyer Michael J. , Nasab Seyyed Hamed Hosseini , Favre Philippe , Amstad Fabian , Crockett Rowena , Taylor William R. , Weisse Bernhard 
Published: December 2024

Abstract
Background
Experimental knee implant wear testing according to ISO 14243 is a standard procedure, but it inherently possesses limitations for preclinical evaluations due to extended testing periods and costly infrastructure. In an effort to overcome these limitations, we hereby develop and experimentally validate a finite-element (FE)-based algorithm, including a novel cross-shear and contact pressure dependent wear and creep model, and apply it towards understanding the sensitivity of wear outcomes to the applied boundary conditions.

Methods
Specifically, we investigated the application of in vivo data for level walking from the publicly available “Stan” data set, which contains single representative tibiofemoral loads and kinematics derived from in vivo measurements of six subjects, and compared wear outcomes against those obtained using the ISO standard boundary conditions. To provide validation of the numerical models, this comparison was reproduced experimentally on a six-station knee wear simulator over 5 million cycles, testing the same implant Stan’s data was obtained from.

Results
Experimental implementation of Stan’s boundary conditions in displacement control resulted in approximately three times higher wear rates (4.4 vs. 1.6 mm3 per million cycles) and a more anterior wear pattern compared to the ISO standard in force control. While a force-controlled ISO FE model was unable to reproduce the bench test kinematics, and thus wear rate, due to a necessarily simplified representation of the simulator machine, similar but displacement-controlled FE models accurately predicted the laboratory wear tests for both ISO and Stan boundary conditions. The credibility of the in silico wear and creep model was further established per the ASME V&V-40 standard.

Conclusions
The FE wear model is suitable for supporting future patient-specific models and development of novel implant designs. Incorporating the Stan data set alongside ISO boundary conditions emphasized the value of using measured kinematics in displacement control for reliably replicating in vivo joint mechanics in wear simulation. Future work should focus on expanding the range of daily activities simulated and addressing model sensitivity to contact mechanics to further enhance predictive accuracy.
Assessing healthcare cost changes associated with transitioning away from cigarette smoking using healthcare claims data: an exploratory study among adult male patients with COPD
Authors: Zhang Mingda , Cheng Hui G. , Noggle Brendan , Janak Jud C. , Richards Megan , Smith David 
Published: December 2024

Abstract
Background
The assessment of potential health effects of switching from cigarette smoking to non-combustible tobacco products has important implications for public health and regulatory decisions. Robust epidemiological evidence requires long-term follow-up of a large number of individuals. Real-world evidence derived from health records has the potential to help fill the gap in the interim. To our knowledge, this is the first study using individual-level healthcare claims data to assess the potential impact of transitioning from cigarette smoking to smokeless tobacco on short-term direct healthcare costs.

Methods
We conducted a retrospective cohort study of adult male patients with COPD who smoked cigarettes at baseline using the MarketScan® Databases. We compared changes in direct healthcare costs between the 12-month periods before (baseline) and after the index date (follow-up) across three cohorts: continued smoking (CS), quit all tobacco (QT), or switched to smokeless tobacco (SW), using a non-linear difference-in-differences model with average marginal effects.

Results
A total of 23,427 COPD patients were included (CS: 11,167; QT: 12,013; SW: 247). At baseline, the QT cohort had the highest total average healthcare costs ($43,771), followed by SW ($38,419), and CS ($27,149). The unadjusted difference-in-differences model revealed no statistically significant differences in total healthcare cost changes when comparing the QT or SW cohorts to the CS cohort (-$1,532 [95% CI: -$3,671, $608] for the QT cohort, and -$452 [95% CI: -$15,415, $14,511] for the SW cohort). After adjusting for Deyo-Charlson Comorbidity Index and COPD exacerbation, assuming patients had two comorbidities and exacerbations, the QT cohort had greater reduction in total healthcare costs compared to the CS cohort (-$2,910 dollars [95% CI: -$4,485, $-1,335]). The same trend was observed for the SW cohort, although the estimate was not statistically significant (-$5,312 [95%CI: -$11,067, $442], p = 0.08).

Conclusions
This study demonstrated the feasibility of using administrative claims to conduct real-world evidence studies on the harm-reduction potential of non-combustible tobacco products and found evidence suggesting reductions in direct healthcare costs after quitting tobacco or switching to smokeless tobacco among patients with COPD. Based on the learnings and limitations identified during the study, we propose concrete recommendations to improve future observational studies by integrating additional real-world healthcare data from multiple data sources.
Technical evaluation of the InBios Strongy Detect IgG ELISA assay for the diagnosis of Strongyloides stercoralis infection
Authors: Roose Sara , Prato Marco , Kazienga Adama , Peelaers Iris , Arens Justien , Leta Gemechu Tadessa , Mazzi Cristina , Buonfrate Dora , Levecke Bruno , Tamarozzi Francesca 
Published: December 2024

Abstract
Background
Strongyloidiasis is a neglected tropical disease (NTD) caused by the soil-transmitted helminth Strongyloides stercoralis, recently included in the 2030 targets of the World Health Organization for the control of STHs. Assessment of infection prevalence is fundamental for decision-making about the implementation of control programs, but diagnostic assays to be applied in such context require evaluation. Seroassays based on recombinant antigens, which could be produced in a standardized and scalable manner, are particularly appealing for use in control programs. In this study, we performed a technical evaluation of the InBios Strongy Detect IgG ELISA, based on recombinant antigens NIE and SsIR, which has shown promising for field use.

Methods
A total of 46 plasma samples from Ethiopian children were used for this technical evaluation. Repeatability was evaluated on duplicate samples per plate, on four plates per day for 3 days using Bland–Altman plots, analysis of residuals, and variance components analysis. Three samples were selected for evaluation of the uniformity of test results within a single plate (border effect) by two-sided t-test. Correlation between samples and internal ELISA positive controls was analyzed using Spearman’s rank correlation coefficient applied on the results of 777 samples analyzed with the assay in a previous field-based study.

Results
Within and between plate residuals ranged from −0.05 to + 0.05 and −0.1 to + 0.1, respectively. Total variance was estimated at 0.327; 99.6% of variation could be attributed to the samples. There was no systematic border effect and a negligible correlation between positive internal control and samples results (R2 = 0.213; p < 0.001).

Conclusion
The results obtained in this study, in highly controlled conditions, point toward the InBios Strongy Detect IgG ELISA assay being reproducible, with no systematic border effect. These results encourage further assay’s development and evaluation for use in practice, including determination of preset cutoff values for positivity, which is currently not provided.

Graphical Abstract
Mll4 in skeletal muscle fibers maintains muscle stem cells
Authors: Kim Yea-Eun , Hann Sang-Hyeon , Jo Young-Woo , Yoo Kyusang , Kim Ji-Hoon , Lee Jae W. , Kong Young-Yun 
Published: December 2024

Abstract
Background
Muscle stem cells (MuSCs) undergo numerous state transitions throughout life, which are critical for supporting normal muscle growth and regeneration. Epigenetic modifications in skeletal muscle play a significant role in influencing the niche and cellular states of MuSCs. Mixed-lineage leukemia 4 (Mll4) is a histone methyltransferase critical for activating the transcription of various target genes and is highly expressed in skeletal muscle. This raises the question of whether Mll4 has a regulatory function in modulating the state transitions of MuSCs, warranting further investigation.

Methods
To assess if myofiber-expressed Mll4, a histone methyltransferase, contributes to the maintenance of MuSCs, we crossed MCKCre/+ or HSAMerCreMer/+ mice to Mll4f/f mice to generate myofiber-specific Mll4-deleted mice. Investigations were conducted using 8-week-old and 4-week-old MCKCre/+;Mll4f/f mice, and adult HSAMerCreMer/+;Mll4f/f mice between the ages of 3 months and 6 months.

Results
During postnatal myogenesis, Mll4 deleted muscles were observed with increased number of cycling MuSCs that proceeded to a differentiation state, leading to MuSC deprivation. This phenomenon occurred independently of gender. When Mll4 was ablated in adult muscles using the inducible method, adult MuSCs lost their quiescence and differentiated into myoblasts, also causing the depletion of MuSCs. Such roles of Mll4 in myofibers coincided with decreased expression levels of distinct Notch ligands: Jag1 and Dll1 in pubertal and Jag2 and Dll4 in adult muscles.

Conclusions
Our study suggests that Mll4 is crucial for maintaining MuSCs in both pubertal and adult muscles, which may be accomplished through the modulation of distinct Notch ligand expressions in myofibers. These findings offer new insights into the role of myofiber-expressed Mll4 as a master regulator of MuSCs, highlighting its significance not only in developmental myogenesis but also in adult muscle, irrespective of sex.
Integrating modern and herbal medicines in controlling malaria: experiences of orthodox healthcare providers in Ghana
Authors: Ampomah Irene G. , Ampomah Genevieve A. , Emeto Theophilus I. 
Published: December 2024

Abstract
Background
In Ghana, the government has integrated herbal medicine into the formal healthcare system in response to widespread use of traditional remedies. However, empirical evidence supporting the contribution of integrated healthcare to malaria control remains limited. This study employed a phenomenological qualitative research design to explore the experiences of medical doctors and pharmacists from the coastal, forest and savannah regions of Ghana regarding the integration of modern and herbal medicine in the treatment and control of malaria. Donabedian’s framework for evaluating the quality of healthcare served as the foundational theoretical framework for this research.

Methods
Data were collected through individual in-depth interviews involving 26 participants and analysed using a framework analytical approach.

Results
The findings revealed that inadequate political commitment to the practice of integration has led to several challenges, including the high cost of herbal anti-malaria medications, limited promotional activities surrounding integration, a shortage of qualified medical herbalists, inconsistent supply chains for herbal anti-malaria treatments, and a lack of standardisation in herbal medicine practices. Participants had divergent views regarding the impact of integration on malaria control; while medical doctors believed that the intervention has not significantly contributed to reducing malaria prevalence in Ghana, pharmacists viewed the presence of herbal clinics within government hospitals as an effective and sustainable alternative for treating malaria.

Conclusion
Reflecting on these results, it is imperative for policymakers to explore strategies that could enhance the effectiveness of an integrated health system, thereby increasing the contribution of herbal medicine towards achieving a malaria free nation. Future research could benefit from including policymakers, heads of health directorates, and community members, regarding the role of public health interventions in addressing health inequities in Ghana.
Characterization and application of biochar derived from greenhouse crop by-products for soil improvement and crop productivity in South Korea
Authors: Lee Yu Na , Kim Sin Sil , Lee Dong Won , Shim Jae Hong , Jeon Sang Ho , Roh Ahn Sung , Kwon Soon Ik , Seo Dong-Cheol , Kim Seong Heon 
Published: December 2024

Abstract
The study examined the optimal production conditions and application rates of biochar derived from greenhouse crop by-products to enhance soil improvement and increase crop yield, thereby promoting sustainable agriculture in South Korea. The expansion of greenhouse cultivation has resulted in significant waste management challenges, and biochar production has emerged as a promising recycling solution for these by-products. Biochar was produced from red pepper stalks through pyrolysis at 200 to 600 °C, and its chemical properties, including pH, EC, T-C, and T-N, were analyzed. In this study, the chemical properties of biochar showed a significant increase in pH (from 5.8 to 10.3), EC (from 46.0 to 119.5 dS m⁻¹), and T-C (from 47.7 to 63.1%) with rising pyrolysis temperatures, while T-N decreased due to nitrogen volatilization above 300 °C. In the lettuce cultivation experiment, biochar application significantly improved fresh weight yield, with the biochar-treated group achieving a maximum of 83.3 g pot− 1 in the first cropping season, compared to 62.8 g pot− 1 in the NPK-only treatment group. However, excessive biochar application rates (≥ 800 kg ha⁻¹) led to yield reductions in the second cropping season, likely due to increased soil pH and EC. These results suggest the potential of recycling greenhouse crop residues into biochar to enhance soil fertility and crop productivity while indicating the need to manage application rates to minimize negative impacts from excessive use.
Inflammasomes in neurodegenerative diseases
Authors: Wang Qianchen , Yang Songwei , Zhang Xuan , Zhang Shanshan , Chen Liping , Wang Wanxue , Chen Naihong , Yan Jiaqing 
Published: December 2024

Abstract
Inflammasomes represent a crucial component of the innate immune system, which respond to threats by recognizing different molecules. These are known as pathogen-associated molecular patterns (PAMPs) or host-derived damage-associated molecular patterns (DAMPs). In neurodegenerative diseases and neuroinflammation, the accumulation of misfolded proteins, such as beta-amyloid and alpha-synuclein, can lead to inflammasome activation, resulting in the release of interleukin (IL)-1β and IL-18. This activation also induces pyroptosis, the release of inflammatory mediators, and exacerbates neuroinflammation. Increasing evidence suggests that inflammasomes play a pivotal role in neurodegenerative diseases. Therefore, elucidating and investigating the activation and regulation of inflammasomes in these diseases is of paramount importance. This review is primarily focused on evidence indicating that inflammasomes are activated through the canonical pathway in these diseases. Inflammasomes as potential targets for treating neurodegenerative diseases are also discussed.
Staging value creation processes in short food supply chains of Italy
Authors: De Rosa Marcello , Charatsari Chrysanthi , Lioutas Evagelos D. , Vecchio Yari , Masi Margherita 
Published: December 2024

AbstractFarmers’ markets, as a short food supply chain system, are considered schemes that can contribute to local development, producing economic, environmental, and social value. These three facets of value can set the stage for building up the farmers' market value proposition. In the present study, we use the theoretical concept of the territorial staging system to identify farmers’ markets as sociotechnical contexts where producers and consumers interact to provide experiential resources and experiential engagement. This paper focused on the supply side of the proposed framework: by interviewing farmers markets’ directors and producers, an empirical analysis has been carried out with the purpose of identifying how these actors evaluate the three facets of value (economic, social, and environmental). The results show that, while directors emphasize economic value, farmers attribute higher importance to the environmental and, especially, social facet of value. These findings, which represent a primary research step that includes the consumers' contribution to the stage setting, highlight the diverging views of the actors involved. Results suggest that developing a stage that enhances consumer experience is a complex process and requires understanding different viewpoints.