bluuebunny/crossref_metadata_2025_split huggingface dataset:
Co-occurrence of mycotoxins and other fungal metabolites in total mixed rations of cows from dairy farms in Punjab, Pakistan
Authors: Penagos-Tabares Felipe , Mahmood Mubarik , Khan Muhammad Zafar Ullah , Talha Hafiz Muhammad Amjad , Sajid Muhammad , Rafique Kanwal , Naveed Saima , Faas Johannes , Artavia Juan Ignacio , Sulyok Michael , Müller Anneliese , Krska Rudolf , Zebeli Qendrim 
Published: September 2023

AbstractAfter India and the USA, Pakistan is the third country leading in global dairy production, a sector of very high socioeconomic relevance in Asia. Mycotoxins can affect animal health, reproduction and productivity. This study analysed a broad range of co-occurring mycotoxins and fungal secondary metabolites derived from Alternaria, Aspergillus, Fusarium, Penicillium and other fungal species. To complete this, a validated multi-metabolite liquid chromatography/electrospray ionization-tandem mass spectrometric (LC/ESI–MS/MS) method was employed, detecting 96 of > 500 tested secondary fungal metabolites. This first preliminary study demonstrated that total mixed rations (TMRs) (n = 30) from big commercial dairy cattle farms (> 200 lactating cows) in Punjab, Pakistan, presented ubiquitous contamination with mixtures of mycotoxins. The mean of mycotoxins per sample was 14, ranging from 11 to 20 mycotoxins among all TMR samples. Metabolites derived from other fungi and Fusarium spp. showed the highest levels, frequency and diversity among the detected fungal compounds. Among the most prevalent mycotoxins were Fusarium toxins like fumonisins B1 (FB1) (93%), B2 (FB2) (100%) and B3 (FB3) (77%) and others. Aflatoxin B1 (AFB1) was evidenced in 40% of the samples, and 7% exceeded the EU maximum limit for feeding dairy cattle (5 µg/kg at 88% dry matter). No other mycotoxin exceeds the EU guidance values (GVs). Additionally, we found that dietary ingredients like corn grain, soybean meal and canola meal were related to increased contamination of some mycotoxins (like FB1, FB2 and FB3) in TMR from the province of Punjab, Pakistan. Among typical forage sources, the content of maize silage was ubiquitous. Individually, the detected mycotoxins represented relatively low levels. However, under a realistic scenario, long-term exposure to multiple mycotoxins and other fungal secondary metabolites can exert unpredictable effects on animal health, reproduction and productivity. Except for ergot alkaloids (73%), all the groups of metabolites (i.e. derived from Alternaria spp., Aspergillus spp., Fusarium spp., Penicillium spp. and other fungi) occurred in 100% of the TMR samples. At individual levels, no other mycotoxins than AFB1 represented a considerable risk; however, the high levels of co-occurrence with several mycotoxins/metabolites suggest that long-term exposure should be considered because of their potential toxicological interactions (additive or synergistic effects).
Natural killer cells modified with a Gpc3 aptamer enhance adoptive immunotherapy for hepatocellular carcinoma
Authors: Zheng Youshi , Lai Zisen , Wang Bing , Wei Zuwu , Zeng Yongyi , Zhuang Qiuyu , Liu Xiaolong , Lin Kecan 
Published: September 2023

Abstract
Introduction
Natural killer cells can attack cancer cells without prior sensitization, but their clinical benefit is limited owing to their poor selectivity that is caused by the lack of specific receptors to target tumor cells. In this study, we aimed to endow NK cells with the ability to specifically target glypican-3+ tumor cells without producing cell damage or genetic alterations, and further evaluated their therapeutic efficiency.

Methods
NK cells were modified with a Gpc3 DNA aptamer on the cell surface via metabolic glycoengineering to endow NK cells with specific targeting ability. Then, the G-NK cells were evaluated for their specific targeting properties, cytotoxicity and secretion of cytokines in vitro. Finally, we investigated the therapeutic efficiency of G-NK cells against glypican-3+ tumor cells in vivo.

Results
Compared with NK cells modified with a random aptamer mutation and unmodified NK cells, G-NK cells induced significant apoptosis/necrosis of GPC3+ tumor cells and secreted cytokines to preserve the intense cytotoxic activities. Moreover, G-NK cells significantly suppressed tumor growth in HepG2 tumor-bearing mice due to the enhanced enrichment of G-NK cells at the tumor site.

Conclusions
The proposed strategy endows NK cells with a tumor-specific targeting ability to enhance adoptive therapeutic efficiency in GPC3+ hepatocellular carcinoma.
Re-immunotherapy with nivolumab plus ipilimumab in advanced non-small cell lung cancer patients previously treated with anti-programmed death-1 and/or anti-programmed death ligand-1 antibodies
Authors: Imakita Takuma , Fujita Kohei , Ito Takanori , Saito Zentaro , Oi Issei , Kanai Osamu , Tachibana Hiromasa , Sawai Satoru , Mio Tadashi 
Published: September 2023

Abstract
Background
The role of re-immunotherapy in advanced non-small cell lung cancer (NSCLC) remains unclear. No studies have evaluated the re-immunotherapy regimen including anti-cytotoxic T-lymphocyte antigen-4 antibody for lung cancer treatment. This study aimed to investigate the efficacy and safety of re-immunotherapy with nivolumab plus ipilimumab in patients with advanced NSCLC previously treated with anti-programmed death-1 (PD-1) and/or anti-programmed death ligand-1 (PD-L1) antibodies.

Methods
We retrospectively reviewed patients with advanced or recurrent NSCLC who received immunotherapy with nivolumab plus ipilimumab (without concomitant cytotoxic chemotherapy) between November 2020 and November 2022 at the National Hospital Organization Kyoto Medical Center, Kyoto, Japan. Data were extracted from patients who had previously received immunotherapies with anti-PD-1 and/or anti-PD-L1 antibodies. Treatment responses and adverse events were evaluated.

Results
Of the 67 patients who received immunotherapy with nivolumab plus ipilimumab, 23 were included in final analysis. The objective response rate was 17%, and the disease control rate was 48% for nivolumab plus ipilimumab therapy. The highest grade of immune-related adverse events was grade 3, occurring in 11% of cases.

Conclusion
Re-immunotherapy with nivolumab plus ipilimumab after anti-PD-1 and/or anti-PD-L1 immunotherapy may be feasible and provide clinical benefit in selected patients. Further prospective studies are warranted to identify the patient population that may benefit from re-immunotherapy.
Immune checkpoint inhibitors combined with or without radio(chemo)therapy for locally advanced or recurrent/metastatic esophageal squamous cell carcinoma
Authors: Zhao Xiao-Han , Gao Hong-Mei , Wen Jing-Yuan , Wang He-Song , Wu Luan-Ying , Song Chun-Yang , Deng Wen-Zhao , Zhu Shu-Chai , Shen Wen-Bin 
Published: September 2023

Abstract
Objective
This study was designed to investigate the efficacy and prognostic factors for immune checkpoint inhibitors (ICIs) combined with or without radio(chemo)therapy and to evaluate their toxicity in patients with locally advanced or recurrent/metastatic esophageal squamous cell carcinoma (LA/RM ESCC).

Methods
In this study, 198 patients with locally advanced or recurrent/metastatic (LA/RM) ESCC who received ICIs combined with or without radiotherapy/chemotherapy in the Department of Radiotherapy of the Fourth Hospital of Hebei Medical University were retrospectively analyzed. Univariate and multivariate analyses were performed to determine the prognostic factors for overall survival (OS) and progression free survival (PFS). The factors affecting treatment response and the occurrences of treatment-related adverse events (trAEs) were analyzed.

Results
The median OS and PFS were 30.4 months (95% confidence interval [CI] 15.1–45.7 months) and 15.3 months (95% CI 12.8–17.8 months), respectively. Univariate and multivariate analysis showed that the number of ICI cycles, the intervention of radiotherapy and dysphagia were independent factors affecting OS (Hazard ratio [HR] = 0.39, 2.043 and 0.365, respectively; P = 0.018, 0.001 and 0.032, respectively). The intervention of radiotherapy was an independent factor for PFS (hazard ratio [HR] = 18.149, P = 0.013). The median OS and PFS for patients who had complete response and partial response (Objective response, ORR) were 50.8 months (95% CI 25.8–75.7 months) and 20.5 months (95% CI 14.1–27.0), respectively, which were significantly higher than those in the non-ORR group (OSnon-ORR:17.5 months, 95% CI 14.0–21.0; χ2 = 13.881, P < 0.001; PFSnon-ORR: 12.1 months, 95% CI 10.1–14.1, χ2 = 10.676, P = 0.001). The intervention of radiotherapy could improve treatment response (χ2 = 47.725, P = 0.000). In entire study population, 83 patients (41.9%) had ≥ grade 2 trAEs.

Conclusions
ICIs combined with radiotherapy/chemotherapy are safe and effective in LA/RM ESCC patients. Intervention of radiotherapy, the number of immunotherapy cycles and occurrence of dysphagia affecting the overall survival of LR/RM ESCC patients. Intervention of radiotherapy was an independent prognosis factor for OS and PFS and associated with better treatment response.
The role of conservation agriculture practices in mitigating N2O emissions: A meta-analysis
Authors: Li Yue , Chen Ji , Drury Craig F. , Liebig Mark , Johnson Jane M. F. , Wang Zhaozhi , Feng Hao , Abalos Diego 
Published: September 2023

Abstract Conservation agriculture is often assumed to reduce soil N2O emissions. Yet, studies analyzing the specific effect of conservation agriculture practices on N2O emissions give contradictory results. Herein, we synthesized a comprehensive database on the three main conservation agriculture practices (cover crops, diversified crop rotations, and no-till and/or reduced tillage (NT/RT)) to elucidate the role of conservation practices on N2O emissions. Further, we used a random meta-forest approach to identify the most important predictors of the effects of these practices on soil N2O emissions. Averaged across all comparisons, NT/RT significantly decreased soil N2O emissions by 11% (95% CI: –19 to –1%) compared to conventional tillage. The reductions due to NT/RT were more commonly observed in humid climates and in soils with an initial carbon content < 20 g kg–1. The implementation of cover crops and diversified crop rotations led to variable effects on soil N2O emissions. Cover crops were more likely to reduce soil N2O emissions at neutral soil pH, and in soils with intermediate carbon (~20 g kg–1) and nitrogen (~3 g kg–1) contents. Diversified crop rotations tended to increase soil N2O emissions in temperate regions and neutral to alkaline soils. Our results provide a comprehensive predictive framework to understand the conditions in which the adoption of various conservation agriculture practices can contribute to climate change mitigation. Combining these results with a similar mechanistic understanding of conservation agriculture impacts on ecosystem services and crop production will pave the way for a wider adoption globally of these management practices.
Creating equality through differentiation in doping control
Authors: Viret Marjolaine , Saugy Martial , Botrè Francesco 
Published: September 2023

AbstractAwareness of human rights and related principles, such as equality and non-discrimination, is growing in sports. While debates on doping regulation typically target the contours of the prohibition and the sanctioning regime, much less attention has been given to how anti-doping detection impacts the level playing field, i.e. whether equality is realised in the manner in which the substances and methods are detected in athletes’ samples, or whether athletes are all equal when it comes to the analytical cut-offs that the regulations set. This article seeks to fill this gap and explores the implications of differentiation—or non-differentiation—in anti-doping detection for principles of equality and non-discrimination. After discussing notions related to equality in anti-doping detection, the article presents case studies from current anti-doping analytics, to make differentiation in that context tangible. Based on case law of the European Court of Human Rights, the Swiss Supreme Court and the Court of Arbitration for Sport, we submit that anti-doping authorities should resort to an operational ‘discrimination test’ when drafting technical regulation for anti-doping, in order to incorporate these principles ‘by design’ into the detection system. The article also demonstrates that—apparently—technical rules are not value-neutral, but that scientific data and policy choices are entwined in a way that warrants debate on the political scene, and creates duties of transparency and justification on part of the decision-makers.
Essential steps in primary care management of older people with Type 2 diabetes: an executive summary on behalf of the European geriatric medicine society (EuGMS) and the European diabetes working party for older people (EDWPOP) collaboration
Authors: Bourdel-Marchasson Isabelle , Maggi Stefania , Abdelhafiz Ahmed , Bellary Sri , Demurtas Jacopo , Forbes Angus , Ivory Philip , Rodríguez-Mañas Leocadio , Sieber Cornel , Strandberg Timo , Tessier Daniel , Vergara Itziar , Veronese Nicola , Zeyfang Andrej , Christiaens Antoine , Sinclair Alan 
Published: September 2023

AbstractWe present an executive summary of a guideline for management of type 2 diabetes mellitus in primary care written by the European Geriatric Medicine Society, the European Diabetes Working Party for Older People with contributions from primary care practitioners and participation of a patient’s advocate. This consensus document relies where possible on evidence-based recommendations and expert opinions in the fields where evidences are lacking. The full text includes 4 parts: a general strategy based on comprehensive assessment to enhance quality and individualised care plan, treatments decision guidance, management of complications, and care in case of special conditions. Screening for frailty and cognitive impairment is recommended as well as a comprehensive assessment all health conditions are concerned, including end of life situations. The full text is available online at the following address: essential_steps_inprimary_care_in_older_people_with_diabetes_-_EuGMS-EDWPOP___3_.pdf.
Mesoscopic study on instability characteristics of residual coal pillars–roof system based upon domino effect in pillar goaf
Authors: Wang Zhiqiang , Li Jingkai , Lin Lu , Liu Binyu , Ushakov Ivan 
Published: September 2023

AbstractThe stability of pillar goaf is affected by the composite structure composed of residual coal pillars and roof, it is necessary to study the instability characteristics of residual coal pillars–roof system. Double coal pillar–roof combined bodies were constructed based on single coal pillar–roof combined body to characterize coal pillars–roof system in this paper. Through particle flow code (PFC), the instability modes of single combined body and double combined bodies with different combinations under uniaxial compression were studied from a mesoscopic perspective. With that, the instability criterions of double combined bodies were analyzed theoretically. The results show that the damage of single combined body and double combined bodies both have domino—type characteristics. During the single combined body is compressed, coal is broken firstly and induces rock damage. Meanwhile, the rock damage aggravates the destruction of coal in turn. Finally, the overall body loses bearing capacity based upon domino effect. During the double combined bodies with same mechanical properties are compressed, the component bodies bear the external load evenly and deform harmoniously. During the double bodies with different mechanical properties are compressed, the low-strength component body is destroyed and reaches its bearing limit firstly. Synchronously, the whole system reaches the bearing peak. Thereafter, the external load originally borne by low-strength body gradually transfers to high-strength body. The high-strength body also reaches the bearing limit over time, and the second bearing peak appears synchronously for the whole system. The instability of a single coal pillar is the initial cause of the instability of the whole coal pillars–roof system. The instability of any single component body can be regarded as the overall instability criterion for double bodies with same properties, while the instability of the single component body with high strength should be regarded as the instability criterion for double bodies with different properties.
Long-term strength and durability performance of eco-friendly concrete with supplementary cementitious materials
Authors: Miah Md Jihad , Huaping Ren , Paul Suvash Chandra , Babafemi Adewumi John , Li Ye 
Published: September 2023

AbstractResearch has shown that adding supplementary cementitious materials (SCMs), such as fly ash (FA) and slag (SL), to concrete improves its mechanical and durability properties up to certain limits. However, the long-term performance of concrete made with FA and SL is not fully known. This study investigates the impact of FA and SL on the long-term (up to 900 days) performance of concrete. The concrete specimens were made with six replacement percentages (0, 10, 20, 30, 45 and 60 by weight) of ordinary Portland cement (OPC). The short-term fresh and hardened properties of all concrete mixes were assessed after 14, 28, 60, and 90 days of water curing. After 120, 365, 730, and 900 days of water curing, the long-term performance was investigated for 100% OPC (control), 30% FA, and 30% SL concretes. At 28 days, no significant difference in strength development was observed for the concrete mixes containing up to 30% FA and 30% SL than the control concrete (100% OPC). In contrast, a remarkable enhancement in strength development was registered for all mixes containing up to 30% FA and 30% SL at 60 and 90 days of tests. Likewise, 30% FA and 30% SL showed the lowest porosity and water absorption than the control. The mechanical strength of concrete prepared with 30% FA and 30% SL gradually rises over time (from 14 to 900 days) compared to the control concrete. With increasing concrete age, a reduction in porosity and capillary water absorption was seen (up to 900 days).
Real-world data in rheumatoid arthritis: patient similarity networks as a tool for clinical evaluation of disease activity
Authors: Janca Ondrej , Ochodkova Eliska , Kriegova Eva , Horak Pavel , Skacelova Martina , Kudelka Milos 
Published: September 2023

AbstractHospital databases provide complex data on individual patients, which can be analysed to discover patterns and relationships. This can provide insight into medicine that cannot be gained through focused studies using traditional statistical methods. A multivariate analysis of real-world medical data faces multiple difficulties, though. In this work, we present a methodology for medical data analysis. This methodology includes data preprocessing, feature analysis, patient similarity network construction and community detection. In the theoretical sections, we summarise publications and concepts related to the problem of medical data, our methodology, and rheumatoid arthritis (RA), including the concepts of disease activity and activity measures. The methodology is demonstrated on a dataset of RA patients in the experimental section. We describe the analysis process, hindrances encountered, and final results. Lastly, the potential of this methodology for future medicine is discussed.
Analysis of the international trade networks of COVID-19 medical products
Authors: Kurbucz Marcell T. , Sugár András , Keresztély Tibor 
Published: September 2023

AbstractThis research aimed to gain a deeper understanding of how and for what reasons the world trade networks of medical products were reorganized during the novel coronavirus (COVID-19) pandemic. To do this, first, the trade data of eight COVID-19-related product categories (such as medical test kits and protective garments) were collected for the years 2019 and 2020. Then it was examined which countries’ exports and imports changed the most between the studied time period in each product category. In addition, gravity models containing additional economic, geographic, and COVID-19-related variables were used to analyze the impact of the pandemic on the investigated trade networks. Based on the results, China achieved the highest cumulative export growth, surpassing the second-highest value by approximately 14.66. Hungary, with a population of only 9.7 million, stood out as a major importer of ventilators. Additionally, a higher incidence of COVID-19 among importers typically led to reduced traded values, while European Union membership and innovation capacity had the opposite effect.
Hybrid Additive Manufacturing of Forming Tools
Authors: Dardaei Joghan Hamed , Hölker-Jäger Ramona , Komodromos Anna , Tekkaya A. Erman 
Published: September 2023

AbstractAdditive manufacturing (AM) is widely used in the automotive industry and has been expanded to include aerospace, marine, and rail. High flexibility and the possibility of manufacturing complex parts in AM motivate the integration of additive manufacturing with classical forming technologies, which can improve tooling concepts and reduce costs. This study presents three applications of this integration. First, the possibility of successful utilization of selective laser melting for manufacturing extrusion tools with complex cooling channels and paths for thermocouples is reported, leading to significantly reduced inner die temperatures during the extrusion process. Second, sheet lamination is integrated with laser metal deposition (LMD) to manufacture deep-drawing dies. Promising results are achieved in reducing the stair step effect, which is the main challenge in sheet lamination, by LMD and following post-processing such as milling, ball burnishing, and laser polishing. The new manufacturing route shows that LMD can economically and efficiently reduce the stair step effect and omit the hardening step from the conventional manufacturing process route. Finally, LMD is used to manufacture a hot stamping punch with improved surface roughness by ball burnishing and near-surface complex cooling channels. The experimental results show that the manufactured punch has lower temperatures during hot stamping compared with the conventionally manufactured punch. This study shows the successful integration of AM processes with classical forming processes.