bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ezabenlimab (BI 754091), an anti-PD-1 antibody, in patients with advanced solid tumours
Authors: Patel Manish R. , Johnson Melissa , Winer Ira , Arkenau Hendrik-Tobias , Cook Natalie , Samouëlian Vanessa , Aljumaily Raid , Kitano Shigehisa , Duffy Christine , Ge Miaomiao , Elgadi Mabrouk , Siu Lillian L. 
Published: March 2024

Abstract
Background
Ezabenlimab (BI 754091) is a humanised monoclonal antibody targeting programmed cell death protein-1. We report results from open-label, dose-escalation/expansion, Phase I trials that evaluated the safety, maximum tolerated dose (MTD), pharmacokinetics and antitumour activity of ezabenlimab at the recommended Phase II dose in patients with selected advanced solid tumours.

Study design
Study 1381.1 (NCT02952248) was conducted in Canada, the United Kingdom and the United States. Study 1381.4 (NCT03433898) was conducted in Japan. Study 1381.3 (NCT03780725) was conducted in the Netherlands. The primary endpoints were: number of patients experiencing dose-limiting toxicities (DLTs) in the first cycle (dose escalation parts), number of patients with DLTs during the entire treatment period and objective response (dose expansion part of Study 1381.1).

Results
Overall, 117 patients received ezabenlimab intravenously every 3 weeks (80 mg, n = 3; 240 mg, n = 111; 400 mg, n = 3). No DLTs were observed and the MTD was not reached. Fifty-eight patients (52.3%) had grade ≥ 3 adverse events, most commonly anaemia (10.8%) and fatigue (2.7%). In 111 assessed patients treated with ezabenlimab 240 mg, disease control rate was 56.8% and objective response rate was 16.2%. Three patients had complete response; at data cut-off (November 2021) one remained in response and was still receiving ongoing treatment (duration of response [DoR]: 906 days). Partial responses occurred across several tumour types; DoR ranged from 67 to 757 days.

Conclusions
Ezabenlimab was well tolerated and associated with durable antitumour activity in multiple solid tumours, comparable to other immune checkpoint inhibitors in similar patient populations and treatment settings.
TGF-β1 and TGF-βR1 variants are associated with clinical outcomes in smoking-related head and neck cancer patients treated with chemoradiation through modulating microRNA-mediated regulation
Authors: Niu Zihao , Sun Peng , Zafereo Mark E. , Liu Hongliang , Wei Peng , Wu Jia , Gross Neil D. , Shete Sanjay , Wei Qingyi , Zheng Guibin , Sikora Andy G. , Calin George A. , Li Guojun 
Published: March 2024

AbstractTGF-β1 and TGF-βR1 play important roles in immune and inflammatory responses. Genetic variants of TGF-β1 rs1800470 and TGF-βR1 rs334348 have emerged as potentially prognostic biomarkers for HPV-related head and neck cancer, while their prognostic effect on survival of smoking-related head and neck cancer remains unknown. This study included 1403 patients with smoking-related head and neck cancer, and all these patients were genotyped for TGF-β1 rs1800470 and TGF-βR1 rs334348. Both univariate and multivariate analyses were performed to evaluate associations between the two functional genetic variants in microRNA binding sites of TGF-β1 and TGF-βR1 and survivals. Patients with TGF-β1 rs1800470 CT or CC genotype had 30–35% risk reductions for OS, DSS, and DFS compared to patients with TT genotype among overall patients, ever smokers, and patients administered chemoradiation. Furthermore, patients with TGF-βR1 rs334348 GA or GG genotype had significant 50–60% risk reductions for OS, DSS, and DFS compared to patients with AA genotype among overall patients and patients administered chemoradiation; among ever smokers, the risk reductions even reached 60–70%. The TCGA dataset was used for validation. These findings suggest that TGF-β1 rs1800470 and TGF-βR1 rs334348 significantly affect survival outcomes in patients with smoking-related head and neck cancer, especially in the subgroups of ever smokers and patients treated with chemoradiation. These genetic variants may serve as prognostic indicators for patients with smoking-related head and neck cancer and could play a role in advancing the field of personalized chemoradiation, thereby improving patient survival and quality of life.
The ERUS course on robot-assisted kidney transplantation
Authors: Campi Riccardo , Pecoraro Alessio , Piramide Federico , Gallo Maria Lucia , Serni Sergio , Mottrie Alex , Territo Angelo , Decaestecker Karel , Breda Alberto ,   On behalf of the European Association of Urology (EAU) Robotic Urology Section (ERUS) Robot-assisted Kidney Transplantation working group
Published: March 2024

Abstract
Purpose
Robot-assisted kidney transplantation (RAKT) is being increasingly performed at selected referral institutions worldwide. Yet, surgical training in RAKT is still unstructured and not grounded into formal credentialing courses including simulation, lab facilities, and modular training with animal models. As such, developing standardized, modular training programs is warranted to provide surgeons with the RAKT-specific skillset needed for a “safe” learning curve.

Methods
The 3-day course on RAKT developed at the EAU Skills Center in Orsi Academy was designed as a standardized, modular, step-by-step approach aiming to provide theoretical and practical skills. The course is held by expert proctors with extensive experience in RAKT. To maximize the course’s usefulness, a solid knowledge of robotics and transplantation is desirable for participants.

Results
From January 2016 to July 2023, 87 surgeons from 23 countries (of which 36% from extra-European countries) participated in the RAKT course performed at the EAU Skills Center in Orsi Academy. Of these, 58/87 (67%) were urologists, while 27/87 (31%) were general surgeons and 2/87 (2%) were vascular surgeons. To date, 18 participants (20.6%) are actively involved in RAKT programs at institutions included in the European Association of Urology (EAU) Robotic Urology Section (ERUS)–RAKT network.

Conclusion
Leveraging the potential of simulation, wet-lab training, live porcine models, and experienced proctors, the RAKT course performed at the EAU Skills Center in Orsi Academy represents the first structured teaching effort aiming to offer surgeons a full immersion in RAKT to train the core technical skills.
Impartiality and relative utilitarianism
Authors: Karni Edi , Weymark John A. 
Published: March 2024

AbstractA novel axiomatization of relative utilitarianism is provided using the single-profile setting used in Harsanyi’s Social Aggregation Theorem. Harsanyi’s axioms are supplemented with an impartiality axiom that requires social alternative lotteries p and q to be socially indifferent when (i) two individuals have conflicting preferences for them and everybody else is indifferent and (ii) the concerned individuals’ strengths of preference for p over q have the same magnitude. This axiomatization shows that equality of the social weights can be obtained in a single-profile setting and that no interprofile condition is needed to obtain profile-independent weights in a multi-profile setting.
Impact of the medial displacement calcaneal osteotomy on foot biomechanics: a systematic literature review
Authors: Mueller Gunnar , Frosch Karl-Heinz , Barg Alexej , Schlickewei Carsten , Weel Hanneke , Krähenbühl Nicola , Priemel Matthias , Mueller Elena 
Published: March 2024

Abstract
Introduction
Progressive collapsing foot deformity (PCFD), formally known as “adult-acquired flatfoot deformity” (AAFFD), is a complex foot deformity consisting of multiple components. If surgery is required, joint-preserving procedures, such as a medial displacement calcaneal osteotomy (MDCO), are frequently performed. The aim of this systematic review is to provide a summary of the evidence on the impact of MDCO on foot biomechanics.

Materials and methods
A systematic literature search across two major sources (PubMed and Scopus) without time limitation was performed according to the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) criteria. Only original research studies reporting on biomechanical changes following a MDCO were included. Exclusion criteria consisted of review articles, case studies, and studies not written in English. 27 studies were included and the methodologic quality graded according to the QUACS scale and the modified Coleman score.

Results
The 27 included studies consisted of 18 cadaveric, 7 studies based on biomechanical models, and 2 clinical studies. The impact of MDCO on the following five major parameters were assessed: plantar fascia (n = 6), medial longitudinal arch (n = 9), hind- and midfoot joint pressures (n = 10), Achilles tendon (n = 5), and gait pattern parameters (n = 3). The quality of the studies was moderate to good with a pooled mean QUACS score of 65% (range 46–92%) for in-vitro and a pooled mean Coleman score of 58 (range 56–65) points for clinical studies.

Conclusion
A thorough knowledge of how MDCO impacts foot function is key in properly understanding the postoperative effects of this commonly performed procedure. According to the evidence, MDCO impacts the function of the plantar fascia and Achilles tendon, the integrity of the medial longitudinal arch, hind- and midfoot joint pressures, and consequently specific gait pattern parameters.
Health-related quality of life (EQ-5D) after revision arthroplasty following periprosthetic femoral fractures Vancouver B2 and B3 in geriatric trauma patients
Authors: Pavlović Melina , Bliemel Christopher , Ketter Vanessa , Lenz Julia , Ruchholtz Steffen , Eschbach Daphne 
Published: March 2024

Abstract
Introduction
The aim of this study was to determine the outcome parameters of revision arthroplasties for periprosthetic femoral fractures (PPFF) with a particular attention to quality of life (QoL) and mobility.

Materials and methods
Retrospective single-center study of PPFF with loose implants that underwent revision arthroplasty. Depending on individual patient characteristics, either an uncemented or cemented revision stem was chosen. Data collection included demographics, complications, clinical course and outcome parameters. Follow-up took place at least one year postoperatively.

Results
Between 2008 and 2016, 43 patients could be included. Most patients (63%) were able to walk independently or with a walking aid after one year and amongst the surveyed patients 77% were able to reside at home. Concerning the QoL assessment, a high index of 0.8 ± 0.1 has been reached after one year. Mortality pointed out to be 9% after one year and 28% in general.

Conclusion
The treatment of PPFF remains challenging. Although complication rates and mortality are high in this frail collective of geriatric patients, revision arthroplasty leads to good postoperative results regarding mobility and quality of life.
Li concentration change around Cu/LiPON interface measured by TOF-ERDA
Authors: Kurihara Kyoshi , Nakamizo Shuri , Yamamoto Satoshi , Yasuda Keisuke , Majima Takuya , Yajima Takeshi , Iriyama Yasutoshi 
Published: March 2024

AbstractLithium metal is a promising anode material for the development of advanced all-solid-state batteries (ASSBs) with high energy density. Among the various solid electrolytes, lithium phosphorus oxynitride glass electrolyte (LiPON) is notable for facilitating stable Li plating-stripping reactions in ASSBs employing Li metal. The aim of this study is to examine the Li/LiPON interface, with a specific emphasis on the reductive decomposition of LiPON near this interface. We employed time-of-flight elastic recoil detection analysis (TOF-ERDA) to assess changes in Li concentration around the Cu/LiPON interface immediately prior to the Li plating reaction. Our electrochemical measurements indicate that critical decomposition of LiPON occurs when the voltage at the Cu electrode is reduced to 0.1 V vs. Li/Li+ at 25 °C, resulting in the in situ formation of Li3P operating at 0.7 V vs. Li/Li+ as an anode material. The TOF-ERDA findings reveal that this decomposition reaction results in a layer with partial decomposition (ranging from 5 to 25% on average) extending up to approximately 30 nm from the Cu/LiPON interface. This insight is vital for enhancing the design and performance of ASSBs.
Graphical abstract
Development and validation of a novel prognostic nomogram for advanced diffuse large B cell lymphoma
Authors: Wan Mengdi , Zhang Wei , Huang He , Fang Xiaojie , Chen Yungchang , Tian Ying , Yao Yuyi , Weng Huawei , Chen Zegeng , Yu Le , Tian Yuke , Huang Huageng , Li Xudong , Hong Huangming , Lin Tongyu 
Published: March 2024

AbstractAdvanced diffuse large B cell lymphoma (DLBCL) is a common malignant tumor with aggressive clinical features and poor prognosis. At present, there is lack of effective prognostic tool for patients with advanced (stage III/IV) DLBCL. The aim of this study is to identify prognostic indicators that affect survival and response and establish the first survival prediction nomogram for advanced DLBCL. A total of 402 patients with advanced DLBCL were enrolled in this study. COX multivariate analysis was used to obtain independent prognostic factors. The independent prognostic factors were included in the nomogram, and the nomogram to predict the performance of the model was established by R rms package, C-index (consistency index), AUC curve and calibration curve. The training and validation cohorts included 281 and 121 patients. In the training cohort, multivariate analysis showed that Ki-67 (70% (high expression) vs ≤ 70% (low expression), p < 0.001), LDH (lactate dehydrogenase) (elevated vs normal, p = 0.05), FER (ferritin) (elevated vs normal, p < 0.001), and β2-microglobulin (elevated vs normal, p < 0.001) were independent predictors and the nomogram was constructed. The nomogram showed that there was a significant difference in OS among the low-risk, intermediate-risk and high-risk groups, with 5-year survival rates of 81.6%, 44% and 6%, respectively. The C-index of the nomogram in the training group was 0.76. The internal validation of the training group showed good consistency. In the internal validation cohort of the training group, the AUC was 0.828, and similar results were obtained in the validation group, with a C-index of 0.74 and an AUC of 0.803. The proposed nomogram provided a valuable individualized risk assessment of OS in advanced DLBCL patients.
Novel microbial synthesis of titania nanoparticles using probiotic Bacillus coagulans and its role in enhancing the microhardness of glass ionomer restorative materials
Authors: Mansoor Afsheen , Mansoor Emaan , Mehmood Mazhar , Hassan Syed Mujtaba Ul , Shah Atta Ullah , Asjid Uzma , Ishtiaq Muhammad , Jamal Asif , Rai Akhilesh , Palma Paulo J. 
Published: March 2024

AbstractDental caries is a commonly occurring non-communicable disease throughout the world that might compromise the quality of any individual’s life. Glass ionomer cements (GIC) are the most acceptable restorative materials due to their ease of manipulation, minimal tooth loss and least invasive strategy; however, they lack mechanical stability that has become a point of concern. Nanoparticles (NPs) are an outstanding option for modifying and enhancing the properties of dental materials. The focus of this study was to prepare novel, biocompatible titania dioxide (TiO2) NPs as a dental-restorative material using an efficient probiotic Bacillus coagulans. The prepared NPs were incorporated into glass ionomer restorative material at varying concentrations and investigated for cell viability percentage, microhardness and surface morphology. Results indicated that pure 100% anatase phase TiO2 NPs with particle size of 21.84 nm arranged in smooth, spherical agglomerates and clusters forms. These NPs depicted cell viability > 90%, thus confirming their non-cytotoxic behavior. GIC restorative materials reinforced by 5% titania (TiO2) NPs demonstrated the highest microhardness in comparison to the control group and other experimental groups of the study. Surface morphology analysis revealed a reduction in cracks in this novel dental-restorative material supporting its compatible biological nature with better hardness strength and negligible crack propagation. Overall, these results indicated that TiO2 NPs produced using a biological approach could be easily used as restorative materials in dental applications.
Graphical Abstract
Protecting breeding sites: a critical goal for the conservation of the golden eagle in Mexico under global change scenarios
Authors: Gama-Rodríguez Andrea M. , García Juan A. , Lozano Luis F. , Prieto-Torres David A. 
Published: March 2024

AbstractImpacts of global climate and land‐use changes on distribution patterns and breeding sites remain today poorly studied for several vulnerable emblematic bird species, including the Golden Eagle (Aquila chrysaetos). Herein, we analyzed the potential effect of global climate changes and agricultural activities on the distribution patterns of this top predator across Mexico. We assessed the long-term role of protected areas (PAs) for safeguarding the species’ overall distribution and its breeding sites. We evaluated current and future (2040s, 2060s, and 2080s) threats from global change using ecological niche modeling and geographic information system approaches to determine the percentage of the species’ distribution area that overlaps with highly human-modified areas and PAs under each climate scenario. We also used niche overlap tests to assess whether the species’ breeding sites show equivalence or similarity of climatic conditions over time. Our findings revealed shifts in the Golden Eagle’s distributional area, with an overall size reduction (by ~ 57% in the 2040s and ~ 78% in the 2080s) due to future environmental changes, mainly attributable to increasingly dry and warm conditions. Mexican PAs cover ~ 12% of the Golden Eagle’s range across country, but this decreased by > 33% on average under the species’ future distributions. Although the hypothesis of equivalent climatic conditions at breeding sites over time was rejected, those sites did have long-term climate similarity (niche overlap: 0.75–0.83; P < 0.05). Considering the species’ nest site fidelity and that colonization of new areas within Mexico seems unlikely, protection of these breeding sites is a critical step for the long-term conservation of this emblematic species in Mexico.
Substrate-borne vibrations produced during the interaction with natural enemies alter aphids probing behavior
Authors: Zippari Caterina , Nieri Rachele , Hamouche Zeinab , Boucherf Abderrahmane , Tamburini Giovanni , Anfora Gianfranco , Verrastro Vincenzo , Mazzoni Valerio , Cornara Daniele 
Published: March 2024

AbstractThe “ecology of fear”, i.e., physiological and behavioral alterations displayed by pests in response to predation risk, has recently been proposed as a sustainable alternative to chemicals for pest control. However, the development of such a strategy requires a detailed understanding of the signals and cues underlying the pest-antagonist interaction and eliciting the prey behavioral alteration. Here, we characterized the substrate-borne vibrations produced during the interaction between the green peach aphid Myzus persicae and its antagonists, the parasitoid wasp Aphidius colemani and the ladybug Adalia bipunctata. Thereafter, coupling the electrical penetration graph (EPG) with a stimulus controller, we evaluated whether the playback of the vibrations, alone and in combination with the alarm pheromone, impacted aphid probing behavior and interaction with the host plant. Aphids responded to vibrations exhibiting longer non-probing, shorter intracellular probes, i.e. the behavior through which the insect evaluates host plant quality, delay in accessing the phloem vessels and decrease of the frequency of phloem salivation events. In contrast, on plants treated with the alarm pheromone, insects displayed longer intracellular probes. We hypothesize that the alarm pheromone, signaling a distant threat, might induce a careful evaluation of the host plant in order to decide the magnitude of the reaction. On the other hand, vibrations might indicate a closely approaching threat pushing the aphid to rush the host evaluation process and the whole feeding process. The possible repercussion of the behavioral alterations observed on the dynamics of aphid-borne plant virus transmission is also discussed.
Physical decomposition stage and ergosterol content predict the chemical composition of downed dead wood in Mediterranean dehesas
Authors: Micó Estefanía , Aguirrebengoa Martin , Quinto Javier , Juárez Margarita , Marmaneu José , Sánchez Antonio 
Published: March 2024

AbstractDead wood is a key substrate of forests that plays an important role in fertility and productivity. However, dead wood is scarce in traditionally managed forests like Mediterranean dehesas. The chemical composition of downed dead wood in Quercus pyrenaica dehesas was analysed in different physical decomposition stages as a proxy of dead wood decay length. We also assessed the contribution of fungal activity, by quantifying ergosterol, to the chemical composition of deadwood. Chemical analyses included elemental composition determination, thermogravimetry and infrared spectroscopy. Our results showed that both the physical decomposition stage and ergosterol content extensively predicted the chemical composition of Q. pyrenaica dead wood decay processes under field conditions. The physical stage was a better predictor of the C/P ratio and polysaccharides proportion, while ergosterol better predicted P content and the N/P ratio. In other cases like lignin, the relation between ergosterol content and chemical composition varied depending on the physical stage. In addition, environmental local factors differentially affected chemical composition across physical decomposition stages. We conclude that the physical decomposition stage and ergosterol content complementarily contribute to estimate the temporal behaviour of the chemical composition of dead wood in Mediterranean areas. Moreover, we recommend using the FT-IR analysis to assess the nature of temporal chemical changes in downed dead wood. Finally, our study claims to consider the potential impact of local environmental factors, such as air temperature and relative humidity, on dead wood decay processes in traditionally managed forests in the current global change scenario.