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Abstract Background and Objective Biological medicinal products improve patients’ lives, but access is limited, mainly due to high costs. Patents for many existing biological products are expiring, and generic versions, which are referred to as biosimilars, are produced to serve as an alternative to the reference medicinal product (RMP) cutting down the costs and expanding access. The present paper assesses the analytical similarity between Formycon’s FYB206 pembrolizumab biosimilar candidate and Keytruda®, an RMP that is approved to treat various types of cancer, with the intention of determining FYB206’s suitability to enter clinical biosimilar trials. Methods Monoclonal antibodies (mAbs) are biological medicinal products that are characterized by a high overall heterogeneity. Due to the complex nature of these molecules, a comprehensive comparative analytical assessment was designed to demonstrate analytical similarity in all clinically relevant quality attributes between RMP and the corresponding biosimilar candidate. This exercise addresses physicochemical, biophysical as well as functional characteristics. Results The comparative analytical evaluation results demonstrate that the proposed biosimilar is structurally and functionally highly similar to the RMP, showing only minor differences for some quality attributes that are justified to be noncritical for clinical efficacy and safety. Conclusion Based on physicochemical and biological characteristics, FYB206 is suitable to enter the clinical phase.

Nanoclusters are promising materials for catalysis and sensing due to their large surface areas and unique electronic structures which can be tailored through composition, geometry, and chemistry. However, relationships correlating synthesis parameters directly to outcomes are limited. While previous computational studies have mapped the potential energy surface of specific systems of bare nanoclusters by generating and calculating the energies of reasonable structures, it is known that environmental ions and ligands crucially impact the final shape and size. In this work, phosphine-stabilized gold is considered as a test system and DFT calculations are performed for clusters with and without ligands, producing a database containing >10000 structures for Aun(PH3)m (n ≤ 12). We find that the ligation of phosphines affects the thermodynamic stability, bonding, and electronic structure of Au nanoclusters, specifically such that "hidden" ground state cluster geometries are stabilized that are dynamically unstable in the pure gold system. Further, the addition of phosphine introduces steric effects that induce a transition from planar to nonplanar structures at 4-5 Au atoms rather than up to 13-14 Au atoms, as previously predicted for bare clusters. This work highlights the importance of considering the ligand environment in the prediction of nanocluster morphology and functionality, which adds complexity as well as a rich opportunity for tunability.

Colloidal semiconductor nanocrystals (NCs) are used as bright chromatic fluorophores for energy-efficient displays. We focus here on the size-dependent Stokes shift for CsPbBr3 nanocrystals. The Stokes shift, i.e., the difference between the wavelengths of absorption and emission maxima, is crucial for display application, as it controls the degree to which light is reabsorbed by the emitting material reducing the energetic efficiency. One major impediment to the industrial adoption of NCs is that slight deviations in manufacturing conditions may result in a wide dispersion of the product's properties. A data-driven analysis of over 2000 reactions comparing two data sets, one produced via standard colloidal synthesis and the other via high-throughput automated synthesis is discussed. We show that differences in the reaction conditions of colloidal CsPbBr3 nanocrystals yield nanocrystals with opposite Stokes shift size-dependent trends. These match the morphologies of two-dimensional nanoplatelets (NPLs) and nanocrystal cubes. The Stokes shift size dependence trend of NPLs and nanocubes is non-monotonic indicating different physics is at play for the two nanocrystal morphologies. For nanocrystals with cubic shape, with the increase of edge length, there is a significant decrease in Stokes shift values. However, for NPLs with the increase of thickness (1-4 ML), Stokes shift values will increase. The study emphasizes the transition from a spectroscopic point of view and relates the two Stokes shift trends to 2D and 0D exciton dimensionalities for the two morphologies. Our findings highlight the importance of CsPbBr3 nanocrystal morphology for Stokes shift prediction.

Advances in laboratory-based X-ray computed tomography (CT) have enabled X-ray 3D virtual histology. This method shows a great potential as a complementary technique to conventional 2D histology where extensive volumetric sampling is necessary. While formalin-fixed paraffin-embedded (FFPE) tissue blocks are the backbone of clinical histology, there exists no generic optimization, and technical study of the X-ray 3D virtual histology of FFPE blocks. X-ray micro-CT of FFPE blocks is studied and optimized in their native state within the cassette to minimize the interference of X-ray 3D virtual histology with clinical workflows and standards, hence facilitating the technology transfer to the clinics. The optimization is carried on the sample positioning, tungsten tubes acceleration voltage, and artifact reduction. Then propagation-based imaging of FFPE blocks is extensively discussed. Hierarchical (local) tomography and laminography are presented as viable approaches for achieving higher spatial resolutions. In the end, future perspectives are given by considering state-of-the-art micro-CT scanners using liquid-metal-jet sources, large-area detectors, and photon counting detectors. The results achieved here are generic and can be applicable to any laboratory-based scanner with a tungsten target source and cone-beam geometry. This article provides a starting point for anyone new to X-ray 3D virtual histology on FFPE blocks, but also serves as a useful source for more experienced users.

Abstract Climate change and human activity threaten sea turtle nesting beaches through increased flooding and erosion. Understanding the environmental characteristics that enable nesting can aid to preserve and expand these habitats. While numerous local studies exist, a comprehensive global analysis of environmental influences on the distribution of sea turtle nesting habitats remains largely unexplored. Here, we relate the distribution of global sea turtle nesting to 22 coastal indicators, spanning hydrodynamic, atmospheric, geophysical, habitat, and human processes. Using state-of-the-art global datasets and a novel 50-km-resolution hexagonal coastline grid (Coastgons), we employ machine learning to identify spatially homogeneous patterns in the indicators and correlate these to the occurrence of nesting grounds. Our findings suggest sea surface temperature, tidal range, extreme surges, and proximity to coral and seagrass habitats significantly influence global nesting distribution. Low tidal ranges and low extreme surges appear to be particularly favorable for individual species, likely due to reduced nest flooding. Other indicators, previously reported as influential (e.g., precipitation and wind speed), were not as important in our global-scale analysis. Finally, we identify new, potentially suitable nesting regions for each species. On average, $$23\%$$ 23 % of global coastal regions between $$-39^\circ$$ - 39 ∘ and $$48^\circ$$ 48 ∘ latitude could be suitable for nesting, while only $$7\%$$ 7 % is currently used by turtles, showing that the realized niche is significantly smaller than the fundamental niche, and that there is potential for sea turtles to expand their nesting habitat. Our results help identify suitable nesting conditions, quantify potential hazards to global nesting habitats, and lay a foundation for nature-based solutions to preserve and potentially expand these habitats.

Understanding the motivations and benefits of citizen science (CS) participants is critical to the success of environmental science projects that rely on data collection from engaged citizens. Tailored communication with citizen scientists is essential, leading to the need to target specific societal groups for extensive and high-quality data sets. The purpose of the study was to apply marketing concepts such as stakeholder analysis, value proposition canvas (VPC), and key performance indicators (KPIs) to CS projects. The study examined the extent to which these strategies can be applied to CS projects and add value, resulting in improved recruitment and retention of participants, as well as improved project management. The dynamic landscape of CS projects requires adapted business-oriented approaches supporting ongoing participation with high motivation, acknowledging community needs, and recognizing institutional scientists, akin to targeting potential customers. The case study focuses on the CityCLIM initiative, an EU-funded project collecting urban climate data, especially air temperature, using mobile weather stations. The CityCLIM VPC, analyzing stakeholder groups, facilitated tailored communication strategies by analyzing stakeholder groups and highlighting the effectiveness of the CS cycling initiative within the “Stadtradeln” program. Impact KPIs served as a roadmap for strategic refinement, while data quality KPIs identified deficiencies, guiding adjustments to the campaign. Applied marketing tools improved project planning, engagement, and evaluation, demonstrating the potential of this concept. Adapting marketing tools to recruitment and communication strategies benefits CS projects by targeting specific groups. The holistic integration of stakeholder analysis, VPC, and KPIs streamlines project management and creates a framework for sustainable success. This adaptation forms a robust toolkit for CS project coordinators, contributing to effective communication, engagement, and impact assessment. Applying marketing tools significantly increases CS projects’ reach and impact, ensuring long-term success and meaningful scientific contributions.

Abstract The present study investigated to what extent a systematic evaluation of electronic condylar motion recordings leads to reproducible results in different examiners. The study was based on the anonymized condylar motion recordings of 20 patients (Cadiax compact II system). These were recruited consecutively from the examinations in a center specializing in diagnosing and managing temporomandibular disorders (TMD). Four trained practitioners independently evaluated the identical movement recordings of all patients after calibration. The evaluation was based on the previously published evaluation system. The results were recorded digitally in a database. The findings were then compared, and the matching values were determined (Fleiss' Kappa). The evaluation, according to Fleiss' Kappa, showed that the consistency of the assessment of the findings among the examiners is excellent (mean value 0.88, p

The synthesis quality of artificial inorganic nanocrystals is most often assessed by transmission electron microscopy (TEM) for which high-throughput advances have dramatically increased both the quantity and information richness of metal nanoparticle (mNP) characterization. Existing automated data analysis algorithms of TEM mNP images generally adopt a supervised approach, requiring a significant effort in human preparation of labeled data that reduces objectivity, efficiency, and generalizability. We have developed an unsupervised algorithm AutoDetect-mNP for automated analysis of TEM images that objectively extracts morphological information on convex mNPs from TEM images based on their shape attributes, requiring little to no human input in the process. The performance of AutoDetect-mNP is tested on two data sets of bright field TEM images of Au nanoparticles with different shapes and further extended to palladium nanocubes and cadmium selenide quantum dots, demonstrating that the algorithm is quantitatively reliable and can thus serve as a generalizable measure of the morphology distributions of any mNP synthesis. The AutoDetect-mNP algorithm will aid in future developments of high-throughput characterization of mNPs and the future advent of time-resolved TEM studies that can investigate reaction mechanisms of mNP synthesis and reactivity.

Increasing access to undergraduate research is critical in efforts to retain students pursuing careers in STEM. Alternatives to traditional research positions, such as course based undergraduate research experiences (CUREs), have played important roles in engaging more undergraduates in research. However, these opportunities are only a subset of possible nontraditional research experiences which can enrich the undergraduate experience. In this study, we critically examined and improved the research-group-led undergraduate research program (GURP) to better meet the needs of undergraduates seeking research. Specifically, we investigated if the program was successful with a greater diversity of data sets, if assessments of learning were consistent across different data sets and teaching environments, and if the program promoted student engagement in research. We have found that this model is scalable, robust, and adaptable to different implementations while producing consistent and positive learning outcomes for students. Especially remarkable are students' increased self-identification as scientists and statistically significant gains in self-perceived competency across multiple domains of knowledge. This program model has shown promising results as a partially and fully online research experience for undergraduates and has benefited program alumni in their research careers. To assist research groups starting similar programs, we have created public data sets and instructional resources. We believe that GURP programs can work in a variety of situations and hope that they can become a tool to increase interest and build communities for young researchers.

Lead toxicity has sparked interest into alternative halide nanomaterials with properties similar to CsPbX 3 perovskites. A promising alternative suggested from bulk studies is the family of double perovskites of the form Cs 2 AgMX 6 . Here, we report the synthesis of colloidal Cs 2 AgInCl 6 and Cs 2 AgSbCl 6 nanocrystals via injection of acyl halides into a metal acetate solution under atmospheric conditions and relatively mild temperatures. We demonstrate the synthesis of single-crystalline cubic nanocrystals of ca. 10 nm side length and their morphological similarities to other double perovskite nanostructures in terms of their [200] facet termination and decoration with Ag (0) smaller nanocrystallites. To compare the stabilities of the synthesized materials, we develop a titration assay based on the degradation of nanocrystals with amines as a proxy for degradation by humidity, which provides a quantifiable stability metric. This measurement shows that Cs 2 AgSbCl 6 releases more than twice the decomposition energy compared to Cs 2 AgInCl 6 or CsPbCl 3 and degrades in the presence of approximately one molar equivalent of amine, whereas the other two materials require more than a 100-fold excess. Using facile chemical titration to quantitatively determine chemical stability provides an additional tool to aid in the basic understanding of what makes some of these materials more environmentally stable than others.

There is no doubt that the Milky Way is a barred galaxy; however, factors that establish its prominent morphology remain largely elusive. In this work, we attempt to constrain the history of the MW by tracing the present-day parameters and evolution of a set of MW and M31 analogues from the TNG50 simulations. We find that the strength of bars at |$z=0$| correlates well not only with the stellar mass build-up but also, more crucially, with the time of onset of stellar discs. Discs of strongly barred galaxies form early (⁠|$z \gtrsim 2-3$|⁠), compared to weakly and non-barred galaxies (⁠|$z \approx 1-1.5$|⁠). Although we are cautious to draw ultimate conclusions about the governing factor of discs formation due to the complexity and correlations between different phenomena, the observed morphological diversity can be tentatively explained by a substantial variation in the gas angular momentum around proto-galaxies already at |$z\approx 3-5$|⁠ ; in such a way, early discs formed from gas with larger angular momentum. By comparing the formation time-scales of discs of barred galaxies in the TNG50 sample, we infer that the MW has a strong bar (⁠|$0.35\lt A_2\lt 0.6$|⁠), and that its stellar disc started to dominate over the spheroidal component already at |$z \approx 2$|⁠ , with a mass of |$\approx 1 \pm 0.5 \times 10^{10} M_\odot$|⁠. We conclude that the presence of a strong bar in the MW is a natural manifestation of the early formation of the stellar disc, which made possible bursty but highly efficient star formation at high redshift. [ABSTRACT FROM AUTHOR]

ABSTRACT Background Objective Methods Results Conclusions Tooth wear is a multifactorial process resulting in the loss of dental hard tissues. For its assessment, the tooth wear evaluation system (TWES) 2.0 has been published. Previous studies on the TWES involved well‐trained practitioners, rather than nonexperts.The first aim of this study was to investigate the reliability of the assessment of tooth wear severity on dental hard tissues, using the TWES 2.0, by nonexperts. The second aim was to investigate the reliability of assessment of wear severity on dental restorations, using a third scale.Forty‐seven dental students evaluated at least 9 of 14 possible patient cases on dental casts and intraoral photographs. Cohen's kappa (agreement with sample solution) and Fleiss' kappa (Inter‐rater reliability) were calculated.The agreements of the operators' ratings compared to the sample‐solution resulted in Cohen's kappa between 0.02 and 0.9. The agreements were 0.34 for occlusal; 0.43 for vestibular; 0.57 for oral surfaces.Inter‐rater reliability (Fleiss' kappa) was 0.35 for occlusal, 0.17 for vestibular and 0.24 for oral assessment. The inter‐rater reliability of the ratings on tooth surfaces with restorations was lower with 0.21 (occlusal), 0.14 (vestibular) and 0.39 (oral). The agreement on different restorations differed tremendously.The ability to correctly assess the cases varied considerably between individual examiners. Within the limits of this study, assessment of restorations was slightly more challenging compared to natural teeth, particularly in occlusal regions or when the restorative material is gold. Subsequent studies should address whether enhanced training and improved definition of tooth wear grades result in higher reliability scores. [ABSTRACT FROM AUTHOR]

Background and Objective: Biological medicinal products improve patients' lives, but access is limited, mainly due to high costs. Patents for many existing biological products are expiring, and generic versions, which are referred to as biosimilars, are produced to serve as an alternative to the reference medicinal product (RMP) cutting down the costs and expanding access. The present paper assesses the analytical similarity between Formycon's FYB206 pembrolizumab biosimilar candidate and Keytruda®, an RMP that is approved to treat various types of cancer, with the intention of determining FYB206's suitability to enter clinical biosimilar trials. Methods: Monoclonal antibodies (mAbs) are biological medicinal products that are characterized by a high overall heterogeneity. Due to the complex nature of these molecules, a comprehensive comparative analytical assessment was designed to demonstrate analytical similarity in all clinically relevant quality attributes between RMP and the corresponding biosimilar candidate. This exercise addresses physicochemical, biophysical as well as functional characteristics. Results: The comparative analytical evaluation results demonstrate that the proposed biosimilar is structurally and functionally highly similar to the RMP, showing only minor differences for some quality attributes that are justified to be noncritical for clinical efficacy and safety. Conclusion: Based on physicochemical and biological characteristics, FYB206 is suitable to enter the clinical phase. [ABSTRACT FROM AUTHOR]

Objective: To investigate the initial set of patient-reported outcomes (PROs) in the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) and their associations with 30-day surgical outcomes. Background: PROs provide important information that can be used to improve routine care and facilitate quality improvement. The American College of Surgeons conducted a demonstration project to capture PROs into the NSQIP to complement clinical data. Methods: From February 2020 to March 2023, 65 hospitals collected Patient-Reported Outcomes Measurement Information System measures assessing global health, pain interference, fatigue, and physical function from patients accrued into the NSQIP. Using multivariable mixed regression, we compared the scores of patients with and without 30-day complications and further analyzed scores exceeding 1-SD worse than national benchmarks. Results: Overall, 33842 patients completed the Patient-Reported Outcomes Measurement Information System measures with a median of 58 days (IQR: 47-72) postoperatively. Among patients without complications (n = 31210), 33.9% had PRO scores 1-SD worse than national benchmarks. Patients with complications were 1.7 times more likely to report worse PROs (95% CI: 1.6-1.8). Patients with complications had lower scores for global physical health [adjusted mean difference (AMD): 2.6, 95% CI: 2.2-3.0], lower for global mental health (AMD: 1.8, 95% CI: 1.4-2.2), higher for pain interference (AMD: 2.4, 95% CI: 2.0-2.8), higher fatigue (AMD: 2.7, 95% CI: 2.3-3.1), and lower physical function (AMD: 3.2, 95% CI: 2.8-3.5). Conclusions: Postoperative complications negatively affect multiple key dimensions of patients' health-related quality of life. PROs were well below national benchmarks for many patients, even among those without complications. Identifying solutions to improve PROs after surgery remains a tremendous quality improvement opportunity. [ABSTRACT FROM AUTHOR]

Background and Objective: Biological medicinal products improve patients' lives, but access is limited, mainly due to high costs. Patents for many existing biological products are expiring, and generic versions, which are referred to as biosimilars, are produced to serve as an alternative to the reference medicinal product (RMP) cutting down the costs and expanding access. The present paper assesses the analytical similarity between Formycon's FYB206 pembrolizumab biosimilar candidate and Keytruda®, an RMP that is approved to treat various types of cancer, with the intention of determining FYB206's suitability to enter clinical biosimilar trials. Methods: Monoclonal antibodies (mAbs) are biological medicinal products that are characterized by a high overall heterogeneity. Due to the complex nature of these molecules, a comprehensive comparative analytical assessment was designed to demonstrate analytical similarity in all clinically relevant quality attributes between RMP and the corresponding biosimilar candidate. This exercise addresses physicochemical, biophysical as well as functional characteristics. Results: The comparative analytical evaluation results demonstrate that the proposed biosimilar is structurally and functionally highly similar to the RMP, showing only minor differences for some quality attributes that are justified to be noncritical for clinical efficacy and safety. Conclusion: Based on physicochemical and biological characteristics, FYB206 is suitable to enter the clinical phase. [ABSTRACT FROM AUTHOR]

Abstract This study explores the impact of antibody surface charge on tissue distribution into various tissues including tumor. Tumor-bearing mice were dosed intravenously with a mixture comprising three antibodies engineered to carry negative charge patches, a balanced charge distribution, or positive patches, respectively (cassette dosing). Tissue levels were analyzed with a specific LC-MS/MS method. In addition, the antibody mix was administered to non-tumor bearing mice. Muscle and skin interstitial fluid were obtained by centrifugation and analyzed by LC-MS/MS. An in vitro endothelium model was explored for its feasibility to mimic the observed distribution differences. A balanced charge distribution was optimal in terms of total tumor exposure, while in other tissues, negatively charged and balanced charged antibodies gave similar results. In contrast, positive charge patches generally resulted in increased serum clearance but markedly enhanced tumor and organ uptake, leading to higher tissue-to-serum ratios. The uptake and availability in the interstitial space were confirmed by specific assessment of antibody levels in the interstitial fluid of the muscle and skin, with similar charge impact as in total tissue. The in vitro model was able to differentiate the transport propensity of this series of antibody variants. In summary, our results show the differential effects of charge patches on an antibody surface on biodistribution and tumor uptake. These insights may help in the design of molecules with biodistribution properties tailored to their purpose, and an optimized safety profile.

Small polaron formation limits the mobility and lifetimes of photoexcited carriers in metal oxides. As the ligand field strength increases, the carrier mobility decreases, but the effect on the photoexcited small polaron formation is still unknown. Extreme ultraviolet transient absorption spectroscopy is employed to measure small polaron formation rates and probabilities in goethite (α-FeOOH) crystalline nanorods at pump photon energies from 2.2 to 3.1 eV. The measured polaron formation time increases with excitation photon energy from 70 ± 10 fs at 2.2 eV to 350 ± 30 fs at 2.6 eV, whereas the polaron formation probability (85 ± 10%) remains constant. By comparison to hematite (α-Fe2O3), an oxide analogue, the role of ligand composition and metal center density in small polaron formation time is discussed. This work suggests that incorporating small changes in ligands and crystal structure could enable the control of photoexcited small polaron formation in metal oxides.

Small polaron formation limits the mobility and lifetimes of photoexcited carriers in metal oxides. As the ligand field strength increases, the carrier mobility decreases, but the effect on the photoexcited small polaron formation is still unknown. Extreme ultraviolet transient absorption spectroscopy is employed to measure small polaron formation rates and probabilities in goethite (α-FeOOH) crystalline nanorods at pump photon energies from 2.2 to 3.1 eV. The measured polaron formation time increases with excitation photon energy from 70 ± 10 fs at 2.2 eV to 350 ± 30 fs at 2.6 eV, whereas the polaron formation probability (85 ± 10%) remains constant. By comparison to hematite (α-Fe2O3), an oxide analogue, the role of ligand composition and metal center density in small polaron formation time is discussed. This work suggests that incorporating small changes in ligands and crystal structure could enable the control of photoexcited small polaron formation in metal oxides.

Replacing lead in halide perovskites is of great interest due to concerns about stability and toxicity. Recently, lead free double perovskites in which the unit cell is doubled and two divalent lead cations are substituted by a combination of mono- and trivalent cations have been synthesized as bulk single crystals and as thin films. Here, we study stability and optical properties of all-inorganic cesium silver(I) bismuth(III) chloride and bromide nanocrystals with the double perovskite crystal structure. The cube-shaped nanocrystals are monodisperse in size with typical side lengths of 8 to 15 nm. The absorption spectrum of the nanocrystals presents a sharp peak, which we assign to a direct bismuth s-p transition and not to a quantum confined excitonic transition. Using this spectroscopic handle combined with high-resolution transmission electron microscopy (TEM) based elemental analysis, we conduct stoichiometric studies at the single nanocrystal level as well as decomposition assays in solution and observe that Ag+ diffusion and coalescence is one of the pathways by which this material degrades. Drying the nanocrystals leads to self-assembly into ordered nanocrystal solids, and these exhibit less degradation than nanocrystals in solution. Our results demonstrate that Cs2AgBiX6 (X = Cl, Br) nanocrystals are a useful model system to study structure-function relationships in the search for stable nontoxic halide perovskites.