bluuebunny/crossref_metadata_2025 huggingface dataset:
A Comparative Study of Inference Models Based on Image Recognition
Authors: Zhao Deling
Published: February 2025

Due to the limitation of web-side processing capabilities, the existing mainstream inference models adopt the client-to-server operation mode, and the emergence of WebAssembly has brought opportunities for the client to run the inference model alone for image recognition, and soon, the browser will fully support the standard. Therefore, on the basis of image recognition, this paper runs the mainstream inference model on the client and server side, and then compares the inference rate of different inference models at different batch sizes and the inference efficiency of the same inference model on the client and server side, conducts a large number of comparative experiments to record the experimental results, and then uses the method of averaging the experimental data to obtain a set of reliable experimental conclusions. Experimental results show that the performance of server-side TensorRT is better than other models under the same configuration conditions, ONNXRuntime is better than PyTorch in small batches, and PyTorch's performance improvement in accuracy has more room for optimization. The results of web-side experiments show that the inference model has a large difference in GPU usage, ONNXRuntime shows a greater performance advantage in the efficiency of GPU inference, while TensorRT will show better performance with the increase of batch. Compared with server-side inference, web-side inference shows stronger stability because it relies less on network transmission, so it can be preferred to direct inference when the batch is small, and server inference is preferred when the client configuration does not meet the conditions.
Getting Effect Prediction Model of CVTPD-PSL Technology Based on Artificial Neural Network
Authors: Zhang Caizhen , Li Zongzhi , Wang Zaixing
Published: February 2025

In view of technology characteristic of Continuously Variable Phosphorous Getting Process Using a Porous Silicon Layer (PSL-CVTPDG), a prediction model based on Artificial Neural Network(ANN) is put forward for predicting effect of PSL-CVTPDG process. Establish, train, test and verify as long as simulation of the prediction model were finished by means of ANN function in MATLAB. Experimental results show that the prediction and actually measured values are very close to, the output follows the tracks of the expectation value very well, which reflects that the ANN is an effective method for predicting the gettering effect of porous silicon materials.
Hybrid high-energy factorization and evolution at NLO from the high-energy limit of collinear factorization
Authors: van Hameren Andreas , Nefedov Maxim
Published: February 2025

Abstract

We derive the scheme of NLO computations of generic observables in high-energy hadron-hadron collisions within the framework of high-energy factorization (HEF) with one off-shell initial-state parton, by taking a high-energy limit of the NLO computation in collinear factorization (CF). The NLO terms belonging to the projectile and target are identified and the ambiguity of projectile-target separation is related with the Collins-Soper scale (μY). The NLO unintegrated PDF(UPDF) is constructed in terms of the usual PDFs, and its μY-evolution reproduces the Collins-Soper-Sterman equation in the TMD limit (|k⊥| ≪ μY). The resummation of high-energy logarithms is taken care of by the BFKL-Collins-Ellis evolution of the Green’s function in the UPDF.
e+e− → ZH process in the SMEFT beyond leading order
Authors: Asteriadis Konstantin , Dawson Sally , Giardino Pier Paolo , Szafron Robert
Published: February 2025

Abstract

We systematically study potential effects of Beyond the Standard Model physics in the e
+
e
− → ZH process. To this end, we include all relevant dimension-6 Standard Model Effective Field Theory operators and work to next-to-leading order (NLO) accuracy in the electroweak coupling. We consider both polarized and unpolarized electron and positron beams and present results for

$$ \sqrt{s} $$

s

= 240, 365 and 500 GeV, emphasizing contributions where the NLO predictions differ significantly from the leading order results. At NLO, a sensitivity arises to operators that do not contribute at tree level, such as the Higgs tri-linear coupling, CP-violating operators, and dimension-6 operators involving the top quark, among many others. We compare the prospects of future e
+
e
− colliders to explore these new physics effects with existing measurements from the LHC, electron EDMs (for CP violating operators), and Z pole measurements.
Erratum to: Inclusive semileptonic $$ b\to c\ell \overline{\nu} $$ decays to order $$ 1/{m}_b^5 $$
Authors: Mannel Thomas , Milutin Ilija S. , Vos K. Keri
Published: February 2025

A correction to this paper has been published: https://doi.org/10.1007/JHEP02(2024)226
All class $$ \mathcal{S} $$ theories of type-A originate from orbi-instantons
Authors: Giacomelli Simone , Harding William , Mekareeya Noppadol , Mininno Alessandro
Published: February 2025

Abstract

A surprising relation between 4d

$$ \mathcal{N} $$

N

= 2 class

$$ \mathcal{S} $$

S

superconformal field theories of Type-A and 6d

$$ \mathcal{N} $$

N

= (1, 0) orbi-instanton theories is investigated. We find that all of the theories in the former class can be obtained by a series of deformations of the 4d theories arising from compactifying the latter on a torus. This is demonstrated by examining Fayet-Iliopoulos (FI) deformations of the E
8-shaped magnetic quivers of the orbi-instanton theories whose body fits into the affine E
8 Dynkin diagram with a tail attached. Turning on FI parameters at the appropriate gauge groups leads, in stages, to E
7-shaped, E
6-shaped, and general star-shaped quivers, where the latter are magnetic quivers for the class

$$ \mathcal{S} $$

S

theory of Type-A on a sphere with punctures. Deforming a suitable star-shaped quiver, one obtains a magnetic quiver of the Type-A class

$$ \mathcal{S} $$

S

theory with general genus and an arbitrary number of punctures. Given such a theory, we also propose the inverse algorithm, thereby determining a parent orbi-instanton theory. This is achieved by uplifting the corresponding magnetic quiver step by step to the star-shaped, E
6-shaped, E
7-shaped, and E
8-shaped quivers, where at each step all of the underbalanced nodes, possessing non-zero FI parameters, are dualized. The latter E
8-shaped quiver then characterizes the 6d orbi-instanton theory from which the class

$$ \mathcal{S} $$

S

theory in question originates.
Deformation, alteration and implicit 3D geomodelling of deposit-scale controls of vein-hosted copper mineralization of the Frontier Mine, Democratic Republic of Congo
Authors: Fourie Heike , Kisters Alexander , Basson Ian James
Published: February 2025

The structurally controlled, vein-hosted copper deposit of the Frontier Mine is distinct from the vast majority of sediment-hosted, stratiform Cu(-Co) deposits of the Zambian Copperbelt. Successively emplaced vein sets document the close interplay between the progressive structural evolution of the deposit, recording northeast-southwest shortening, and associated hydrothermal fluid flow and alteration (albitization). The deposit is hosted by greenschist-facies metasedimentary rocks of the Mwashya Subgroup in the first-order hinge zone of a regional-scale, refolded, recumbent fold (F1/F2). Early bedding/S1-parallel veins (Vein Set 1) formed during layer-parallel shearing and the onset of recumbent folding (F1). This early vein generation is relatively poorly mineralized, but was associated with a near-pervasive, bedding-parallel albitization and replacement of the mainly metapelitic wall rocks. The reaction hardening process promoted brittle deformation during the subsequent upright refolding (F2) of the rocks and the formation of a second generation of highly mineralized, saddle-reef type veins (Vein Set 2) in the hinges of particularly upright F2 folds (F1/F2). The controls of Vein Set 2 by fold hinges defines the overall shoot-like geometry of the orebody, parallel to the SE-plunging folds. The subhorizontal orientation and brecciated textures of a subsequent Vein Set 3 underline the formation of veins through continued northeast-southwest shortening of the brittle wall rocks during the lock up of the refolded first-order fold. The overprinting and structural relationships between vein sets, alteration and the regional fold structures signify a syn-tectonic, long-lived, multi-phase mineralization history during the Lufilian Orogeny.
Improved FAPI-radiopharmaceutical pharmacokinetics from the perspectives of a dose escalation study
Authors: Bilinska Adrianna , Ballal Sanjana , Bal Chandrasekhar , Läppchen Tilman , Pilatis Eirinaios , Menéndez Elena , Moon Euy Sung , Martin Marcel , Rösch Frank , Rominger Axel , Gourni Eleni
Published: February 2025

Purpose

This study explores the use of fibroblast activation protein inhibitors (FAPI) targeting radiopharmaceuticals as a new approach for pan-cancer treatment, focusing on key factors affecting their effectiveness. We hypothesized that adjusting the administered radiotracer dose one could enhance the tumor-to-background ratios.

Methods

In a dose-escalation study with PC3 xenografts, all radiotracers were administered at doses between 10 and 1500 pmol, followed by biodistribution and PET/CT imaging. Their selectivity towards FAP, PREP, and DDP4, along with their stability in vivo, was assessed by biodistribution and metabolite analysis, respectively. Organ FAP expression was quantified using qPCR, and circulating FAP (sFAP) levels were measured in mouse and human blood samples via ELISA. Proof-of-principle human studies were also conducted.

Results

Increasing the dose from 10 to 600 pmol significantly reduced blood uptake and enhanced tumor uptake, optimizing their in vivo performance. All radiotracers showed peak efficacy at 350–600 pmol, with altered pharmacokinetics beyond 600 pmol. Biodistribution studies validated the in vivo selectivity of all radiotracers towards FAP, even in the presence of PREP and DPP4 inhibitors, while they demonstrated remarkable stability in vivo. FAP expression was confirmed in various organs, with sFAP quantified in both healthy mice and humans. Human studies with [68Ga]Ga-DOTA.SA.FAPI revealed reduced off-target uptake (e.g., pancreas, salivary glands, heart), aligning with the preclinical findings.

Conclusion

The study highlights the crucial need for precise FAPI-radiotracer dosing, optimizing PET imaging, reducing radiation exposure, and enhancing treatment by accounting for FAP biology and sFAP’s influence on pharmacokinetics.
A mathematical model for the investigation of combined treatment of radiopharmaceutical therapy and PARP inhibitors
Authors: Ryhiner Marc , Song Yangmeihui , Hong Jimin , Ferreira Carlos Vinícius Gomes , Rominger Axel , Kossatz Susanne , Glatting Gerhard , Weber Wolfgang , Shi Kuangyu
Published: February 2025

Background

Although the combined treatment with radiopharmaceutical therapy (RPT) and poly (ADP-ribose) polymerase inhibitors (PARPi) shows promise, a critical challenge remains in the limited quantitative understanding needed to optimize treatment protocols. This study introduces a mathematical model that quantitatively represents homologous recombination deficiency (HRD) and facilitates patient-specific customization of therapeutic schedules.

Methods

The model predicts therapeutic outcomes based on the absorbed dose by DNA and the resulting radiobiological responses, with DNA double-strand breaks (DSBs) being the critical determinant of cancer cell fate. The effect of PARPi is modeled by the accelerated conversion of single-strand breaks (SSBs) to DSBs due to PARP-trapping in the S phase, while HRD is represented by defects in DSB repair in replicated DNA. In vitro experiments are used to calibrate the model parameters and validate the model. In silico tests are designed to extensively investigate various combination protocols including the LuPARP trial.

Results

Model calibration was performed using data from the treatment of NCI-H69 cells with [177Lu]Lu-DOTA-TOC and PARPi. Previously published in vivo studies were integrated into the presented model. Model validation using in vitro data showed deviations within the experimental error margins, with average deviations of 5.3 ± 3.2% without PARPi, 6.1 ± 4.4% with Olaparib, and 12 ± 18% with Rucaparib. Rucaparib radiosensitization reduces number of tumor cells during lutetium therapy by 99.2% and 99.99% (HRD). The highest radiosensitizing effect in vivo and in vitro was observed with Talazoparib (IC50: 4.8 nM), followed by Rucaparib (IC50: 1.4 µM). The model predicts relative tumor shrinkage after 14 days of combination treatment with Olaparib (250 mg) based on patient body weight (e.g. 60 kg: 99.6%; 90 kg: 98.0%).

Conclusion

Results demonstrate the potential of this computational model as a step toward the development of the digital twin for systematic exploration and optimization of clinical protocols.
3-year overall survival benefit of systematic follow-up with 18F-FDG PET/CT in asymptomatic patients treated for head and neck squamous cell carcinoma: a multicenter study
Authors: Mahéo C. , Abgral R. , Clément C. , Malard O. , Espitalier F. , Ferron C. , Delcroix O. , Le Pennec R. , Schick U. , Tissot V. , Le Gal G. , Kraeber-Bodéré F. , Eugène T. , Marianowski- R. , Salaün P. Y. , Leclère- Jean-Christophe
Published: February 2025

Purpose

Patients diagnosed with head and neck squamous cell carcinoma (HNSCC) face a significant risk of locoregional recurrence within the first two years after treatment. While early detection of recurrence could potentially improve patient outcomes, the impact of such detection on survival remains uncertain. The aim was to assess the potential benefit of a systematic post-treatment follow-up strategy using 18 F-FDG PET/CT imaging on overall survival.

Methods

In this multicenter case-control study, patients were treated in two health areas from two different regions in France. All adults diagnosed with histologically confirmed HNSCC and treated between January 2017 and December 2020 with curative intent, with a complete response on imaging were included in the study. Primary endpoint was 3-year overall survival. The log-rank test was used to compare 3-year OS rates between the CFU (conventional follow-up) and PET/CT groups. A Cox regression model was used to assess the effect of the addition of 18 F-FDG PET/CT on survival outcomes.

Results

A total of 697 patients were included (534 males [77%], median age[IQR] 62[57–69] years); 508 patients had CFU and 189 patients had CFU + systematic annual 18 F-FDG PET/CT. Cox regression analysis showed a protective effect (OR = 0.56, 95%CI:0.397–0.795, p = 0.001) of systematic 18 F-FDG PET/CT. The 3-year OS in the PET/CT group was better than in the CFU group (83.5 ± 2.8% vs. 73.4 ± 2.1%, p = 0.008). The analysis based on stage showed a significantly better 3-year OS for advanced stage III/IV in the PET/CT group (n = 124) than in the CFU group (n = 312)(79.9 ± 3.7% vs. 71.5 ± 2.7%, p = 0.045) as well as for early stage I/II (90.5 ± 3.7% vs. 76.3 ± 3.2%, p = 0.047).

Conclusion

In this multicenter study, the use of 18 F-FDG PET/CT as an alternative to annual chest CT in the follow-up of head and neck squamous cell carcinoma (HNSCC) is associated to a survival benefit at 3 years.

Clinical trial number

Not applicable (retrospective study).
Neuro-toxoplasmosis in haploidentical haematopoietic stem cell transplant
Authors: Galli Marco , Masina Lorenzo , Magliano Gabriele , Morello Enrico , Van Hauwermeiren Evelyn , Malagola Michele , Farina Mirko , Radici Vera , Russo Domenico , Avenoso Daniele
Published: February 2025

Allogeneic haematopoietic stem cell transplant is a routine procedure for several haematological disorders though infections are the main cause of morbidity and mortality. Rare infections, such as protozoan reactivations, can be life-threatening and clinicians should be aware of these possibilities. Herein, we present a case of neuro-toxoplasmosis post haploidentical haematopoietic stem cell transplant.
Exponential speedup over locality in MPC with optimal memory
Authors: Balliu Alkida , Brandt Sebastian , Fischer Manuela , Latypov Rustam , Maus Yannic , Olivetti Dennis , Uitto Jara
Published: February 2025

Locally Checkable Labeling () problems are graph problems in which a solution is correct if it satisfies some given constraints in the local neighborhood of each node. Example problems in this class include maximal matching, maximal independent set, and colorings. A successful line of research has been studying the complexities of s on paths/cycles, trees, and general graphs, providing many interesting results for the model of distributed computing. In this work, we initiate the study of problems in the low-space Massively Parallel Computation () model. In particular, on forests, we provide a method that, given the complexity of an problem in the model, automatically provides an exponentially faster algorithm for the low-space setting that uses optimal global memory, that is, truly linear. While restricting to forests may seem to weaken the results, we emphasize that all known (conditional) lower bounds for the setting are obtained through lower bounds for problems in the distributed setting in tree-like networks (either trees or high-girth graphs), and hence the problems that we study are challenging already on trees. Moreover, our algorithms use optimal global memory, i.e., memory linear in the number of edges of the graph. In contrast, most of the state-of-the-art algorithms use more than linear global memory. Further, they typically start with a dense graph, sparsify it, and then solve the problem on the residual graph, exploiting the relative increase in global memory. On forests this is not possible, hence using optimal memory requires new solutions.
Marginal adaptation analysis of CAD/CAM resin crown with non-invasive methods
Authors: Zeng Chen , Tabata Tomoko , Takahashi Rena , Ikeda Masaomi , Shinagawa Junichi , Nakagawa Hisaichi , Tsuchida Yumi , Takano Shunsuke , Sumi Yasunori , Shimada Yasushi
Published: February 2025

Objectives

This study compared the silicone replica method with swept-source optical coherence tomography (SS-OCT) to analyze marginal adaptation and investigated the effect of the light incidence angle of SS-OCT on measurement precision.

Materials and methods

A typodont-prepared mandibular right first molar was scanned using an intraoral scanner (Trios 3). Fourteen crowns were fabricated from CAD/CAM resin blocks (Katana Avencia P) using a 5-axis milling machine (DWX-50). Marginal adaptation at the buccal, lingual, mesial, and distal points was assessed using the silicone replica method and SS-OCT at light incidence angles of 60°, 75°, and 90°. Statistical comparisons were performed using two-way analysis of variance (ANOVA) and t-tests with Bonferroni correction, and t-tests at a significance level of 0.05.

Results

At 60°, SS-OCT showed significantly larger marginal discrepancies than the silicone replica method at the buccal, lingual, and mesial points (p < 0.05). At 75°, only the lingual point showed a significantly larger value than the silicone replica method (p < 0.05). At 90°, no significant differences were observed between the SS-OCT and silicone replica methods (p > 0.05). Marginal discrepancy values increased as the angle changed from 90° to 75° to 60°, with significant differences between 60° and 75° and between 60° and 90° at the buccal and lingual points (p < 0.05).

Conclusions

SS-OCT is a viable alternative to the silicone replica method for assessing marginal adaptation at an incidence angle of 90 °.

Clinical relevance

SS-OCT, a non-invasive method, has the potential to be applied clinically for evaluating marginal fit in indirect restorations in vivo.
Neurology and physician-assisted suicide: glossary of definitions and terminology
Authors: Solari Alessandra , Ticozzi Nicola , Comi Giancarlo , Mancardi Gianluigi , Provinciali Leandro , Padovani Alessandro , Pucci Eugenio
Published: February 2025

The progress of biomedical technologies has expanded the boundaries of care, offering new treatment options and prolonging patients’ survival even in conditions of great suffering and dependence. End-of-life decisions are an important topic in contemporay bioethics and physician-assisted suicide (PAS) is a still controversial topic, with Neurology at the forefront.

This glossary provides a set of definitions to improve clarity and use of a consistent language in the bioethical debate on patients’ autonomy, treatment limitations, palliative care, PAS, euthanasia, and related issues. The objective of the glossary, which is aligned with most recent international consensus documents and with the italian regulatory frameworks, is to clarify and harmonize the practical use of terms.

The glossary, together with the companion paper outlining the position of the Italian Society of Neurology (SIN) regarding PAS, are living documents subject to revision. They can serve as a foundation for a pluralistic discussion in the debate on the ethical issues related to the care of individuals with neurological diseases characterized by poor prognosis in terms of severe disability or limited biological and biographical life expectancies, as well as their families and caregivers. An even more ambitious goal of these documents is to enhance research and inform the development of national regulation in these areas.
Cross-border seasonal migrant labour and agricultural commodity production in the Ethiopia–Sudan borderlands
Authors: Moreda Tsegaye
Published: February 2025

The Ethiopia-Sudan borderlands have long been a hub of capitalist production of lucrative agricultural commodities such as sesame that profoundly shape the political economy of these borderlands. Cross-border seasonal migrant labour is central to this capitalist commodity production but is often neglected in discussions, which chiefly focus on economic and geopolitical wranglings between different groups over the control of land and commodity production in these areas. If there is any talk of migrant labour, it is reduced a priori to how these agricultural commodity production sites are crucial in providing employment opportunities to migrant workers and how the flow of such labour should be governed. Thus, the role of migrant labour is rarely recognized, and the associated dynamics of exploitation in its varied manifestations remain obscure. This paper argues that the history and profitability of commodity production in the borderlands are connected to, and rooted in, the availability of vast, cheap, flexible and exploited migrant agricultural labour. This labour is the result of various processes, including land grabs, landlessness, conflict and climate change. The paper argues that the dynamics of exploitation occur not only to seasonal migrants in the capitalist production sites but also to their families and communities back home who shoulder the responsibilities of family subsistence and reproducing the labour of the migrant. The paper contributes to an understanding of the relationship between migrant labour and capitalist commodity production, particularly the crucial role of seasonal migrant labour and the dynamics of exploitation, both in the places of origin and the areas of seasonal migrant work. This will, in turn, contribute to identifying the needs of seasonal migrants and the challenges they face, necessary for informing political struggles for labour justice and socio-economic policies.
Improving the hydrophilic microenvironment surrounding the catalytic site of fructosyltransferase enhances its catalytic ability
Authors: Wang Fanzhi , Singh Suren , Permaul Kugen
Published: February 2025

The hydrophilic microenvironment surrounding an enzyme's active site can influence its catalytic activity. This study examines the effect of enhancing this environment in the Aspergillus niger fructosyltransferase, SucC. Bioinformatics analysis identified a cysteine residue (C66) near the catalytic triad (D64, D194, E271) as vital for maintaining the active site's structure and facilitating substrate transport. Simulated mutagenesis suggested that mutating cysteine to serine (C66S) could increase hydrophilicity without altering the structure significantly. This mutation was predicted to enhance substrate affinity, with binding energy changing from −3.65 to −4.14 kcal mol−1. The C66S mutant, expressed in Pichia pastoris GS115, showed a 61.3% increase in specific activity, a 13.5% decrease in K
m (82.20/71.14 mM), and a 21.6% increase in k
cat (112.23/136.48 min−1), resulting in a 40.1% increase in catalytic efficiency (1.37/1.92 min−1 mM−1). For fructooligosaccharides (FOS) production, C66S demonstrated enhanced transfructosylation, particularly in the initial stages of the reaction, achieving higher overall FOS yields. These findings highlight that modifying the active site hydrophilicity, without causing major structural changes, is a promising strategy for improving an enzyme’s catalytic efficiency.
Augmented Graphical Ridge Estimation with Application in the Cryptocurrency Market
Authors: Bekker A. , Kheyri A. , Arashi M.
Published: February 2025

Cryptocurrency markets exhibit complex and evolving structures, making it challenging to identify appropriate models that can effectively capture their returns, particularly in high-dimensional settings. This paper presents a two-step augmented graphical ridge estimator for precision matrix estimation in Gaussian graphical models. The proposed estimator combines

$$L_1$$

L
1

and Frobenius norm penalties to improve estimation accuracy compared to existing methods. Simulation studies demonstrate its superior performance under various conditions. When applied to thirty cryptocurrencies from 2019 to 2021, the estimator reveals the dynamic interconnections within the market, offering valuable insights into the structure of the cryptocurrency network and dependencies across assets.
Scientific Theory and Possibility
Authors: Baron Sam , Le Bihan Baptiste , Read James
Published: February 2025

It is plausible that the models of scientific theories correspond to possibilities. But how do we know which models of which scientific theories so correspond? This paper provides a novel proposal for guiding belief about possibilities via scientific theories. The proposal draws on the notion of an effective theory: a theory that applies very well to a particular, restricted domain. We argue that it is the models of effective theories that we should believe correspond, at least in part, to possibilities. It is thus effective theories that should guide modal reasoning in science.
Certolizumab enhances spinal cord injury recovery in rats through inhibition of the TNF-α signaling pathway and neuronal apoptosis
Authors: Küçükatalay Ozan , Türk Çağlar , Gürel Çevik , Kuşçu Gökçe Ceren , Yüncü Mustafa Eren , Karakoyun İnanç , Akşit Murat , Sarıkaya Onur , Karadağ Ali , Çamlar Mahmut
Published: February 2025

Objective

Spinal cord injury (SCI), which is characterized by motor and/or sensory dysfunction, presents a significant health challenge resulting from mechanical trauma. Secondary injury, which follows the mechanical trauma and is driven by factors such as inflammation, plays a critical role in the SCI pathophysiology. Scientific evidence indicates that treatment strategies aimed at modulating inflammation during the acute phase of SCI alleviate the seconder injury. In this regard, the present study seeks to evaluate the effectiveness of certolizumab, a monoclonal antibody targeting TNF-α that is widely used in the treatment of various inflammatory diseases, in a SCI model.

Methods

In this study, Control, Trauma, and Trauma + Certolizumab groups were established, each comprising eight male rats. One hour after SCI induction, rats in the Trauma + Certolizumab group were administered 10 µg Certolizumab dissolved in saline intraperitoneally, while rats in the Control and Trauma groups received an equivalent volume of saline. After Modified Tarlov Scoring was performed on the seventh day of the experiment, all rats were sacrificed. The effects of certolizumab on neuroinflammation and apoptosis in the SCI model were evaluated using histological, biochemical, and molecular analyses of blood and tissue samples obtained from the rats.

Results

Certolizumab downregulated the expression of TNF-α, NF-κB, and IL-6. In addition, as evidenced by the TUNEL assay, Caspase-3 expression (an apoptotic marker), and Modified Tarlov Score results, certolizumab effectively suppressed inflammation-induced neural apoptosis and alleviated locomotor deficits.

Conclusion

Certolizumab treatment exerts a neuroprotective effect against secondary damage in SCI through the inhibition of neuroinflammation and apoptosis.
"It has to do with timing and context”: Theoretical models as tools in formative interventions in research-practice partnerships
Authors: Ødegaard Kjersti Løken
Published: February 2025

Partnerships between researchers and educators have become a common mode of working to support processes of school improvement. However, research on the processes and outcomes of long-term partnerships remains marginal. This paper increases our knowledge about the processes and experiences involved when researcher–interventionists introduce theoretical models as tools to facilitate reflection and change in long-term partnerships with upper secondary school leadership teams when working on specific challenges and dilemmas. Through an analysis of 41 hours of video data from Change Laboratories and 11 interviews with three upper secondary leadership teams in Norway, the paper examines what unfolds in such research-practice partnerships. The analysis is informed by cultural historical activity theory, with a focus on tools and mediation. The findings suggest that the introduction of theoretical models mediated the sharing of information and alignment of opinions and experiences, identifying issues and altering work procedures, but the participants found it challenging to utilise theoretical models perceived as more general and conceptual compared to those they regarded as organisation-specific and directly applicable. The paper argues that theoretical models may function as bridges to development by clarifying the object and stimulating change in research-practice partnerships, but to do so, researchers need to align the presentations of such models to context and timing.
Local structure propensities in disordered proteins from cross-correlated NMR spin relaxation
Authors: Braun Daniel , Kauffmann Clemens , Beier Andreas , Ceccolini Irene , Lebedenko Olga O. , Skrynnikov Nikolai R. , Konrat Robert
Published: February 2025

Structurally diverse ensembles of intrinsically disordered proteins or regions are difficult to determine, because experimental observables usually report a conformational average. Therefore, in order to infer the underlying distribution, a set of experiments that measure different aspects of the system is necessary. In principle, there exists a set of cross-correlated relaxation (CCR) rates that report on protein backbone geometry in a complementary way. However, CCR rates are hard to interpret, because geometric information is encoded in an ambiguous way and they present themselves as a convolute of both structure and dynamics. Despite these challenges, CCR rates analyzed within a suitable statistical framework are able to identify conformations in structured proteins. In the context of disordered proteins, we find that this approach has to be adjusted to account for local dynamics via including an additional CCR rate. The results of this study show that CCR rates can be used to characterize structure propensities also in disordered proteins. Instead of using an experimental reference structure, we employed computational spectroscopy to calculate CCR rates from molecular dynamics (MD) simulations and subsequently compared the results to conformations as observed directly in the MD trajectory.
Structural insights of AKT and its activation mechanism for drug development
Authors: Kumar B. Harish , Kabekkodu Shama Prasada , Pai K. Sreedhara Ranganath
Published: February 2025

AKT1, a serine/threonine kinase, is pivotal in signaling and regulating cell survival, proliferation, and metabolism. This review focuses on the structural insights and the essential features required for its active conformation. AKT belongs to the AGC kinase group and has three isoforms: AKT1, AKT2, and AKT3. AKT has three functional regions: PH domain, kinase domain, and hydrophobic motif. AKT1 activation involves intricate conformational changes, including transitions in the αC-in, DFG-in, G-loop, activation loop, and PH domain out, S-spine and R-spine formation, as well as phosphorylation at Thr 308 and Ser 473, which enable AKT1 to adopt active conformation. The analysis highlights the limitations of the AlphaFold-predicted AKT1 structure, which lacks key elements of the active state, including ATP, magnesium ion coordination, phosphatidylinositol-(1,3,4,5)-tetraphosphate, substrate peptide, and phosphorylation at Thr 308 and Ser 473. This study underscores the necessity of these features for stabilizing the kinase domain and facilitating efficient substrate phosphorylation. By consolidating structural insights and activation mechanisms, this review aims to inform the development of computational models and targeted therapeutics for AKT1 activators in diseases such as hepatic ischemia–reperfusion injury, cerebral ischemia, acute hepatic failure, subarachnoid hemorrhage, and alzheimer’s disease.
Regulatory and Industry Perspective on the Model Master File Framework for Locally Acting Drug Products
Authors: Walenga Ross L. , Alam Khondoker , Clarke James F. , De Backer Jan , Fridén Markus , Hamadeh Abdullah , Mowli Jay , Sonti Sujatha , Spires Jessica , Tan Ming-Liang , Musuamba Flora T. , Tsakalozou Eleftheria
Published: February 2025

Graphical Abstract
Proxy reporting in health: a scoping review of instructions, perspectives, and reporting experiences
Authors: Dagne Henok , Doherty Kathleen , Campbell Julie , Saul Alice , Roydhouse Jessica
Published: February 2025

Background

Informal carers (‘proxies’), who typically provide unpaid care and have a personal relationship with the care recipient, are often asked to report on the health of individuals who are unable to self-report. However, this task is not without its challenges. Little is known about how proxies approach this task, which poses challenges for optimal questionnaire design.

Purpose

The review had three aims: (1) to identify the questionnaire perspective instructions provided to proxies i.e., whether the proxy was asked to answer from their own (proxy–proxy) or the person’s (proxy–patient) perspective when reporting, (2) identify which perspective instruction the proxies followed, if reported, and (3) what information, if any, was captured about the proxy’s experience of reporting about someone else. In the proxy–proxy perspective, proxies report from their own perspective, but in the proxy–patient perspective they report from the perspective of the person living with the condition.

Methods

A systematic search was conducted across Medline, Psych Info, CINAHL, and Embase. Only published articles meeting the criteria of informal carers providing proxy reports for adults were considered.

Results

Of 5816 publications, 60 articles were eligible for full-text review, and 12 were included for data extraction. Instructions varied, with proxies asked to adopt both proxy–proxy and proxy–patient perspectives in eight studies and only the proxy–patient in four of them. Whether proxies followed the provided instructions consistently is not known. Proxies’ reporting experiences were not reported in the included studies.

Conclusion

Proxies are provided with different perspective instructions, but proxy adherence to instructions is not known. Additionally, proxy reporting experience was not described. Providing clear instructions, evaulating proxy adherence to instructions and collecting proxies’ reporting experiences can inform optimal questionnaire design to help proxies better report about the health of others.

Review registration

Registered at open science framework: https://osf.io/j4t87.
Widerruf einer Einwilligung zur Anonymisierung: Möglich, aber ohne Auswirkungen
Authors: Kneuper Ralf
Published: February 2025

In seinem DuD-Beitrag untersucht Mannah die Herausforderungen beim Widerruf einer Einwilligung in
die Anonymisierung personenbezogener Daten. Anders als dort beschrieben ist das Widerrufsrecht auch in
diesem Fall anwendbar, da ein Widerruf die davor durchgeführte Verarbeitung nicht betrifft. Ein Widerruf
ist also möglich, auch wenn er ins Leere greift, wenn die Anonymisierung bereits abgeschlossen ist.
Situating high-level darknet drug vending: an emancipation from open and closed market drug dealing?
Authors: Joyce Thomas
Published: February 2025

While existing research has readily applied perspectives garnered from open and closed market dealing to conceptualise darknet drug vending, this has been done without clear empirical consideration of the applicability of traditional market dealing to darknet drug vending. This research addresses this gap by considering these three forms of drug dealing in light of key typological features: motivation, environment, methods, business model, and offender profile. These features are then applied to 80 arrest cases of high-level darknet vendors to determine their applicability in understanding vendor behaviour. The results show that high-level darknet drug vendors reflect the characteristics of their highly anonymised, libertarian market, distinguishing them from traditional drug sellers.
Sleep and binge eating in early adolescents: a prospective cohort study
Authors: Nagata Jason M. , Huynh Rachel , Balasubramanian Priyadharshini , Lee Christopher M. , Helmer Christiane K. , Ganson Kyle T. , Testa Alexander , He Jinbo , Lavender Jason M. , Kiss Orsolya , Baker Fiona C.
Published: February 2025

Purpose

To determine the prospective associations between sleep disturbance and binge-eating disorder and behaviors in a national sample of early adolescents in the United States (US).

Methods

We analyzed prospective cohort data from the Adolescent Brain Cognitive Development Study (N = 9428). Logistic regression analyses were used to determine the associations between several sleep variables (e.g., overall sleep disturbance, disorders of initiating and maintaining sleep [insomnia], duration; Year 2) and binge-eating disorder and behaviors (Year 3), adjusting for sociodemographic Year 2 binge-eating covariates.

Results

Overall sleep disturbance was prospectively associated with higher odds of binge-eating disorder (OR = 3.62, 95% CI 1.87–6.98) and binge-eating behaviors (OR = 1.59, 95% CI 1.17–2.16) 1 year later. Disorders of initiating and maintaining sleep were prospectively associated with higher odds of binge-eating disorder (OR = 1.12, 95% CI 1.05–1.19) and binge-eating behaviors (OR = 1.06, 95% CI 1.03–1.10). Sleep duration under 9 h was prospectively associated with greater binge-eating behaviors.

Conclusions

Sleep disturbance, insomnia symptoms, and shorter sleep duration were prospectively associated with binge eating in early adolescence. Healthcare providers should consider screening for binge-eating symptoms among early adolescents with sleep disturbance.

Level of evidence

Level III: Evidence obtained from well-designed cohort or case–control analytic studies.
Severe cognitive disability, medically complex children and long-term ventilation
Authors: Turnham Helen , Wilkinson Dominic
Published: February 2025

Children with complex medical conditions including those with severe intellectual disability are living longer. For some, support with medical technology such as Long-Term Ventilation can prolong their lives further. Such technological supports can have significant implications for the child and her family and consume considerable resources though they can also offer real benefits. Sometimes clinicians question whether children with very severe cognitive impairments should have their life prolonged by technology, though they would be prepared to provide the same treatment in equivalent cases without cognitive disability. We describe and analyse four ways in which this view might be justified. Although it could be claimed that children with severe cognitive disability have lives that are not worth living, in most cases this view can and should be rejected. However, the burdens of life-prolonging technology may outweigh the benefits of such treatment either in the present or in the future. Consequently it might not be in their interests to provide such technology, or to ensure that it is provided as part of a time-limited trial. We also consider circumstances where medical technology could offer modest benefits to an individual, but resources are scarce. In the face of resource imitation, treatment may be prioritised to children who stand to benefit the most. This may in some circumstances, justify selectively withholding treatment from some medically complex children.
Additive manufacturing of Ni62Nb38 metallic glass via laser powder bed fusion
Authors: Frey Maximilian , Wegner Jan , Ruschel Lucas Matthias , Barreto Erika Soares , Riegler Sascha Sebastian , Adam Bastian , Ellendt Nils , Kleszczynski Stefan , Busch Ralf
Published: February 2025

The binary Ni62Nb38 bulk metallic glass exhibits attractive mechanical properties like a yield strength of more than 3 GPa and a hardness of more than 900 Vickers. Due to its limited glass forming ability in casting processes, industrial applications of this impressive material are still pending. Additive manufacturing via laser powder bed fusion (PBF-LB/M) can allow to overcome these limitations. Therefore, we present the first PBF-LB/M parameter study on Ni62Nb38. We are able to achieve high densification and almost fully amorphous samples, thereby demonstrating the general applicability of PBF-LB/M to process binary amorphous Ni–Nb alloys. Furthermore, two challenges can be identified, which have to be addressed before additively formed Ni62Nb38 can be considered for commercial use. Future parameter fine-tuning must lead to fully vitrified samples, and one must also find a way to avoid crack formation during processing, which was found to be one of the main issues in the present study.
Crafting for Health: A Longitudinal Study of Job and Off-Job Crafting Changes during the COVID-19 Pandemic
Authors: Morstatt Anja Isabel , Bauer Georg F. , de Bloom Jessica , Roman Zachary J. , Tušl Martin , Kerksieck Philipp
Published: February 2025

We examined the association between changes in employee job and off-job crafting and their self-rated health during the COVID-19 pandemic. Further, we investigated how these associations differed across sample subgroups, contrasting differences in work location, living situation, and contractual changes (short-time work). We used four waves of a longitudinal dataset surveying NTotal = 783 German-speaking employees from Germany, Switzerland, and Austria from 2019 to 2021. We applied latent change score modeling and multigroup analyses to investigate our research questions. Results indicated that the mean job and off-job crafting and self-rated health trajectories remained relatively stable. However, we observed significant interindividual variance in job and off-job crafting changes. We found a consistent small positive relationship between crafting changes in both life domains over time, indicating that employees tended to change their crafting efforts similarly across domains. Additionally, job crafting increases between Waves 1 and 2 were linked to higher subsequent self-rated health at Wave 2, and similarly, off-job crafting increases between Waves 3 and 4 were linked to higher self-rated health at Wave 4. We observed only minor differences in this pattern across subgroups. Our results show how adaptive changes in crafting are linked to broader interindividual health differences and help identify groups who are not able to increase crafting during crises and thus could benefit from targeted support. Crafting can be an effective individual strategy for maintaining health, complementing organizational and public health measures. We encourage future research to incorporate temporal and contextual phenomena into crafting research.
Experimental and numerical evaluation of friction behaviour between hardwood timber and brick masonry in earth mortar: cyclic triplet shear test and pull-out test
Authors: Endo Yohei , Waki Y. , Goda T.
Published: February 2025

Brick masonry in earth mortar is a traditional construction technique still used in South and Southeast Asia. Timber beams and columns are often taken advantage of to improve the seismic performance of such structures. Nonetheless, the contribution of these timber elements has not been fully understood yet partially due to the complex friction behaviour between timber and masonry. In the present research, a cyclic loading triplet test is performed on two specimen types. In one type, units are fired solid bricks while in the other they are timber blocks. Joints are composed of earth mortar. Results between the two types are compared, paying attention to friction coefficients and damage patterns. Then, numerical analysis is performed to reproduce a previously performed pull-out test, taking advantage of the results obtained from the triplet test. Though the analysis, frictional behaviour between a timber beam and masonry wall in earth mortar was closely observed in terms of normal and shear stress distributions in the contact surfaces and the deformation of earth mortar. The test showed the contrasts of the frictional performance between brick–mortar and timber-mortar contact surfaces. The analysis suggested that it was effective to physically discretise earth mortar. In this way, frictional behaviour between a timber element and masonry wall was properly reproduced. This paper sheds light on the interaction between timber and brick masonry in earth mortar under lateral loading such as earthquakes.
Sphericity Test on Variance-Covariance Matrix with Monotone Missing Data
Authors: Sato Tetsuya , Yagi Ayaka , Seo Takashi
Published: February 2025

This study considers the sphericity test, a specific test of variance-covariance matrix under monotone missing data for a one-sample problem. We provide the likelihood ratio (LR) and derive an asymptotic expansion of the likelihood ratio test (LRT) statistic and modified LRT statistic for the null distribution. We also derive the upper percentiles of the LRT statistic and modified LRT statistic when the null hypothesis holds, and provide approximate upper percentiles. Furthermore, we prove that the LR under monotone missing data is affine invariant under the null hypothesis. For complete data, we provide an asymptotic expansion of the LRT statistic and modified LRT statistic for the null distribution. Furthermore, we numerically evaluate the actual type I error rates for the approximate upper percentiles using Monte Carlo simulation and provide examples of the LRT statistic and modified LRT statistic and approximate upper percentiles under monotone missing data.