bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of secondary radiation dose between pencil beam scanning and scattered delivery for proton and VHEE radiotherapy
Authors: Ronga Maria Grazia , Gesualdi Flavia , Bonfrate Anthony , Patriarca Annalisa , Ferrand Régis , Créhange Gilles , Buvat Irène , De Marzi Ludovic
Published: February 2025

Background

Very high‐energy electrons (VHEEs) in radiotherapy may offer several potential advantages over conventional electron beams and other techniques, for example, the fact that they can be used at ultra‐high dose rates (UHDRs), therefore enabling FLASH radiotherapy. However, the production of secondary particles at high energies (50–200 MeV) has yet to be studied in detail for this technique currently under development.

Purpose

The aim of this work was to examine the secondary dose produced by VHEEs, with particular emphasis on bremsstrahlung photons and neutrons, for two beam delivery systems (double scattering [DS] and pencil beam scanning [PBS]).

Methods

The electron, X‐ray, and neutron doses arising from two beam delivery systems (DS or PBS) were computed using Monte Carlo (MC) simulations in the TOPAS (TOol for PArticle Simulation)/Geant4 toolkit, and a preliminary assessment of the secondary dose for a clinical VHEE treatment was performed using a whole‐body phantom. An evaluation of the secondary dose produced by this preliminary design of a VHEE nozzle set in a clinical proton facility was performed, taking into account realistic PBS or DS nozzle configurations.

Results

The mean doses received by a patient undergoing DS‐VHEE irradiation were found to be up to 5.3‐fold and 6.8‐fold higher for in‐field or out‐of‐field organs for photons and neutrons, respectively, compared to the PBS‐VHEE plan. The results for the secondary neutron dose in intracranial treatments also demonstrate the characteristic of VHEE compared to proton beams for reducing the out‐of‐field secondary neutron dose. The dose to the public area that could be delivered to meet regulatory limits surrounding a possible treatment room in a proton therapy facility was assessed. A regulatory limit of 0.5 µSv/h would give a restriction of 49 and 83 Gy per patient and per fraction for DS and PBS, respectively.

Conclusions

This work describes a method to simulate and compare secondary radiation doses resulting from scattered, scanned VHEE or proton therapy treatments. The results indicate that a conventionally shielded proton therapy room results in acceptable public doses for a preliminary VHEE design and could be of interest for radiation protection purposes and for similar setups. Other facilities with differing layouts may, however, lead to different conclusions, requiring further studies.
Multiscale Topology Optimization Applying FFT‐Based Homogenization
Authors: Matsui Masayoshi , Hoshiba Hiroya , Nishiguchi Koji , Ogura Hiroki , Kato Junji
Published: February 2025

Advances in 3D‐printing technology have enabled the fabrication of periodic microstructures that exhibit characteristic mechanical performances. In response, multiscale topology optimization, which finds the optimal design of microstructure for the macrostructure geometry and performance requirements, has become a hot topic in the field of structural optimization. While the basic optimization framework based on the homogenization theory spanning macro and microscales is available, it is computationally expensive and not easily applicable in practical scenarios such as high‐resolution design for precision modeling and reliable design considering non‐linearities. To address this issue, we focus on a homogenization analysis using a fast Fourier transform as an alternative approach to conventional finite element analysis and develop an optimization method with fast computing speed and low memory requirements. In this paper, we define a simple stiffness maximization problem with linear elastic materials and conduct two and three‐dimensional optimization analyses to evaluate the validity and performance of the proposed method. We discuss the advantages of computational cost, the influence of the filtering process, and the appropriate setting of material contrast.
B,N‐Doped Activated Carbon‐Based Electrodes from Potato Peels for Energy Storage Applications
Authors: Straten Jan Willem , Alhnidi Muhammad‐Jamal , Alchoumari Ghassan , Sangam Krishna , Kruse Andrea
Published: February 2025

Potato peels (PPs) as waste biomass were selected as the biobased carbon source for this study, using urea as N precursor and boron trioxide as B precursor for the “in situ doping” via hydrothermal carbonization (HTC). During HTC, the feedstocks decompose over a wide range of complex chemical degradation mechanisms that finally form single B‐ and N‐ as well as B,N‐co‐doped hydrochars (HCs). Upon chemical ZnCl2 activation, the single B‐doped activated carbon (AC) possessed a maximum B content of 0.2 wt%, whereas co‐doped B,N‐AC had the highest N content of 5.7 wt% with a B content of 0.1 wt%. The influence of single and B,N‐co‐doping on the physical‐chemical material properties of the AC electrodes was analyzed and compared, in combination with its effect on the electrochemical performance for energy storage application. Compared to pristine AC derived from PPs, the B‐doped and B,N‐co‐doped AC depicted increased electrical conductivity (EC) values of 50.3 S ⋅ m−1 and 34.0 S ⋅ m−1, respectively. In addition, the B,N‐co‐doped AC unveiled the highest average specific capacitances of 51.7 F ⋅ g−1 at 100 mV ⋅ s−1 and of 71.9 F ⋅ g−1 at 5 mV ⋅ s−1 outperforming the specific capacitance values of the reference material AC from peat.
Variants of Uncertain Significance in Vascular Anomalies: The Role of Reclassification
Authors: Blatt Julie , Hildebrandt Clara , Nieman Elizabeth , Adams Michael C. , McNamee Lucy , Borst Alexandra J.
Published: February 2025

Background

Vascular anomalies (VA) are rare developmental disorders due to somatic variants in intracellular growth signaling pathways. Although genetic evaluation is considered the standard of care for optimizing management, the frequency of variants of uncertain significance (VUS) in VA and their clinical implications are not defined.

Methods

Medical records were reviewed on all patients seen in our VA clinic from January 2014 to August 2024 with vascular malformations or related disorders who had undergone genetic testing. The year and patient age at the time of genetic testing, whether testing was done on peripheral blood or involved tissue, and results were noted. Laboratory vendors were queried about policies for reclassifying VUS and selective re‐evaluations of VUS were requested.

Results

In all, 154 patients underwent single gene or gene panel evaluations, with the number of patients tested increasing from zero in 2014 to 39 in 2023; 21 patients had testing done during the first 7 months of 2024. VUS were reported in 22 patients (14%). Many laboratory vendors maintain a policy of revisiting these nonpathogenic variants only when requested by the treating physician. Unsolicited reclassification was reported in a single patient whose VUS was found to be a normal variant. No changes were identified in six other patients whose VUS were re‐examined.

Conclusions

VUS are not uncommon in VA. Reclassification may be possible as more variant‐specific data become available and more testing is performed. Centers need to be aware that reclassification efforts are not automatic and should be considered where changes in therapy might result.
Comparison of Analytical Methods Used for Standardization of Triterpenoid Saponins in Herbal Monographs Included in the Russian and Other Pharmacopeias
Authors: Frolova Larisa N. , Kovaleva Elena L. , Shelestova Valentina V. , Kuteynikov Vladislav Yu. , Flisyuk Elena V. , Pozharitskaya Olga N. , Shikov Alexander N.
Published: February 2025

Introduction

Harmonization of methodological approaches to the analysis of herbal substances containing triterpenoid saponins, considered the largest group of phytochemicals, is essential for the pharmaceutical industry worldwide.

Objectives

This review aimed to perform a comparative analysis of the requirements for the standardization of herbal substances, herbal medicinal products (HMPs), and other herbal materials containing triterpenoid saponins in the pharmacopeial texts of the Russian Federation and the world's leading pharmacopeias.

Materials and Methods

The review covers the data on the quantitative and qualitative analysis of herbal substances containing triterpenoid saponins, as presented in the State Register of Medicinal Products of Russia and the monographs of the world's leading pharmacopeias: the European Pharmacopeia, United States Pharmacopeia, British Pharmacopeia, Japanese Pharmacopeia, and the national pharmacopeias of the Eurasian Economic Union (EEU) Member States.

Results

This review compares and discusses the analytical methods used for the standardization of Aesculus hippocastanum L. seeds, Aralia elata (Miq.) Seem roots, Glycyrrhiza spp. roots, Orthosiphon aristatus (Blume) Miq. leaves, and Polemonium caeruleum L. rhizomes with roots. The most common analytical methods used are (HP)TLC and (U)HPLC. The Russian Pharmacopeia also includes titrimetry and spectrophotometry.

Conclusions

The appropriate selection of a group of biologically active compounds for HMP standardization is still challenging. We believe that a rational approach to the standardization of herbal substances and HMPs should be based on the use of herbal substances with maximum extractability and specific pharmacological activity. The harmonized procedures and reference substances for the identification and assay of active metabolites in HMPs must be implemented at all stages of production control from herbal substances to finished dosage forms.
Experimental study of the effect of nanoparticles on liquid jet in airflow spinning
Authors: Tian Hongliu , Gao Ya , Zeng Lian , Wang Yudong , Sun Guangwu , Xiao Changfa
Published: February 2025

Airflow spinning involves a polymer nanocomposite solution composed of nanoparticles and a polymer solution extruded through spray holes and then blown and finely deposited by a high‐speed gas jet onto a mesh curtain to form a composite fiber material. It is widely used in various fields owing to its high efficiency. To investigate the effect of the nanoparticles on the fibers, online high‐speed camera observations were used to capture the dynamics of the liquid jets (liquid jets online and fibers when deposited on the mesh curtain) in the nozzle exit region after the addition of nanoparticles. Because the initiation and propagation of a liquid jet are three‐dimensional processes, two orthogonal planes that can provide a large amount of information regarding the motion of fiber particles were selected for observation in this study. The results indicated that the difference between the liquid‐jet diameters observed in the two planes was approximately within 20 μm. The nanoparticles accelerate the decay of the liquid‐jet diameter to different extents. Moreover, it increases the probability of defects such as shots. Additionally, we studied the effects of different nanoparticle sizes and concentrations on liquid‐jet dynamics. A new explanation for shot formation was proposed. The findings of this study provide valuable insights into the three‐phase flow in the field of spinning and a solid experimental foundation for the development of composite fibers.

Highlights

The diameter of the liquid jet differs by 10–20 microns in two planes.

First study of three‐phase flow with nanoparticles in air spinning.

Explained “shots” formation through experiments and simulations.
Patient and Family Caregiver Perspectives on Therapy De‐Escalation in Cancer: A Scoping Review
Authors: Hamilton Rachel , Hashemi Elham , Uthayakumar Annothayan , Liang Megan , Mayo Samantha , Parker Kellee , Jibb Lindsay
Published: February 2025

Background

Cancer therapy de‐escalation aims to reduce treatment intensity, minimizing the burden of short‐ and long‐term toxicities on patients and family caregivers while maintaining current survival rates. While this approach holds potential benefits, it comes at a risk of worse patient health outcomes or treatment failure. An understanding of patient and family caregiver perspectives regarding cancer therapy de‐escalation is required to design successful patient‐and‐caregiver‐informed clinical trials, and optimally provide related patient‐centered care.

Aim

To identify and synthesize the literature about patient and family caregiver perspectives of cancer therapy de‐escalation to guide clinical care, research, decision‐support resources, and education.

Methods

Following the Joanna Briggs Institute methodology, a systematic literature search was conducted in MEDLINE, EMBASE, PsycINFO, and CINAHL. We included quantitative, qualitative, and mixed‐methods studies involving patients of all ages and cancer diagnoses and their family caregivers that focused on perceptions of cancer therapy de‐escalation. Extracted data were organized according to the Framework for De‐implementation in Cancer Care Delivery. Study quality was appraised.

Results

Twenty studies were included. De‐escalation perspectives varied between patients and family caregivers, with factors including clinician trust and desire to improve quality of life noted as influential in de‐escalation decisions. The decision‐making process could be better supported through the provision of timely patient and family caregiver information and clinician communication training.

Conclusion

Cancer therapy de‐escalation decisions are complex and multifactorial. Future research exploring which factors influence patient and family decision‐making may offer insight into the design of optimal informational and supportive interventions.
Advances in Permafrost Representation: Biophysical Processes in Earth System Models and the Role of Offline Models
Authors: Matthes Heidrun , Damseaux Adrien , Westermann Sebastian , Beer Christian , Boone Aaron , Burke Eleanor , Decharme Bertrand , Genet Hélène , Jafarov Elchin , Langer Moritz , Parmentier Frans‐Jan , Porada Philipp , Gagne‐Landmann Anna , Huntzinger Deborah , Rogers Brendan M. , Schädel Christina , Stacke Tobias , Wells Jon , Wieder William R.
Published: February 2025

Permafrost is undergoing rapid changes due to climate warming, potentially exposing a vast reservoir of carbon to be released to the atmosphere, causing a positive feedback cycle. Despite the importance of this feedback, its specifics remain poorly constrained, because representing permafrost dynamics still poses a significant challenge for Earth System Models (ESMs). This review assesses the current state of permafrost representation in land surface models (LSMs) used in ESMs and offline permafrost models, highlighting both the progress made and the remaining gaps.

We identify several key physical processes crucial for permafrost dynamics, including soil thermal regimes, freeze–thaw cycles, and soil hydrology, which are underrepresented in many models. While some LSMs have advanced significantly in incorporating these processes, others lack fundamental elements such as latent heat of freeze–thaw, deep soil columns, and Arctic vegetation dynamics. Offline permafrost models provide valuable insights, offering detailed process testing and aiding the prioritization of improvements in coupled LSMs.

Our analysis reveals that while significant progress has been made in incorporating permafrost‐related processes into coupled LSMs, many small‐scale processes crucial for permafrost dynamics remain underrepresented. This is particularly important for capturing the complex interactions between physical and biogeochemical processes required to model permafrost carbon dynamics. We recommend leveraging advancements from offline permafrost models and progressively integrating them into LSMs, while recognizing the computational and technical challenges that may arise in coupled simulations. We highlight the importance of enhancing the representation of physical processes, including through improvements in model resolution and complexity, as this is a fundamental precursor to accurately incorporate biogeochemical processes and capture the permafrost carbon feedback.
Developing a Neonatal Pulmonary Hypertension Core Outcome Set (NeoPH COS)—A Study Protocol
Authors: Morgan Cara Ellen , Woolfall Kerry , Aikman Natasharazia , Gale Crhistopher , Subhedar Nimish ,   the RePHyNe Consortium
Published: February 2025

Pulmonary hypertension (PH) in newborn babies is a relatively rare, heterogeneous condition that has high associated mortality in the neonatal period and beyond. There are limited evidence‐based strategies to treat or prevent this condition. Over the last two decades, there has been an increase in the number of studies assessing new therapies and treatment strategies in babies with PH. However, comparison of different treatments between studies is limited by inconsistency in outcome reporting. To address this issue, we aim to develop a core outcome set (COS) for neonates and infants less than 3 months of age, corrected for prematurity, diagnosed with PH, through international consensus with key stakeholders including parents and/or guardians, healthcare professionals and researchers. The development of the COS will be divided into two stages: (1) identification of potential outcomes through a mixed methods systematic literature review and qualitative interviews with parents and/or guardians of babies with pulmonary hypertension; (2) determining core outcomes through an online Delphi survey and consensus meeting. An advisory group with global membership including parents and/or guardians, healthcare professionals, and researchers recruited internationally was formed to guide the COS. The methodology utilized to develop a neonatal PH COS aims to ensure applicability and adoption in international settings and relevance across disciplines. The COS will help to improve trial design and homogeneity of outcomes reported in neonatal trials of PH. This will translate into higher‐quality evidence for therapeutic strategies for PH in neonates.
Pulmonary Enteric Adenocarcinoma in a Super‐Elderly Patient: A Case Report and Literature Review
Authors: Shimamoto Akira , Kojo Natsumi , Saiki Haruko , Hayashi Akinobu , Takao Motoshi
Published: February 2025

Pulmonary enteric adenocarcinoma (PEAC) is an extremely rare subtype of non‐small cell lung cancer, characterised by histopathological features that resemble colorectal adenocarcinoma. Here, we report a case of PEAC in an 85‐year‐old male who presented with a pulmonary nodule initially identified at the age of 76. Initial PET‐CT (maximum standardised uptake value [SUVmax] = 2.8) was inconclusive, leading to strict follow‐up. Over 9 years, the nodule enlarged significantly (3.2 cm, SUVmax = 8.4). A transbronchial biopsy confirmed adenocarcinoma, and the patient underwent successfully video‐assisted thoracoscopic surgery with lymph node dissection. The histopathological analysis revealed CK7 and CK20 positivity, focal CDX2 positivity, and TTF‐1 negativity, confirming PEAC. Despite advanced age, the patient tolerated surgery well without adjuvant therapy. At the one‐year postoperative follow‐up, he remained disease‐free. This case emphasises the diagnostic utility of immunohistochemistry and the feasibility of surgical management, even in super‐elderly patients with PEAC.
Hybrid Photoelectrodes Based on Electropolymerized Conjugated Porous Polymers for Enhanced Solar Energy Conversion
Authors: Alfonso‐González Elena , Gomez‐Mendoza Miguel , López‐Calixto Carmen G. , García‐Tecedor Miguel , Villar‐García Ignacio J. , Oropeza Freddy , Liras Marta , Barawi Moran Mariam , de la Peña O´Shea Víctor A.
Published: February 2025

This work highlights and offers fundamental insights on the potential of electropolymerized conjugated porous polymers in developing efficient hybrid photoelectrodes for photoelectrochemical applications. A simple and cost‐effective electropolymerization strategy to create hybrid organic–inorganic photoelectrodes based on two thiophene‐based conjugated porous polymers (CPP‐3TB and IEP‐19) for enhanced solar energy conversion is used. These polymers, when integrated with TiO2 to form hybrid photoanodes, exhibit enhanced photopotentials and photocurrents compared to bare TiO2. This synergetic behavior is attributed to an increased visible light absorption, reduced charge transfer resistance, and minimized electron–hole recombination. In particular, detailed electrochemical and spectroscopic analyses, including electrochemical impedance spectroscopy and transient absorption spectroscopy, reveal that the hybrid systems’ superior charge transport and longer photogenerated charge lifetimes contribute to their increased efficiency in solar energy conversion. Moreover, by comparing the structure and behavior of both hybrid systems, corner stone knowledge for the synthesis of CPPs to guide the construction of the future photoelectrochemical cells for solar energy conversion is offered.
Interdisciplinary Approach to Monkeypox Prevention: Integrating Nanobiosensors, Nanovaccines, Artificial Intelligence, Visual Arts, and Social Sciences
Authors: Chaudhary Vishal , Lucky Lucky , Sable Harsh , Bhalla Nikhil
Published: February 2025

To effectively address crisis emergence of new virus such as monkeypox, a collective and collaborative effort between scientists, engineers, innovators, and artists from all ages, regions, and diverse fields is required. This review explores a holistic approach to addressing the monkeypox crisis by integrating nanobiosensors, artificial intelligence, visual arts, humanities, and social sciences. Traditional diagnostic methods are often limited by time, accessibility, and accuracy, but the advancement of point‐of‐care smart nanobiosensors offers a promising shift toward rapid, precise, and accessible diagnostics. They enhance the ability to screen, diagnose, and monitor monkeypox infections efficiently, contributing to better disease management. Beyond technological innovation, the essential role of arts, humanities, and social sciences in fostering public engagement, understanding, and acceptance of new diagnostic tools is emphasized. Visual arts can illustrate scientific concepts, making them more relatable, while storytelling through various media can reduce stigma and promote preventive measures. Social sciences provide insights into cultural attitudes, behaviors, and public health challenges, ensuring that technological solutions are effectively integrated into diverse communities. By combining these disciplines, this review presents a comprehensive framework for a more resilient global health system that aligns with One Health principles, emphasizing the interconnectedness of human, animal, and environmental health.
DigiLex—A Checklist for the Evaluation of Digital Tools for Second and Foreign Language Lexical Learning
Authors: Lehmkuhl Paulina , Wagner Benedikt , Frisch Stefanie , Rumlich Dominik , Visser Judith
Published: February 2025

The use of digital tools for second and foreign language lexical learning is increasingly popular and research in this area is constantly expanding. However, little has been written about specific criteria that could be used to identify tools with high‐quality lexical input, as available checklists and frameworks for digital media tend to neglect detailed analyses of the vocabulary domain. This article addresses this issue by presenting the Checklist for Evaluating Digital Resources for Lexical Learning (DigiLex), which combines important digital language learning criteria with an extensive evaluation of lexical content. The checklist is both theory‐based and user‐friendly, aiming to fill a gap between theory and practice in the field of digital lexical learning. The article discusses the theoretical basis of the checklist and integrates the results of a small pilot study with pre‐service and in‐service teachers, emphasizing feasibility in everyday learning and teaching. By providing an easy‐to‐use tool for identifying suitable digital resources, the DigiLex checklist aims to support language learners and teachers in self‐regulated lexical learning.
Complicated Conversation as Curriculum in Language Teacher Education Amid Rapid Change
Authors: Salerno April S. , Kibler Amanda K. , Andrei Elena
Published: February 2025

As language teacher educators, we consider how times of flux bring opportunities for re‐envisioning curriculum as conversation. We have found ourselves and our students to be situated at the nexus of tensions between sometimes fast‐moving societal shifts and sometimes slow‐moving changes in educational systems and institutions. One approach we have found for bridging the fast and the slow worlds is to rethink how we define curriculum. We draw from Pinar (1995) in re‐envisioning curriculum as “complicated conversation” between teachers and students. Pinar and colleagues view curriculum as verb (currere, or “to run” in Latin) in which students' lived experiences – combined with planned materials – become the curriculum. In this teaching issues article, we explore how we as teacher educators have engaged our students (who are current, in‐service teachers) in complicated conversation around recent moments of flux. We consider examples of how, in our English as a Second Language teacher‐education courses, we have talked with teachers about two such moments: advocating for students amid recent global conflicts and navigating the advent of artificial intelligence. We underscore the idea that curriculum as currere requires a balance between being responsive and proactive.
Are Electric Vehicles Always Green? An Argumentation for the Need of Narrative Change
Authors: Matusiewicz Maria
Published: February 2025

This investigation examines the impact of electric vehicle (EV) adoption on greenhouse gas (GHG) emissions across European Union countries between 2012 and 2021. Employing multi‐method analysis, it assesses the correlation between EV usage and GHG emission trends. Despite EU policies promoting EVs to reduce emissions, our findings indicate a complex and nonlinear relationship, with no clear evidence of significant emission reductions directly attributed to increased EV usage. This study underscores the intricate interplay between EVs, GHG emissions, and external factors like electricity generation sources and the environmental footprint of EV production and disposal. Our results advocate for a comprehensive approach to emission reduction, emphasizing the need for renewable energy integration and region‐specific strategies. This research adds to the sustainable transportation dialogue, highlighting the necessity of nuanced, informed policymaking that considers the diverse environmental impacts of Evs.
Genomic and phenomic prediction for soybean seed yield, protein, and oil
Authors: Van der Laan Liza , Parmley Kyle , Saadati Mojdeh , Pacin Hernan Torres , Panthulugiri Srikanth , Sarkar Soumik , Ganapathysubramanian Baskar , Lorenz Aaron , Singh Asheesh K.
Published: February 2025

Developments in genomics and phenomics have provided valuable tools for use in cultivar development. Genomic prediction (GP) has been used in commercial soybean [Glycine max L. (Merr.)] breeding programs to predict grain yield and seed composition traits. Phenomic prediction (PP) is a rapidly developing field that holds the potential to be used for the selection of genotypes early in the growing season. The objectives of this study were to compare the performance of GP and PP for predicting soybean seed yield, protein, and oil. We additionally conducted genome‐wide association studies (GWAS) to identify significant single‐nucleotide polymorphisms (SNPs) associated with the traits of interest. The GWAS panel of 292 diverse accessions was grown in six environments in replicated trials. Spectral data were collected at two time points during the growing season. A genomic best linear unbiased prediction (GBLUP) model was trained on 269 accessions, while three separate machine learning (ML) models were trained on vegetation indices (VIs) and canopy traits. We observed that PP had a higher correlation coefficient than GP for seed yield, while GP had higher correlation coefficients for seed protein and oil contents. VIs with high feature importance were used as covariates in a new GBLUP model, and a new random forest model was trained with the inclusion of selected SNPs. These models did not outperform the original GP and PP models. These results show the capability of using ML for in‐season predictions for specific traits in soybean breeding and provide insights on PP and GP inclusions in breeding programs.
Duodenal Laser Ablation for Treatment of Type 2 Diabetes: Results of First in Human Study
Authors: Kovarova Viktorie , Lankova Ivana , Machytka Evzen , Knotkova Katerina , Kratochvílová Helena , Beneš Marek , Spicak Julius , Vasura Adam , Goldin Eran , Munter Gavriel , Zima Tomas , Mraz Milos , Dagan Hila , Levy Brian , Haluzik Martin , Kral Jan
Published: February 2025

Background

Diabetes mellitus (DM) significantly impacts global health and economies. Despite various therapies, managing DM remains challenging. Bariatric surgery has shown efficacy in obese patients with type 2 diabetes mellitus (T2DM), but its utilization remains low. Innovative, less invasive endoscopic approaches such as duodenal mucosal resurfacing show potential in treating T2DM. This article presents the results of a First in Human (FIH) study using a duodenal submucosal laser ablation investigational device for T2DM treatment.

Methods

A prospective, single‐arm, open‐label study evaluated the safety and efficacy of the Digma System Endoscopic procedure for duodenal submucosal laser ablation in consecutive enrolled T2DM patients.

Results

The study was conducted from July 2017 to December 2020 and enrolled 31 patients for the Digma System Endoscopic procedure. The Dose Escalation Cohort (DEC) used sub‐therapeutic laser doses for training and safety. The Treatment Cohort (TC) of 25 patients received therapeutic doses, resulting in HbA1c reductions of −0.6% at 6 months (p = 0.014) and −0.4% at 12 months (p = 0.062). Fasting glucose dropped 17.3 mg/dL (p = 0.173) at 6 months and 28 mg/dL (p = 0.022) at 12 months. Post‐prandial glucose improvements were also observed. HOMA‐IR improved at 3 and 6 months. PAGI‐SYM and PAGI‐QOL showed stable to slightly improved GI symptoms and quality of life. Two severe adverse events were unrelated to the procedure.

Conclusion

The study demonstrates the safety, feasibility, and potential efficacy of the Digma System Endoscopic procedure. Evidence suggests improvements in HbA1c, fasting and post‐prandial glucose, and HOMA‐IR levels could be attributed to the Digma System Endoscopic procedure.
Higher-order gaugino condensates on a twisted $$ {\mathbbm{T}}^4 $$
Authors: Anber Mohamed M. , Poppitz Erich
Published: February 2025

Abstract

We compute the gaugino condensates,

$$ \left\langle {\Pi}_{i=1}^k\textrm{tr}\left(\uplambda \uplambda \right)\left({x}_i\right)\right\rangle $$

Π

i
=
1

k

tr

λλ

x
i

for 1 ≤ k ≤ N − 1, in SU(N) super Yang-Mills theory on a small four-dimensional torus

$$ {\mathbbm{T}}^4 $$

T
4

, subject to ’t Hooft twisted boundary conditions. Two recent advances are crucial to performing the calculations and interpreting the result: the understanding of generalized anomalies involving 1-form center symmetry and the construction of multi-fractional instantons on the twisted

$$ {\mathbbm{T}}^4 $$

T
4

. These self-dual classical configurations have topological charge k/N and can be described as a sum over k closely packed lumps in an instanton liquid. Using the path integral formalism, we perform the condensate calculations in the semi-classical limit and find, assuming gcd(k, N) = 1,

$$ \left\langle {\Pi}_{i=1}^k\textrm{tr}\left(\uplambda \uplambda \right)\left({x}_i\right)\right\rangle $$

Π

i
=
1

k

tr

λλ

x
i

=

$$ {\mathcal{N}}^{-1} $$

N

−
1

N
2 (16π
2Λ3)
k
, where Λ is the strong-coupling scale and

$$ \mathcal{N} $$

N

is a normalization constant. We determine the normalization constant, using path integral, as

$$ \mathcal{N} $$

N

= N
2, which is N times larger than the normalization used in our earlier publication [1]. This finding resolves the extra-factor-of-N discrepancy encountered there, aligning our results with those obtained through direct supersymmetric methods on ℝ
4. The normalization constant

$$ \mathcal{N} $$

N

can be understood within the Euclidean path-integral framework as the Witten index I

W
. From the Hamiltonian approach, it is well-established that I

W
= N. While the value

$$ \mathcal{N} $$

N

= N
2 correctly reproduces the condensate result, this discrepancy between the Hamiltonian and path-integral formulations calls for reconciliation. We attempt to provide a potential solution we outline in our discussion.
Towards an automated evaluation of design processes—an algorithm to predict critical situations during concept synthesis
Authors: Zimmerer Christoph , Wittig Christoph , Matthiesen Sven
Published: February 2025

In design research, there is a need for research methods that allow for larger numbers of participants in empirical studies, as small sample sizes lead to less statistically reliable results. The number of participants is limited by current research methods, such as protocol analysis, interviews, or analysis of eye tracking videos, because they require a lot of manual work during the evaluation. This is particularly noticeable in studies that analyze the cognitive processes of designers, e.g., during concept synthesis. Therefore, the goal of this paper is to develop an algorithm that automates the analysis of eye tracking data to predict designer perceived difficulties—critical situations in which methodical support could be beneficial—during design processes. By linking eye tracking data with retrospective think aloud data, a dataset was created for training different machine learning algorithms. The dataset was further processed, and three algorithms were evaluated regarding their suitability for automated detection of difficulties. The best algorithm, a cascading one-against-all classifier, achieved an accuracy of 62% and a false-negative rate of 26.6%. Depending on the type of difficulty, different eye tracking features were relevant for the decisions of the algorithms, highlighting the importance of tailored feature selection for each type of difficulty. The findings suggest that the automated analysis of eye tracking data using machine learning potentially facilitates larger studies and statistically more reliable findings, representing a significant step toward more efficient and insightful analysis of design cognition.
Non-melanoma skin cancer of the external auditory canal: long-term outcomes of a tertiary head and neck unit
Authors: Apthorp Eleanor , Lam Rebecca , Obholzer Rupert , Jeannon Jean-Pierre , Oakley Richard , Rovira Aleix
Published: February 2025

Purpose

External auditory canal (EAC) skin cancer is often diagnosed at advanced stages, leading to poor survival outcomes. Our study aims to describe disease characteristics, treatments and outcomes of patients with EAC cancer, increasing understanding of the management of this rare disease.

Methods

Retrospective, observational study including patients with non-melanoma EAC skin cancer treated at Guy’s and St Thomas’ Head and Neck Unit from 2012 to 2021, with follow-up until October 2023. Patient with EAC or auricular primaries extending into the EAC were included. Demographic, histopathological, and surgical data were obtained from electronic records.

Results

Thirty-eight patients were included, 86.8% treated with curative intent. The median follow-up was 49.9 months. One, three, and five-year overall survival for patients treated curatively were 100%, 96.9% and 75.3%, respectively, versus 40.0%, 0.0% and 0.0% for palliative. 68.4% had advanced disease (Pittsburgh staging, III: 18.4%, IV: 50.0%). 39.5% were treated after recurrent or persistent disease. Histological subtypes included squamous cell carcinoma (60.5%), basal cell carcinoma (26.3%) and others (13.2%). Among those treated surgically (n = 31), 74.2% underwent lateral temporal bone resection and 29.0% wide local excision. 83.9% had parotidectomy, neck dissection or both. 51.6% received post-operative radiotherapy/chemoradiotherapy. Advanced stage was significantly associated with reduced overall survival (p = 0.05) but not disease-free survival (p = 0.25). No primary site features, regional metastasis (p = 0.63), direct parotid invasion (p = 0.71) or age (p = 0.15) significantly impacted survival.

Conclusion

According to the good outcomes reported, this study suggests lowering the threshold for radical treatment may improve outcomes for patients with potentially poor prognostic features.
Clinical effectiveness of dupilumab in CRSwNP: unaffected by baseline nasal polyp size in real-world settings
Authors: Habenbacher Michael , Moser Ulrich , Abaira Ahmed , Kiss Peter , Holzmeister Clemens , Pock Jakob , Walla Katharina , Lang Angelika , Andrianakis Alexandros
Published: February 2025

Purpose

This study aimed to investigate the impact of baseline nasal polyp score (NPS) on the effectiveness of dupilumab treatment in patients with chronic rhinosinusitis with nasal polyps (CRSwNP).

Methods

In this retrospective observational study, 80 CRSwNP patients treated with dupilumab 300 mg biweekly at a tertiary referral center were stratified according to the baseline NPS into two groups: low-NPS (< 5) and high-NPS (≥ 5). Treatment outcomes were evaluated at the 6-month follow-up visit and compared.

Results

Both groups showed significant clinical improvements. The NPS decreased significantly in both low- and high-NPS groups, from a mean score of 3.2 to 0.8 and from 6.1 to 1.4, respectively (p < 0.001 for both). SNOT-22 scores improved significantly in both groups (p < 0.001 for both), though the reduction was greater in the high-NPS group (35.5 vs. 23.9, p = 0.018). There were no significant differences between low- and high NPS groups in proportions of NPS reduction of ≥ 1 (89% vs. 95%, p = 0.396) and clinically significant SNOT-22 improvement (= reduction > 12 or follow-up SNOT < 40; 80% vs. 86%, p = 0.544).

Conclusions

Our results suggests that dupilumab is effective in CRSwNP treatment, regardless of baseline nasal polyp size. Both small and large polyp groups showed significant improvements in NPS and patient-reported outcome measures. Future, prospective studies are warranted to validate these findings.
Efficacy and safety of patiromer for hyperkalemia: a randomized, placebo-controlled phase 3 study
Authors: Kashihara Naoki , Okada Hirokazu , Suzuki Yusuke , Iwamoto Tamio , Yasutomi Masashi , Matsui Masaru , Takezawa Ryo , Ishii Takayuki , Tomioka Yusuke
Published: February 2025

Background

This is the phase 3 study in Japan designed to verify the superiority of patiromer over placebo using the change in serum potassium level (sK-level).

Methods

This study was a multicenter, randomized withdrawal study targeting Japanese hyperkalemic patients. It consisted of the run-in period and the double-blind period. The run-in period was an active single-arm, open-label period (4 or 5 weeks). The double-blind period was a randomized, placebo-controlled, parallel-group, double-blind period (4 weeks). Patients whose sK-level was within the normal range at week 4 or 5 of the run-in period entered the double-blind period. Patients who entered the double-blind period were randomly assigned to the patiromer group or the placebo group.

Results

As a result of the primary analysis, the change of the sK-level (95% CI) from baseline to week 4 in the double-blind-period, was – 0.02 (– 0.19, 0.15) mmol/L in the patiromer group, and 0.78 (0.60, 0.96) mmol/L in the placebo group, with a statistically significant difference between the two treatment groups (p < 0.001). Similarly, statistically significant differences were also observed between the two groups at weeks 1, 2, and 3. Furthermore, the proportion of patients whose sK-level was maintained within the normal range were statistically significantly higher in the patiromer group than in the placebo group at all time points. No adverse events requiring particular attention were observed.

Conclusion

Patiromer can improve hyperkalemia by lowering sK-level and can suppress the recurrence of hyperkalemia with continued administration, and is safe and easy-to-use for a wide range of patients.
Prevention of bisphosphonate-related osteonecrosis of the jaw with basic fibroblast growth factor: an experimental study in rats
Authors: Kurokawa Satoshi , Yagyuu Takahiro , Funayama Naoki , Imada Mitsuhiko , Kirita Tadaaki
Published: February 2025

Bisphosphonate-related osteonecrosis of the jaw (BRONJ), characterized by persistent jaw bone exposure, is believed to result from the inhibition of bone remodeling and wound healing, often associated with potent intravenous bisphosphonates such as zoledronic acid (ZA). These bisphosphonates are known to significantly impact the healing of soft and bone tissues due to their anti-angiogenic properties. Our study aimed to explore whether applying the basic fibroblast growth factor (bFGF), known for its ability to promote angiogenesis and bone remodeling, over extraction sockets could prevent the onset of BRONJ in rats administered with ZA. The experimental protocol involved administering each rat with two intravenous injections of 60 μg/kg of ZA, followed by tooth extraction. Rats were then divided into two groups: the test group (n = 12), which had a mixture of 3% hydroxypropyl cellulose (HPC) and 0.3% bFGF applied over their extraction sockets, and the control group (n = 12), which received only a 3% HPC application. Wound healing was monitored for 8 weeks post-extraction and assessed using micro-computed tomography, histological evaluations, and immunohistochemical analysis of CD31- and CD105-positive vessels. Results showed a BRONJ incidence rate of 100% (12/12) in the control group, whereas the rate was significantly lower in the test group at 8.3% (1/12). Furthermore, the test group demonstrated marked increases in both angiogenesis and new bone formation. Our findings suggest that the local application of bFGF might serve as an effective therapeutic approach to prevent the onset of BRONJ following tooth extraction in patients receiving bisphosphonate therapy.
Hunting Iberian ibex: from a threat factor to a conservation tool
Authors: Pérez Jesús M. , Mesa-Pérez Fabiola , Fernández-Muñoz María J. , Granados José E. , Fandos Paulino , Soriguer Ramón C. , Acevedo Pelayo , Refoyo Pablo , Barreñada Enrique , Peral Juan Carlos , Fernández-Arias Alberto , Martínez José A. , Vargas María J. , Rubio Montserrat , López-Martín Josep M. , Olivé-Boix Xavier , Serrano Juan J. , Carro Francisco , Modesto María J. , Lara José , Gil-Carrera Alberto , López-Montoya Antonio J.
Published: February 2025

In this study we have compiled the information from official databases about Iberian ibex, Capra pyrenaica, hunting yields, hunting trophies and hunting licenses in the Spanish regions where the species is present and hunted. Such quotas showed an increasing trend between 2005–2021 and, on average, during this period, ≈ 6400 animals were yearly harvested. Despite this number decreased in 2019 and 2020 (in this last year, mainly due to the lock down caused by the COVID pandemia), the annual quota raised, reaching over 12,000 ibexes in 2021. The number of trophies increased since the 1970s and peaked in the period 2001–2005, and then declined during the period 2006–2020. At national level, the number of hunting licenses decreased from 2006 to 2021 by a 36.5%. The regional average hunting yield was significantly correlated with a regional-based ibex abundance estimation. The current situation of continued population increase together with the trophy reduction might suggest that the overall population is exceeding the carrying capacity. In this context, if hunting activity was one of the main factors involved in local extinction of the species, currently it should be considered a tool for sustainable managing of ibex populations in an scenario of increasing demographic trends and generalized absence of predators.
Chitin and its effects when included in aquafeed
Authors: G. Pascon , R. Opere Akinyi , G. Cardinaletti , E. Daniso , M. Messina , F. Tulli
Published: February 2025

Chitin, the second most abundant polysaccharide in nature after cellulose, has been the subject of increasing interest in recent years, particularly in the aquaculture sector. This review focuses on the effects of chitin in aquafeed on growth, nutrient utilization, gut microbiome modulation, and the immune system of aquatic organisms. Data from the literature showed significant variability in response to chitin by species, with some species benefiting from dietary chitin supplementation in terms of growth and immune health. However, excessive chitin inclusion led to negative effects on the protein and lipid digestibility. These results suggest that optimizing the amount of chitin-containing ingredients in aquafeed requires a deep understanding of each species’ nutritional needs and other studies needed for different aquaculture species. Furthermore, studies have highlighted the potential of chitin as an immunostimulant and promoter of gut health. In conclusion, chitin appears to be a promising additive for sustainable aquaculture, but further research is needed to define best practices for its use.
Pushed to the Edge? Entrepreneurs with Disabilities and the Post-socialist Experience of Ableism
Authors: Csillag Sára , Svastics Carmen , Hidegh Anna Laura , Győri Zsuzsanna
Published: February 2025

In this study, we examine the narratives of Hungarian entrepreneurs with disabilities (EWD) of the post-socialist era, using microhistory. Our research question concerns how ableism appears in the lives of EWD and how the aftermath of socialism emerges in their experience of ableism. We believe that a state-socialist past influences the lives and careers of EWD in a way that is unique in entrepreneurial and disability literature. Drawing on the accounts of 29 Hungarian entrepreneurs, we identified four mechanisms that make post-socialist ableism specific: invisibility; passivity and welfare dependency; the legitimacy of disability organisations; as well as the limitations of economic participation. Our research suggests that these effects, embedded in the current political, social, and economic environment, can only change slowly and over a long time.
Substrate preferences and the effect of temperature on planulae settlement of the scyphozoan Rhopilema nomadica
Authors: Dror Hila , Angel Dror L.
Published: February 2025

Rhopilema nomadica is the most prominent jellyfish species in the eastern Mediterranean, forming huge annual summer swarms. Although planula settlement success is essential in the formation of jellyfish outbreaks, quantitative studies to examine its response to environmental variables have not been performed thus far due to the difficulty in collecting planulae. We concentrated large numbers of R. nomadica planulae to study the effect of substrate type and seawater temperature on planula settlement. In the substrate preferences experiment, two natural substrates (bivalve shells and kurkar rock) and two artificial substrates (concrete and plastic (PVC)) were offered for planula settlement. Settlement success was not different between concrete, PVC, and kurkar substrates, but was significantly lower on the shells. In the temperature experiment, planulae were able to settle and metamorphose into polyps at all five temperatures (16—32 °C) tested, on glass slides, and most settled within three days. Higher temperatures were not only associated with accelerated settlement but also increased settlement success. The anticipated increase in marine infrastructures (potential settlement substrates), and rising seawater temperatures may favor planula settlement success and further enhance outbreaks of R. nomadica in the Mediterranean.