bluuebunny/crossref_metadata_2025 huggingface dataset:
Mechanistic pharmacokinetic–pharmacodynamic modeling and simulations of naloxone auto‐injector 10 mg reversal of opioid‐induced respiratory depression
Authors: Yang Tae Eun , Del Bene Francesca , Lavezzi Silvia Maria , Iavarone Laura , Zhang Jianping , Kim Joseph , Gjurich Breanne , Kessler Catherine
Published: September 2024

The purpose of the analysis was to evaluate if 10 mg naloxone, administered intramuscularly, could reverse or prevent opioid‐induced respiratory depression (OIRD), including OIRD associated with the administration of lethal doses of high‐potency opioids. A naloxone population pharmacokinetic (PK) model was generated using data from two naloxone auto‐injector (NAI) clinical PK studies. Mechanistic OIRD PK‐pharmacodynamic (PD) models were constructed using published data for buprenorphine, morphine, and fentanyl. Due to the lack of published carfentanil data in humans, interspecies allometric scaling methods were used to predict carfentanil PK parameters in humans. A PD model of a combined effect‐compartment and receptor kinetics model with a linear relationship between ventilation and carbon dioxide was used to predict the respiratory depression induced by carfentanil. Model‐based simulations were performed using the naloxone population PK model and the constructed mechanistic OIRD PK–PD models. Changes in ventilation were assessed after opioid exposure and treatment with 2 mg naloxone or one or two doses of 10 mg naloxone. A higher percentage of subjects recovered back to the rescue ventilation thresholds and/or had a faster recovery to 40% or 70% of baseline ventilation with 10 mg compared with 2 mg naloxone. A second dose of 10 mg naloxone, administered 60 min post‐opioid exposure, expedited recovery to 85% of baseline ventilation and delayed time to renarcotization compared with a single dose. In addition, when 10 mg naloxone was administered at 5, 15, 30, or 60 min before fentanyl or carfentanil exposure, rapid and profound OIRD was prevented.
A Double Fish‐Shaped Metamaterial with Variable Bending Stiffness and Damping under Elastic Tension
Authors: Guo Ronghui , Feng Ning , Biczo Andras , Pantke Klaus , Yuan Qingwen , Guo Junxian
Published: September 2024

The study of bionic metamaterials with unique properties has gained increasing attention in recent years. This article introduces a double fish‐shaped metamaterial (DFSM) and investigates its elasticity and deformation behaviors. The Poisson's ratio of DFSM is derived from the energy principle and Mohr's theorem. The bending deformation behaviors of DFSM under given elastic strains are observed and tested by using the homemade experimental bench, which is further compared with finite element (FE) methods. The FE results show good agreement with experimental results. The bending vibration of DFSM under elastic tension is recorded and analyzed using a homemade prestrain bench in conjunction with a high‐speed camera. The present study proposes a straightforward and valid approach for incorporating the variable bending stiffness and the variable bending damping into DFSM. The revealed mechanical properties of DFSM in this article demonstrate its potential for engineering applications that require multistiffness and multidamping capabilities.
Applications of Ion Exchange in Environmental Remediation: Removal of Heavy Metals From Wastewater
Authors: Reda Hamed Mohamed Ahmed , Abdallah Marwa Abdelfattah
Published: September 2024

The concern over heavy metal contamination and its impact on human health and the environment has led to a growing interest in cost‐effective and sustainable remediation technologies. Ion exchange is recognized as an efficient method for removing heavy metal ions from wastewater. This study focused on the removal of heavy metal ions (Ni, Cu, Zn, and Pb) from aqueous solutions using the extended batch equilibrium technique. Experimental trials were conducted using Purolite C100, a strong acid ion‐exchange resin, to assess the influence of various treatment parameters such as pH, contact time, sorbent dosages, and initial heavy metal concentrations on the removal efficiency. The results indicated that significant treatment equilibrium could be achieved within 1 h. Notably, pH levels between 5 and 6 had a significant impact on heavy metal removal, with adsorption capacities of 71, 67, 66, and 62 mg/g for Ni, Cu, Zn, and Pb, respectively. Furthermore, the equilibrium data obtained from the batch experiments were well fitted with Langmuir, Freundlich, and pseudo‐first‐order kinetic models. Statistical analysis revealed a strong correlation with the Langmuir isotherm model, highlighting its superiority over the Freundlich isotherm and pseudo‐first‐order kinetic models.
Trivariate Joint Modeling for Family Data with Longitudinal Counts, Recurrent Events and a Terminal Event with Application to Lynch Syndrome
Authors: Lu Jingwei , Yi Grace Y. , Rustand Denis , Parfrey Patrick , Briollais Laurent , Choi Yun‐hee
Published: September 2024

Trivariate joint modeling for longitudinal count data, recurrent events, and a terminal event for family data has increased interest in medical studies. For example, families with Lynch syndrome (LS) are at high risk of developing colorectal cancer (CRC), where the number of polyps and the frequency of colonoscopy screening visits are highly associated with the risk of CRC among individuals and families. To assess how screening visits influence polyp detection, which in turn influences time to CRC, we propose a clustered trivariate joint model. The proposed model facilitates longitudinal count data that are zero‐inflated and over‐dispersed and invokes individual‐specific and family‐specific random effects to account for dependence among individuals and families. We formulate our proposed model as a latent Gaussian model to use the Bayesian estimation approach with the integrated nested Laplace approximation algorithm and evaluate its performance using simulation studies. Our trivariate joint model is applied to a series of 18 families from Newfoundland, with the occurrence of CRC taken as the terminal event, the colonoscopy screening visits as recurrent events, and the number of polyps detected at each visit as zero‐inflated count data with overdispersion. We showed that our trivariate model fits better than alternative bivariate models and that the cluster effects should not be ignored when analyzing family data. Finally, the proposed model enables us to quantify heterogeneity across families and individuals in polyp detection and CRC risk, thus helping to identify individuals and families who would benefit from more intensive screening visits.
Mo‐Induced Surface Reconstruction in Ni/Co‐OOH Prickly Flower Clusters for Improving the Hydrogen Production in Alkaline Seawater Splitting
Authors: Zhang Wen , Gao Jianyang , Gong Qinzhen , Liu Fusheng , Zhang Yang , Xu Guang‐Rui , Wu Zexing , Wang Lei
Published: September 2024

Seawater electrolysis is the most promising technology for hydrogen production, in which surface reconstruction on the interface of electrode/electrolyte plays a crucial role in activating the catalytic reactions with a low activation energy barrier. Herein, an efficient Mo modifying NiCoMo prickly flower clusters electrocatalyst supported on nickel foam (Mo‐doped Ni/Co‐OOH prickly flower clusters) is obtained, which serves as an eminently active and durable catalyst for both hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) due to the surface reconstruction during the alkaline seawater electrolysis with ultralow overpotentials. It just requires a cell voltage of 1.52 V to achieve the current density of 10 mA cm−2 for water electrolysis along with robust durability over 30 h. Mo doping effectively regulates the surface reconstruction of Ni/Co‐OOH, which facilitates the adsorption of oxygen‐containing intermediates on the active center, and the nonhomogeneous interface induces charge rearrangement for the catalytic process to improve efficiency, providing a new strategy for revealing the seawater electrolytic mechanism.
A Noncationic Biocatalytic Nanobiohybrid Platform for Cytosolic Protein Delivery Through Controlled Perturbation of Intracellular Redox Homeostasis
Authors: Lu Wanyue , Wang Weidong , Gong Yimin , Li Jianing , Zhou Yaming , Yang Yannan
Published: September 2024

Intracellular delivery of proteins has largely been relying on cationic nanoparticles to induce efficient endosome escape, which, however, poses serious concerns on the inflammatory and cytotoxic effects. Herein, a versatile noncationic nano biohybrid platform is introduced for efficient cytosolic protein delivery by utilizing a nano‐confined biocatalytic reaction. This platform is constructed by co‐immobilizing glucose oxidase (GOx) and the target protein into nanoscale hydrogen‐bonded organic frameworks (HOFs). The biocatalytic reaction of nano‐confined GOx is leveraged to induce controlled perturbation of intracellular redox homeostasis by sustained hydrogen peroxide (H2O2) production and diminishing the flux of the pentose phosphate pathway (PPP). This in turn induces the endosome escape of nanobiohybrids. Concomitantly, GOx‐mediated hypoxia leads to overexpression of azo reductase that initiated the materials' self‐destruction for releasing target proteins. These biological effects collectively induce highly efficient cytosolic protein delivery. The versatility of this delivery platform is further demonstrated for various types of proteins, different protein loading approaches (in situ immobilization or post‐adsorption), and in multiple cell lines. Finally, the protein delivery efficiency and biosafety are demonstrated in a tumor‐bearing mouse model. This nanohybrid system opens up new avenues for intracellular protein delivery and is expected to be extensively applicable for a broad range of biomolecuels.
Electrolyte Engineering with TFA− Anion‐Rich Solvation Structure to Construct Highly Stable Zn2+/Na+ Dual‐Salt Batteries
Authors: Liang Xiedong , Liang Yao , Gao Yuxing , Qiao Wenfeng , Yin Dongming , Huang Pai , Wang Chunli , Wang Limin , Cheng Yong
Published: September 2024

Electrolyte engineering is recognized as an effective technique for high‐performance aqueous zinc‐ion rechargeable batteries, addressing difficulties such as free water decomposition, zinc anode corrosion, and zinc dendrite growth. Different from traditional strategies in aqueous electrolyte systems, this work focuses on organic electrolytes involving zinc trifluoroacetate hydrate (Zn(TFA)2·xH2O), sodium trifluoroacetate (NaTFA) dual‐salt and acetonitrile (AN) solvent, in which trifluoroacetate anions (TFA− anions) have strong affinity toward zinc ions to form anion‐rich solvates, thus inducing an inorganic‐rich solid electrolyte interphase (SEI) to protect Zn from dendrite growth and side reactions. The Zn anode manifests long‐term cycling over 2400 h at a current density of 0.5 mA cm−2 with a high Coulombic efficiency (CE) of 99.75%, showing an areal capacity as high as 5 mAh cm−2. Owing to the high reversibility of the sodium ions intercalation/deintercalation process in Na2MnFe(CN)6, the Zn//Na2MnFe(CN)6 full cells with the dual‐salt electrolyte perform much better in terms of capacity retention than a device with Zn(TFA)2/AN electrolyte. This approach may open a new avenue for efficient zinc‐ion rechargeable batteries via developing organic electrolytes.
Flexible Phototransistors on Paper: Scalable Fabrication of PEDOT:PSS Devices Using a Pen Plotter
Authors: Sozen Yigit , Ersu Gülsüm , Pucher Thomas , Quereda Jorge , Castellanos‐Gomez Andres
Published: September 2024

Phototransistors are used in plenty of diverse applications such as optical communication systems, light sensors, imaging devices, and biomedical instruments for detecting and amplifying light signals. Herein, an approach for the large‐scale production of low‐cost and flexible phototransistors by integrating the inks of PEDOT:PSS, and graphite with paper, which serves as an ionic conductor material to gate the PEDOT:PSS channel, is proposed. The fabrication of the devices is carried out by sequentially depositing the PEDOT:PSS channel and graphite electrodes onto paper using a benchtop XY plotter. To characterize device‐to‐device variability, 200 devices are fabricated and their electrical and optical properties are statistically analyzed. By performing a detailed characterization on the optical properties under varying wavelength, power, and bias conditions, it is found that devices exhibit good photoresponse across a wide spectrum range. Moreover, devices maintain their photoactive characteristics even when subjected to high mechanical tensile strain, indicating the suitability of these paper‐supported devices for flexible electronic applications. Time and photocurrent magnitude can be tuned via gate voltages applied through the graphite‐based back‐gate configuration.
Making Friends as Interactional Work: Young Refugees in Germany
Authors: Schwittek Jessica , König Alexandra
Published: September 2024

This article focuses on the friendships that young refugees make in Germany as their country of arrival. Although friends are highly relevant in children's lives, little attention has been paid to this subject regarding young refugees. We conducted ego‐network interviews with 17 young refugees aged 9–15, with which we explored the opportunity structures in which young refugees choose their friends and their ways of establishing and deepening friendships, as well as the limitations thereof. Core dimensions of friendship, as proposed by Shmuel Eisenstadt, are used as sensitizing concepts: voluntariness, moral quality, unconditionality, trust, deep meaning/brittleness, and ambivalence. By reinterpreting them through an interactionist lens, the analysis reveals the complex work young refugees invest into making friends and establishing themselves in the social world of their school and peer groups.
Microenvironment Effects on Decomposition and Mesofauna of Eucalypt Leaf Litter: A Case Study of High‐Altitude Tropical Climate, Brazil
Authors: de Sá Santos Diacuí Benazir Soares , Barreto‐Garcia Patrícia Anjos Bittencourt , Monroe Paulo Henrique Marques , de Paula Rita de Cássia Antunes Lima , de Carvalho Flávia Ferreira
Published: September 2024

The effects of microenvironmental conditions on decomposition and its interaction with the mesofauna community remain poorly understood. Therefore, our study aimed to answer the following questions: Does the microenvironment influence the decomposition of Eucalyptus leaf litter and the mesofauna community associated with this process? To do so, we evaluated the litter when exposed to an Eucalyptus plantation (EP) environment and a native forest (NF) environment. Senescent leaves were collected at the base of tree crowns in both the EP and NF environments. After collection, 10 g portions of the dried leaves were placed in litter bags, which were then distributed over the litter in both environments. This defined three treatments: Eucalyptus leaves in the plantation environment, Eucalyptus leaves in NF condition, and NF leaves in their original environment. The litterbag collections took place at 30, 90, 120, 180, 240, and 330 days after installation. Thus, the remaining mass percentages, decomposition rates, and half‐life of the leaf litter were estimated from the dry mass results. The edaphic mesofauna community associated with the decomposition process was evaluated at 30, 90, and 120 days using the Berlese–Tullgren funnel method. The microenvironmental conditions of the native forest promoted a higher decomposition rate of Eucalyptus litter, in addition to greater abundance and richness of mesofauna organisms in relation to the Eucalyptus leaf material in the plantation environment.
Are you a supercommunicator?
Authors: Dennis Marguerite J.
Published: September 2024

“The single biggest problem with communication is the illusion it has taken place.”

George Bernard Shaw
When Robots Get Chatty: Grounding Multimodal Human-Robot Conversation and Collaboration
Authors: Allgeuer Philipp , Ali Hassan , Wermter Stefan
Published: September 2024

We investigate the use of Large Language Models (LLMs) to equip neural robotic agents with human-like social and cognitive competencies, for the purpose of open-ended human-robot conversation and collaboration. We introduce a modular and extensible methodology for grounding an LLM with the sensory perceptions and capabilities of a physical robot, and integrate multiple deep learning models throughout the architecture in a form of system integration. The integrated models encompass various functions such as speech recognition, speech generation, open-vocabulary object detection, human pose estimation, and gesture detection, with the LLM serving as the central text-based coordinating unit. The qualitative and quantitative results demonstrate the huge potential of LLMs in providing emergent cognition and interactive language-oriented control of robots in a natural and social manner. Video:https://youtu.be/A2WLEuiM3-s.
Individual variability in the movement ecology of Northern pike Esox lucius in a highly connected wetland system
Authors: Cittadino Simone , Tarkan Ali Serhan , Aksu Sadi , Wright Rosalind M. , Hindes Andrew M. , Lane Steve , Winter Emily , Lyons Jim , Britton J. Robert
Published: September 2024

Maintaining hydrological connectivity is important for sustaining freshwater fish populations as the high habitat connectivity supports large-scale fish movements, enabling individuals to express their natural behaviours and spatial ecology. Northern pike Esox lucius is a freshwater apex predator that requires access to a wide range of functional habitats across its lifecycle, including spatially discrete foraging and spawning areas. Here, pike movement ecology was assessed using acoustic telemetry and stable isotope analysis in the River Bure wetland system, eastern England, comprising of the Bure mainstem, the River Ant and Thurne tributaries, plus laterally connected lentic habitats, and a system of dykes and ditches. Of 44 tagged pike, 30 were tracked for over 100 days, with the majority of detections being in the laterally connected lentic habitats and dykes and ditches, but with similar numbers of pike detected across all macrohabitats. The movement metrics of these pike indicated high individual variability, with total ranges to over 26 km, total movements to over 1182 km and mean daily movements to over 2.9 km. Pike in the Thurne tributary were more vagile than those in the Ant and Bure, and with larger Thurne pike also having relatively high proportions of large-bodied and highly vagile common bream Abramis brama in their diet, suggesting the pike movements were potentially related to bream movements. These results indicate the high individual variability in pike movements, which was facilitated here by their access to a wide range of connected macrohabitats due to high hydrological connectivity.
Vereinbarkeit von Familie und Beruf für Ärztinnen in Deutschland am Beispiel der Urologie
Authors: Wiemer Laura , Knipper Sophie , Herlemann Annika , Welte Maria-Noemi , Siech Carolin , Greiser Eva-Maria , Müller Karina , Bellut Laura , Schönburg Sandra , Walach Margarete , Pompe Raisa , Weinberger Sarah
Published: September 2024

Hintergrund

Der Fachkräftemangel in der Medizin stellt eine der drängendsten Herausforderungen im Gesundheitswesen dar. Die steigende Anzahl von Frauen in der Medizin und im Speziellen in dem Fachbereich der Urologie wirft Fragen zur Vereinbarkeit von Familie und Beruf auf, insbesondere in Bezug auf die Arbeitsumgebung und Arbeitszeitmodelle.

Ziel der Arbeit

Ziel der Arbeit ist es, die Auswirkungen von Mutterschaft auf das Berufsleben von Ärztinnen und Wissenschaftlerinnen im Fachbereich Urologie in Deutschland zu erfassen. Dabei sollen spezifische Herausforderungen in diesem chirurgischen Fachgebiet sowie die Vereinbarkeit von Familie und Beruf beleuchtet werden.

Methode

Die Arbeitsgemeinschaft „Ärztinnen und Wissenschaftlerinnen in der Urologie“ der Deutschen Gesellschaft für Urologie (DGU) e. V. befragte ihre 1343 weiblichen Mitglieder zu demografischen Daten, beruflichem Status und Aspekten der Vereinbarkeit von Familie und Beruf.

Ergebnisse

Unter 487 Urologinnen in Deutschland hatten 53,4 % Kinder. Mütter waren tendenziell älter, seltener in Weiterbildung, seltener im stationären Bereich und seltener operativ tätig. Besonders auffällig war der geringe Anteil von Vollzeit-arbeitenden Müttern (36,2 %) im Vergleich zu den Urologinnen ohne Kinder (92,4 %). Von den Urologinnen mit Kindern gaben 32,3 % an, ihre Arbeitsstätte wegen ihrer Kinder gewechselt zu haben, während 10,7 % angaben, dass sich nach einer Schwangerschaft zumindest ihr Aufgabenbereich geändert hat. Darüber hinaus reduzierten 76,9 % der Mütter ihre Wochenarbeitsstunden aufgrund familiärer Verpflichtungen. In der multivariablen Analyse zeigte sich ein Einfluss von Mutterschaft auf beruflichen Status und Teilzeitarbeit.

Schlussfolgerung

Die Tatsache, dass die Gründung einer Familie für Frauen in der Urologie in Deutschland mit einer Arbeitszeitreduktion und Beendigung der Klinikkarriere einhergeht, legt nahe, dass es in Deutschland die Notwendigkeit einer Optimierung der Vereinbarkeit von Familie und Beruf gibt. Durch die zunehmende Feminisierung des Medizinberufs wird der bestehende Fachkräftemangel durch das Ausscheiden von Müttern aus dem Berufsleben verstärkt. Um den Bedürfnissen von berufstätigen Eltern, insbesondere Müttern, gerecht zu werden, sind daher dringend Anpassungen im Arbeitsumfeld notwendig. Die Förderung flexibler Arbeitszeitmodelle und die Schaffung unterstützender Rahmenbedingungen sind entscheidend, um den Verlust von Fachkräften zu vermeiden und die Arbeitszufriedenheit in diesem Bereich zu erhalten.

Graphic abstract
Structural controls on cobalt mineralisation during regional metamorphism: an example from the Rajapalot area, Finland
Authors: Sayab Mohammad , Menzies Andrew , Palin Richard M. , Butcher Alan R. , Cook Nick , Kuva Jukka , Dehaine Quentin
Published: September 2024

The Rajapalot area of Finnish Lapland hosts an unusually high-grade association of cobalt-only and gold–cobalt deposits (10.91 Mt @ 2.5 g/t Au + 0.044% Co total inferred resources) within multiply folded metasedimentary rocks of the Paleoproterozoic Svecofennian collisional orogeny. Through the integration of X-ray computed micro-tomography and micro-X-ray fluorescence raster imaging of drill-core samples, we produce a model of cobalt-bearing ore mineralisation, which reveals primary fluid transportation mechanisms and precipitation pathways. When combined with the deposit-scale, high-resolution ground-based magnetic geophysical data, we show that cobalt-bearing ores in the Rajapalot region occur mostly as saddle reefs located in dilated fold hinges, which formed by simultaneous synthetic and antithetic shearing along developing crenulation-cleavage planes and incompetent bedding layers, respectively. We suggest that multi-layered rock complexes with alternations of competent and incompetent layers deformed and metamorphosed to upper greenschist-lower amphibolite facies should represent focus regions for cobalt exploration targeting campaigns in orogenic belts. The non-destructive workflow presented in this study could be an integral part of an early stage of cobalt mineral processing and traceability before metallurgical treatment.
Conservative nonsurgical knowledge of German orthopedic and trauma surgeons—Present state of affairs
Authors: Youssef Yasmin , Toussaint Rene , Ansorg Jörg , Dimanski Götz , Adl Amini Dominik
Published: September 2024

Background

After the fusion of the fields of orthopedics and trauma surgery in 2006 the educational content significantly increased. The acquisition of non-surgical diagnostic and treatment skills seems to fall behind in the classical operatively focused residency programs. This study presents a status quo of the non-surgical education and knowledge in the field of orthopedics and traumatology in Germany.

Methods

An online-based voluntary and anonymous questionnaire was conducted between June and August 2023. The questionnaire was distributed through the email lists of the German Society for Orthopedics and Traumatology (DGOU) and the German Professional Association for Orthopedics and Traumatology (BVOU).

Results

A total of 486 German orthopedic and trauma surgeons answered the online questionnaire (77.9% male; mean age 50.2 ± 11.8 years) and 11.5% were residents. Only 27.1% spent part of the residency training in the outpatient sector. In total 84.2% wish for an increased focus on non-operative treatment options during further education, 81.1% agreed that they have a good general understanding of non-operative treatment options and 81.0% felt confident to apply them in the daily clinical routine (residents 35.4% and 41.7%, respectively). The highest self-assessed competences were knowledge on the application of splints and casts and physiotherapy, ergotherapy and sports therapy, the lowest were knowledge on acupuncture, magnetic field therapy and nutritional aspects after trauma. In total, 77.7% stated non-surgical research projects are not supported at their institution.

Conclusion

Orthopedic and trauma surgeons in Germany subjectively have solid knowledge on treatment options while resident physicians still need to strengthen their skills. Rotation into the outpatient sector and rehabilitation facilities as well as supporting research in the field could further improve the non-surgical skills.
Biomechanische In-vitro-Testmethoden am Kniegelenk
Authors: Deichsel Adrian , Günther Daniel , Ackermann Jakob , Münch Lukas N. , Mathis Dominic T. , Schüttler Karl F. , Wafaisade Arasch , Laky Brenda , Eggeling Lena , Herbst Elmar ,   Research-Komitee der Arbeitsgemeinschaft für Arthroskopie AGA
Published: September 2024

Biomechanische Studien kommen in der Sporttraumatologie häufig vor und werden regelmäßig zur Entscheidungsfindung in der Therapie von Patienten verwendet. In der biomechanischen In-vitro-Forschung können verschiedene Testmethoden zum Einsatz kommen, welche von Belastungstests von Implantaten mittels Materialprüfmaschinen, über passive humane Gelenkmodelle, bis zu komplexen aktiven Gelenkaufbauten mit physiologischen Belastungen reichen. Dieser Artikel beschreibt die grundlegenden Begriffe und Testmethoden der In-vitro-Kniegelenkbiomechanik, ihre Vorteile, Schwächen sowie Besonderheiten bei der Interpretation biomechanischer Studienergebnisse.
Mourre Theory and Asymptotic Observables in Local Relativistic Quantum Field Theory
Authors: Kruse Janik
Published: September 2024

We prove the convergence of Araki–Haag detectors in any Haag–Kastler quantum field theory with an upper and lower mass gap. We cover the case of a single Araki–Haag detector on states of bounded energy, which are selected from the absolutely continuous part of the energy-momentum spectrum sufficiently close to the lower boundary of the multi-particle spectrum. These states essentially encompass those states in the multi-particle spectrum lying below the three-particle threshold. In our proof, we draw on insights from proofs of asymptotic completeness in quantum mechanics. Notably, we apply Mourre’s conjugate operator method for the first time within the framework of Haag–Kastler quantum field theory. Furthermore, we discuss applications of our findings for the problem of asymptotic completeness in local relativistic quantum field theory.
On the existence of minimal expansive solutions to the $N$-body problem
Authors: Polimeni Davide , Terracini Susanna
Published: September 2024

We deal, for the classical $N$
N
-body problem, with the existence of action minimizing half entire expansive solutions with prescribed asymptotic direction and initial configuration of the bodies. We tackle the cases of hyperbolic, hyperbolic-parabolic and parabolic arcs in a unified manner. Our approach is based on the minimization of a renormalized Lagrangian action on a suitable functional space. With this new strategy, we are able to confirm the already-known results of the existence of both hyperbolic and parabolic solutions, and we prove for the first time the existence of hyperbolic-parabolic solutions for any prescribed asymptotic expansion in a suitable class. Associated with each element of this class we find a viscosity solution of the Hamilton-Jacobi equation as a linear correction of the value function. Besides, we also manage to give a precise description of the growth of parabolic and hyperbolic-parabolic solutions.
Strengths and weaknesses of automated scoring of free-text student answers
Authors: Bexte Marie , Horbach Andrea , Zesch Torsten
Published: September 2024

Free-text tasks, where students need to write a short answer to a specific question, serve as a well-established method for assessing learner knowledge. To address the high cost of manually scoring these tasks, automated scoring models can be used. Such models come in various types, each with its own strengths and weaknesses. Comparing these models helps in selecting the most suitable one for a given problem. Depending on the assessment context, this decision can be driven by ethical or legal considerations. When implemented successfully, a scoring model has the potential to substantially reduce costs and enhance the reliability of the scoring process. This article compares the different categories of scoring models across a set of crucial criteria that have immediate relevance to model employment in practice.
Dysregulated FOXO1 activity drives skeletal muscle intrinsic dysfunction in amyotrophic lateral sclerosis
Authors: Zufiría Mónica , Pikatza-Menoio Oihane , Garciandia-Arcelus Maddi , Bengoetxea Xabier , Jiménez Andrés , Elicegui Amaia , Levchuk María , Arnold-García Olatz , Ondaro Jon , Iruzubieta Pablo , Rodríguez-Gómez Laura , Fernández-Pelayo Uxoa , Muñoz-Oreja Mikel , Aiastui Ana , García-Verdugo José Manuel , Herranz-Pérez Vicente , Zulaica Miren , Poza Juan José , Ruiz-Onandi Rebeca , Fernández-Torrón Roberto , Espinal Juan Bautista , Bonilla Mario , Lersundi Ana , Fernández-Eulate Gorka , Riancho Javier , Vallejo-Illarramendi Ainara , Holt Ian James , Sáenz Amets , Malfatti Edoardo , Duguez Stéphanie , Blázquez Lorea , López de Munain Adolfo , Gerenu Gorka , Gil-Bea Francisco , Alonso-Martín Sonia
Published: September 2024

Amyotrophic Lateral Sclerosis (ALS) is a multisystemic neurodegenerative disorder, with accumulating evidence indicating metabolic disruptions in the skeletal muscle preceding disease symptoms, rather than them manifesting as a secondary consequence of motor neuron (MN) degeneration. Hence, energy homeostasis is deeply implicated in the complex physiopathology of ALS and skeletal muscle has emerged as a key therapeutic target. Here, we describe intrinsic abnormalities in ALS skeletal muscle, both in patient-derived muscle cells and in muscle cell lines with genetic knockdown of genes related to familial ALS, such as TARDBP (TDP-43) and FUS. We found a functional impairment of myogenesis that parallels defects of glucose oxidation in ALS muscle cells. We identified FOXO1 transcription factor as a key mediator of these metabolic and functional features in ALS muscle, via gene expression profiling and biochemical surveys in TDP-43 and FUS-silenced muscle progenitors. Strikingly, inhibition of FOXO1 mitigated the impaired myogenesis in both the genetically modified and the primary ALS myoblasts. In addition, specific in vivo conditional knockdown of TDP-43 or FUS orthologs (TBPH or caz) in Drosophila muscle precursor cells resulted in decreased innervation and profound dysfunction of motor nerve terminals and neuromuscular synapses, accompanied by motor abnormalities and reduced lifespan. Remarkably, these phenotypes were partially corrected by foxo inhibition, bolstering the potential pharmacological management of muscle intrinsic abnormalities associated with ALS. The findings demonstrate an intrinsic muscle dysfunction in ALS, which can be modulated by targeting FOXO factors, paving the way for novel therapeutic approaches that focus on the skeletal muscle as complementary target tissue.
Patient-reported outcomes during first-line palliative systemic therapy alternated with pressurized intraperitoneal aerosol chemotherapy for unresectable colorectal peritoneal metastases: a single-arm phase II trial (CRC-PIPAC-II)
Authors: van de Vlasakker Vincent C. J. , Rauwerdink Paulien , Rovers Koen. P. B. , Wassenaar Emma C. , Creemers Geert-Jan , Los Maartje , Burger Jacobus . W. A. , Nienhuijs Simon W. , Kranenburg Onno , Wiezer Marinus J. , Lurvink Robin J. , Boerma Djamila , de Hingh Ignace H. J. T.
Published: September 2024

Background

The CRC-PIPAC-II study prospectively assessed bidirectional therapy (BT) consisting of first-line palliative systemic therapy and electrostatic precipitation oxaliplatin-based pressurized intraperitoneal aerosol chemotherapy (ePIPAC-OX) in patients with unresectable colorectal peritoneal metastases (CPM). This study describes the exploration of patient-reported outcomes (PROs).

Methods

In this phase II trial, 20 patients with isolated CPM were treated with up to three cycles of BT, each cycle consisting of two to three courses of systemic therapy, followed by ePIPAC-OX (92 mg/m2). Patients were asked to complete the EuroQoL EQ-5D-5L, EORTC QLQ-C30, and EORTC QLQ-CR29 questionnaires at baseline, during the first cycle of BT, and one and four weeks after each consecutive BT cycle. PRO scores were calculated and compared between baseline and each subsequent time point using linear-mixed modeling (LMM). PROs were categorized into symptom scales and function scales. Symptom scales ranged from 0 to 100, with 100 representing the maximum symptom load. Function scales ranged from 0 to 100, with 100 representing optimal functioning.

Results

Twenty patients underwent a total of 52 cycles of bidirectional therapy. Most PROs (29 of 37, 78%) were not significantly affected during trial treatment. In total, only eight PROs (22%) were significantly affected during trial treatment: Six PROs (index value, global health status, emotional functioning, C30, appetite, and insomnia) showed transient improvement at different time points. Two PROs transiently deteriorated: pain initially improved during the first BT cycle [− 16, p < 0.001] yet worsened temporarily one week after the first two BT cycles (+ 20, p < 0.001; + 17, p = 0.004; respectively). Abdominal pain worsened temporarily one week after the first BT cycle (+ 16, p = 0.004), before improving again four weeks after treatment ended (− 10, p = 0.004). All significant effects on Pros were clinically significant and all deteriorations in PROs were of temporary nature.

Discussion

Patients undergoing BT for unresectable CPM had significant, but reversible alterations in several PROs. Most affected PROs concerned improvements and only two PROs showed deteriorations. Both deteriorated PROs returned to baseline after trial treatment and were of a temporary nature. These outcomes help to design future studies on the role of ePIPAC in the palliative setting.
A calculator for musculoskeletal injuries prediction in surgeons: a machine learning approach
Authors: Sánchez-Guillén Luis , Lozano-Quijada Carlos , Soler-Silva Álvaro , Hernández-Sánchez Sergio , Barber Xavier , Toledo-Marhuenda José V. , López-Rodríguez-Arias Francisco , Poveda-Pagán Emilio J. , Mora César González , Arroyo Antonio
Published: September 2024

Background

Surgical specialists experience significant musculoskeletal strain as a consequence of their profession, a domain within the healthcare system often recognized for the pronounced impact of such issues. The aim of this study is to calculate the risk of presenting musculoskeletal injuries in surgeons after surgical practice.

Methods

Cross-sectional study carried out using an online form (12/2021–03/2022) aimed at members of the Spanish Association of Surgeons. Demographic variables on physical and professional activity were recorded, as well as musculoskeletal pain (MSP) associated with surgical activity. Univariate and multivariate analysis were conducted to identify risk factors associated with the development of MSP based on personalized surgical activity. To achieve this, a risk algorithm was computed and an online machine learning calculator was created to predict them. Physiotherapeutic recommendations were generated to address and alleviate each MSP.

Results

A total of 651 surgeons (112 trainees, 539 specialists). 90.6% reported MSP related to surgical practice, 60% needed any therapeutic measure and 11.7% required a medical leave. In the long term, MSP was most common in the cervical and lumbar regions (52.4, 58.5%, respectively). Statistically significant risk factors (OR CI 95%) were for trunk pain, long interventions without breaks (3.02, 1.65–5.54). Obesity, indicated by BMI, to lumbar pain (4.36, 1.84–12.1), while an inappropriate laparoscopic screen location was associated with cervical and trunk pain (1.95, 1.28–2.98 and 2.16, 1.37–3.44, respectively). A predictive model and an online calculator were developed to assess MSP risk. Furthermore, a need for enhanced ergonomics training was identified by 89.6% of surgeons.

Conclusions

The prevalence of MSP among surgeons is a prevalent but often overlooked health concern. Implementing a risk calculator could enable tailored prevention strategies, addressing modifiable factors like ergonomics.
The Arabidopsis KASH protein SINE3 is involved in male and female gametogenesis
Authors: Moser Morgan , Groves Norman R. , Meier Iris
Published: September 2024

Key message

The Arabidopsis KASH protein SINE3 is involved in male and female gametophyte development, likely affecting the first post-meiotic mitosis in both cases, and is required for full seed set.

Linker of nucleoskeleton and cytoskeleton (LINC) complexes are protein complexes spanning the inner and outer membranes of the nuclear envelope (NE) and are key players in nuclear movement and positioning. Through their roles in nuclear movement and cytoskeletal reorganization, plant LINC complexes affect processes as diverse as pollen tube rupture and stomatal development and function. KASH proteins are the outer nuclear membrane component of the LINC complex, with conserved C-termini but divergent N-terminal cytoplasmic domains. Of the known Arabidopsis KASH proteins, SUN-INTERACTING NUCLEAR ENVELOPE PROTEIN 3 (SINE3) has not been functionally characterized. Here, we show that SINE3 is expressed at all stages of male and female gametophyte development. It is located at the NE in male and female gametophytes. Loss of SINE3 results in a female-derived seed set defect, with sine3 mutant ovules arresting at stage FG1. Pollen viability is also significantly reduced, with microspores arresting prior to pollen mitosis I. In addition, sine3 mutants have a minor male meiosis defect, with some tetrads containing more than four spores. Together, these results demonstrate that the KASH protein SINE3 plays a crucial role in male and female gametophyte development, likely affecting the first post-meiotic nuclear division in both cases.
Accurate Simulation of Efimov Physics in Ultracold Atomic Gases with Realistic Three-Body Multichannel Interactions
Authors: Kraats J. van de , Kokkelmans S. J. J. M. F.
Published: September 2024

We give a detailed and self-contained description of a recently developed theoretical and numerical method for the simulation of three identical bosonic alkali-metal atoms near a Feshbach resonance, where the Efimov effect is induced. The method is based on a direct construction of the off-shell two-body transition matrix from exact eigenfunctions of the embedded two-body Hamiltonians, obtained using realistic parameterizations of the interaction potentials which accurately reproduce the molecular energy levels. The transition matrix is then inserted into the appropriate three-body integral equations, which may be efficiently solved on a computer. We focus especially on the power of our method in including rigorously the effects of multichannel physics on the three-body problem, which are usually accounted for only by various approximations. We demonstrate the method for 7Li, where we recently showed that a correct inclusion of this multichannel physics resolves the long-standing disagreement between theory and experiment regarding the Efimovian three-body parameter. We analyze the Efimovian enhancement of the three-body recombination rate on both sides of the Feshbach resonance, revealing strong sensitivity to the spin structure of the model thus indicating the prevalence of three-body spin-exchange physics. Finally, we discuss an extension of our methodology to the calculation of three-body bound-state energies.
Wnt family members regulating osteogenesis and their origins
Authors: Kobayashi Yasuhiro , Iwamoto Rina , He Zhifeng , Udagawa Nobuyuki
Published: September 2024

Wnt signaling plays an important role in the regulation of bone metabolism. Wnt activates the β-catenin-mediated canonical pathway and β-catenin-independent non-canonical pathway. When Wnt ligands bind to the co-receptors low density lipoprotein receptor-related protein (Lrp)5 or Lrp6, and a seven-transmembrane receptor frizzled, the canonical pathway is activated. On the other hand, when Wnt ligands bind to the receptor complex consisting of the co-receptor receptor tyrosine kinase-like orphan receptor (Ror)1 and Ror2 or Ryk and frizzled, the non-canonical pathway is activated. An analysis of loss-of-function and gain-of-function mutations in molecules involved in Wnt signaling (ligands, receptors, and inhibitors) has revealed the mechanisms by which Wnt signaling regulates bone metabolism. In this review, based on transcriptome analyses of Wnt expression in bone tissues including single cell RNA sequence analysis and previous literatures, we herein introduce and discussed the latest findings on the mechanisms by which Wnt ligand mutations impair bone metabolism, especially bone formation.
A versatile framework for attributed network clustering via K-nearest neighbor augmentation
Authors: Li Yiran , Guo Gongyao , Shi Jieming , Yang Renchi , Shen Shiqi , Li Qing , Luo Jun
Published: September 2024

Attributed networks containing entity-specific information in node attributes are ubiquitous in modeling social networks, e-commerce, bioinformatics, etc. Their inherent network topology ranges from simple graphs to hypergraphs with high-order interactions and multiplex graphs with separate layers. An important graph mining task is node clustering, aiming to partition the nodes of an attributed network into k disjoint clusters such that intra-cluster nodes are closely connected and share similar attributes, while inter-cluster nodes are far apart and dissimilar. It is highly challenging to capture multi-hop connections via nodes or attributes for effective clustering on multiple types of attributed networks. In this paper, we first present as an efficient approach to attributed hypergraph clustering (AHC). includes a carefully-crafted K-nearest neighbor augmentation strategy for the optimized exploitation of attribute information on hypergraphs, a joint hypergraph random walk model to devise an effective AHC objective, and an efficient solver with speedup techniques for the objective optimization. The proposed techniques are extensible to various types of attributed networks, and thus, we develop as a versatile attributed network clustering framework, capable of attributed graph clustering, attributed multiplex graph clustering, and AHC. Moreover, we devise with algorithmic designs tailored for GPU acceleration to boost efficiency. We have conducted extensive experiments to compare our methods with 19 competitors on 8 attributed hypergraphs, 16 competitors on 6 attributed graphs, and 16 competitors on 3 attributed multiplex graphs, all demonstrating the superb clustering quality and efficiency of our methods.
Towards Sustainability of AI – Identifying Design Patterns for Sustainable Machine Learning Development
Authors: Leuthe Daniel , Meyer-Hollatz Tim , Plank Tobias , Senkmüller Anja
Published: September 2024

As artificial intelligence (AI) and machine learning (ML) advance, concerns about their sustainability impact grow. The emerging field "Sustainability of AI" addresses this issue, with papers exploring distinct aspects of ML’s sustainability. However, it lacks a comprehensive approach that considers all ML development phases, treats sustainability holistically, and incorporates practitioner feedback. In response, we developed the sustainable ML design pattern matrix (SML-DPM) consisting of 35 design patterns grounded in justificatory knowledge from research, refined with naturalistic insights from expert interviews and validated in three real-world case studies using a web-based instantiation. The design patterns are structured along a four-phased ML development process, the sustainability dimensions of environmental, social, and governance (ESG), and allocated to five ML stakeholder groups. It represents the first artifact to enhance each ML development phase along each ESG dimension. The SML-DPM fuels advancement by aggregating distinct research, laying the groundwork for future investigations, and providing a roadmap for sustainable ML development.
Elizabeth Acevedo, Laura Esquivel, and the Politics of Multilingualism
Authors: Manizza Roszak Suzanne
Published: September 2024

A number of bloggers, journalists, teachers, and librarians have compared Elizabeth Acevedo’s 2019 young adult novel With the Fire on High with Laura Esquivel’s Como agua para chocolate (1989), recommending that fans of Esquivel’s work pick up Acevedo’s—and vice versa. These suggestions echo Acevedo’s own comments about the narrative, which she has characterized as “parecido a ‘Como agua para chocolate,’ pero en el barrio” (Acevedo & Pichardo, 2019). This article takes this recent reception history as an invitation to think through how With the Fire on High deepens and course-corrects the revolutionary path of Esquivel’s earlier text. More specifically, I interrogate how Acevedo and Esquivel engage with linguistic identities and with multilingualism in particular as source material for political resistance and healing. Acevedo, like Esquivel before her, represents multilingual identities in ways that disrupt and resist the neocolonial violence of the United States. However, whereas Como agua para chocolate’s references to minoritized languages are executed in a manner that threatens to reinscribe traumatizing ethnoracial and class hierarchies passed down via colonial history, multilingualism in Acevedo’s novel works more systemically to intervene in and undermine such established matrices of power. Acevedo participates in a project of linguistic resistance and healing that involves reclaiming a heritage language for a multiply marginalized protagonist and, through that act of reclamation, rejecting the received cultural wisdom propagated by both colonial and neocolonial systems.