bluuebunny/crossref_metadata_2025_split huggingface dataset:
Viral-bacterial co-infections screen in vitro reveals molecular processes affecting pathogen proliferation and host cell viability
Authors: Walch Philipp , Broz Petr 
Published: October 2024

AbstractThe broadening of accessible methodologies has enabled mechanistic insights into single-pathogen infections, yet the molecular mechanisms underlying co-infections remain largely elusive, despite their clinical frequency and relevance, generally exacerbating symptom severity and fatality. Here, we describe an unbiased in vitro screening of pairwise co-infections in a murine macrophage model, quantifying pathogen proliferation and host cell death in parallel over time. The screen revealed that the majority of interactions are antagonistic for both metrics, highlighting general patterns depending on the pathogen virulence strategy. We subsequently decipher two distinct molecular interaction points: Firstly, murine Adenovirus 3 modifies ASC-dependent inflammasome responses in murine macrophages, altering host cell death and cytokine production, thereby impacting secondary Salmonella infection. Secondly, murine Adenovirus 2 infection triggers upregulation of Mprip, a crucial mediator of phagocytosis, which in turn causes increased Yersinia uptake, specifically in virus pre-infected bone-marrow-derived macrophages. This work therefore encompasses both a first-of-its-kind systematic assessment of host-pathogen-pathogen interactions, and mechanistic insight into molecular mediators during co-infection.
Light-steerable locomotion using zero-elastic-energy modes
Authors: Deng Zixuan , Li Kai , Priimagi Arri , Zeng Hao 
Published: October 2024

AbstractDriving synthetic materials out of equilibrium via dissipative mechanisms paves the way towards autonomous, self-sustained robotic motions. However, obtaining agile movement in diverse environments with dynamic steerability remains a challenge. Here we report a light-fuelled soft liquid crystal elastomer torus with self-sustained out-of-equilibrium movement. Under constant light excitation, the torus undergoes spontaneous rotation arising from the formation of zero-elastic-energy modes. By exploiting dynamic friction or drag, the zero-elastic-energy-mode-based locomotion direction can be optically controlled in various dry and fluid environments. We demonstrate the ability of the liquid crystal elastomer torus to laterally and vertically swim in the Stokes regime. The torus navigation can be extended to three-dimensional space with full steerability of the swimming direction. These results demonstrate the possibilities enabled by prestrained topological structures towards robotic functions of out-of-equilibrium soft matter.
Preclinical comparison of prolgolimab, pembrolizumab and nivolumab
Authors: Gordeev Aleksandr , Vaal Andrei , Puchkova Maria , Smirnova Iana , Doronin Aleksandr , Znobishcheva Anna , Zhmudanova Daria , Aleksandrov Aleksei , Sukchev Mikhail , Imyanitov Evgeny , Solovyev Valery , Iakovlev Pavel 
Published: October 2024

AbstractProlgolimab is a recombinant IgG1-based anti-PD-1 antibody, whose properties were improved by the introduction of the LALA mutation, and which has demonstrated high efficacy in patients with metastatic melanoma. This paper presents the results of comparative preclinical studies of antigen-binding and effector functions involving prolgolimab and conventional IgG4 antibodies, nivolumab and pembrolizumab. None of the studied antibodies had undesirable antibody-dependent cellular cytotoxicity activity. Prolgolimab has shown higher PD-1 receptor occupancy and T-cell activation, but lower propensity to activate antibody-dependent cellular phagocytosis as compared to nivolumab and pembrolizumab. An in vivo study in mice inoculated with CT26.wt cancer cells showed that tumor growth inhibition was 16% for pembrolizumab and 56% for prolgolimab. This study warrants clinical comparison of IgG1- and IgG4-based anti-PD-1 antibodies.
Novel ophthalmic hyaluronic acid-hydrogel with curcumin nanoparticles for enhanced healing of ulcerative keratitis in rabbit model
Authors: Sohani Zahra , Jamshidi Shahram , Koohi Mohammad Kazem , Malakootikhah Javad , Abarkar Mohammad , Golchin Diba , Roshani Sarina , Naghdi Haniyeh , Aghajanpour-moghaddam-gazafroudi Negin , Gazafroudi  , Amjadi Nava , Izadi-niaki Reihaneh 
Published: October 2024

AbstractCorneal ulcers, whether melting or indolent, are common in humans and companion animals. Treatment involves local administration of antibiotic eye drops and corneal healing drugs. Compared to traditional treatments for ulcerative keratitis, herbal medicines offer unique advantages, such as potent anti-inflammatory effects and inhibition of proinflammatory cytokines. Curcumin, extracted from the Curcuma Longa plant, possesses extensive pharmacological properties, such as anti-inflammatory, anti-cancer, and antioxidant properties, and is used in various medicines. In this study, we developed a novel ophthalmic drop hydrogel using a formulation of Curcumin NPs encapsulated with β-cyclodextrin and hyaluronic acid, to accelerate corneal healing and improve the quality of healed structures. The formation of Curcumin NPs into Hyaluronic acid-based hydrogels was characterized by zeta, FTIR, and scanning electron microscope (SEM) analyses. A total of 25 healthy male New Zealand Albino rabbits were experimentally induced with ulcerative keratitis and treated individually with topical medication. Rabbits were divided into five groups. Fluorescein dye staining, corneal clarity score, Schirmer tear test, proinflammatory cytokine measurement, and pathologic factors assessments were used to evaluate the optimised Curcumin NPs with β-cyclodextrin in Hyaluronic acid hydrogel. Our results demonstrated that the optimized Curcumin NPs with β-cyclodextrin in hyaluronic acid hydrogel significantly reduced the frequency of medication administration compared to conventional therapies, enhancing the quality of healed structures and effectively treating ulcerative keratitis. All findings in this study provide new insight into designing and fabricating novel ophthalmic medicine for ulcerative keratitis for topical usage.
Longitudinal autophagy profiling of the mammalian brain reveals sustained mitophagy throughout healthy aging
Authors: Rappe Anna , Vihinen Helena A , Suomi Fumi , Hassinen Antti J , Ehsan Homa , Jokitalo Eija S , McWilliams Thomas G 
Published: October 2024

AbstractMitophagy neutralizes mitochondrial damage, thereby preventing cellular dysfunction and apoptosis. Defects in mitophagy have been strongly implicated in age-related neurodegenerative disorders such as Parkinson’s and Alzheimer’s disease. While mitophagy decreases throughout the lifespan of short-lived model organisms, it remains unknown whether such a decline occurs in the aging mammalian brain—a question of fundamental importance for understanding cell type- and region-specific susceptibility to neurodegeneration. Here, we define the longitudinal dynamics of basal mitophagy and macroautophagy across neuronal and non-neuronal cell types within the intact aging mouse brain in vivo. Quantitative profiling of reporter mouse cohorts from young to geriatric ages reveals cell- and tissue-specific alterations in mitophagy and macroautophagy between distinct subregions and cell populations, including dopaminergic neurons, cerebellar Purkinje cells, astrocytes, microglia and interneurons. We also find that healthy aging is hallmarked by the dynamic accumulation of differentially acidified lysosomes in several neural cell subsets. Our findings argue against any widespread age-related decline in mitophagic activity, instead demonstrating dynamic fluctuations in mitophagy across the aging trajectory, with strong implications for ongoing theragnostic development.
The Relation of Linguistic Awareness Skills to Reading and Spelling for Autistic and Non-Autistic Elementary School–Age Children
Authors: Henbest Victoria S. , Apel Kenn 
Published: October 2024

Purpose:
For non-autistic children, it is well established that linguistic awareness skills support their success with reading and spelling. Few investigations have examined whether these same linguistic awareness skills play a role in literacy development for autistic elementary school–age children. This study serves as a first step in quantifying the phonological, prosodic, orthographic, and morphological awareness skills of autistic children; how these skills compare to those of non-autistic children; and their relation to literacy performance.

Method:
We measured and compared the phonological, prosodic, orthographic, and morphological awareness skills of 18 autistic (with average nonverbal IQs) and 18 non-autistic elementary school–age children, matched in age, nonverbal IQ, and real-word reading. The relations between linguistic awareness and the children's word-level literacy and reading comprehension skills were examined, and we explored whether the magnitude of these relations was different for the two groups. Regression analyses indicated the relative contribution of linguistic awareness variables to performance on the literacy measures for the autistic children.

Results:
The non-autistic children outperformed the autistic children on most linguistic awareness measures. There were moderate-to-strong relations between performances on the linguistic awareness and literacy measures for the non-autistic children, and most associations were not reliably different from those for the autistic children. Regression analyses indicate that the performance on specific linguistic awareness variables explains unique variance in autistic children's literacy performance.

Conclusion:
Although less developed than those of their non-autistic peers, the linguistic awareness skills of autistic elementary school–age children are important for successful reading and spelling.
Assessment of Cochlear Implant Rehabilitation Success by Speech-Language Therapists Using International Classification of Functioning, Disability and Health Criteria
Authors: Thyson Susann , Werminghaus Maika , Volpert Simone , Althaus Laurenz , Buscher Lisa , Schatton Dorothee , van Treeck Wiebke , Klenzner Thomas 
Published: October 2024

Purpose:
This study aims to introduce an assessment questionnaire based on the International Classification of Functioning, Disability and Health (ICF) to enable quantifiable clinical documentation. The questionnaire assists speech-language therapists (SLTs) in evaluating both non-audiological and audiological rehabilitation outcomes of patients with cochlear implants (CIs).

Method:
Six SLTs were recruited to evaluate the effectiveness of CI care using ICF criteria. We carefully selected 20 pertinent ICF criteria, and SLTs received thorough training in how to apply them uniformly. A cohort of 48 patients was evaluated at three distinct time points: presurgery, postsurgery, and 6 months post-initial CI fitting. Patients underwent dedicated speech-language therapy sessions throughout the treatment course.

Results:
A total of 144 complete datasets were scrutinized using a two-factor analysis of variance for ranks. Following CI care, patients exhibited substantial improvements in auditory perception, characterized by enhanced sound recognition and speech discrimination. Additionally, patients demonstrated improved attentional focus, proficiency in daily tasks and increased conversational engagement over time. Environmental factors, particularly sound perception, improved markedly, correlating with reported reductions in stress levels. Minimal changes were noted in stress management and communication techniques. Articulatory function, speech functions, and pain perception exhibited the least alteration.

Conclusions:
The data extracted from the ICF-based assessments underscore the vital significance of incorporating speech therapy–based metrics to evaluate both non-audiological and audiological factors in assessing the success of CI care within the SLTs domain. This approach proves to be highly relevant both in terms of demonstration and clinical applicability.
Socio-Communicative Behaviors Involving Minimally Speaking Autistic Preschoolers and Their Typically Developing Peers: Effects of an Augmentative and Alternative Communication Intervention Package
Authors: Edgar Tiffany Chavers , Schlosser Ralf W. , Koul Rajinder 
Published: October 2024

Purpose:
The purpose of this study was to examine the effectiveness of an augmentative and alternative communication (AAC) intervention package consisting of systematic instruction and aided AAC modeling with speech-output technology on the acquisition, maintenance, and generalization of socio-communicative behaviors in four minimally speaking, preschool-aged, autistic children.

Method:
A multiple-probe design across behaviors (i.e., initiating a request for a turn, answering questions, and commenting) replicated across participants was implemented to evaluate the effects of the intervention package on socio-communicative behaviors. Furthermore, a pretreatment and posttreatment multiple-generalization-probe design was used to assess generalization across typically developing peers who were not a part of the intervention. Maintenance data were collected 3 weeks post intervention.

Results:
Visual analysis, corroborated by nonoverlapping of all pairs statistics, established a strong functional relationship between the AAC intervention package and all targeted socio-communicative outcomes for two participants. For the other two participants, inconsistent intervention effects were observed. In terms of generalization from interacting with the researcher to typically developing peers, a functional relationship between the intervention and generalization outcomes for all targeted behaviors was established for only one participant (i.e., Aiden).

Conclusion:
The outcomes of this study suggest that aided AAC modeling and systematic instruction using a speech-output technology may lead to gains in socio-communicative behaviors in some minimally speaking, preschool-aged, autistic children.

Supplemental Material:

https://doi.org/10.23641/asha.27091879
Intertwined formation of H2, dust, and stars in cosmological simulations
Authors: Ragone-Figueroa Cinthia , Granato Gian Luigi , Parente Massimiliano , Murante Giuseppe , Valentini Milena , Borgani Stefano , Maio Umberto 
Published: October 2024

Context. Molecular hydrogen (H2) plays a crucial role in the formation and evolution of galaxies, serving as the primary fuel reservoir for star formation. In a metal-enriched Universe, H2 forms mostly through catalysis on interstellar dust grain surfaces. However, due to the complexities of modelling this process, star formation in cosmological simulations often relies on empirical or theoretical frameworks that have only been validated in the local Universe to estimate the abundance of H2.
Aims. The goal of this work is to model the connection between the processes of star, dust, and H2 formation in our cosmological simulations.
Methods. Building upon our recent integration of a dust evolution model into the star formation and feedback model MUPPI, we included the formation of molecular hydrogen on the surfaces of dust grains. We also accounted for the destruction of molecules and their shielding from harmful radiation.
Results. The model reproduces, reasonably well, the main statistical properties of the observed galaxy population for the stellar, dust, and H2 components. The evolution of the molecular hydrogen cosmic density (ρH2) in our simulated boxes peaks around redshift z = 1.5, consistent with observations. Following its peak, ρH2 decreases by a factor of two towards z = 0, which is a milder evolution than observed. Similarly, the evolution of the molecular hydrogen mass function since z = 2 displays a gentler evolution when compared to observations. Our model recovers satisfactorily the integrated molecular Kennicut-Schmidt (mKS) law between the surface star formation rate (ΣSFR) and surface H2 density (ΣH2) at z = 0. This relationship is already evident at z = 2, albeit with a higher normalization. We find hints of a broken power law with a steeper slope at higher ΣH2. We also study the H2-to-dust mass ratio in galaxies as a function of their gas metallicity and stellar mass, observing a decreasing trend with respect to both quantities. The H2-to-dust mass fraction for the global population of galaxies is higher at higher redshift. The analysis of the atomic-to-molecular transition on a particle-by-particle basis suggests that gas metallicity cannot reliably substitute the dust-to-gas ratio in models attempting to simulate dust-promoted H2.
Baseline Platelet Count Predicts Infarct Size and Mortality after Acute Myocardial Infarction
Authors: Dutsch Alexander , Graesser Christian , Kessler Thorsten , Sager Hendrik B. , Novacek Sophie , Krefting Johannes , Schories Viktoria , Niedermeier Benedikt , Voll Felix , Kufner Sebastian , Xhepa Erion , Joner Michael , Cassese Salvatore , Schunkert Heribert , Ndrepepa Gjin , Kastrati Adnan 
Published: October 2024

Abstract
Introduction Platelets greatly contribute to cardiovascular diseases. We sought to explore the association of platelet counts with infarct size and outcome in patients presenting with acute ST-segment elevation MI (STEMI) treated with primary percutaneous coronary intervention (PPCI).
Methods and Results In this retrospective study, we grouped 1,198 STEMI patients into tertiles (T) based on platelet count on admission: T1 = 102–206 [109 platelets/L] (n = 402), T2 = 207–259 [109 platelets/L] (n = 396), and T3 = 260–921 [109 platelets/L] (n = 400). Primary endpoint was 1-year all-cause mortality. Patients with highest platelet counts on admission showed the greatest area at risk and infarct size: area at risk (median) was 22.0% (interquartile range [IQR]: 12.0–39.8%) in T1, 21.0% (IQR: 11.0–37.1%) in T2, and 26.0% (IQR: 14.9–45.0%) of the left ventricle in T3 (p = 0.003); final infarct sizes after 7 to 14 days were as follows: 10.0% (IQR: 2.0–21.0%) in T1, 9.0% (IQR: 2.0–20.7%) in T2, and 12.0% (IQR: 3.0–27.3%) of the left ventricle in T3 (p = 0.015) as serial imaging revealed. At 1 year, 16 all-cause deaths occurred in T1, 5 in T2, and 22 in T3 (log-rank test, p = 0.006). After adjustment, T1 and T3 were associated with all-cause 1-year mortality (T1: hazard ratio [HR] = 3.40, 95% confidence interval [CI] = 1.23–9.54, p = 0.02; T3: HR = 3.55, 95% CI = 1.23–9.78, p = 0.01) compared with T2. At 5 years, all-cause mortality remained numerically higher in the T1 and T3.
Conclusions In patients with STEMI undergoing PPCI, low and high blood platelet levels on admission were associated with increased long-term mortality (Fig. 1).
Surveillance bei Watch-and-Wait nach neoadjuvanter Therapie beim Rektumkarzinom
Authors: Wiegering Armin , Kastner Carolin , Meir Michael , Flemming Sven , Reibetanz Joachim , Germer Christoph Thomas 
Published: October 2024

ZusammenfassungRund ein Drittel aller kolorektalen Karzinome (KRK) sind im Rektum lokalisiert. Im Rahmen
eines multimodalen Therapiekonzeptes wird durch eine neoadjuvante Therapie in 50–60% der Fälle
ein Downstaging des Tumors und in 10–30% der Fälle eine sog. Complete Clinical Response (cCR),
definiert als klinisch (und radiologisch) nicht mehr detektierbarer Residualtumor nach
Abschluss der neoadjuvanten Therapie, erzielt.Vor dem Hintergrund perioperativer Morbidität und Mortalität einer radikalen
Rektumresektion, mit u. a. Auftreten des Symptomkomplexes des sog. Low Anterior Resection
Syndrome (LARS) sowie der zumindest passager gegebenen Notwendigkeit zur Deviation, wird die
Frage nach einer Nutzen-Risiko-Abwägung einer Organresektion bei Vorliegen eines cCR
aufgeworfen. In diesem Zusammenhang trat das therapeutische Konzept eines
„Watch-and-Wait“-Vorgehens mit Unterlassung einer unmittelbaren Organresektion und Einschluss
in ein strukturiertes Surveillance-Regime in den Vordergrund.Zur sicheren, onkologischen Durchführung dieser Option ist es notwendig, Standards in der
Definition einer geeigneten Patientenklientel sowie der Umsetzung des Konzepts zu erarbeiten.
Dabei ist das inhärente Ziel neben der zunächst korrekten Selektion der Patientengruppe, die
sich für ein primär nicht chirurgisches Vorgehen eignet, die frühzeitige und suffiziente
Detektion eines Tumorwiederauftretens (sog. Local Regrowth) während der Phase des
„Watch-and-Wait“ (Surveillance).In diesem Zusammenhang adressieren wir in dieser Arbeit die Fragen: 1. nach dem optimalen
Zeitpunkt des initiales Re-Stagings, 2. nach den Kriterien zur Beurteilung des klinischen
Ansprechens und der Selektion der geeigneten Patientenklientel, 3. nach Rhythmus und
Ausgestaltung des Surveillance-Protokolls.
Acceptance and feasibility of an augmented reality-based navigation system with optical tracking for percutaneous procedures in interventional radiology – a simulation-based phantom study
Authors: Rohmer Karl , Becker Mathias , Georgiades Marilena , March Christine , Melekh Bohdan , Sperka Piotr , Spinczyk Dominik , Wolińska-Sołtys Anna , Pech Maciej 
Published: October 2024

AbstractAugmented reality (AR) projects additional information into the user’s field of view during interventions. The aim was to evaluate the acceptance and clinical feasibility of an AR system and to compare users with different levels of experience. A system was examined that projects a CT-generated 3D model of a phantom into the field of view using a HoloLens 2, whereby the tracked needle is displayed and navigated live. A projected ultrasound image is used for live control of the needle positioning. This should minimize radiation exposure and improve orientation.The acceptance and usability of the AR navigation system was evaluated by 10 physicians and medical students with different levels of experience by performing punctures with the system in a phantom. The required time was then compared and a questionnaire was completed to assess clinical acceptance and feasibility. For statistical analysis, frequencies for qualitative characteristics, location and dispersion measures for quantitative characteristics and Spearman rank correlations for correlations were calculated.9 out of 10 subjects hit all 5 target regions in the first attempt, taking an average of 29:39 minutes for all punctures. There was a significant correlation between previous experience in interventional radiology, years in the profession, and the time required. Overall, the time varied from an average of 43:00 min. for medical students to 15:00 min. for chief physicians. All test subjects showed high acceptance of the system and rated especially the potential clinical feasibility, the simplification of the puncture, and the image quality positively. However, the majority require further training for sufficient safety in use.The system offers distinct advantages for navigation and orientation, facilitates percutaneous interventions during training and enables professionally experienced physicians to achieve short intervention times. In addition, the system improves ergonomics during the procedure by making important information always directly available in the field of view and has the potential to reduce the radiation exposure of staff in particular by combining AR and sonography and thus shortening CT-fluoroscopy times.