bluuebunny/crossref_metadata_2025 huggingface dataset:
Imaginação de dentro para fora, de fora para dentro
Authors: Jacques de Moraes Dalgalarrondo Luisa
Published: July 2024

Este artigo pretende trazer algumas formas de entender a imaginação, principalmente através da leitura dos trabalhos dos filósofos Gaston   Bachelard e Henry Corbin e articular esses entendimentos ao lugar ocupado pela imaginação nas artes da cena. Para tanto, será analisada a imaginação no trabalho de Konstantin Stanislavski, através de elementos como “as circunstâncias dadas”, o “e se…’mágico’” e o “filme de visões” e na prática de Michael Chekhov, com estratégias e conceitos como o “gesto psicológico” e o “corpo imaginário”.
Biografia das ideias de D. W. Winnicott
Authors: Palomo Alves Alvaro Marcel
Published: July 2024

A psicologia do jogo é uma área que se estende desde os primórdios da psicologia, sendo objeto de análise das primeiras investigações em psicologia científica e mesmo do período pré-institucionalização. O desenvolvimento humano é objeto de estudo de múltiplas áreas nas ciências humanas e muito investigado no campo da educação. Aqui, elaboramos um ensaio teórico que traz as contribuições do psicanalista inglês D. W. Winnicott, particularmente suas investigações sobre o amadurecimento emocional, o jogo infantil e a criatividade. Esse autor é importante na história dos jogos porque localiza o jogo infantil em um espaço que não é puramente objetivo tão pouco subjetivo, ele surge e se desenvolve no espaço potencial, herdeiro dos fenômenos transicionais. O jogo auxilia não apenas na superação de dificuldades emocionais, mas projeta um caminho em direção à criatividade e à liberdade de expressão. Acreditamos que Winnicott pode auxiliar educadoras(es) em suas atividades e compreensão do psiquismo da criança.
A Importância da Brincadeira na Mediação Docente na Primeira Infância
Authors: Rodrigues Teixeira Caroline , Kloeckner Sbardelotto Denise
Published: July 2024

Este artigo tem como temática a importância da utilização da brincadeira como recurso na primeira infância, com base na teoria Histórico-Cultural, visto que a mesma defende a mediação para o desenvolvimento infantil. A pesquisa nos faz refletir sobre a necessidade da mediação para o desenvolvimento infantil, visando a importância da intervenção do adulto para o desenvolvimento da criança. Portanto, apresentamos a explicação sobre como ocorre o desenvolvimento infantil, com foco na primeira infância; uma análise sobre a importância da mediação docente nos processos de ensino e de aprendizagem nesse período e, por fim, a relevância da brincadeira como recurso mediador. A pesquisa é caracterizada como bibliográfica, de cunho qualitativo. O estudo concluiu que, além da importância da mediação, a brincadeira é importante e facilitadora no processo de ensino, proporcionando um aprendizado ativo, prazeroso e que contribui para o desenvolvimento infantil.
EXPERIENCIA DEL ESTUDIANTE UNIVERSITARIO EN EL USO DE AMBIENTES VIRTUALES DE APRENDIZAJE
Authors: Linares Aldana Monica
Published: July 2024

El mundo actual exige nuevos paradigmas que permitan tanto a los alumnos como a los docentes implementar procesos de aprendizaje dinámicos utilizando diferentes tecnologías ajustándolas a las exigencias de las futuras generaciones, en este sentido el presente artículo tiene en cuenta la experiencia desarrollada en la Corporación Universitaria Iberoamericana (CUI) en la práctica de Ambientes Educativos 2020 -1 a través del uso de ambientes virtuales de aprendizaje a partir de la decisión del Gobierno Nacional de realizar aislamiento obligatorio para todo el territorio nacional por el Coronavirus de tipo 2 causante del síndrome respiratorio agudo severo (SRAS -CoV-2), (Organización Mundial de la Salud – OMS, 2019) a través del Decreto 457, (Ministerio del Interior, 2020).
Corrosion Assessment of Arc Thermal Sprayed Al and its Alloy Coatings in Aggressive Environments: An Overview
Authors: Singh Prakhar , Singh Jitendra Kumar
Published: July 2024

Arc thermal sprayed coatings have a wide range of applications, including corrosion resistance, wear resistance, thermal barriers, and electromagnetic pulse protection. However, these coatings often suffer from significant defects and pore formation, which can reduce their overall effectiveness. This overview focuses on the corrosion resistance properties of Al and its alloys. Al coatings demonstrate good corrosion resistance in marine environments due to the formation of sparingly soluble corrosion products on the surface. When Zn is alloyed with Al, the initial corrosion resistance decreases due to an increased number of pores. However, over extended exposure, these coatings exhibit excellent corrosion resistance as corrosion products fill the pores, providing barrier protection. Additionally, incorporating 5 wt.% Mg in Al coatings enhances bond adhesion and improves corrosion resistance in aggressive environments. To further reduce porosity and enhance corrosion resistance, the use of phosphate-based eco-friendly pore sealing agents is discussed. Optimizing the amount of phosphate during treatment is crucial, as it significantly reduces porosity and enhances corrosion resistance. Both insufficient and excessive amounts of phosphate can deteriorate the coating, while the optimal amount improves corrosion resistance over prolonged exposure to aggressive conditions.
The science of snacks: a review of dog treats
Authors: Calancea Bogdan-Alexandru , Daina Sorana , Macri Adrian
Published: July 2024

The global growth in canine population has led to a thriving market for pet food, especially treats sector. This review explores the growing market for canine treats, revealing a deep emotional connection between pet owners and their pets, evident in feeding practices. With six distinct categories of treats, meat-based treats dominate due to perceptions of naturalness and health, high-lighting an increased focus on dog nutrition and a preference for raw, locally sourced alternatives. However, labeling discrepancies and a lack of clear nutritional information present a challenge for owners looking for quality treats. Variations in nutritional values and sensory qualities of treats require informed choices to prevent excessive calorie consumption and potential health implications. Effective communication between the veterinarian and pet owners is crucial to adapting treats recommendations based on the individual needs of dogs, taking into account potential health risks and obesity. In conclusion, the use of treats provides several benefits such as positive reinforcement, promoting dental health and providing nutritional support for senior dogs. However, certain aspects that may limit their use should be considered, such as the risk of microbiological contamination, accidents related to incorrect administration, obesity and environmental impacts associated with treat production.
CAEM-GBDT: a cancer subtype identifying method using multi-omics data and convolutional autoencoder network
Authors: Shen Jiquan , Guo Xuanhui , Bai Hanwen , Luo Junwei
Published: July 2024

The identification of cancer subtypes plays a very important role in the field of medicine. Accurate identification of cancer subtypes is helpful for both cancer treatment and prognosis Currently, most methods for cancer subtype identification are based on single-omics data, such as gene expression data. However, multi-omics data can show various characteristics about cancer, which also can improve the accuracy of cancer subtype identification. Therefore, how to extract features from multi-omics data for cancer subtype identification is the main challenge currently faced by researchers. In this paper, we propose a cancer subtype identification method named CAEM-GBDT, which takes gene expression data, miRNA expression data, and DNA methylation data as input, and adopts convolutional autoencoder network to identify cancer subtypes. Through a convolutional encoder layer, the method performs feature extraction on the input data. Within the convolutional encoder layer, a convolutional self-attention module is embedded to recognize higher-level representations of the multi-omics data. The extracted high-level representations from the convolutional encoder are then concatenated with the input to the decoder. The GBDT (Gradient Boosting Decision Tree) is utilized for cancer subtype identification. In the experiments, we compare CAEM-GBDT with existing cancer subtype identifying methods. Experimental results demonstrate that the proposed CAEM-GBDT outperforms other methods. The source code is available from GitHub at https://github.com/gxh-1/CAEM-GBDT.git.
Hydrogel-chitosan and polylactic acid-polycaprolactone bioengineered scaffolds for reconstruction of mandibular defects: a preclinical in vivo study with assessment of translationally relevant aspects
Authors: Ferrari Marco , Taboni Stefano , Chan Harley H. L. , Townson Jason , Gualtieri Tommaso , Franz Leonardo , Ruaro Alessandra , Mathews Smitha , Daly Michael J. , Douglas Catriona M. , Eu Donovan , Sahovaler Axel , Muhanna Nidal , Ventura Manuela , Dey Kamol , Pandini Stefano , Pasini Chiara , Re Federica , Bernardi Simona , Bosio Katia , Mattavelli Davide , Doglietto Francesco , Joshi Shrinidh , Gilbert Ralph W. , Nicolai Piero , Viswanathan Sowmya , Sartore Luciana , Russo Domenico , Irish Jonathan C.
Published: July 2024

Background: Reconstruction of mandibular bone defects is a surgical challenge, and microvascular reconstruction is the current gold standard. The field of tissue bioengineering has been providing an increasing number of alternative strategies for bone reconstruction.

Methods: In this preclinical study, the performance of two bioengineered scaffolds, a hydrogel made of polyethylene glycol-chitosan (HyCh) and a hybrid core-shell combination of poly (L-lactic acid)/poly (ε-caprolactone) and HyCh (PLA-PCL-HyCh), seeded with different concentrations of human mesenchymal stromal cells (hMSCs), has been explored in non-critical size mandibular defects in a rabbit model. The bone regenerative properties of the bioengineered scaffolds were analyzed by in vivo radiological examinations and ex vivo radiological, histomorphological, and immunohistochemical analyses.

Results: The relative density increase (RDI) was significantly more pronounced in defects where a scaffold was placed, particularly if seeded with hMSCs. The immunohistochemical profile showed significantly higher expression of both VEGF-A and osteopontin in defects reconstructed with scaffolds. Native microarchitectural characteristics were not demonstrated in any experimental group.

Conclusion: Herein, we demonstrate that bone regeneration can be boosted by scaffold- and seeded scaffold-reconstruction, achieving, respectively, 50% and 70% restoration of presurgical bone density in 120 days, compared to 40% restoration seen in spontaneous regeneration. Although optimization of the regenerative performance is needed, these results will help to establish a baseline reference for future experiments.
Fabrication and characterization of Ti–12Mo/xAl2O3 bio-inert composite for dental prosthetic applications
Authors: Yehia Hossam. M. , El-Tantawy Ahmed , Elkady Omayma A. , Ghayad Ibrahim M. , Daoush Walid M.
Published: July 2024

Introduction: Titanium (Ti)-molybdenum(Mo) composites reinforced with ceramic nanoparticles have recently significant interest among researchers as a new type of bio-inert material used for dental prosthetic applications due to its biocompatibility, outstanding physical, mechanical and corrosion properties. The current work investigates the impact of alumina (Al2O3) nanoparticles on the properties of the Ti–12Mo composite, including microstructure, density, hardness, wear resistance, and electrochemical behavior.

Methods: Ti–12Mo/xAl2O3 nanocomposites reinforced with different Al2O3 nanoparticles content were prepared. The composition of each sample was adjusted through the mechanical milling of the elemental constituents of the sample for 24 h under an argon atmosphere. The produced nanocomposite powders were then cold-pressed at 600 MPa and sintered at different temperatures (1,350°C, 1,450°C, and 1,500°C) for 90 min. Based on density measurements using the Archimedes method, the most suitable sintering temperature was found to be 1,450°C. The morphology and chemical composition of the milled and sintered composites were analyzed using back-scattering scanning electron microscopy (SEM) and X-ray diffraction (XRD).

Results and Discussion: The results showed that the addition of Mo increased the Ti density from 99.11% to 99.46%, while the incorporation of 15wt% Al2O3 in the Ti–12Mo composite decreased the density to 97.28%. Furthermore, the Vickers hardness and wear behavior of the Ti–Mo composite were enhanced with the addition of up to 5 wt% Al2O3. The sample contains 5 wt% Al2O3 exhibited a Vickers hardness of 593.4 HV, compared to 320 HV for pure Ti, and demonstrated the lowest wear rate of 0.0367 mg/min, compared to 0.307 mg/min for pure Ti. Electrochemical investigations revealed that the sintered Ti–12Mo/xAl2O3 nanocomposites displayed higher corrosion resistance against a simulated artificial saliva (AS) solution than pure Ti. The concentrations of Ti, Mo, and Al ions released from the Ti–12Mo/xAl2O3 nanocomposites in the AS solution were within the safe levels. It was found from this study that; the sample of the composition Ti–12Mo/5wt%Al2O3 exhibited appropriate mechanical properties, biocompatibility, corrosion resistance against the AS solution with acceptable ion concentration released in the biological fluids. Therefore, it can be considered as a new bio-inert material for potential applications in dental prosthetics.
Non-canonical functions of regulated cell death machinery regulate cellular growth, invasion and the interplay between cell death modalities
Authors: Shan Y. , Mollereau B.
Published: July 2024

The exploration of multiple regulated cell death (RCD) pathways and the recognition that several cell death-related proteins, including caspases, serve non-canonical roles have significantly expanded and diversified cell death research. Caspases not only cleave cellular substrates, triggering apoptosis, but also impact essential processes such as cellular differentiation, proliferation, growth, and migration. These novel caspase-dependent regulatory networks are extensively studied during development, with Drosophila providing a diverse range of developmental models for investigating these phenomena. Moreover, recent insights into the non-canonical functions of cell death proteins have highlighted their pivotal role in cancer aggressiveness. Ultimately, understanding these non-canonical functions sheds light on the intricate connections between RCD pathways and their significance in promoting anti-oncogenic responses.
The inotropic and arrhythmogenic effects of acutely increased late INa are associated with elevated ROS but not oxidation of PKARIα
Authors: Gissibl Theresa , Stengel Laura , Tarnowski Daniel , Maier Lars S. , Wagner Stefan , Feder Anna-Lena , Sag Can Martin
Published: July 2024

Background

Acute stimulation of the late sodium current (INaL) as pharmacologically induced by Anemonia toxin II (ATX-II) results in Na+-dependent Ca2+ overload and enhanced formation of reactive oxygen species (ROS). This is accompanied by an acute increase in the amplitude of the systolic Ca2+ transient. Ca2+ transient amplitude is determined by L-type Ca2+-mediated transsarcolemmal Ca2+ influx (ICa) into the cytosol and by systolic Ca2+ release from the sarcoplasmic reticulum (SR). Type-1 protein kinase A (PKARIα) becomes activated upon increased ROS and is capable of stimulating ICa, thereby sustaining the amplitude of the systolic Ca2+ transient upon oxidative stress.

Objectives

We aimed to investigate whether the increase of the systolic Ca2+ transient as acutely induced by INaL (by ATX-II) may involve stimulation of ICa through oxidized PKARIα.

Methods

We used a transgenic mouse model in which PKARIα was made resistant to oxidative activation by homozygous knock-in replacement of redox-sensitive Cysteine 17 with Serine within the regulatory subunits of PKARIα (KI). ATX-II (at 1 nmol/L) was used to acutely enhance INaL in freshly isolated ventricular myocytes from KI and wild-type (WT) control mice. Epifluorescence and confocal imaging were used to assess intracellular Ca2+ handling and ROS formation. A ruptured-patch whole-cell voltage-clamp was used to measure INaL and ICa. The impact of acutely enhanced INaL on RIα dimer formation and PKA target structures was studied using Western blot analysis.

Results

ATX-II increased INaL to a similar extent in KI and WT cells, which was associated with significant cytosolic and mitochondrial ROS formation in both genotypes. Acutely activated Ca2+ handling in terms of increased Ca2+ transient amplitudes and elevated SR Ca2+ load was equally present in KI and WT cells. Likewise, cellular arrhythmias as approximated by non-triggered Ca2+ elevations during Ca2+ transient decay and by diastolic SR Ca2+-spark frequency occurred in a comparable manner in both genotypes. Most importantly and in contrast to our initial hypothesis, ATX-II did not alter the magnitude or inactivation kinetics of ICa in neither WT nor KI cells and did not result in PKARIα dimerization (i.e., oxidation) despite a clear prooxidant intracellular environment.

Conclusions

The inotropic and arrhythmogenic effects of acutely increased INaL are associated with elevated ROS, but do not involve oxidation of PKARIα.
Early clinical outcomes of Portico and Edwards Sapien 3 valve prosthesis in transcatheter aortic valve replacement: propensity-matched analysis
Authors: Primessnig Uwe , Wiedenhofer Julia M. , Trippel Tobias D. , Loddenkemper Carina M. , Schrader Helene , Brand Anna , Spethmann Sebastian , Stangl Karl , Haghikia Arash , Landmesser Ulf , Boldt Leif-Hendrik , Blaschke Florian , Hindricks Gerhard , Sündermann Simon H. , Grubitzsch Herko , Falk Volkmar , Dreger Henryk , Sherif Mohammad
Published: July 2024

Introduction

There is a lack of real-world data directly comparing different valve prostheses for transaortic valve replacement (TAVR). We aimed to compare early clinical outcomes at 30-days between the self-expandable Portico valve (Abbott) with the balloon-expandable Edwards Sapien 3 valve (Edwards Lifesciences) (ES3).

Methods

Out of 1,901 patients undergoing TAVR between January 2018 and December 2021, all patients who received either Portico valve or ES3 valve via transfemoral TAVR were matched using nearest-neighbor (1:1) propensity scoring. Primary endpoints were single safety endpoints and early safety composite endpoints defined by Valve Academic Research Consortium-2 (VARC-2) criteria. The secondary endpoint was to analyze risk predictors for new permanent pacemaker (PPM) implantation in TAVR.

Results

Out of 661 complete cases, a total of 434 patients were successfully matched based on age, sex, Euro Score II and STS-score. In the matched cohort, 217 received either a Portico or valve and 217 received an ES3 valve. The VARC-2 early safety composite scores indicated a significantly greater overall 30-day safety risk in the Portico group at 9.2% (n = 20) compared to 3.7% (n = 8) in the ES3 group (p = 0.032). The requirement for new permanent pacemaker (PPM) implantation was also higher in the Portico group, at 21.2% (n = 46) vs. 13.4% (n = 29) in the ES3 group (p = 0.042). 30-day mortality was higher was 3.7% (n = 8) in Portico group compared to 0.9% in ES3 group (p = 0.11). Furthermore, implantation of the Portico valve was identified as a significant risk predictor for new PPM implantation, alongside higher age, preprocedural atrioventricular block (AVB) and longer total procedure duration.

Conclusion

This study shows significantly higher rates of early clinical complications for Portico valve prostheses compared to ES3. These findings should be especially taken into consideration when selecting valve prosthesis for high-risk patients.
Multi-fractal characteristics of pore system in deep organic-rich shales of the Wufeng-Longmaxi formation in the Sichuan Basin and their geological significance
Authors: Xie Guogen , Xie Guoliang , Jiao Kun
Published: July 2024

The heterogeneity of pore system of deep shale reservoir determines the occurrence, enrichment and migration behavior of shale gas within shales. In this study, multi-fractal analysis was applied to analyze CO2 and N2 adsorption data for obtaining multi-fractal parameters including Hurst index and multi-fractal spectrum (D5--D5+) of the deep Wufeng-Longmaxi shales collected from the Sichuan Basin, China, in order to study the connectivity and heterogeneity of micropore pores and meso-macropores as well as their influencing factors. The results showed that pore system of the Wufeng-Longmaxi deep shale exhibits distinct multifractal nature. There exists significant differences in the pore volume (PV) of micropores (<2 nm), mesopore (2–50 nm), and macropore (>50 nm) across different shale lithofacies due to their differences in TOC content and mineral composition. The heterogeneity and connectivity of micropores and meso-macropores within deep shales in the Sichuan Basin are controlled by multiple factors including shale lithofacies, burial depth, and pressure coefficients. Notably, siliceous shale (SL) and calcareous/argillaecous siliceous shale (C/ASL), known as sweet spot for current shale gas exploitation, exhibits characteristics such as relative low micropore connectivity, high micropore heterogeneity, high micropore PV and low meso-macropore connectivity. These suggest that isolated pressure-sealing compartment is easier formed within the overpressured SL and C/ASL. Thus, pressure in these shales is less likely to release during the Yanshanian-Xishanian tectonic uplift process, favoring the preservation of organic matter (OM) pores and residual interparticle pores, which is conducive to the accumulation of deep shale gas dominated by free gas.
Metabolomics and network pharmacology exploration of the effects of bile acids on carotid atherosclerosis and potential underlying mechanisms
Authors: Cheng Xing , Zhang Ruijing , Qi Xiaotong , Wang Heng , Gao Tingting , Zheng Lin , Qiao Maolin , Li Yaling , Gao Siqi , Chen Jinshan , Chang Runze , Zheng Guoping , Dong Honglin
Published: July 2024

Background

Bile acids (BAs), products of gut microbiota metabolism, have long been implicated in atherosclerotic disease pathogenesis. Characterizing the serum bile acid profile and exploring its potential role in carotid atherosclerosis (CAS) development are crucial tasks.

Methods

In this study, we recruited 73 patients with CAS as the disease group and 77 healthy individuals as the control group. We systematically measured the serum concentrations of 15 bile acids using ultrahigh-performance liquid chromatography-mass spectrometry (UPLC-MS/MS). Multivariate logistic regression and least absolute shrinkage and selection operator (LASSO) regression were applied to analyze the impact of bile acids on the disease and select the key BAs. The possible molecular mechanism was elucidated by network pharmacology.

Results

(1) The BA profile of patients with CAS significantly differed. (2) Multifactorial logistic regression analysis identified elevated levels of GCDCA (OR: 1.01, P < 0.001), DCA (OR: 1.01, P = 0.005), and TDCA (OR: 1.05, P = 0.002) as independent risk factors for CAS development. Conversely, GCA (OR: 0.99, P = 0.020), LCA (OR: 0.83, P = 0.002), and GUDCA (OR: 0.99, P = 0.003) were associated with protective effects against the disease. GCA, DCA, LCA, and TDCA were identified as the four key BAs. (3) TNF, FXR, GPBAR1, ESR1 and ACE were predicted to be targets of BAs against AS. These four BAs potentially impact AS progression by triggering signaling pathways, including cAMP, PPAR, and PI3K-AKT pathways, via their targets.

Conclusion

This study offers valuable insights into potential therapeutic strategies for atherosclerosis that target bile acids.
The effectiveness of applying the economic and technological dimensions of the kingdom of Saudi Arabia’s vision 2030 to achieve the competitive advantage of the Hail Region
Authors: Alhamad Samer Hussein , Bani Hani Sylvia Ismail , Dakhli Abdesselem Chedli , Almahayreh Abdulah Salamah
Published: July 2024

This research focuses on examining the impact of Saudi Arabia’s Vision 2030 on the energy industry, specifically in the Hail region, by exploring the role of technological and economic strategies in fostering sustainable energy development. The study aims to identify key factors that facilitate the implementation of Vision 2030 to assess the current energy landscape in Saudi Arabia. By delving into the economic and technological dimensions of Vision 2030, the research seeks to determine the essential components that the Kingdom of Saudi Arabia needs to establish systems and initiatives that align with global scientific and technological advances, ensuring competitiveness and progress in the global arena. By surveying 60 faculty members from Hail University, the study employs a descriptive-analytical approach to unravel how economic activities and technological advancements collaborate to shape a sustainable and competitive energy sector. The findings highlight the crucial role of technological innovations, including advances in administrative processes, human resource management, regulatory frameworks, and technical infrastructure related to energy efficiency and renewable energy technologies. Furthermore, the study evaluates economic aspects such as labor market reforms, skill development programs, and support for emerging energy enterprises. The results underscore the positive impact of technological and economic interventions on the energy sector in the Hail region, with significant improvements in energy project management efficiency and the creation of a conducive environment for sustainable energy practices. The study reveals that the integration of technological and economic initiatives has led to notable improvements in the energy sector, reflected in average values ranging from 68% to 84%. These results underscore the fundamental role of Vision 2030 in advancing sustainable energy development and underscore the importance of leveraging economic and technological strategies to achieve energy sustainability and competitive advantage. This research contributes to understanding how Saudi Arabia’s Vision 2030 is driving progress in the energy industry and emphasizes the importance of integrating economic and technological approaches in shaping a sustainable energy landscape. The findings provide valuable information for policymakers and stakeholders in the energy sector, highlighting the need for concerted efforts to harness economic and technological advancements to promote sustainable energy development. By showcasing the transformative impact of Vision 2030 on the energy sector in the Hail region, this study underscores the originality and importance of research in advancing the goals of sustainable energy development in Saudi Arabia.
Harmonizing hope: navigating the osteoarthritis melody through the CCL2/CCR2 axis for innovative therapeutic avenues
Authors: Abbasifard Mitra , Khorramdelazad Hossein
Published: July 2024

Osteoarthritis (OA) is characterized by a complex interplay of molecular signals orchestrated by the CCL2/CCR2 axis. The pathogenesis of OA has been revealed to be influenced by a multifaceted effect of CCL2/CCR2 signaling on inflammation, cartilage degradation, and joint homeostasis. The CCL2/CCR2 axis promotes immune cell recruitment and tips the balance toward degeneration by influencing chondrocyte behavior. Insights into these intricate pathways will offer novel therapeutic approaches, paving the way for targeted interventions that may redefine OA management in the future. This review article explores the molecular symphony through the lens of the CCL2/CCR2 axis, providing a harmonious blend of current knowledge and future directions on OA treatment. Furthermore, in this study, through a meticulous review of recent research, the key players and molecular mechanisms that amplify the catabolic cascade within the joint microenvironment are identified, and therapeutic approaches to targeting the CCL2/CCR axis are discussed.
Effectiveness of baricitinib in acquired reactive perforating collagenosis: a case report
Authors: Zheng Jianfeng , Ding Yangfeng , Chen Yuanyuan , Shi Yuling , Gao Yunlu
Published: July 2024

Background

Acquired reactive perforating collagenosis (ARPC) poses a clinical challenge with an unclear pathogenesis. This disease has been frequently proven resistant to immunosuppressive treatments, significantly affecting the quality of life of patients. In this report, we highlight the efficacy of baricitinib as a viable option for maintenance therapy in ARPC.

Case summary

An 81-year-old woman presented to our hospital with recurrent pruritus and cup-like ulcerated lesions on her trunk and limbs persisting for 1 year. She exhibited limited response to oral antihistamines and topical steroids. Past medical history revealed a prolonged history of coronary heart disease and type 2 diabetes spanning several years to decades. Histopathological examination revealed cup-shaped depressions filled with necrotic inflammatory debris. In the dermis, a mixed inflammatory infiltrate composed of lymphocytes and histiocytes was observed. Van Gieson staining indicated the elimination of fibrous tissue extending from the dermis into the epidermis. Consequently, a diagnosis of ARPC was established. Due to the inadequate response to conventional treatments and the severe itching, we initiated baricitinib therapy for ARPC, resulting in gradual symptom improvement. Follow-up assessments showed no adverse reactions and normal laboratory findings.

Conclusion

The case report suggests that baricitinib might offer significant therapeutic benefits for ARPC.
Immune dysregulation due to bi-allelic mutation of the actin remodeling protein DIAPH1
Authors: Bhattad Sagar , Ramakrishna Somashekara H. , Kumar Ratan , Choi Joseph M. , Markle Janet G.
Published: July 2024

Children with severe inflammatory diseases are challenging to diagnose and treat, and the etiology of disease often remains unexplained. Here we present DIAPH1 deficiency as an unexpected genetic finding in a child with fatal inflammatory bowel disease who also displayed complex neurological and developmental phenotypes. Bi-allelic mutations of DIAPH1 were first described in patients with a severe neurological phenotype including microcephaly, intellectual disability, seizures, and blindness. Recent findings have expanded the clinical phenotype of DIAPH1 deficiency to include severe susceptibility to infections, placing this monogenic disease amongst the etiologies of inborn errors of immunity. Immune phenotypes in DIAPH1 deficiency are largely driven aberrant lymphocyte activation, particularly the failure to form an effective immune synapse in T cells. We present the case of a child with a novel homozygous deletion in DIAPH1, leading to a premature truncation in the Lasso domain of the protein. Unlike other cases of DIAPH1 deficiency, this patient did not have seizures or lung infections. Her major immune-related clinical symptoms were inflammation and enteropathy, diarrhea and failure to thrive. This patient did not show T or B cell lymphopenia but did have dramatically reduced naïve CD4+ and CD8+ T cells, expanded CD4-CD8- T cells, and elevated IgE. Similar to other cases of DIAPH1 deficiency, this patient had non-hematological phenotypes including microcephaly, developmental delay, and impaired vision. This patient’s symptSoms of immune dysregulation were not successfully controlled and were ultimately fatal. This case expands the clinical spectrum of DIAPH1 deficiency and reveals that autoimmune or inflammatory enteropathy may be the most prominent immunological manifestation of disease.
Neoadjuvant immunochemotherapy improves clinical outcomes of patients with esophageal cancer by mediating anti-tumor immunity of CD8+ T (Tc1) and CD16+ NK cells
Authors: He Yunlong , Yang Depeng , Lin Xiaoyu , Zhang Jinfeng , Cheng Rui , Cao Liangyu , Yang Lijun , Zhang Mengmeng , Shi Xinyue , Jin Xiyun , Sun Handi , Sun Haoxiu , Zang Jingyu , Li Yu , Ma Jianqun , Nie Huan
Published: July 2024

Background

Esophageal cancer (ESCA) is one of the most common tumors in the world, and treatment using neoadjuvant therapy (NT) based on radiotherapy and/or chemotherapy has still unsatisfactory results. Neoadjuvant immunochemotherapy (NICT) has also become an effective treatment strategy nowadays. However, its impact on the tumor microenvironment (TME) and regulatory mechanisms on T cells and NK cells needs to be further elucidated.

Methods

A total of 279 cases of ESCA who underwent surgery alone [non-neoadjuvant therapy (NONE)], neoadjuvant chemotherapy (NCT), and NICT were collected, and their therapeutic effect and survival period were compared. Further, RNA sequencing combined with biological information was used to analyze the expression of immune-related genes. Immunohistochemistry, immunofluorescence, and quantitative real-time PCR (qRT-PCR) were used to verify the activation and infiltration status of CD8+ T and CD16+ NK cells, as well as the function and regulatory pathway of killing tumor cells.

Results

Patients with ESCA in the NICT group showed better clinical response, median survival, and 2-year survival rates (p < 0.05) compared with the NCT group. Our RNA sequencing data revealed that NICT could promote the expression of immune-related genes. The infiltration and activation of immune cells centered with CD8+ T cells were significantly enhanced. CD8+ T cells activated by PD-1 inhibitors secreted more IFN-γ and cytotoxic effector factor cells through the transcription factor of EOMES and TBX21. At the same time, activated CD8+ T cells mediated the CD16+ NK cell activation and secreted more IFN-γ to kill ESCA cells. In addition, the immunofluorescence co-staining results showed that more CD276+ tumor cells and CD16+ NK cells were existed in pre-NCT and pre-NICT group. However, CD276+ tumor cells were reduced significantly in the post-NICT group, while they still appeared in the post-NCT group, which means that CD16+ NK cells can recognize and kill CD276+ tumor cells after immune checkpoint blocker (ICB) treatment.

Conclusion

NICT can improve the therapeutic effect and survival period of resectable ESCA patients. NICT could promote the expression of immune-related genes and activate CD8+ T and CD16+ NK cells to secrete more IFN-γ to kill ESCA cells. It provides a theoretical basis and clinical evidence for its potential as an NT strategy in ESCA.
Implication of the Annexin 1/FPR axis in leishmanial exosome-mediated Leishmania major skin hyperpathogenesis
Authors: da Silva Lira Filho Alonso , Lafleur Andrea , Alvarez Fernando , Piccirillo Ciriaco A. , Olivier Martin
Published: July 2024

Introduction

Exosomes produced by the protozoan parasite Leishmania (LeishEXO) are well-established drivers of virulence, though mechanisms underlying their exacerbation of experimental leishmaniasis remain elusive. Expression of Annexin A1 (ANXA1), a protein implicated in exosome-mediated pathologies and viral internalization, has been shown to correlate with cutaneous leishmaniasis severity. Given ANXA1’s regulation of myeloid cells – the canonical hosts for Leishmania – we studied the potential role of ANXA1 and its receptors FPR1/2 in exerting LeishEXO’s effects.

Methods

Murine and in vitro ANXA1-/- models were used to study the generation of protective TH1 responses during experimental L. major infection with and without LeishEXO. Recruitment of inflammatory cells was assessed using a peritoneal cell recruitment assay and immunophenotyping, and production of inflammatory mediators was measured using a cytokine and chemokine array. Treatment of experimental models with FPR2 antagonist WRW4 and FPR1/2 agonist WKYMVm was used to delineate the role of the FPR/ANXA1 axis in LeishEXO-mediated hyperpathogenesis.

Results

We established that ANXA1 deficiency prohibits LeishEXO-mediated pathogenesis and myeloid cell infection, with minimal alterations to adaptive and innate immune phenotypes. FPR2 blockade with WRW4 similarly inhibited leishmanial hyperpathogenesis, while direct activation of FPRs with WKYMVm enhanced infection and recapitulated the LeishEXO-mediated phenotype. This research describes LeishEXO’s utilization of the ANXA1/FPR axis to facilitate parasitic internalization and pathogenesis, which may be leveraged in the development of therapeutics for leishmaniasis.
Using passive acoustics to identify a quiet winter foraging refuge for an endangered beluga whale population in Alaska
Authors: Castellote Manuel , Gill Verena A. , Garner Christopher D. , Gilstad Andrea J , Hou Benjamin X. , Brewer Arial M. , Knoth Jessica M.
Published: July 2024

Cook Inlet beluga (CIB),Delphinapterus leucas, have not recovered from subsistence overharvest despite conservation efforts initiated in 2000. Reasons for this lack of recovery are still unclear with anthropogenic noise identified as a high threat in this population’s recovery plan. Baseline information on CIB habitat use and soundscape characterization is crucial in evaluating impacts from anthropogenic activities. Using passive acoustic monitoring, we documented the seasonality and foraging occurrence of CIB, together with killer whale (Orcinus orca), harbor porpoise (Phocoena phocoena) and humpback whale (Megaptera novaeangliae), for one year in Chinitna and Tuxedni bays and rivers, two historically important but recently overlooked areas of their critical habitat in western lower Cook Inlet, Alaska. This area’s ecological interest converges with planned mining, marine renewable energy, offshore oil and gas production, and commercial shipping. Results revealed higher presence of harbor porpoise, killer whale, and humpback whale in Chinitna compared to Tuxedni but much lower CIB presence. CIB were not detected in Chinitna Bay but were in the river on 21 days September-February and one day in June. However, CIB were never detected feeding in Chinitna River. CIB acoustic crypsis and preferential use of very shallow habitat in Chinitna revealed a perceived predation risk from killer whales. In contrast, CIB were recorded foraging in both Tuxedni Bay and River and were detected September-April on 127 days making it an important winter foraging ground. Low levels of anthropogenic noise disturbance were quantified in both bays making them some of the most undisturbed sections of their critical habitat, but at the same time highly sensitive to further noise disturbance. Commercial shipping was the main noise source likely causing acoustic disturbance to CIB due to communication masking despite current low levels of temporal overlap with beluga presence. We recommend that applicable regulators consider restricting high sound producing anthropogenic activities in and adjacent to Tuxedni Bay from September 1st to May 15th when CIB are actively using this area. Managing future anthropogenic activities to minimize habitat degradation and acoustic disturbance in this winter foraging refuge will be a key component to support the recovery of this endangered population.
Deep underwater image compression for enhanced machine vision applications
Authors: Zhang Hanshu , Fan Suzhen , Zou Shuo , Yu Zhibin , Zheng Bing
Published: July 2024

Underwater image compression is fundamental in underwater visual applications. The storage resources of autonomous underwater vehicles (AUVs) and underwater cameras are limited. By employing effective image compression methods, it is possible to optimize the resource utilization of these devices, thereby extending the operational time underwater. Current image compression methods neglect the unique characteristics of the underwater environment, thus failing to support downstream underwater visual tasks efficiently. We propose a novel underwater image compression framework that integrates frequency priors and feature decomposition fusion in response to these challenges. Our framework incorporates a task-driven feature decomposition fusion module (FDFM). This module enables the network to understand and preserve machine-friendly information during the compression process, prioritizing task relevance over human visual perception. Additionally, we propose a frequency-guided underwater image correction module (UICM) to address noise issues and accurately identify redundant information, enhancing the overall compression process. Our framework effectively preserves machine-friendly features at a low bit rate. Extensive experiments across various downstream visual tasks, including object detection, semantic segmentation, and saliency detection, consistently demonstrated significant improvements achieved by our approach.
Short-term time-series observations of phytoplankton light-absorption and productivity in Prydz Bay, coastal Antarctica
Authors: Tripathy Sarat C. , Kerkar Anvita U. , Sabu P. , Padhi Sunil K. , Pandi Sudarsana R. , Sarkar Amit , Parli Bhaskar V. , Mohan Rahul
Published: July 2024

The optical characteristics of coastal Antarctic waters exhibit complexity due to the dynamic hydrography influenced by meltwater intrusion, which alters nutrient levels, thermohaline structure, and optically active substances (OAS) regimes. Studies on bio-optical variability and its implications on phytoplankton productivity (PP) are scanty in coastal polar regions. On this backdrop, time-series measurements (72 h at 6 h intervals) of bio-optical properties such as phytoplankton biomass (chlorophyll-a), absorption (aph), and total suspended matter (TSM) concurrently with PP were measured to understand their interplay and variability in relation to the ambient physicochemical settings in the under-sampled Prydz Bay, coastal Antarctica. Our findings revealed thermohaline stratification within the bay, likely attributed to the inflow of less saline meltwater from nearby glaciers and minimal wind activity. The consistent presence of sub-surface chlorophyll maximum (SCM) beneath the stratified layer underscored the light-acclimatization response of shade-adapted phytoplankton. Surface waters exhibited higher TSM compared to deeper layers, indicating glacial melt influence, while the depth of the sunlit layer remained relatively stable, suggesting limited water mass movement and/or variability in OAS at the study site. An inverse relation between chlorophyll-a and chlorophyll-a-specific phytoplankton light absorption (a*ph(λ)) manifested ‘pigment package effect’ within the prevailing phytoplankton community, implying reduced light-absorption efficiency and consequent lower PP. Compared to chlorophyll-a, the phytoplankton light absorption (aph(λ)) emerged as a better proxy for explaining PP variability. Nutrient availability was not limiting, which was conducive to micro (large) phytoplankton growth. Classification of phytoplankton size classes (micro, nano, and pico) based on the B/R ratio (aph at Blue (443 nm)/Red (676 nm) region) confirmed the dominance of larger (micro) phytoplankton that are more susceptible to package effect, thus have implications on reduced PP potential of this polar marine ecosystem.
Glucose-albumin ratio (GAR) as a novel biomarker of postoperative urinary tract infection in elderly hip fracture patients
Authors: Wang Wei , Tang Wanyun , Yao Wei , Lv Qiaomei , Ding Wenbo
Published: July 2024

Purpose

Postoperative urinary tract infections (UTIs) worsen the prognosis of elderly patients with hip fractures. This study aimed to assess the predictive ability of blood-based biomarkers, specifically the glucose-albumin ratio (GAR), in predicting postoperative UTIs.

Methods

A retrospective observational study of 1,231 patients from a Level I trauma center was conducted. We evaluated the prognostic and predictive value of 15 biomarkers, including the glucose-albumin ratio, in elderly patients with hip fractures. The primary outcome measure was the incidence of postoperative UTIs.

Results

The glucose to albumin ratio transformed into GAR was superior to any other biomarker in predicting postoperative UTIs in elderly hip fracture patients (AUC = 0.756, p < 0.001). Elevated GAR (using the best cut-off value of 0.18) was independently associated with postoperative UTIs (OR 3.20, 95% CI 2.23–4.58). Further analysis dividing GAR levels into four groups according to quartiles showed that compared to patients with GAR levels of Q1 (< 0.14), GAR levels of Q2 (0.14–0.17; OR 2.11, 95% CI 1.07–4.15), Q3 (0.17–0.21; OR 3.36, 95% CI 1.74–6.52) and Q4 (> 0.21; OR 7.55, 95% CI 3.84–14.83) patients had significantly higher odds of UTIs.

Conclusion

GAR holds potential as a novel biomarker for predicting postoperative UTIs in elderly patients with hip fractures.
5-aminolevulinic acid induced photodynamic reactions in diagnosis and therapy for female lower genital tract diseases
Authors: Chen Yuqing , Guo Peng , Chen Lihong , He Dalin
Published: July 2024

Since the patients suffering from female lower genital tract diseases are getting younger and younger and the human papilloma virus (HPV) infection is becoming more widespread, the novel non-invasive precise modalities of diagnosis and therapy are required to remain structures of the organ and tissue, and fertility as well, by which the less damage to normal tissue and fewer adverse effects are able to be achieved. In all nucleated mammalian cells, 5-Aminolevulinic acid (5-ALA) is an amino acid that occurs spontaneously, which further synthesizes in the heme biosynthetic pathway into protoporphyrin IX (PpIX) as a porphyrin precursor and photosensitizing agent. Exogenous 5-ALA avoids the rate-limiting step in the process, causing PpIX buildup in tumor tissues. This tumor-selective PpIX distribution after 5-ALA application has been used successfully for tumor photodynamic diagnosis (PDD) and photodynamic therapy (PDT). Several ALA-based drugs have been used for ALA-PDD and ALA-PDT in treating many (pre)cancerous diseases, including the female lower genital tract diseases, yet the ALA-induced fluorescent theranostics is needed to be explored further. In this paper, we are going to review the studies of the mechanisms and applications mainly on ALA-mediated photodynamic reactions and its effectiveness in treating female lower genital tract diseases.