bluuebunny/crossref_metadata_2025 huggingface dataset:
METHODS OF IMPROVING THE DESIGN OF THE NTU WEBSITE FROM THE POINT OF VIEW OF THE EFFECTIVENESS OF INFORMATION PRESENTATION
Authors:   National Transport University, Bezverkhy Oleksandr , Boretskyi Vladyslav ,   National Transport University, Zubretska Nataliya ,   National Transport University, Karmanov Roman ,   National Transport University
Published: December 2023

The main concepts of website design - skeuomorphism, neomorphism, glassomorphism, minimorphism - are considered in the work and their main advantages and disadvantages are analyzed; The peculiarities of website operation on devices of different types, sizes, lighting levels and usage environments were analyzed; A prototype of the design of the NTU website based on the concept of glass-morphic interfaces was developed using Figma and Photoshop software, and a prototype of a universal multi-platform interface based on the glass-morphic concept was implemented, the effectiveness of key changes was tested for a wide range of devices.
AIRFIELD PAVEMENT MANAGEMENT SYSTEM OF TECHNICAL AND OPERATING FACILITY
Authors:   National Transport University, Gameliak Igor , Dmytrychenko Andij ,   National Transport University
Published: December 2023

The article explores an overview of APMS to understand its successful implementation. Once an airport pavement has been opened to traffic, proper maintenance and rehabilitation work is essential to maintain the pavement's functionality at a satisfactory level and extend its service life. Maintenance and restoration-reconstruction strategies were tentatively based on the empirical and subjective judgments of airport administration employees. This required a systematic method of performing maintenance and restoration-reconstruction works, i.e. the Airport Pavement Management System (APMS). Some APMS subsystems have been developed through the exchange of ideas, information and resources and are entering practical use. Based on various airport pavement studies, such as surface condition assessment studies, structural evaluations, failure and serviceability predictions, and maintenance and rehabilitation strategies, design, assessment and rehabilitation procedures have been developed that form the subsystems of the complete APMS. The maintenance and recovery subsystem of the airport pavement management system consists of three phases: the inspection and maintenance phase, the reliability evaluation phase, and the recovery optimization phase.
THE RECONSTRUCTION OF UKRAINE'S TRANSPORT INFRASTRUCTURE IN THE FIELD OF LOGISTICS AND TRANSPORT TECHNOLOGIES
Authors:   National Transport University, Dovbii Valentyna , Mnyshenko Roman ,   National Transport University
Published: December 2023

This article explores the importance of restructuring Ukraine's transportation infrastructure for the development of logistics and transportation technologies. The development and improvement of infrastructure are critical to ensuring efficiency and competitiveness of the country. The article examines key components of the transportation infrastructure restructuring, including the development of railway, maritime, river, and aviation infrastructure, the implementation of information technologies, and the development of roads and logistics centers. It highlights how these measures contribute to improving transportation efficiency, regional connectivity, and cost reduction. It emphasizes that successful restructuring of the transportation infrastructure requires collaboration among various stakeholders, such as the government, private sector, academic community, and society. It is important to consider the social aspect and meet the needs of society, ensuring environmental sustainability and the preservation of natural resources. In conclusion, the article underscores that the success of Ukraine's transportation infrastructure restructuring is a crucial strategic priority for the country's development. This opens up opportunities for transportation improvement.
IMPACTS OF PUBLIC TRANSPORT TO MACROSCOPIC CHARACTERISTICS OF TRAFFIC FLOW
Authors:   National Transport University, Polishchuk Volodymyr , Popov Stanislav ,   National Transport University
Published: December 2023

Public transport (buses) have similar to each other type of vehicles. Movement of public transport on automobile roads has signs of stationarity. For this reason scientific task has been designed. The authors in research evaluate the level of safety of the passenger transport through the consideration of the characteristics of the traffic of passenger transport in terms of the characteristics of the traffic flow. Analysis of the problem formulate influence system between three elements: traffic flow, passenger transport, road environment. Establish criteria for determining the characteristics of the buses movement in terms of the characteristics of the traffic flow. Shown criteria gives the possibility to assess the level of unsafety on the route. Presented general characteristic allows to estimate indirectly the level of road safety of passenger transport.
DIGITAL CULTURE IN TRANSPORT PERSONNEL MANAGEMENT INDUSTRIES OF UKRAINE
Authors:   National Transport University, Spitsyna Anhelina
Published: December 2023

The article examines the evolution of the development and formation of the digital culture of personnel as a promising area of activity of transport enterprises. The theoretical foundations of the development of digital culture are analyzed and summarized. Existing approaches to the interpretation of digital culture proposed by various authors are considered. The structure of digital competence was studied, taking into account world experience, which includes the following components: communication and cooperation, information literacy, ability to solve problems and tasks, information security, digital erudition, digital talent, digital enthusiasm, creation of digital content, etc. As a result of the study, it was established that digital culture should be considered as a set of principles, values and methods in the personnel management system using information and communication technologies for the interaction of management, employees and solving tasks in professional activities. This is the formed way and nature of the behavior of the company's employees, which arose under the influence of the transformation of the digital society and implies an increase in the level of digital skills, literacy and the ability to use modern information and communication technologies and software. The key principles of the formation and development of the digital culture of enterprises in the conditions of the digital economy are defined: organizational flexibility; result orientation; insight; technological literacy; adaptability to global challenges and organizational changes; network approach to the formation of digital platforms; continuous learning.
SUSTAINABLE DEVELOPMENT AS A PROSPECTIVE DIRECTION FOR IMPROVING THE LOGISTICS ACTIVITIES OF THE ENTERPRISE
Authors:   National Transport University, Volynets Lyudmyla , Dobrovolskа Anna ,   National Transport University, Dobrovolskiy Oleksandr ,   National Transport University, Penkivska Kateryna ,   National Transport University, Yanishevskyi Andrii ,   National Transport University
Published: December 2023

The article is devoted to the study of the importance of sustainable development for improving the efficiency and quality of logistics activities in Ukraine. The goals of the sustainable development of Ukraine for the period until 2030 foresee the need to ensure the national interests of Ukraine regarding the sustainable development of the economy, civil society and the state in order to achieve an increase in the level and quality of life of the population. In the context of ensuring the specified goal, special attention is paid to ensuring the balance of the economic, social and ecological dimensions of sustainable development of Ukraine, which, among other things, should include the need to ensure the appropriate development of the logistics activities of enterprises. The article considers the definition of the concept of sustainable development and its evolution. The analysis of the essence, features and advantages of improving the logistics activities of enterprises according to the concept of sustainable development was carried out. Theoretical provisions on improving logistics support for the sustainable development of enterprises are proposed. It was determined that the globalization of business leads to the allocation of new logistics functions, which will be the driving force for the enterprise to acquire innovative development positions. New challenges are proposed, which dictate the need for a qualitative change in the field of logistics - its functional load and information display. Various areas of activity that will contribute to achieving sustainability are substantiated. Economic benefits from the implementation of the strategy of sustainable development are studied. An overview of modern trends in sustainability development is presented, problems and obstacles faced by logistics companies in Ukraine are highlighted. The importance of the interaction of various sectors of society to achieve the common goal of transition to a model of sustainable development and increase the competitiveness of the national logistics system is substantiated. Thus, taking into account environmental norms of behavior requires changing traditional approaches to managing logistics activities, reorienting enterprises to the use of environmentally safe logistics technologies, giving way to sustainable logistics.
VALIDITY AND PRACTICALITY OF FLASH CARD PUZZLE AS A LEARNING MEDIA IN EARTH LAYERS CLASS VII
Authors: Nisak Ummi Nazikhah  , Af'idah Noer
Published: December 2023

The role of learning media was important to helped students for understood learning proccesed. The selection of learning media was concerned about the suitability of students and the material being studied. The earth layers materials in science lesson was materials that needed a learning media. For this reason, researchers developed a flash card puzzle learning media. This study aims to produced flash card puzzle learning media on class VII SMP/MTs earth layer material that is valid and practical. This development used the ADDIE development model which had step of analize, design, development, implementation, and evaluation. The validity test was conducted by media assessment by validator, they were media expert, material expert, and science teachers. The practicality test was carried out by assessing the activities of teachers (researchers) when was using the media, assessing the activities of students when was using the media, and filling out questionnaires of student responses about satisfaction after used flash card puzzle media. The results of the validity test and practicality test of flash card puzzle media obtained an average score of 3.44 with very valid criteria and 87% with very practical criteria. Based on these data, the development of flash card puzzle media learning media was valid and practical to be used in the learning process of class VII earth layer material.
Офтальмологическая конференция в Баку
Authors: Editorial Article
Published: December 2023

29 октября в г. Баку прошла конференция «Современные возможности в борьбе с миопией», организатором которой выступила давний партнер компании OKVision доктор Гюнай Видадиевна Алиева, член Американской академии ортокератологов, директор первого в Азербайджане Центра контроля миопии и лазерной коррекции зрения, открытие которого было анонсировано не так давно
THE APPLICATION OF BROWN SUGAR GRATER MACHINE TECHNOLOGY FOR GINGER FLAVOURED VARIANT
Authors: Bahtiar Ahmad , Hendarti Devina Rosa , Arif Saiful , Hamidah Fitria nur , Mubarok Ahsin fahmi
Published: December 2023

Brown sugar is one of the natural sweeteners in the community. Where the sale of brown sugar has fluctuated due to the constant demand for brown sugar. Researchers aim to increase productivity and increase interest in brown sugar, so a new product is made, namely brown sugar with a ginger flavor. Therefore, the researchers made a ginger- flavoured brown sugar machine as a souvenir drink typical of the city of Kediri with a capacity of 150 liters/hour. the method used is a design method, which includes the planning stage, calculation, manufacture or assembly, and testing the machine. Which in this section explain more on the transmission system, which cover electric. In the results of the report above, it can be concluded that the planning for the number of scar teeth obtained a cylinder length of 90 mm and a cylinder diameter of 50 mm and the distance between the teeth of the scar 1 and the teeth of the scar 2 is 3 mm and the number of teeth planned for scarring is 840 teeth of the scar. The correction factor has a value of 0.186 kW. In machine testing, the comparison results obtained that 20 liters of brown sugar requires 1.134 kg of ginger and the grating process takes 13 minutes. Using an electric motor as a power source with a size of 1/4 HP, 220 volts, 200 watts and a speed of 2800 rpm. The quality of the grated ginger produced is very soft motor dynamo, grater eye, grater cover, fiter
The Role of Subjective Task Value and Prior Achievement in the Relationship between Personal Epistemology and Science Self-efficacy Beliefs: A Moderated Mediation Analysis
Authors:   Department of Science Education, Faculty of Education, Middle East Technical University, Ankara, Turkey, Şahin Feride , Sungur Semra ,   Department of Science Education, Faculty of Education, Manisa Celal Bayar University, Manisa, Turkey, Ateş Salih ,   Department of Science Education, Faculty of Education, Gazi University, Ankara, Turkey
Published: December 2023

The purpose of this study is to test the relationship between seventh-grade students’ personal epistemology for science, subjective task value, and science self-efficacy, with prior achievement serving as a moderator. The mediating role of subjective task value is proposed in the prediction of the relationship between personal epistemology for science and science self-efficacy. To achieve this aim, a model that explains the relationships among the specified variables is proposed, and then this model is tested using moderated mediation techniques, controlling for the effects of gender and parental educational background variables. The study sample comprises 312 seventh-grade students, determined through stratified random sampling. The analyses confirm the mediating effect of subjective task value and reveal the moderator effect of prior achievement on the prediction of personal epistemology for science and science self-efficacy. Finally, the results of the study are compared with existing research in the field, and recommendations are provided to researchers and practitioners in science education based on these findings.
How a Digital Educational Game can Promote Learning about Sustainability
Authors:   Department of Science Education, University of Bamberg, 96047 Bamberg, Germany, Muenz Thomas S. , Schaal Steffen ,   Department of Biology Education, Ludwigsburg University of Education, 71634 Ludwigsburg, Germany, Groß Jorge ,   Department of Biology Education, University of Marburg, 35032 Marburg, Germany, Paul Jürgen ,   Department of Biology and Chemistry Education, University of Bayreuth, 95447 Bayreuth, Germany
Published: December 2023

Education for Sustainable Development (ESD) has become an essential issue for schools facing major challenges such as bridging the knowledge-action-gap. Interactive simulations could help to focus on action-oriented learning. As part of a design-based research (DBR) process, we investigated the learning potential of game elements within a digital educational game for ESD we are currently developing. The final game aims to convey specific aspects of ESD ranging from sustainable land use to personal power consumption. Seven groups of 2–3 secondary school students (9th and 10th grade, n = 18) played the educational game in an early prototype phase. Following the DBR approach, students were shown screenshots of specific game situations in subsequent group interviews to reveal their conceptions and conceptual developments regarding sustainability. To analyze the causes of possible learning processes, we used the retrospective query on the learning process and qualitative content analysis. The results indicate that the observed learning processes can be primarily traced back to feedback mechanisms and the visualization of processes that would be too complex and long-termed to be experienced by students in real-life. This is how a simulation game, which makes complex interrelations tangible, can contribute to ESD. The possibility to make decisions and act (digitally) within the game allowed students to experience immediate feedback and self-efficacy. Therefore, the easily accessible visualizations and the immediate feedback are essential elements for the final game. It appears however necessary to embed the game in well-structured reflective processes. The study also contributes to adaptive game-based learning as a growing branch of research in which game elements are adopted and adapted for learning based on learner characteristics and the thematic context.
Improving Conceptual Understanding of Density and Buoyancy of Liquids through Common Knowledge Construction Model
Authors:   Department of Mathematics and Science Education, Faculty of Education, Uşak University, Türkiye, Taşdere Ahmet , Kaya Mehmet Fatih ,   Department of Educational Sciences, Faculty of Education, Uşak University, Türkiye
Published: December 2023

The aim of the study was to investigate the effect of the Common Knowledge Construction Model (CKCM) on 10th-grade students’ conceptual understanding of the buoyancy and density of liquids topic. Within a pre-experimental (one group pre-test/post-test) research design, this study was conducted with 22 of 10th-grade students. To collect data, the Word Association Test (WAT) and Structural Grid (SG) were employed as pre- and post-test. Students’ conceptual understanding of the states of objects in different positions (swimming, sinking, and suspending) in the liquid was determined by means of the SG. Through the WAT, the cognitive structure of the students for the stimulus words of mass, volume, density, buoyancy, and Archimedes was determined. According to the post-tests for the SG questions, it was determined that there was a significant increase in the number of correct boxes selected and a significant decrease in the number of incorrect boxes selected. In addition, it was determined that the mind map obtained from the post-WAT, which revealed the cognitive structures of the students, had a much more interrelated and complex network. The findings obtained are compared with other related studies in the literature and some suggestions for teaching science subjects of CKCM are given.
Editorial
Authors: Souza Thais Regina Ravazi de , Santos João Marcelo de Almeida
Published: December 2023

É com grande entusiasmo e comprometimento com a promoção da Educação Física, Saúde e Desempenho que apresentamos a mais recente publicação da Revista REBESDE, que tem como propósito disseminar conhecimento e estimular reflexões que contribuam para a evolução constante da Educação Física e áreas afins. Na presente edição da Revista REBESDE, estamos orgulhosos de oferecer uma contribuição significativa para a área científica, abordando questões cruciais que permeiam a interseção entre Educação Física, Saúde e Desempenho. Os artigos cuidadosamente selecionados e as análises aprofundadas presentes nesta edição não apenas refletem a atualidade e relevância desses temas, mas também proporcionam insights valiosos que enriquecem o corpo de conhecimento em nossa disciplina. Acreditamos que a convergência entre as ciências do movimento, saúde e desempenho esportivo desempenha um papel crucial na expansão das fronteiras do entendimento humano e na formulação de abordagens mais eficazes para a promoção da qualidade de vida. A segunda edição reitera seu compromisso em ser uma fonte confiável de conhecimento científico, contribuindo de maneira significativa para o seu avanço e, por conseguinte, para o bem-estar da sociedade. Artigos que fazem inferência à Inclusão de Pessoas com Deficiência, a arte de brincar, a estímulos motores por meio da Psicomotricidade, a atividades na musculação e obesidade Infantil, todos estes são estudos relacionados às temáticas do periódico e que estão publicados no mesmo. Agradecemos a todos os autores, revisores e leitores que contribuíram para a realização desta edição e esperamos que as reflexões apresentadas inspirem novas ideias, debates e avanços em prol de uma sociedade mais ativa, saudável e capacitada. Boa leitura a todos!
Exploring sex differences in lung cancer risk among workers in Ontario, Canada's Occupational Disease Surveillance System
Authors: Sritharan Jeavana , Christopher Gabriella , Eros Fanni R. , Demers Paul A.
Published: December 2023

Background

While it is well-established that occupational exposures significantly contribute to the risk of developing lung cancer, there remains a notable gap in understanding the specific sex differences in lung cancer risk, particularly among female workers. This study aimed to examine sex differences in lung cancer risk across various occupations, with an emphasis on the female workforce.

Methods

A cohort of approximately 2.37 million workers with lost-time compensation claims were linked to the Ontario Cancer Registry and followed until lung cancer diagnosis, age 85, emigration, death, or end of follow-up (Dec 31, 2020). Cox proportional hazards models were used to estimate sex-specific hazard ratios (HRs) and 95% confidence intervals (CIs) for lung cancer by occupational group (division, major and minor levels), adjusted for birth-year and age and indirectly adjusted for cigarette smoking.

Results

A total of 12,216 and 30,291 incident lung cancer cases were identified among females and males, respectively. Several occupations demonstrated stronger associations for lung cancer in females, with at least a 20% increased risk compared to males. These occupations at the major level include food and beverage preparation services (HR = 1.19, 95% CI = 1.13–1.26); materials processing (chemical, petroleum, rubber, plastic) (HR = 1.35, 95% CI = 1.19–1.52); wood processing (HR = 1.87, 95% CI = 1.22–2.87); metal machining (HR = 1.56, 95% CI = 1.21–2.00); metal shaping and forming (HR = 1.46, 95% CI = 1.32–1.62); fabricating and assembling metal products (HR = 1.37, 95% CI = 1.25–1.51), other construction trades (HR = 1.54, 95% CI = 1.16–2.05), motor transport operating (HR = 1.69, 95% CI = 1.48–1.94), mechanic and repair work (HR = 1.39, 95% CI = 1.04–1.85); and printing (HR = 1.51, 95% CI = 1.30–1.75). These patterns were similar across minor level occupations.

Conclusions

This study identified sex differences across various occupations, with some occupational groups demonstrating stronger associations among female workers. However, these findings should be interpreted with caution. The observed differences may be attributed to various factors that influence risk, such as occupational exposures, use and effectiveness of personal protective equipment, and other biological or lifestyle factors.
Light-enhanced VEGF121/rGel induce immunogenic cell death and increase the antitumor activity of αCTLA4 treatment
Authors: Longva Ane Sager , Berg Kristian , Weyergang Anette
Published: December 2023

Background

Immune-checkpoint inhibitors (ICIs) represent a revolution in cancer therapy and are currently implemented as standard therapy within several cancer indications. Nevertheless, the treatment is only effective in a subset of patients, and immune-related adverse effects complicate the improved survival. Adjuvant treatments that can improve the efficacy of ICIs are highly warranted, not only to increase the response rate, but also to reduce the therapeutic ICI dosage. Several treatment modalities have been suggested as ICI adjuvants including vascular targeted treatments and photodynamic therapy (PDT). Photochemical internalization (PCI) is a drug delivery system, based on PDT. PCI is long known to generate an immune response in murine models and was recently shown to enhance the cellular immune response of a vaccine in a clinical study. In the present work we evaluated PCI in combination with the vascular targeting toxin VEGF121/rGel with respect to induction of immune-mediated cell death as well as in vitro ICI enhancement.

Methods

DAMP signaling post VEGF121/rGel-PCI was assessed in CT26 and MC38 murine colon cancer cell lines. Hypericin-PDT, previously indicated as an highly efficient DAMP inducer (but difficult to utilize clinically), was used as a control. ATP release was detected by a bioluminescent kit while HMGB1 and HSP90 relocalization and secretion was detected by fluorescence microscopy and western blotting. VEGF121/rGel-PCI was further investigated as an αCTLA enhancer in CT26 and MC38 tumors by measurement of tumor growth delay. CD8+ Dependent efficacy was evaluated in vivo using a CD8+ antibody.

Results

VEGF121/rGel-PCI was shown to induce increased DAMP signaling as compared to PDT and VEGF121/rGel alone and the magnitude was found similar to that induced by Hypericin-PDT. Furthermore, a significant CD8+ dependent enhanced αCTLA-4 treatment effect was observed when VEGF121/rGel-PCI was used as an adjuvant in both tumor models.

Conclusions

VEGF121/rGel-PCI describes a novel concept for ICI enhancement which induces a rapid CD8+ dependent tumor eradication in both CT26 and MC38 tumors. The concept is based on the combination of intracellular ROS generation and vascular targeting using a plant derived toxin and will be developed towards clinical utilization.
Risk of osteoarthritis in patients with hidradenitis suppurativa: a global federated health network analysis
Authors: Chang Hui-Chin , Wu Chih-Lung , Chiu Tsu-Man , Liao Wen-Chieh , Gau Shuo-Yan
Published: December 2023

Background

Osteoarthritis and hidradenitis suppurativa (HS) share a common inflammatory pathway. However, whether patients with HS have higher risk developing osteoarthritis remained unclear.

Methods

A retrospective cohort design was adopted in this study. Electronic medical records had been retrieved from the US collaborative network in the TriNetX research network. A propensity score matching of 1:1 was performed to match for covariates. In total, 50,931 patients with HS and the same amount of non-HS controls were identified for analyses. Hazard ratio (HR) of osteoarthritis in patient with HS was calculated.

Results

Risk of patients with HS developing osteoarthritis was 1.37-fold higher than that of non-HS controls [95% confidence interval (CI), 1.21–1.55] when followed up for 1 year. The significance remained when the follow-up periods were extended to 3 years and 5 years. When osteoarthritis was stratified on occurring sites, the HR of knee osteoarthritis was 1.19 (95% CI, 1.09–1.29) and the HR of hip osteoarthritis was 1.17 (95% CI, 1.01–1.35) in the 5-year follow-up. The 5-year risk of osteoarthritis remained significant in sensitivity models.

Conclusion

Patients with HS were of high risk of developing osteoarthritis compared with people without HS. The clinical association was recommended to be considered while approaching patients with HS.
Identifying the programmed cell death index of hepatocellular carcinoma for prognosis and therapy response improvement by machine learning: a bioinformatics analysis and experimental validation
Authors: Shi Yuanxin , Feng Yunxiang , Qiu Peng , Zhao Kai , Li Xiangyu , Deng Zhengdong , Wang Jianming
Published: December 2023

Background

Despite advancements in hepatocellular carcinoma (HCC) treatments, the prognosis for patients remains suboptimal. Cumulative evidence suggests that programmed cell death (PCD) exerts crucial functions in HCC. PCD-related genes are potential predictors for prognosis and therapeutic responses.

Methods

A systematic analysis of 14 PCD modes was conducted to determine the correlation between PCD and HCC. A novel machine learning-based integrative framework was utilized to construct the PCD Index (PCDI) for prognosis and therapeutic response prediction. A comprehensive analysis of PCDI genes was performed, leveraging data including single-cell sequencing and proteomics. GBA was selected, and its functions were investigated in HCC cell lines by in vitro experiments.

Results

Two PCD clusters with different clinical and biological characteristics were identified in HCC. With the computational framework, the PCDI was constructed, demonstrating superior prognostic predictive efficacy and surpassing previously published prognostic models. An efficient clinical nomogram based on PCDI and clinicopathological factors was then developed. PCDI was intimately associated with immunological attributes, and PCDI could efficaciously predict immunotherapy response. Additionally, the PCDI could predict the chemotherapy sensitivity of HCC patients. A multilevel panorama of PCDI genes confirmed its stability and credibility. Finally, the knockdown of GBA could suppress both the proliferative and invasive capacities of HCC cells.

Conclusion

This study systematically elucidated the association between PCD and HCC. A robust PCDI was constructed for prognosis and therapy response prediction, which would facilitate clinical management and personalized therapy for HCC.
Anti-SRP immune-mediated necrotizing myopathy responsive to ofatumumab: a case report
Authors: Chen Sihui , Yang Jing , He Du , Fu Jiajia , Lai Xiaohui , Zhao Bi , Chen Xueping , Shang Huifang
Published: December 2023

Background

Immune-mediated necrotizing myopathies (IMNM) is a rare disease that was first described in 2004. Due to the lack of large case series, there are no formal treatment recommendations for IMNM.

Methods

We presented a case of a 47-year-old woman who experienced progressive limb weakness, starting from the lower limbs and gradually affecting the upper limbs. She also reported experiencing dyspnea after engaging in daily activities. When she was admitted to the hospital, her upper limbs were almost unable to move and she could not stand even with support. Her Creatine kinase (CK) level significantly increased (> 3500 u/l). Electromyography showed myogenic damage, anti-Signal recognition particle (anti-SRP) and anti-Ro52 antibodies were highly positive. Pathological biopsy of the right biceps muscle showed necrotizing myopathy in the skeletal muscle. She was ultimately diagnosed with anti-SRP IMNN, and was given monotherapy with methylprednisolone and combination therapy with immunoglobulin, but her symptoms continued to worsen. The patient refused to bear the possible further liver dysfunction and blood system damage caused by Cyclophosphamide and Rituximab, and she chose to try to use Ofatumumab (OFA).

Results

After receiving three doses of OFA treatment without any adverse reactions, she reported that her muscle strength had basically recovered and she was able to walk independently. The B cells in the circulatory system have been depleted, and blood markers such as liver function have consistently remained within normal range. During the follow up, her activity tolerance continued to improve.

Discussion

We have presented a severe case of SRP-IMNM in which the patient showed poor response to conventional immunotherapy. However, rapid symptom relief was achieved with early sequential use of OFA treatment. This provides a new option for the treatment of SRP-IMNM, and more large-scale studies will be needed in the future to verify our results.
Causal functional connectivity in Alzheimer's disease computed from time series fMRI data
Authors: Biswas Rahul , Sripada SuryaNarayana
Published: December 2023

Functional connectivitybetween brain regions is known to be altered in Alzheimer's disease and promises to be a biomarker for early diagnosis. Several approaches for functional connectivity obtain an un-directed network representing stochastic associations (correlations) between brain regions. However, association does not necessarily imply causation. In contrast, Causal Functional Connectivity (CFC) is more informative, providing a directed network representing causal relationships between brain regions. In this paper, we obtained the causal functional connectome for the whole brain from resting-state functional magnetic resonance imaging (rs-fMRI) recordings of subjects from three clinical groups: cognitively normal, mild cognitive impairment, and Alzheimer's disease. We applied the recently developed Time-aware PC (TPC) algorithm to infer the causal functional connectome for the whole brain. TPC supports model-free estimation of whole brain CFC based on directed graphical modeling in a time series setting. We compared the CFC outcome of TPC with that of other related approaches in the literature. Then, we used the CFC outcomes of TPC and performed an exploratory analysis of the difference in strengths of CFC edges between Alzheimer's and cognitively normal groups, based on edge-wisep-values obtained by Welch'st-test. The brain regions thus identified are found to be in agreement with literature on brain regions impacted by Alzheimer's disease, published by researchers from clinical/medical institutions.
Western diet-induced obesity results in brain mitochondrial dysfunction in female Ossabaw swine
Authors: Kelty Taylor J. , Taylor Chris L. , Wieschhaus Nicole E. , Thorne Pamela K. , Amin Amira R. , Mueller Christina M. , Olver T. Dylan , Tharp Darla L. , Emter Craig A. , Caulk Alexander W. , Rector R. Scott
Published: December 2023

Diet-induced obesity is implicated in the development of a variety of neurodegenerative disorders. Concurrently, the loss of mitochondrial Complex I protein or function is emerging as a key phenotype across an array of neurodegenerative disorders. Therefore, the objective of this study was to determine if Western diet (WD) feeding in swine [carbohydrate = 40.8% kCal (17.8% of total calories from high fructose corn syrup), protein = 16.2% kcal, fat = 42.9% kCal, and 2% cholesterol] would result in Complex I syndrome pathology. To characterize the effects of WD-induced obesity on brain mitochondria in swine, high resolution respirometry measurements from isolated brain mitochondria, oxidative phosphorylation Complex expression, and indices of oxidative stress and mitochondrial biogenesis were assessed in female Ossabaw swine fed a WD for 6-months. In line with Complex I syndrome, WD feeding severely reduced State 3 Complex I, State 3 Complex I and II, and uncoupled mitochondrial respiration in the hippocampus and prefrontal cortex (PFC). State 3 Complex I mitochondrial respiration in the PFC inversely correlated with serum total cholesterol. WD feeding also significantly reduced protein expression of oxidative phosphorylation Complexes I–V in the PFC. WD feeding significantly increased markers of antioxidant defense and mitochondrial biogenesis in the hippocampi and PFC. These data suggest WD-induced obesity may contribute to Complex I syndrome pathology by increasing oxidative stress, decreasing oxidative phosphorylation Complex protein expression, and reducing brain mitochondrial respiration. Furthermore, these findings provide mechanistic insight into the clinical link between obesity and mitochondrial Complex I related neurodegenerative disorders.
Footprint analysis of CO2 in microbial community succession of raw milk and assessment of its quality
Authors: Zheng Anran , Liu Jun , Wang Mengsong , Bu Ningxia , Liu Dunhua , Wei Chaokun
Published: December 2023

With the growing production of raw milk, interest has been increasing in its quality control. CO2, as a cold processing additive, has been studied to extend the cold storage period and improve the quality of raw milk. However, it is yet uncertain how representative microbial species and biomarkers can succeed one another at distinct critical periods during refrigeration. Therefore, the effects of CO2 treatment on the succession footprint of the microbial community and changes in quality during the period of raw milk chilling were examined by 16S rRNA analysis combined with electronic nose, and electronic tongue techniques. The results indicated that, the refrigeration time was shown to be prolonged by CO2 in a concentration-dependent way. And CO2 treatment was linked to substantial variations in beta and alpha diversity as well as the relative abundances of various microbial taxa (p < 0.01). The dominant bacterial phylum Proteobacteria was replaced with Firmicutes, while the major bacterial genera Acinetobacter and Pseudomonas were replaced with lactic acid bacteria (LAB), including Leuconostoc, Lactococcus, and Lactobacillus. From the perspective of biomarkers enriched in CO2-treated sample, almost all of them belong to LAB, no introduction of harmful toxins has been found. The assessment of the quality of raw milk revealed that CO2 improved the quality of raw milk by lowering the acidity and the rate of protein and fat breakdown, and improved the flavor by reducing the generation of volatiles, and increasing umami, richness, milk flavor and sweetness, but reducing sourness. These findings offer a new theoretical foundation for the industrial use of CO2 in raw milk.
Butyrate interacts with the effects of 2’FL and 3FL to modulate in vitro ovalbumin-induced immune activation, and 2’FL lowers mucosal mast cell activation in a preclinical model for hen’s egg allergy
Authors: Zuurveld M. , Diks M. A. P. , Kiliaan P. C. J. , Garssen J. , Folkerts G. , van’t Land B. , Willemsen L. E. M.
Published: December 2023

Background

Early life provides a window of opportunity to prevent allergic diseases. With a prevalence of 0.5–2% in infants, hen’s egg allergy is one of the most common food allergies. The immunomodulatory effects of human milk oligosaccharides (HMOs), 2′-fucosyllactose (2’FL), and 3-fucosyllactose (3FL) were studied in an in vitro mucosal immune model and an in vivo murine model for hen’s egg (ovalbumin) allergy.

Methods

Intestinal epithelial cell (IEC)/dendritic cell (DC) and DC/T cell cocultures were used to expose IECs to ovalbumin (OVA) in an in vitro mucosal immune model. The effects of epithelial pre-incubation with 0.1% 2’FL or 3FL and/or 0.5 mM butyrate were studied. Three- to four-weeks-old female C3H/HeOuJ mice were fed AIN93G diets containing 0.1–0.5% 2’FL or 3FL 2 weeks before and during OVA sensitization and challenge. Allergic symptoms and systemic and local immune parameters were assessed.

Results

Exposing IECs to butyrate in vitro left the IEC/DC/T cell cross-talk unaffected, while 2’FL and 3FL showed differential immunomodulatory effects. In 3FL exposed IEC-DC-T cells, the secretion of IFNγ and IL10 was enhanced. This was observed upon pre-incubation of IECs with 2’FL and butyrate as well, but not 2’FL alone. The presence of butyrate did not affect OVA activation, but when combined with 3FL, an increase in IL6 release from DCs was observed (p < 0.001). OVA allergic mice receiving 0.5% 3FL diet had a lower %Th2 cells in MLNs, but the humoral response was unaltered compared to control mice. OVA-allergic mice receiving 0.1 or 0.5% 2’FL diets had lower serum levels of OVA-IgG2a (p < 0.05) or the mast cell marker mMCP1, in association with increased concentration of cecal short-chain fatty acids (SCFAs) (p < 0.05).

Conclusion

In vitro butyrate exposure promotes the development of a downstream type 1 and regulatory response observed after 2’FL exposure. 2’FL and 3FL differentially modulate ovalbumin-induced mucosal inflammation predominantly independent of butyrate. Mice receiving dietary 3FL during ovalbumin sensitization and challenge had lowered Th2 activation while the frequency of Treg cells was enhanced. By contrast, 2’FL improved the humoral immune response and suppressed mast cell activation in association with increased SCFAs production in the murine model for hen’s egg allergy.
Detectable ctDNA at the time of treatment cessation of ipilimumab and nivolumab for toxicity predicts disease progression in advanced melanoma patients
Authors: Warburton Lydia , Reid Anna , Amanuel Benhur , Calapre Leslie , Millward Michael , Gray Elin
Published: December 2023

Background

Immune checkpoint inhibition (ICI) has led to unprecedented outcomes for melanoma patients but is associated with toxicity. ICI resumption after high grade irAEs poses a significant challenge in the clinical management of melanoma patients and there are no biomarkers that can help identify patients that might benefit from resuming treatment. This study aims to determine if circulating tumor DNA (ctDNA) levels at the time of treatment-limiting irAE could guide treatment decisions in this clinical context.

Methods

This is a retrospective exploratory biomarker study from 34 patients treated with combination ICI for stage IV melanoma. Patients had a treatment-limiting toxicity and a baseline plasma collection prior to commencing ICI and within 6 weeks of stopping therapy. Blood samples were tested for ctDNA at baseline and cessation therapy.

Results

Median progression free survival (PFS) and overall survival (OS) have not been reached (24-month PFS rate 54% and OS rate 72.3%). PD occurred in 47% (16/34) of patients. Median PFS with detectable ctDNA from plasma collected at the time of toxicity was 6.5 months while not reached (NR) with undetectable levels (HR: 4.0, 95% CI 0.95-17.5, p=0.0023). Median OS with detectable ctDNA at cessation for toxicity was 19.4 months and NR for undetectable ctDNA (HR: 3.9, 95%CI 20.8-18.6, p=0.024). Positive ctDNA at the time of cessation was highly specific (specificity 0.94, 95% CI 0.74-0.99, PPV 0.88, 95% CI 0.53-0.99). However, ctDNA negativity has low sensitivity as a predictor of ongoing disease control (sensitivity 0.437, 95% CI 0.23-0.67). Notably, 4/9 (44%) ctDNA negative patients who had disease progression had brain only disease progression.

Conclusions

Undetectable ctDNA and CR on imaging after stopping immunotherapy for toxicity results in high rates of long-term durable control. For patients with immunotherapy related toxicity, who have persistent ctDNA at 8 – 12 weeks, the risk of disease progression is significant.
Quantitative functional imaging with CT perfusion: technical considerations, kinetic modeling, and applications
Authors: Chung Kevin J. , De Sarno Danny , Lee Ting-Yim
Published: December 2023

CT perfusion (CTP)-derived quantitative maps of hemodynamic parameters have found important clinical applications in stroke, cancer, and cardiovascular disease. Blood flow, blood volume, transit time, and other perfusion parameters are sensitive markers of pathophysiology with impaired perfusion. This review summarizes the basic principles of CTP including image acquisition, tracer kinetic modeling, deconvolution algorithms, and diagnostic interpretation. The focus is on practical and theoretical considerations for accurate quantitative parametric imaging. Recommended CTP scan parameters to maintain CT number accuracy and optimize radiation dose versus image noise are first reviewed. Tracer kinetic models, which describe how injected contrast material is distributed between blood and the tissue microenvironment by perfusion and bidirectional passive exchange, are then derived. Deconvolution algorithms to solve for hemodynamic parameters of kinetic models are discussed and their quantitative accuracy benchmarked. The applications and diagnostic interpretation of CTP in stroke, cancer, and cardiovascular disease are summarized. Finally, we conclude with a discussion of future directions for CTP research, including radiation dose reduction, new opportunities with novel CT hardware, and emerging diagnostic applications.
Regulatory mechanisms controlling store-operated calcium entry
Authors: Kodakandla Goutham , Akimzhanov Askar M. , Boehning Darren
Published: December 2023

Calcium influx through plasma membrane ion channels is crucial for many events in cellular physiology. Cell surface stimuli lead to the production of inositol 1,4,5-trisphosphate (IP3), which binds to IP3 receptors (IP3R) in the endoplasmic reticulum (ER) to release calcium pools from the ER lumen. This leads to the depletion of ER calcium pools, which has been termed store depletion. Store depletion leads to the dissociation of calcium ions from the EF-hand motif of the ER calcium sensor Stromal Interaction Molecule 1 (STIM1). This leads to a conformational change in STIM1, which helps it to interact with the plasma membrane (PM) at ER:PM junctions. At these ER:PM junctions, STIM1 binds to and activates a calcium channel known as Orai1 to form calcium release-activated calcium (CRAC) channels. Activation of Orai1 leads to calcium influx, known as store-operated calcium entry (SOCE). In addition to Orai1 and STIM1, the homologs of Orai1 and STIM1, such as Orai2/3 and STIM2, also play a crucial role in calcium homeostasis. The influx of calcium through the Orai channel activates a calcium current that has been termed the CRAC current. CRAC channels form multimers and cluster together in large macromolecular assemblies termed “puncta”. How CRAC channels form puncta has been contentious since their discovery. In this review, we will outline the history of SOCE, the molecular players involved in this process, as well as the models that have been proposed to explain this critical mechanism in cellular physiology.
The neuroscience of respect: insights from cross-cultural perspectives
Authors: Khalaila Rabia , Dasgupta Jayashree , Sturm Virginia
Published: December 2023

Cultural values such as respect influence cognition, emotion, and behavior by modulating brain functioning. This mini-review discusses the cultural differences of respect as an essential human value, and the neural underpinnings accompanying them. Although neuroscientific studies are limited, we outline potential brain structures and networks that contribute to respect and use clinical examples to illustrate how behavior changes when these neural systems fail. A better understanding of the neuroanatomical basis of respect and its neural manifestations across cultures will help to advance current conceptualizations of the biology of human values.
Velocity Estimation Using Time-Differenced Carrier Phase and Doppler Shift with Different Grades of Devices: From Smartphones to Professional Receivers
Authors: Angrisano Antonio , Cappello Giovanni , Gaglione Salvatore , Gioia Ciro
Published: December 2023

Velocity estimation has a key role in several applications; for instance, velocity estimation in navigation or in mobile mapping systems and GNSSs is currently a common way to achieve reliable and accurate velocity. Two approaches are mainly used to obtain velocity based on GNSS measurements, i.e., Doppler observations and carrier phases differenced in time (that is, TDCP). In a benign environment, Doppler-based velocity can be estimated accurately to within a few cm/s, while TDCP-based velocity can be estimated accurately to within a few mm/s. On the other hand, the TDCP technique is more prone to availability shortage and the presence of blunders. In this work, the two mentioned approaches are tested, using three devices of different grades: a high-grade geodetic receiver, a high-sensitivity receiver, and a GNSS chip mounted on a smartphone. The measurements of geodetic receivers are inherently cleaner, providing an accurate solution, while the remaining two receivers provide worse results. The case of smartphone GNSS chips can be particularly critical owing to the equipped antenna, which makes the measurements noisy and largely affected by blunders. The GNSSs are considered separately in order to assess the performance of the single systems. The analysis carried out in this research confirms the previous considerations about receiver grades and processing techniques. Additionally, the obtained results highlight the necessity of adopting a diagnostic approach to the measurements, such as RAIM-FDE, especially for low-grade receivers.