bluuebunny/crossref_metadata_2025 huggingface dataset:
Biological Activities and Annotation of Bioactive Principle by Mass Spectrometry in the Root Extract of Boerhavia diffusa
Authors: Bhattarai Keshav , Pandey Indira , Sharma Khaga Raj
Published: July 2024

Boerhavia diffusa is a well-known plant for ethnomedical uses. The plant is well known for its antioxidant and antidiabetic properties. Therefore, in addition to the antioxidant and antidiabetic properties of this plant, the present study focuses on exploring antibacterial properties, and metabolites present in Boerhavia diffusa. The preliminary phytochemistry was studied by the colour differentiation method. The phenolic and flavonoid content of the plant extracts was calculated using the Folin-Ciocalteu phenol and aluminum chloride colorimetry methods. Similarly, to find out the radical scavenging capacity of the available samples, one of the reliable methods (DPPH assay) was conducted. To evaluate the antidiabetic property, α-amylase and α-glucosidase inhibition were conducted by colorimetry methods. Results of phytochemical screening indicate that the plant is rich in metabolites including alkaloids, flavonoids, and terpenoids. Along with this, root extracts were found to be rich in total phenolic and flavonoid content with calculated values of 40.84±1.90 mg GAE/g and 37.01±1.61 mg QE/g, respectively. Similarly, among three methanolic extracts of root, stem, and leaf; the root showed the highest antioxidant activity with IC50 value 152.83±4.85 µg/mL. Among different solvent fractions of the stem of the same plant, the most potential antioxidant activity was shown by ethyl acetate fractions with an IC50 value of 82.96 ± 2.23 µg/mL. Additionally, no extracts and fractions were significantly active against α-amylase and α-glucosidase inhibition except ethyl acetate fraction. This fraction exhibited the enzyme inhibition property with IC50 value of 493.91±2.53 µg/mL for α-amylase and 96.31±10.65 µg/mL for α-glucosidase. To identify the chemical composition, mass spectrometry-based isolation and molecular annotation were carried out and metabolites like 3,9,10-trimethoxy-13-methyl-5,6-dihydroisoquinoline[2,1-b]isoquinolin-7-ium-2-olate, (E)-3-(4-hydroxy-3-methoxyphenyl)-N-[2-(4-hydroxyphenyl)ethyl]prop-2-enamide, 11,12-dihydro-2,3-(methylenedioxy)-7,8-dimethoxybenzo[c]phenanthridine, and (E)-3-(4-hydroxy-3-methoxyphenyl)-N-[2-(4-hydroxy-3-methoxyphenyl)ethyl]prop-2-enamide were reported. These results provide strong support for the ethnomedical uses of Boerhavia diffusa since the ancient period against diabetes and to cure infections. However, the evaluation of biological activities from the active compounds is not performed in this study.
Landslide Susceptibility Mapping and Vulnerability Assessment in the Badigad Watershed of Western Nepal
Authors: Bhandari Suwash , Ghimire Motilal , Mahat Purusottam
Published: July 2024

The landslide is a major and common natural hazard in the Nepalese Himalayas. This phenomenon is because of its active tectonic setting, extensively deformed rock formation, steep mountain terrain, frequent seismic events, high-intensity rainfall during monsoons, and high rate of weathering it occurs every year, especially during the monsoon season. The landslide susceptibility assessment using the Geographic Information System (GIS) and remote sensing tools helps to display the hazards, and vulnerable zones providing the required knowledge of the susceptibility of landslides in a specific region. Landslide susceptibility with vulnerability assessment covering the comprehensive parameters provides an important understanding of the areas that are more likely to the damaging effect of the landslide hazards and is useful for mitigation, management, and avoiding threats. A total of 339 landslides were identified in the Badigad watershed from the satellite images on Google Earth, out of which 20% were used for model validation. The study was carried out using the Weight of Evidence (WoE) model. Eleven factors were considered as possible causative factors for the hazard assessment. Based on the landslide susceptibility map, 11% to 29 % of the study area is found to be in the range of very high to shallow landslide susceptibility. From the final map prepared it is found that many areas of Satyawati Rural Municipality (RM), Ruru RM, Chandrakot RM, and Chhatrakot RM, along with Musikot Municipality in Gulmi and Badigad RM in Baglung district, exhibit a notable high hazard level. The Receiver Operating Characteristics (ROC) graph with the Area under the curve (AUC) value was used to check the performance of the WoE model which shows that the model has 80.4% prediction accuracy for future events which means, the model shows very good performance. The vulnerability within the study area is assessed by obtaining vulnerability scores. To obtain the vulnerability score, fourteen indicators were analyzed following the Local Disaster and Climate Resilience Planning (LDCRP) guideline. The result obtained from the vulnerability assessment showed that two wards, namely Thulolumpek in Satyawati RM of Gulmi and Bobang in Dhorpatan Municipality of Baglung are highly vulnerable. By analyzing and comparing the vulnerability obtained from susceptibility mapping (using GIS) and social methods (using LDCRP guideline), it is observed that they do not converge based on the factors studied.
Air pollutant dispersion using advection-diffusion equation
Authors: Kafle Jeevan , Adhikari Krishna Prasad , Poudel Eeshwar Prasad
Published: July 2024

The advection-diffusion model is one of the mathematical models that may be used to understand how air pollutants are spread in the environment. It uses the advection-diffusion system with time-dependent prediction of the spread of environmental contamination under various environmental conditions to determine whether the contaminants are more concentrated at ground level or close to the point of emissions. The times, diffusivity, emission sources, and wind profile are all considered by the model. In order to determine the approach’s descriptive characteristics in terms of advection and dispersion coefficients, we evaluate the exact solution to a flow field problem as an initial value problem in space.
LANGUAGE DISCRIMINATION USING BILINGUAL PICTURE EXCHANGE FOR CULTURALLY AND LINGUISTICALLY DIVERSE CHILDREN WITH AUTISM SPECTRUM DISORDER
Authors:   , Watts River
Published: July 2024

Recent research suggests that one-fifth of United States households use non-English languages in the home setting. Ethically and effectively supporting culturally and linguistically diverse (CLD) clients (e.g., autistic individuals) presents a growing challenge to practitioners of Applied Behavior Analysis (ABA). Though efforts to address the linguistic needs of the population have grown in recent years, current literature focuses on language selection for monolingual services and underemphasizes the need for bilingual service provision. Studies were conducted to (I) evaluate the efficacy of bilingual picture exchange (i.e., mand response) across items, speakers, and languages (i.e., English and Spanish) as well as (II) explore the conditions under which, if at all, discrimination between languages emerged during bilingual communication training. Procedures for supporting language discrimination were developed for supporting learners who did not readily demonstrate the emergence of a language discrimination repertoire. Results revealed that multilingual communication training established a mand repertoire across multiple languages, targets, and speakers for two young autistic children. Language discrimination emerged without specific instruction for both learners in all but one target. For this target, language discrimination training procedures were effective in achieving language discrimination. Recommendations are provided related to supporting CLD autistic learners and culturally responsive practices for ABA practitioners.
DEVELOPMENT OF NOVEL NANOPARTICLE DRUG DELIVERY SYSTEMS
Authors:   , Boyd Lucinda
Published: July 2024

"Poor physicochemical properties combined with pharmacokinetics and biodistribution of promising steroidal molecules have hampered clinical advancement to potentially treat cancer effectively. Selective and effective treatment of cancer would improve the quality of life and extend life in various deadly cancer subtypes such as triple negative breast cancer which leads to 150,000 deaths per year.1,2 Therefore, there is an urgent need to develop analytical methods to improve the physicochemical properties of these compounds. Liposomes are amphiphilic molecules that can serve as encapsulating systems to selectively target localized solid tumors, improving the effectiveness of treatment. The development of a general liposomal delivery system for steroidal natural products offers the opportunity to observe the outcomes of breast cancer cell research and potentially improve therapeutic efficacy is the focus of the work presented. While the capacity for the development of liposomal drug delivery systems is great, there is a need for a significant understanding of the microenvironment of the targeted area. Presented herein are analytical methods, both developed and adaptive, which have been used to investigate the encapsulation and release of bioactive steroidal natural products at the targeted site. Natural products are carbon-based and present challenges surrounding solubility, permeability, and bioavailability. This dissertation is focused on utilizing natural products in conjunction with FDA-approved lipids such as dioleoyl phosphatidylcholine (DOPC) and dipalmitoyl phosphatidyl (DPPC) in addition to a synthesized organic compound from the Rivas Group, FR-M002, and ergosterol (ERG). The aims of this work are (1) to develop general nanosized DDSs from liposomes and synthesized organic compounds for the delivery of bioactive steroidal natural product molecules and (2) to investigate the properties of these DDS (size distribution, stability, and cellular uptake). Preliminary studies using these model systems to assess the feasibility of the generation of these DDSs are presented herein. These DDSs are characterized by using dynamic light scattering (DLS) and transmission electron microscopy (TEM). DLS will provide insight into the nanoparticles' polydispersity of size distribution while TEM will image the sample and provide physical information using a beam of electrons to create an image of the sample highlighting size and morphology. Introduced here are the findings and the significance of this work"
Teacher and Student Opinions on Teaching Four Operations with Integer Numbers in 7th Grade with Counting Stamps
Authors: Süzen Ahmet Burak , Tutak Tayfun , İlhan Aziz , Nayıroğlu Büşra
Published: July 2024

The study examines the views of middle school mathematics teachers and 7th-grade students on using counting stamps to teach four operations with integers. The study was conducted with ten mathematics teachers with different professional seniority and ten 7th-grade students studying in these schools. The teachers were asked six open-ended opinion form questions, and the students were simultaneously asked five open-ended opinion form questions. In this qualitative study, the interview technique was used to analyze the views of teachers and students. A structured interview form was preferred as a data collection tool. A qualitative research method was adopted in collecting, analyzing, and interpreting the data of this study. Content analysis was used to analyze and interpret the data. According to the study results, it was determined that teachers and students did not find counting stamps functional and that they needed to be more adequate in operations with integers. Therefore, there is a need for new models that can replace counting stamps.
The Career Orientation Impact in the Livelihood of Rural High School Learners: A Case of Selected High Schools Waterberg District, South Africa
Authors: Sethole Charlıe Pokedı , Ngobeni Elias Tsakane , Sepeng Percy
Published: July 2024

This study analyses how career orientations can help rural high school learners to become more self-directed and flexible in developing their careers in today's dynamic world of work. Career counsellors are needed in schools to guide the way learners subjectively make sense of their self-perceived talents and abilities. The study used a qualitative approach to obtain information about how career orientation can change the lives of rural high school learners. The purposive sampling technique was used to choose rich information from rural high school learners and teachers, councillors, and the surrounding employers/educational institutions in Waterberg District. Data analysis was done through inductive thematic data analysis where themes and categories emanated. The outcome of the study considered the fundamental aspects to develop career paths, career orientation programs, changing the mind set and the impact of career orientation in rural high schools. The product of the study will be shared with all four schools, nearby employers, and the Department of Education, Waterberg District in Limpopo province. The outcomes of the study might help in dealing with persistent educational obstacles like broader educational equity and public funding for developmental career orientation programs that face many youth and adults in rural communities. It is recommended that policy developers establish career orientation models that would benefit the livelihood of rural high schools.
Student Disciplinary Practices in a Boarding School Environment: A Sociological Review
Authors: Noviani Dwi , Azkar Muh.
Published: July 2024

This study aims to explore the practice of disciplining students in a boarding school environment through a sociological approach using qualitative case study research methods. Boarding schools are formal educational institutions that systematically plan guidance, teaching, and training for students with the aim that students can develop according to their potential. The qualitative research method was chosen to explore in depth the social dynamics in boarding schools. Data were collected through interviews with students, educators, dormitory heads, and dormitory coaches, participatory observation, and document analysis related to discipline policies. The results of this study through sociological research, found that discipline occurs in boarding schools through the active role played by educators, dormitory heads, and dormitory coaches in enforcing the rules of discipline to form discipline in students. Disciplinary practices in boarding schools are carried out using two disciplinary mechanisms, namely supervision through disciplinary rules and sanctioning students. The implications of this article can provide insights for the development of disciplinary methods that are more effective and under the social needs of students.
The Influence of Client-Centered Counseling with Self-Reflection on Overthinking Behavior of a Bilingual Islamic Boarding School Student
Authors: Sholihah Maidatus , Ningsih Yusria
Published: July 2024

This research explores an innovative approach to dealing with overthinking behavior in Santri at the Bilingual Islamic Boarding School in Krian, Sidoarjo, through Client-Centered Counseling with Self-Reflection (Muhasabah Diri). This topic involves counseling and psychology, focusing on changing the client's behavior and outlook. This study aims to test the hypothesis that the integration of Client-Centered Counseling with Self-Muhasabah will effectively reduce the level of overthinking among Santri. Using a quantitative method with a single-subject design of A1-B-A2, this study observed behavior before and after the counseling session. Data were collected through observation, interviews, and questionnaires to measure the level of psychological distress. The results showed significant behavioral changes after the counseling sessions. Before counseling, the client showed overthinking behavior that led to self-doubt, excessive worry, anxiety, and difficulty adapting. After counseling, clients showed increased confidence in social situations, were calmer in facing challenges, and were more courageous in interacting with others, especially new people. This research highlights that Client-Centered Counseling with Self-Reflection is effective in overcoming overthinking behavior in students. The integration of Client-Centered Counseling which emphasizes active client involvement and Self-Reflection which focuses on introspection provides a comprehensive and relevant solution. This research contributes by examining the impact of this approach on the emotional, intellectual, physiological, and interpersonal aspects of student, supporting their personal, social, and spiritual development. By enhancing mental and spiritual well-being, this research offers new insights into educational strategies that address the well-being of students.
Pengaruh model pembelajaran Number Head Together terhadap kerjasama siswa
Authors: Eliyana Hastuti , Wijayanto Sukma , Triana Putri Meinita
Published: July 2024

Penelitian ini bertujuan untuk mengetahui pengaruh model pembelajaran Number Head Together terhadap kerjasama siswa kelas IV SD Negeri Sewukan 1. Penelitian ini menggunakan jenis penelitian Pre-Eksperimen dengan tipe One Group Pretest-Posttest Design. Sampel dipilih menggunakan Teknik sampling jenuh. Sampel pada penelitian ini berjumlah 20 siswa. Metode pengumpulan data dilakukan dengan menggunakan angket kerjasama siswa. Uji validitas instrument angket dilakukan oleh ahli dan diujikan statistic parametric dengan bantuan program IBM SPSS Statistic 25 sama halnya dengan uji reliabilitas. Uji prasyarat analisis menggunakan uji normalitas. Dengan analisis data menggunakan teknik statistic parametric yaitu uji Paired Sample T-Test dengan bantuan program aplikasi IBM SPSS Stastitic 25. Hasil penelitian menunjukkan bahwa perhitungan rata-rata hasil posttest sebanyak 3,03 yang lebih besar dibandingkan dengan hasil dari pretest dengan perolehan rata-rata nilai 2,65. Hal ini dibuktikan dengan hasil analisis Paired Sampel T Test yang menunjukkan  sebesar  0,000 dengan nilai signifikan lebih kecil dari < 0,05 artinya ada perbedaan yang signifikan atas hasil pretest dan posttest dengan menggunakan model kooperatif tipe Number Head Together. Hasil penelitian ini dapat disimpulkan bahwa penerapan model pembelajaran kooperatif tipe Number Head Together berpengaruh secara signifikan terhadap kerjasama siswa.
Experimental Research on the Effect of CVT Roller and Spring Parameters on Metic Motorcycle Performance
Authors: Purnomo Bagiyo Condro Purnomo Condro , Farhan Aulia Rahman Muhammad , Biantoro Wahyu , Waluyo Budi
Published: July 2024

The current development of vehicle transmission technology aims to reduce vehicle energy consumption by increasing its performance. Continuously variable transmission (CVT) is an automatic transmission system that is often used in vehicles today. Meanwhile, replacing CVT rollers and springs can affect transmission efficiency, fuel consumption, and overall vehicle performance. So this research aims to explore the impact of replacing roller and spring components on the CVT on engine performance and confirmed by changes in CVT temperature. This research was carried out using a metic motorcycle, by measuring the performance values of the motorcycle in the form of vehicle torque and power using a dynamometer, apart from that the CVT temperature was also measured. The research results show the potential for increasing Torque and Power by using increased roller mass and spring constants. Apart from that, there is an increase in CVT temperature due to the use of an increased spring constant, this shows the potential for wear.
Does Good School Governance Role in The Performance Of School Operational Assistance Fund Management?
Authors: Sohidin Sohidin , Rahmawati Rahmawati , Djuminah Djuminah , Gantyowati E
Published: July 2024

Good school governance can improve the performance of school operational assistance fund management. This research aims to provide empirical evidence of the role of good school governance in the performance of school active assistance fund management. The study consists of 238 State Vocational High Schools in Central Java from 2019 to 2021. The research method used is quantitative, and primary data is obtained from the questionnaire responses of School Operational Assistance fund managers. The purposive sampling technique is used with a total of 952 respondents. Data processing and hypothesis testing are conducted using moderate regression analysis with the help of SPSS. This research has several novelties, including performance measurement based on 12 school operational assistance fund expenditure components. The results show that good school governance positively influences the performance of school active assistance fund management, except for indicators X7 (effectiveness and efficiency) and X8 (consensus-oriented))
A THEORETICAL APPROACH OF DISTINCTIVE ADDITIVES TO OVERCOME THE CHALLENGES IN THE FIELD OF PETROLEUM INDUSTRY
Authors: Modi Prabha , Nagar Ashish
Published: July 2024

The petroleum industry faces various challenges such as improving fuel properties, preventing wax deposition, and enhancing operational efficiency. To overcome these challenges, the use of distinctive additives is necessary. Distinctive additives play a crucial role in optimizing diesel fuel properties, including increasing cetane numbers and improving ignition. They can also modify the rheological properties of base oils such as diesel, mineral oil, and poly alpha olefins to address issues like Asphaltene and paraffin wax deposition, scale formation, and corrosion. These additives are essential for drilling fluids, cementing, completion, stimulation, and production of chemicals in the oil and gas industry. In the efficient recovery of oil and gas from the well to the refinery, the use of chemical additives is critical. By incorporating distinctive additives that are tailored to specific challenges faced in the petroleum field, operators can enhance production processes, ensure flow assurance, and meet regulatory requirements. The use of these additives offers solutions to many issues, including wax deposition, corrosion control, scale formation prevention, and enhancement of drilling fluid properties. As the demand for hydrocarbons continues to rise globally, the strategic use of distinctive additives becomes increasingly vital for efficient and enhanced oil and gas recovery in the petroleum industry.
Konseling Individu Teknik Self Management untuk Mereduksi Kebiasan Merokok Siswa SMP
Authors: Safitri Romadhani Anisa , Hidayati Nur
Published: July 2024

Remaja adalah masa peralihan dari masa anak-anak ke masa dewasa. Remaja sangat mudah untuk terpengaruh oleh lingkungan pertemanannya. Remaja yang kurang mendapatkan bimbingan dan dukungan dalam kehidupan sehari-hari menjadi berani dan mengambil tindakan menyimpang untuk menarik perhatian. Bergam jenis kenakalan yang mungkin dapat terjadi pada remaja, salah satunya adalah merokok. Untuk mereduksi perilaku siswa merokok terdapat salah satu Teknik layanan bimbingan dan konseling yang dapat diterapkan guru BK kepada siswa, salah satunya adalah dengan melalu konseling teknik self management. Dalam artikel ini, peneliti menggunakan teknik literatur, penulis karya ini secara menyeluruh memeriksa referensi dan teori yang relevan dengan situasi atau masalah yang sebanding dengan yang diteliti. self management  merupakan salah satu dari strategi tersebut. self management dipilih sebagai teknik modifikasi perilaku. Berdasarkan penelitian yang dilakukan di SMP Negeri 1 Teriak oleh Rulia dkk. dan penelitian yang dilakukan oleh Ani Devi dipaparkan bahwa pendekatan self management efektif dalam mereduksi perilaku merokok siswa SMP.
Exploration of human resources and tourism potential through POKDARWIS in pioneering a tourism village in Gemawang Village, Ngadirojo Sub-District, Wonogiri District
Authors: Widagdo Yohanes Martono ,   Indonusa Surakarta Polytechnic, Indonesia, Wibiyanto Agung ,   Indonusa Surakarta Polytechnic, Indonesia
Published: July 2024

Tourism village pilot through the formation of POKDARWIS is an initiative that aims to develop tourism villages as attractive tourism destinations. This research aims to explore the potential of human and tourism resources through POKDARWIS activities in an effort to pioneer a Tourism Village in Gemawang Village, Ngadirojo Sub-district, Wonogiri Regency. This research uses descriptive qualitative. Data collection techniques with direct observation and interviews in a structured manner and literature study. The results showed that Gemawang Village has natural and cultural potential that can be developed into an attractive tourist destination. However, this potential has not been fully utilised due to the limited understanding of the community about their tourism potential. Through POKDARWIS activities, the community of Gemawang Village learnt to manage tourism potential sustainably and build close cooperation among residents to improve the attractiveness and quality of tourism services. This research provides new insights into the important role of human resources in local tourism development as well as the benefits of collaboration between the government, community, and other related parties in advancing the tourism sector at the village level.
How Go-Food by GOJEK Apps work on consumer purchase decisions
Authors: Entas Derinta ,   Applied Master in Tourism Planning and Development, Politeknik Sahid, Indonesia, Putri Ni Made Dwiyana Rasuma , Widiastiti A. A. Istri Putra , Hanum Fauziah ,   Hotel Management, Politeknik Sahid, Indonesia,   Hotel Management Institut Pariwisata dan Bisnis Internasional, Indonesia,   Hotel Management, Politeknik Sahid, Indonesia
Published: July 2024

Go-Food by GOJEK Apps is a popular food delivery platform in Indonesia. The main objective of this study is to understand the factors influencing consumer purchase decisions through the Go-Food by GOJEK Apps, such as delivery reliability, menu variety, food quality, price, and service quality. Methods of research are using a quantitative approach by collecting data through a survey using a questionnaire that has been developed. The research sample was taken randomly from the consumer population using the Go-Food by GOJEK Apps. The collected data were analyzed using descriptive statistical analysis and multiple linear regression. The results of the study show that delivery reliability, menu variety, food quality, price and service quality have a significant effect on consumer purchase decisions through the Go-Food by GOJEK Apps. Results of the research show that consumers tend to choose apps that offer fast delivery, a wide menu selection, high-quality food, competitive prices, and responsive service. These findings provide a better understanding of the factors influencing consumer purchase decisions through the Go-Food by GOJEK Apps. This research implies the importance of Go-Food service providers paying attention to these factors in improving user experience and consumer satisfaction. By understanding consumer preferences and needs, service providers can improve service quality, optimize delivery, provide interesting menu variations, and set prices accordingly.
The Post-pandemic MICE digitalization development: A strategy for sustainable tourism in Bali
Authors: Dewi Ni Made Rosita ,   Universitas Pendidikan Nasional, Indonesia, Darma Gede Sri ,   Universitas Pendidikan Nasional, Indonesia
Published: July 2024

The worldwide COVID-19 pandemic has forced numerous businesses to a standstill, with the tourism sector, especially the Meetings, Incentives, Conferences, and Exhibitions (MICE) sector, facing severe challenges. However, this unprecedented situation highlights the unpredictable nature of crises and their potential to reshape travel patterns. This research examines the factors contributing to the success of the digitalization strategy in the MICE industry and explores the impact of digitalization on the industry's pursuit of sustainable tourism goals. The research employs a detailed and all-encompassing examination of the subject, utilizing a case study research methodology in conjunction with a qualitative descriptive research strategy. Data collection involves observation, literature analysis, and interviews conducted with participants in the tourism industry and management of MICE companies. The findings suggest significant potential for Bali as a MICE destination. Digitalization is identified as a pivotal factor in enhancing the future resilience of the MICE industry by creating new prospects, tackling industry challenges, and promoting sustainable event tourism.
Prehistoria y Antigüedad en el Alto Valle del Río Almanzora (Almería, España)
Authors: Martínez Padilla Catalina , de la Paz Román Díaz María , Juana López Medina María
Published: July 2024

This book presents the study of a natural region, the Alto Almanzora, in the north of the province of Almería (Spain), in which 6 campaigns of systematic archaeological prospection were carried out. It is a large basin of 1675 km², at the eastern end of the Betic Cordillera, which slopes towards the Mediterranean Sea, with large differences in altitude between its mountainous edges (reaching over 2000 m a.s.l.) and the valley floor. Its geological formation has provided all kinds of lithic, mineral, forest, agricultural and pastureland resources, in addition to its water resources. All this constitutes a mosaic of different environments and contrasts over short distances. This work presents a historical study on an area of the Southeast of the peninsula that constituted a research gap, considering the societies that occupied it for more than 4000 years until the end of the Roman occupation. The authors expose the theoretical-methodological assumptions that formed the basis of the study, the previous documentation, the analysis of the obtained data and finally its interpretation, coherent with all the above. The results of the Thermoluminescence analysis were essential for this long-term diachronic study. Other specific studies on archaeological elements such as carved lithic industry and archaeometallurgy are also included.
Anexo IV
Authors: Rovira Llorens Salvador
Published: July 2024

Análisis arqueometalúrgico: Estudio de laboratorio de evidencias arqueometalúrgicas recogidas durante el desarrollo del proyecto Ulises
Exploring Causal Relationships Between Gut Microbiota and Alzheimer’s Disease: A Bidirectional Mendelian Randomization Study
Authors: Chen Anqi , Wang Yuquan , Hu Yue-Qing
Published: July 2024

Background:

Many observational studies have investigated the link between the gut microbiota and Alzheimer’s disease (AD), but the causality remains uncertain.

Objective:

This study aimed to evaluate the causal impact of gut microbiota on AD.

Methods:

A two-sample Mendelian randomization (MR) study was conducted employing summary data. Summary statistics for AD were from the latest genome-wide association study (cases and proxy cases: 85,934; controls: 401,577). Summary data for gut microbiota were acquired from MiBioGen consortium. Causal effect estimations primarily relied on the inverse variance weighting method along with the sensitivity analyses for testing for pleiotropy and heterogeneity. Additionally, reverse MR analyses were performed to examine potential reverse causality.

Results:

Seven gut microbiota were identified as associated with AD risk. Order Selenomonadales (odds ratio [OR] 1.13, 95% confidence interval [CI] 1.03–1.24, p = 0.01), Family Pasteurellaceae (OR 1.07, 95% CI 1.01–1.13, p = 0.01), and Genus Methanobrevibacter (OR 1.07, 95% CI 1.00–1.13, p = 0.04) were correlated with an elevated likelihood of AD, while Class Mollicutes (OR 0.87, 95% CI 0.79–0.95, p = 0.00), Genus Ruminiclostridium9 (OR 0.87, 95% CI 0.78–0.97, p = 0.01), Genus Clostridiuminnocuumgroup (OR 0.94, 95% CI 0.89–0.99, p = 0.03), and Genus Eggerthella (OR 0.94, 95% CI 0.89–1.00, p = 0.04) exerted beneficial impact in mitigating AD. No statistically significant reverse causality was found between AD and each of these seven specific gut microbiota species.

Conclusions:

This study unveiled a causal link between certain gut microbiota and AD, offering new insights for advancing clinical treatments.
Analysis of the Association Between Pathogen Exposure and the Risk of Dementia
Authors: Fu Jiajia , Wei Qianqian , Chen Xueping , Lai Xiaohui , Shang Huifang
Published: July 2024

Background:

Previous research has suggested that pathogen infections may serve as potential contributors to dementia.

Objective:

Consequently, the study aimed to evaluate whether pathogen exposure heightens the risk of dementia.

Methods:

Between 2006 and 2010, a total of 8,144 individuals from the UK Biobank had data on pathogen antibodies and were included in the baseline assessment. Cox proportional hazard models were employed for the analysis.

Results:

Out of the 8,144 participants, 107 eventually developed dementia, while 55 participants were diagnosed with Alzheimer’s disease (AD). Multivariate Cox regression analysis revealed that the levels of pathogen antibody titers of EBV and C. trachomatis were associated with an increased risk of dementia/AD. The highest quartile of EBV EBNA-1 and EBV VCA p18, and the second quartile of H. pylori VacA significantly increased the risk of dementia compared lower quartile ( EBV EBNA-1: HR = 1.938, p = 0.018; EBV VCA p18: HR = 1.824, p = 0.040; H. pylori VacA: HR = 1.890, p = 0.033). Besides, the highest quartile of EBV VCA p18 had a higher risk of AD compared lower quartile (HR = 2.755, p = 0.029).

Conclusions:

The study demonstrated that exposure to EBV, H. pylori, and C. trachomatis substantially elevated the risk of dementia/AD. Despite the relatively widespread occurrence of EBV infection in the population, elevated pathogen antibody titers were still found to increase the risk of dementia/AD. Besides, since C. trachomatis and C. pneumoniae are quite homologous, this study found that trachomatis (C. trachomatis/ C. pneumoniae) may be significantly associated with the risk of AD/dementia.
Mayo Normative Studies: Amyloid and Neurodegeneration Negative Normative Data for the Auditory Verbal Learning Test and Sex-Specific Sensitivity to Mild Cognitive Impairment/Dementia
Authors: Stricker Nikki H. , Christianson Teresa J. , Pudumjee Shehroo B. , Polsinelli Angelina J. , Lundt Emily S. , Frank Ryan D. , Kremers Walter K. , Machulda Mary M. , Fields Julie A. , Jack Clifford R. , Knopman David S. , Graff-Radford Jonathan , Vemuri Prashanthi , Mielke Michelle M. , Petersen Ronald C.
Published: July 2024

Background:

Conventional normative samples include individuals with undetected Alzheimer’s disease neuropathology, lowering test sensitivity for cognitive impairment.

Objective:

We developed Mayo Normative Studies (MNS) norms limited to individuals without elevated amyloid or neurodegeneration (A–N–) for Rey’s Auditory Verbal Learning Test (AVLT). We compared these MNS A–N– norms in female, male, and total samples to conventional MNS norms with varying levels of demographic adjustments.

Methods:

The A–N– sample included 1,059 Mayo Clinic Study of Aging cognitively unimpaired (CU) participants living in Olmsted County, MN, who are predominantly non-Hispanic White. Using a regression-based approach correcting for age, sex, and education, we derived fully-adjusted T-score formulas for AVLT variables. We validated these A–N– norms in two independent samples of CU ( n = 261) and mild cognitive impairment (MCI)/dementia participants ( n = 392) > 55 years of age.

Results:

Variability associated with age decreased by almost half in the A–N– norm sample relative to the conventional norm sample. Fully-adjusted MNS A–N– norms showed approximately 7– 9% higher sensitivity to MCI/dementia compared to fully-adjusted MNS conventional norms for trials 1– 5 total and sum of trials. Among women, sensitivity to MCI/dementia increased with each normative data refinement. In contrast, age-adjusted conventional MNS norms showed greatest sensitivity to MCI/dementia in men.

Conclusions:

A–N– norms show some benefits over conventional normative approaches to MCI/dementia sensitivity, especially for women. We recommend using these MNS A–N– norms alongside MNS conventional norms. Future work is needed to determine if normative samples that are not well characterized clinically show greater benefit from biomarker-refined approaches.
Cognition Mediates the Association Between Cerebrospinal Fluid Biomarkers of Amyloid and P-Tau and Neuropsychiatric Symptoms
Authors: Frank Brandon , Walsh Michael , Hurley Landon , Groh Jenna , Blennow Kaj , Zetterberg Henrik , Tripodis Yorghos , Budson Andrew E. , O’Connor Maureen K. , Martin Brett , Weller Jason , McKee Ann , Qiu Wendy , Stein Thor D. , Stern Robert A. , Mez Jesse , Henson Rachel , Long Justin , Aschenbrenner Andrew J. , Babulal Ganesh M. , Morris John C. , Schindler Suzanne , Alosco Michael L.
Published: July 2024

Background:

Neuropsychiatric symptoms (NPS) can be an early manifestation of Alzheimer’s disease (AD). However, the associations among NPS, cognition, and AD biomarkers across the disease spectrum are unclear.

Objective:

We analyzed cross-sectional mediation pathways between cerebrospinal fluid (CSF) biomarkers of AD (Aβ1-42, p-tau181), cognitive function, and NPS.

Methods:

Primary models included 781 participants from the National Alzheimer’s Coordinating Center (NACC) data set who had CSF analyzed for AD biomarkers using Lumipulse. NPS were assessed with the Neuropsychiatric Inventory Questionnaire (NPI-Q). We assessed cognition with the harmonized MMSE/MoCA, as well as neuropsychological tests sensitive to AD pathology: story recall, naming, animal fluency, and Trails B. The Clinical Dementia Rating (CDR®) scale assessed dementia severity. Mediation models were estimated with Kemeny metric covariance in a structural equation model framework, controlling for age, education, sex, and APOE ɛ4.

Results:

The sample was older adults ( M = 73.85, SD = 6.68; 49.9% male, 390; 27.9% dementia, 218) who were predominantly white ( n = 688, 88.1%). Higher p-tau181/Aβ1-42 ratio predicted higher NPI-Q, which was partially mediated by the MMSE/MoCA and, in a second model, story recall. No other pathway was statistically significant. Both the MMSE/MoCA and NPI-Q independently mediated the association between p-tau181/Aβ1-42 ratio and CDR global impairment. With dementia excluded, p-tau181/Aβ1-42 ratio was no longer associated with the NPI-Q.

Conclusions:

NPS may be secondary to cognitive impairment and AD pathology through direct and indirect pathways. NPS independently predict dementia severity in AD. However, AD pathology likely plays less of a role in NPS in samples without dementia.
Is Simpler Always Better? The Case for Going Beyond the Amyloid Hypothesis in Alzheimer’s Disease
Authors: Bocti Christian
Published: July 2024

Alzheimer’s disease (AD) research has been dominated by the single-factor amyloid hypothesis in the last decades. Several other hypotheses have been proposed and increasingly attract attention considering the limited success of amyloid-based therapeutic strategies. Surprisingly, most published alternative etiological hypotheses for AD are similarly single-factor hypotheses, such as vascular, metabolic, mitochondrial, infectious, and inflammatory hypotheses, but the existence of so many different hypotheses suggests that AD is most likely a complex, multifactorial disorder. This inventory of different etiological hypotheses will hopefully help the field to move forward with explanatory models that consider the multifaceted aspects of this devastating disorder.
Characterization of Clinical Phenotypes in Congenital Myasthenic Syndrome Associated with the c.1327delG Frameshift Mutation in CHRNE Encoding the Acetylcholine Receptor Epsilon Subunit
Authors: Kastreva Kristina , Chamova Teodora , Blagoeva Stanislava , Bichev Stoyan , Mihaylova Violeta , Meyer Stefanie , Thompson Rachel , Cherninkova Sylvia , Guergueltcheva Velina , Lochmuller Hanns , Tournev Ivailo
Published: July 2024

Background:

Congenital myasthenic syndromes (CMS) are a group of rare but often treatable inherited disorders of neuromuscular transmission characterized by fatigable skeletal muscle weakness. In this paper we present the largest phenotypic analysis to date of a cohort of patients carrying the pathogenic variant c.1327delG in the CHRNE gene, leading to CHRNE-CMS.

Objective:

This study aims to identify the phenotypic variability in CMS associated with c.1327delG mutation in the CHRNE gene.

Methods:

Disease specific symptoms were assessed using specific standardized tests for autoimmune myasthenia (Quantitative Myasthenia Gravis score) as well as patient-reported scales for symptom severity. Evaluated clinical manifestations included ocular symptoms (ophthalmoparesis and ptosis), bulbar weakness, axial muscle weakness, proximal and distal muscle weakness, and respiratory function. Patients were allocated into three groups according to clinical impression of disease severity: mild, moderate, and severe.

Results:

We studied 91 Bulgarian Roma patients, carrying the same causative homozygous CHRNE c.1327delG mutation. Bulbar weakness was present in patients throughout all levels of severity of CHRNE-CMS in this study. However, difficulties in eating and swallowing are more prominent characteristics in the moderate and severe clinical phenotypes. Diplopia and ptosis resulting from fatigue of the extraocular muscles were permanent features regardless of disease severity or age. Levels of axial, proximal and distal muscle weakness were variable between disease groups. The statistical analysis showed significant differences between the patients in the three groups, emphasizing a possible variation in symptom manifestation in the evaluated patient population despite the disease originating from the same genetic mutation. Impairment of respiratory function was more prominent in severely affected patients, which might result from loss of compensatory muscle function in those individuals.

Conclusion:

Results from our study indicate significant phenotypic heterogeneity leading to mild, moderate, or severe clinical manifestation in CHRNE-CMS, despite the genotypic homogeneity.
Smartphone-Based Assessment of Mobility and Manual Dexterity in Adult People with Spinal Muscular Atrophy
Authors: Arteaga-Bracho Eduardo , Cosne Gautier , Kanzler Christoph , Karatsidis Angelos , Mazzà Claudia , Penalver-Andres Joaquin , Zhu Cong , Shen Changyu , Erb M. Kelley , Freigang Maren , Lapp Hanna-Sophie , Thiele Simone , Wenninger Stephan , Jung Erik , Petri Susanne , Weiler Markus , Kleinschnitz Christoph , Walter Maggie C. , Günther René , Campbell Nolan , Belachew Shibeshih , Hagenacker Tim
Published: July 2024

Background:

More responsive, reliable, and clinically valid endpoints of disability are essential to reduce size, duration, and burden of clinical trials in adult persons with spinal muscular atrophy (aPwSMA).

Objective:

The aim is to investigate the feasibility of smartphone-based assessments in aPwSMA and provide evidence on the reliability and construct validity of sensor-derived measures (SDMs) of mobility and manual dexterity collected remotely in aPwSMA.

Methods:

Data were collected from 59 aPwSMA (23 walkers, 20 sitters and 16 non-sitters) and 30 age-matched healthy controls (HC). SDMs were extracted from five smartphone-based tests capturing mobility and manual dexterity, which were administered in-clinic and remotely in daily life for four weeks. Reliability (Intraclass Correlation Coefficients, ICC) and construct validity (ability to discriminate between HC and aPwSMA and correlations with Revised Upper Limb Module, RULM and Hammersmith Functional Scale - Expanded HFMSE) were quantified for all SDMs.

Results:

The smartphone-based assessments proved feasible, with 92.1% average adherence in aPwSMA. The SDMs allowed to reliably assess both mobility and dexterity (ICC > 0.75 for 14/22 SDMs). Twenty-one out of 22 SDMs significantly discriminated between HC and aPwSMA. The highest correlations with the RULM were observed for SDMs from the manual dexterity tests in both non-sitters (Typing, ρ= 0.78) and sitters (Pinching, ρ= 0.75). In walkers, the highest correlation was between mobility tests and HFMSE (5 U-Turns, ρ= 0.79).

Conclusions:

This exploratory study provides preliminary evidence for the usability of smartphone-based assessments of mobility and manual dexterity in aPwSMA when deployed remotely in participants’ daily life. Reliability and construct validity of SDMs remotely collected in real-life was demonstrated, which is a pre-requisite for their use in longitudinal trials. Additionally, three novel smartphone-based performance outcome assessments were successfully established for aPwSMA. Upon further validation of responsiveness to interventions, this technology holds potential to increase the efficiency of clinical trials in aPwSMA.
Analysis of effect of colonoscopy combined with laparoscopy in the treatment of colorectal tumors
Authors: Zhao Deyu , Sun Xun , Guo Xun , Jianfeng Wang
Published: July 2024

BACKGROUND: Colorectal cancer is one of the most common digestive tract tumors. OBJECTIVE: To evaluate the feasibility and safety of laparoscopic colorectal cancer surgery. METHODS: This study retrospectively analyzed early postoperative clinical data of 48 patients with colorectal cancer treated in our hospital between 2015 and 2021, of which 21 underwent laparoscopic colorectal surgery, and 27 underwent laparotomy. There was no significant difference in clinical data. Patients were included if they had colorectal cancer (confirmed by colonoscopy and biopsy pathological examination before surgery), were evaluated for possible radical surgery before surgery, and had no intestinal obstruction, tumor invasion of adjacent organs (by digital rectal examination and preoperative abdominal color Doppler ultrasound, CT confirmed) and no other history of abdominal surgery. Using the method of clinical control study, operation time, intraoperative blood loss, postoperative general condition, surgical lymph node removal (postoperative pathology), surgical complications, gastrointestinal function recovery, surgical before and after blood glucose, body temperature, white blood cells, pain visual analog scale (VAS) and other conditions were compared and analyzed to determine feasibility and safety of laparoscopic surgery for colorectal cancer. RESULTS: Colorectal cancer was successfully removed by laparoscopic radical resection without any significant problems or surgical fatalities. Age, gender, tumor location, stage, and duration of surgery did not differ between laparoscopic and laparotomy operations. Compared to laparotomy, postoperative eating, bowel movements, and blood sugar levels improved. Variations in the length of surgically removed specimens after VAS measurements revealed open and laparoscopic operations. The overall lymph node count was 10.8 ± 1.6, with no variation between the two techniques. CONCLUSION: Laparoscopic colorectal cancer radical surgery is safe and feasible. Also, it has the advantages of minimally invasive surgery. Laparoscopic colorectal cancer radical surgery can comply with the principles of oncology revolutionary.