bluuebunny/crossref_metadata_2025 huggingface dataset:
Convergence and Disparities in Higher Education Fiscal Expenditures in China: A Regional Perspective
Authors: Yu Yang , Ruoxi Li , Tingting Yin , Xinxin Wang
Published: October 2023

This research investigates the disparities and convergence in higher education fiscal expenditures across different regions in China. The study utilises Gini coefficient analysis and σ-convergence/β-convergence tests to quantify the extent of disparities and explore convergence trends over a twelve-year investigation period (2007–2018). The results shed light on the imbalances in resource allocation and provide valuable insights into the efforts required to achieve a more equitable distribution of fiscal resources for higher education. The findings reveal significant disparities in higher education fiscal expenditures between the Eastern, Central, Western, and Northeastern regions, with the Eastern region exhibiting the largest gap compared to others. Remarkably, the disparity between the Eastern and Central regions is even greater than that between the Eastern and Western regions, emphasising the need for targeted interventions to address regional imbalances. Over the study period, the gap between the Eastern and Central regions remained consistently higher than other regional disparities. Moreover, the research shows a general trend towards narrowing regional fiscal expenditure disparities, with the most pronounced convergence observed between the Central and Northeastern regions. The Western region exhibits slightly larger disparities than the Central and Northeastern regions, possibly attributed to greater fiscal policy support and lower student enrollments. Nevertheless, the fiscal expenditure gap between the Western and Central regions has shown a trend towards reduction. The study also explores absolute and conditional β-convergence, revealing notable convergence patterns in the Eastern and Central regions. However, the Western and Northeastern regions exhibit varying degrees of convergence, indicating the necessity for region-specific convergence mechanisms. To achieve a balanced allocation of financial resources for higher education across regions, the study recommends targeted fiscal policies, additional funding, and improved transparency and accountability. Policymakers should focus on enhancing convergence mechanisms to ensure a more equitable distribution of resources and foster the sustainable development of higher education throughout the country. While this research provides valuable insights, it is essential to consider other potential factors influencing fiscal expenditure disparities, such as policy orientation, economic disparities, and demographic structures, for a more comprehensive understanding. Future research may benefit from qualitative investigations to further explore the complexities of higher education fiscal expenditure imbalances and identify effective policy interventions.
Bank- specific determinants of liquidity risk for commercial banks in Algeria: Panel data analysis during 2005-2020
Authors: Benchenna Fatma
Published: October 2023

This study aims to monitor a group of factors that cause liquidity risks and contribute to the occurrence of liquidity problems by testing the determinants of liquidity risk and the explanatory factors of the liquidity problem in Algerian commercial banks. This study seeks to highlight the importance of commercial banks’ liquidity in financing investments to generate profits and the need to maintain appropriate levels to meet liquidity needs. Using panel data for a sample of nine Algerian banks during the period 2005–2020, the study found that the explanatory variables of the liquidity risks that cause liquidity problems in Algerian commercial banks by using the liquid assets to total assets index ratio are: return on assets, return on equity, and capital adequacy ratio, with an explanatory capacity of 59.44%. Analysis of the results of the fixed effect model showed an inverse correlation between the return on assets and liquidity risks. There was a statistically significant positive relationship between the return on equity, capital adequacy ratio, and liquidity risk. There was a negative, but not statistically significant, relationship between bank size, the loan loss provisions to total loans ratio, and liquidity risk. The study recommends that to increase the volume of assets, there should be a corresponding increase in liquid assets as a precaution against liquidity risks in Algerian banks. Also, other determinants are not addressed in the study, which requires further research into the determinants of liquidity risk in Algerian banks.
Educational reform for middle-income trap under digitalization: Culprits, challenges, and strategies in the Philippines
Authors: Masatoshi Hara
Published: October 2023

The concept of the middle-income trap (MIT) asserts that economies with middle-income levels often struggle to progress to higher income levels, which is particularly evident in Southeast Asia. Escaping the MIT has been a significant concern, with various factors like governance, infrastructure, and labor markets identified as contributors. Education is a crucial element for developing human capital and driving economic growth. Despite efforts to enhance education, the Philippines has a historical challenge of being stuck in the lower-middle-income trap (LMIT). Limited research on effective education reform strategies to overcome the LMIT in the Philippines is available in government plans and existing studies. The research utilized a mixed method involving both qualitative and quantitative approaches. In the initial qualitative phase, the analysis drew from the Murdoch School’s critical political economy and strategic management framework. It revealed that insufficient funding for education, unequal allocation of resources between urban and rural areas, and unfavorable home learning environments are significant factors hindering progress. To address these issues and escape the LMIT, a development strategy was proposed, combining formulation and execution into a unified concept. By tackling problems like misaligned investment priorities, improper resource distribution, lack of mobile infrastructure, and unsupportive learning environments, collaboration among private sectors and universities as cluster networks could drive educational reforms. This, in turn, would lead to societal transformation and economic growth by aligning with societal needs and market demands. Focusing on relevant skills in the digital age is a suitable approach, where skill-oriented education could serve as a cornerstone of the reform efforts.
A Comprehensive Program for the Development of Independence Skills in Adolescents with Mental Disabilities. Pilot study
Authors:   Regional non-profit social organization “Center for Curative Pedagogics”, Moscow, Russian Federation, Maltseva Natalia A. , Melnikova Daria A. , Shvedovskiy Evgeny F. ,   Mental Health Research Center, Moscow, Russian Federation
Published: October 2023

within the framework of the project "Scientific and Methodological Center" of Regional non-profit social organization "Center for Curative Pedagogy", the first stage of the longitudinal study was carried out in a model group of adolescents with mental disabilities. The work of the model group is aimed at developing independence, self-service and communication skills, social and household skills. The purpose of the study is to identify the characteristics of social adaptation of adolescents participating in the program "Development of Independence in Adolescents with Developmental Disabilities". The adolescents have relatively low communication skills with a higher level of household skills. They also demonstrated a low level of self-service skills. Identifying these deficits allows you to determine and focus on specific group work tasks
A arte de Envelhecer
Authors: J. R. Santos Eduardo , Pocinho Ricardo , De Vilhena Junia , Navarro-Pardo Esperanza , Alves da Silva Ana
Published: October 2023

Ao lançarmos o primeiro número da Revista Ibero-Americana de Gerontologia, queremos deixar uma homenagem a todos os que envelhecendo nos permitem, pela sua arte, escrever um pouco sobre este processo.
Motivações para o consumo de televisão pelos seniores – da televisão generalista à informação televisiva (uma revisão do estado da arte)
Authors: Pato Luís Miguel , Torrijo Fincias Patricia , Margarido Cristóvão , Pocinho Ricardo
Published: October 2023

Ao abordar os media pode ver-se que se está perante uma enunciação de manifestações comunicacionais norteadas por uma relação direta, de causa e efeito, que ocorre em dois domínios – o estímulo codificado, que é proposto pelos media, e as múltiplas respostas que compõem a interação com o público. É na vastidão deste eixo, que é caraterizado por uma constante permuta de códigos, signos e suportes linguísticos, que ocorre o paradigma da construção e transmissão da realidade para o homem através dos artefactos mediáticos. No caso da televisão, historicamente, está-se perante um meio de comunicação com uma presença e um impacto que são inauditos na história da humanidade. Dos seus conteúdos destaca-se a informação. No que concerne ao consumidor idoso, pode verse que se regista uma grande adesão ao meio a este género em particular. Esta aspeto deve-se ao cumprimento de necessidades relacionadas não só com a sua dieta mediática, como também à resposta a dinâmicas muito particulares desta faixa etária. Neste trabalho, que se encontra ainda em fase de revisão literária, à luz da abordagem dos Usos & Gratificações (U&G), pretende-se, num primeiro momento, fazer uma revisão dos motivos que sustentam e particularizam o consumo de TV e da informação televisiva, compreendendo não só as motivações para o consumo deste meio e este género em particular para os idosos, como também a pluralidade que especificam as aplicações práticas que representa no quotidiano e na qualidade de vida dos idosos.
Salud biopsicosocial y relación con la carga experimentada por cuidadores familiares de personas mayores dependientes
Authors: Flores Noelia , Jenaro Cristina , Navarro-Pardo Esperanza , Vega Vanessa , Vázquez-Martínez Andrea
Published: October 2023

El trabajo que se presenta tiene como objetivo analizar las repercusiones biológicas, psicológicas y sociales que afectan a la salud y calidad de vida del cuidador familiar por el hecho de tener a su cargo a una persona mayor en situación de dependencia. Así, se analiza la sobrecarga experimentada como una condición generadora de consecuencias negativas en la salud de la persona cuidadora. Concretamente se presentan los resultados obtenidos tras la evaluación de 203 cuidadores a quienes se evaluó la carga o estrés experimentado, su estado de salud general (ansiedad, depresión, insomnio, disfunción social) y su calidad de vida percibida.

Los resultados obtenidos ponen de manifiesto la existencia de problemas de salud física y psicológica en aquellos cuidadores que experimentan niveles más elevados de carga. Así mismo, la sobrecarga afecta también a la calidad de vida, tanto personal como laboral, familiar y social de las personas cuidadoras. Finalmente, se señala la importancia de contar con servicios y programas que ayuden a la mejora de la salud del cuidador.
A METHODICAL APPROACH TO DETERMINING THE LEVEL OF DEVELOPMENT OF DIGITAL TRADE IN GLOBAL MARKETS
Authors:   West Ukrainian National University, Ternopil, Ukraine, Shevchenko Iryna
Published: October 2023

The global digital transformation market is showing increasing performance every year, and growth forecasts have a long-lasting effect. In the conditions of digitalization of the economy, the relevance of research in the field of digital economy in general and digital trade in particular is increasing. The study developed a methodical approach to determining the level of development of digital trade on global markets by determining the integral indicator and clustering countries. The research is based on categories of theoretical and empirical levels of knowledge. With the help of cluster analysis, the classification of countries was carried out by methods of classification of multidimensional indicators, based on the definition of the concept of distance between objects, followed by the selection of their groups of clusters. Using the cluster method, countries were represented, which made it possible to visualize the result of the mental process when building a methodical approach to determining the level of development of digital trade on global markets. The proposed methodological approach makes it possible to assess the level of development of digital trade, taking into account the specifics of the development of a certain country. The implementation of the proposed approach will make it possible to conduct a more complete analysis of digital trade and ensure the sustainable development of the economic system.
PERANCANGAN DAN PENGEMBANGAN PRODUK PROTOTYPE MESIN CNC LASER BERBASIS ARDUINO UNO DENGAN PENDEKATAN QFD
Authors: Nur Sulaiman1 Renaldy
Published: October 2023

Teknologi industri pemesinan di Indonesia semakin meningkatkan. Hal ini di buktikan dengan semakin modern nya pemesinan yang digunakan untuk mengerjakan suatu produk, seperti Computerized Numerical Control (CNC) yaitu mesin perkakas yang dilengkapi dengan komputer untuk memudahkan proses kerja mesin. Dengan  mesin perkakas CNC, ketelitian suati produk dapat dijamin, pengerjaan produk masal dengan hasil yang persis dan waktu proses pemesinan yang yang cepat. Mesin CNC adalah suatu mesin perkakas yang di control oleh computer dengan menggunakan Bahasa Numerik (data perintah dengan kode angka, huruf, dan simbol) sesuai dengan standar ISO ( International Organization for Standarization). Teori yang digunakan dalam penelitian adalah Quality Function Depoloyment (QFD) untuk mengetahui dan menentukan dasar keinginan atau kebutuhan konsumen. Dengan pembentukan matrik House Of Quality (HOQ) untuk mengetahui tingkat kepentingan pelanggan. Menghitung waktu siklus perancangan Mesin Prototype Mini CNC Laser dengan menggunakan OPC dan membuat Bill Of Material (BOM). Kesimpilan Perancangan Mesin Prototype Mini Laser dengan pendekatan Quality Fucttion Deployment (QFD) berdasarkan analisis telah didapatkan hasil HOQ yang didapat disimpulkan bahwa untuk memenuhi kebutuhan konsumen maka dibuat lah Mesin Prototype Mesin Mini CNC Laser dengan harga yang lebih ekonomis dengan mnggunakan DVD ROM yang berbeda dengan Mesin CNC laser sebelumnya
ANALISIS PENGENDALIAN KUALITAS DI LINE DOOR MIRROR DALAM UPAYA MENURUNKAN RASIO PART REJECT DENGAN METODE FMEA
Authors: Harist Saputra Ade Rizky
Published: October 2023

PT Honda Lock Indonesia merupakan salah satu perusahaan manufacturing dan assembly yang bergerak dibidang otomotif. Produk-produk yang dibuat antara lain Door Mirror, Out Handle, Key Set, Light License Switch, dan Lock Assy Steering. Berdasarkan data produksi dibulan Oktober 2021-Mei 2022, disetiap bulan terdapat reject pada produk door mirror  yang menyebabkan tidak tercapainya target zero defect perusahaan. Berdasarkan pengolahan data menggunakan pareto chart diketahui bahwa door mirror noise memiliki reject terbesar dengan total 40 pcs. Oleh karena itu dibutuhkan penanganan untuk menghilangkan reject tersebut dengan menggunakan FMEA (Failure Mode and Effect Analysis) untuk mencari akar-akar penyebab dari masalah yang ditimbulkan. Dari hasil analisa diketahui penyebab kegagalan yaitu adanya gompal pada gear motor yang dihasilkan dari kotoran atau benda asing yang menempel. Tindakan yang dilakukan untuk mengurangi reject yaitu melakukan otomasisasi proses greasing gear motor dan otomasisasi pengecekan noise. Dampak setelah perbaikan yaitu menurunnya reject door mirror noise hingga tercapainya target zero defect Perusahaan
ANALISIS FAKTOR-FAKTOR KINERJA PEMASARAN TERHADAP KUALITAS PRODUK PAKAN TERNAK PADA CV. DALIJO ULAM UPADI DI MUARA BADAK
Authors: Aswardin  , Ilham  , Akhmadiansyah
Published: October 2023

CV. Dalijo Ulam Upadi feels that he has not reached the sales volume according to the target, which is affecting the company's income. Apart from that, product quality is often less than optimal in processing because the raw materials the company receives are sometimes not good or only a small amount. so the fear of producers is that it can make livestock less healthy when consumed so that it can make livestock less healthy, this most often happens because the raw material for making fertilizer is made from pure fish, this causes a decrease in production due to a lack of fish supply to the company, this can also causing the company to suffer losses or lose consumers so that consumers look for animal feed from other competitors. The aim of this research is to find out what factors influence the quality of animal feed products at CV. Dalijo Ulam Upadi in Muara Badak. This research uses a quantitative approach, the sample used is all CV employees. Dalijo Ulam Upadi in Muara Badak, numbering 27 people. Then the data uses the factor analysis method. The results of this research are based on the calculations obtained where the results of the calculations obtained as a whole are declared to have met the requirements, meaning that the first hypothesis proposed is that there are marketing performance factors on the quality of animal feed products at CV. Dalijo Ulam Upadi was accepted because it was proven to be true. The second hypothesis proposed was that the factor that the proposed hypothesis is accepted because it is proven to be true.
ANALISIS PROFITABILITAS USAHA PADA DERMAGA UMUM DI MUARA BADAK
Authors: Haidir Muhammad Kurnia , Saher Sayid , Hendra
Published: October 2023

The birth of several small businesses as well as large businesses in the Muara Badak District, especially in the field of transportation services, has provided evidence that economic development in the Muara Badak District is increasingly advanced. The evidence can be seen with the variety of types of businesses that began to develop, one of which is the Public Docksin Muara Badak, which is one of the crossing businesses with a tariff of Rp. 2,000 per person at Pangempang Road Rt 05. No 28. Muara Badak Distric. The main objective of this study is to find out and assess the financial performance of Orange Pier which is reviewed using profitability ratios in 2017 and 2018. The analytical tool used in this study is a financial ratio analysis tool as a basis for measuring profitability ratios for analysis results. Profit Margin is the company's ability to generate profits compared to sales achieved. From the results of the calculation of profit margins in 2017 showed 57.37% and 2018 showed 62.88% of the difference in increase achieved 5.51% from 2017. Turnover of Operating assets shows the company's ability with all the capital in it to generate profits. This ratio is calculated by comparing earnings before interest and taxes with total assets. This ratio is used to measure the ability to generate net income based on the level of assets. From the results of calculations in 2017 showed 71.02% and 2018 showed 75.30% difference experienced an increase in 2018 was 4.28%. Return On Investment (ROI) is used to determine the effectiveness of the company in utilizing funds from the company. From the calculation results obtained ROI increased in 2018 by 6.60% from the results of 2017 showing 40.74 and 2018 showing 47.34%.
ANALISIS PENGARUH CITRA MEREK, KUALITAS LAYANAN, DAN HARGA TERHADAP KEPUTUSAN PEMBELIAN PADA RESTORAN CEPAT SAJI KFC DI TENGGARONG
Authors: Purnamasari Sarwindah , Wijayanti Silvana Kardinar , Fahleti Widya Hana
Published: October 2023

The purpose of this study was to determine the effect of brand image, service quality and price on purchasing decisions at KFC fast food restaurants in Tenggarong. This type of research used in this research is expalanatory with a quantitative approach. The number of population in this study obtained an average of 486 buyers per day. So the researchers used sampling using the Slovin formula with a = 10%, the sample obtained was 83 respondents. The method used in sampling is non-propability sampling with the type of accidental sampling. Data collection techniques using a questionnaire using multiple linear regression analysis tools using SPSS version 22 software. The multiple linear regression equation obtained in this study is Y = 0.772 + 0.154X1 + 0.147X2 + 0.627X3. The results of this study are the brand image, service quality, and price either simultaneously or together or partially have a positive and significant effect on purchasing decisions at KFC fast food restaurants in Tenggarong. The price variable is the variable that has the most influence on purchasing decisions, seen from the t test results, the price variable has a t count of 7.377, which is greater than the other two variables. The resulting R square value is 0.695, this means that 69.5% of purchasing decisions are influenced by the variables of brand image, service quality and price, while the rest (100% - 69.5% = 30.5%) is influenced by other variables such as promotion and product quality.
Le conflit, moteur et paradigme du progrès scientifique, social et moral
Authors:   Faculté de Lettres et Sciences Humaines, Université de l’Assomption au Congo, Butembo P.O. Box 104, République Démocratique du Congo, Kibanda Wilfried Kasereka
Published: October 2023

Le mot conflit (du latin conflictus, du verbe « confligere »), réfère originellement à une expérience de lutte armée, de combat entre deux ou plusieurs puissances humaines ou organisationnelles se disputant un pouvoir. Pris dans ce contexte, le concept de conflit semble suggérer la destruction mutuelle. Il s’applique à toute opposition entre des personnes ou des idées, voire des états psychiques ou mentaux. Mais, faut-il en rester à ce sens désobligeant ? Les roses ne poussentelles pas sur des épines ? Comment l’expérience du conflit est-elle appréhendée par les sciences sociales et humaines ? Y a-t-il quelque chose de constructif ? Cet article présente une lecture appréciative du phénomène de conflit dans la pensée philosophique, où il apparait avec quelque vertu, celle d’être le moteur du progrès scientifique, social et moral. Le conflit est devenu un paradigme explicatif du progrès humain.
El derecho a recibir información y el derecho a comunicar: claves de la política de traducción e interpretación en los centros penitenciarios de Rumanía
Authors: Vitalaru Bianca
Published: October 2023

Este artículo analiza la legislación penitenciaria de Rumanía para describir el elemento normativo de su política de traducción e interpretación (T&I) en lo referente a las personas alóglotas. Para ello, se aplica una versión modificada del modelo de Martínez-Gómez (2018) para la clasificación de sistemas penitenciarios en función de la madurez de sus políticas lingüísticas. Este modelo destaca las disposiciones relativas a la T&I para hacer efectivos los derechos de base lingüística. Nuestro artículo añade una distinción para determinar si la legislación prevé los mismos derechos para las personas alóglotas en situaciones informativas, donde reciben información, y en situaciones comunicativas, donde pueden expresarse y ser escuchadas. Se añade, además, una comparación con los instrumentos internacionales en la materia para determinar cuántas situaciones discursivas reconocidas en aquellos se han contemplado en la legislación pertinente. Los resultados muestran que el sistema penitenciario rumano prevé pocas medidas específicas de T&I como parte de los derechos lingüísticos de la población reclusa alóglota y presenta un nivel intermedio de transposición en relación con las situaciones previstas en instrumentos internacionales. El estudio observa desequilibrios entre las medidas adoptadas para el disfrute de los derechos a la comunicación y a la información, y abre el debate sobre en qué grado la legislación silencia a la población reclusa alóglota.
Utilization of PVP-PLA Combination in Fabricating Theophylline-loaded Filament for 3D Printing with Immediate Release Behavior
Authors:   Laboratory of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Universitas Indonesia, Depok, West Java, 16424, Indonesia, Surini Silvia
Published: October 2023

Fused deposition modeling (FDM), known as a highly effective 3D printing technique, holds promise as an alternative approach to tablet manufacturing. While commonly employing thermoplastic polymers as starting materials, the integration of established pharmaceutical excipients remains unexplored. Polyvinyl pyrrolidone (PVP) is a frequently used excipient known for its potential to confer immediate-release properties to drugs. However, its suitability for extrusion is hindered by its thermal and melt-rheological properties. In contrast, polylactic acid (PLA), which has robust mechanical strength and thermal plasticity, was expected to overcome PVP’s limitations. This study aims to obtain drug-loaded filaments using the combination of PVP and PLA through a hot-melt extrusion process, aiming for favorable mechanical properties and immediate-release behavior. Utilizing a twin-screw extruder, and theophylline was used as the model drug, three formulations were optimized –FP1, FP2, and FP3– containing 0%, 10%, and 20% theophylline, respectively. Subsequent evaluation including filament morphology, mechanical properties, drug content, and drug release profile, were performed to each filament. FP2 emerged as the most promising formulation, with 10.35% (w/w) drug load and over 95% drug released in an hour. All formulations exhibited slightly rough filament surfaces with diameters averaging 1.4-1.6 mm. Notably, an increase in the theophylline content correlates with the diminished filament strength, evident in reduced hardness and a rise in brittleness. This study emphasized the potential of PVP-PLA-based filaments for future pharmaceutical 3D printing formulations, providing immediate drug release characteristics.
Using multi-modal neuroimaging to characterise social brain specialisation in infants
Authors: Siddiqui Maheen , Pinti Paola , Brigadoi Sabrina , Lloyd-Fox Sarah , Elwell Clare E , Johnson Mark H , Tachtsidis Ilias , Jones Emily JH
Published: October 2023

The specialised regional functionality of the mature human cortex partly emerges through experience-dependent specialisation during early development. Our existing understanding of functional specialisation in the infant brain is based on evidence from unitary imaging modalities and has thus focused on isolated estimates of spatial or temporal selectivity of neural or haemodynamic activation, giving an incomplete picture. We speculate that functional specialisation will be underpinned by better coordinated haemodynamic and metabolic changes in a broadly orchestrated physiological response. To enable researchers to track this process through development, we develop new tools that allow the simultaneous measurement of coordinated neural activity (EEG), metabolic rate, and oxygenated blood supply (broadband near-infrared spectroscopy) in the awake infant. In 4- to 7-month-old infants, we use these new tools to show that social processing is accompanied by spatially and temporally specific increases in coupled activation in the temporal-parietal junction, a core hub region of the adult social brain. During non-social processing, coupled activation decreased in the same region, indicating specificity to social processing. Coupling was strongest with high-frequency brain activity (beta and gamma), consistent with the greater energetic requirements and more localised action of high-frequency brain activity. The development of simultaneous multimodal neural measures will enable future researchers to open new vistas in understanding functional specialisation of the brain.
Competing neural representations of choice shape evidence accumulation in humans
Authors: Bond Krista , Rasero Javier , Madan Raghav , Bahuguna Jyotika , Rubin Jonathan , Verstynen Timothy
Published: October 2023

Making adaptive choices in dynamic environments requires flexible decision policies. Previously, we showed how shifts in outcome contingency change the evidence accumulation process that determines decision policies. Using in silico experiments to generate predictions, here we show how the cortico-basal ganglia-thalamic (CBGT) circuits can feasibly implement shifts in decision policies. When action contingencies change, dopaminergic plasticity redirects the balance of power, both within and between action representations, to divert the flow of evidence from one option to another. When competition between action representations is highest, the rate of evidence accumulation is the lowest. This prediction was validated in in vivo experiments on human participants, using fMRI, which showed that (1) evoked hemodynamic responses can reliably predict trial-wise choices and (2) competition between action representations, measured using a classifier model, tracked with changes in the rate of evidence accumulation. These results paint a holistic picture of how CBGT circuits manage and adapt the evidence accumulation process in mammals.
A three filament mechanistic model of musculotendon force and impedance
Authors: Millard Matthew , Franklin David W , Herzog Walter
Published: October 2023

The force developed by actively lengthened muscle depends on different structures across different scales of lengthening. For small perturbations, the active response of muscle is well captured by a linear-time-invariant (LTI) system: a stiff spring in parallel with a light damper. The force response of muscle to longer stretches is better represented by a compliant spring that can fix its end when activated. Experimental work has shown that the stiffness and damping (impedance) of muscle in response to small perturbations is of fundamental importance to motor learning and mechanical stability, while the huge forces developed during long active stretches are critical for simulating and predicting injury. Outside of motor learning and injury, muscle is actively lengthened as a part of nearly all terrestrial locomotion. Despite the functional importance of impedance and active lengthening, no single muscle model has all these mechanical properties. In this work, we present the viscoelastic-crossbridge active-titin (VEXAT) model that can replicate the response of muscle to length changes great and small. To evaluate the VEXAT model, we compare its response to biological muscle by simulating experiments that measure the impedance of muscle, and the forces developed during long active stretches. In addition, we have also compared the responses of the VEXAT model to a popular Hill-type muscle model. The VEXAT model more accurately captures the impedance of biological muscle and its responses to long active stretches than a Hill-type model and can still reproduce the force-velocity and force-length relations of muscle. While the comparison between the VEXAT model and biological muscle is favorable, there are some phenomena that can be improved: the low frequency phase response of the model, and a mechanism to support passive force enhancement.
Multimodal analysis of methylomics and fragmentomics in plasma cell-free DNA for multi-cancer early detection and localization
Authors: Nguyen Van Thien Chi , Nguyen Trong Hieu , Doan Nhu Nhat Tan , Pham Thi Mong Quynh , Nguyen Giang Thi Huong , Nguyen Thanh Dat , Tran Thuy Thi Thu , Vo Duy Long , Phan Thanh Hai , Jasmine Thanh Xuan , Nguyen Van Chu , Nguyen Huu Thinh , Nguyen Trieu Vu , Nguyen Thi Hue Hanh , Huynh Le Anh Khoa , Tran Trung Hieu , Dang Quang Thong , Doan Thuy Nguyen , Tran Anh Minh , Nguyen Viet Hai , Nguyen Vu Tuan Anh , Ho Le Minh Quoc , Tran Quang Dat , Pham Thi Thu Thuy , Ho Tan Dat , Nguyen Bao Toan , Nguyen Thanh Nhan Vo , Nguyen Thanh Dang , Phu Dung Thai Bieu , Phan Boi Hoan Huu , Vo Thi Loan , Nai Thi Huong Thoang , Tran Thuy Trang , Truong My Hoang , Tran Ngan Chau , Le Trung Kien , Tran Thanh Huong Thi , Duong Minh Long , Bach Hoai Phuong Thi , Kim Van Vu , Pham The Anh , Tran Duc Huy , Le Trinh Ngoc An , Pham Truong Vinh Ngoc , Le Minh Triet , Vo Dac Ho , Tran Thi Minh Thu , Nguyen Minh Nguyen , Van Thi Tuong Vi , Nguyen Anh Nhu , Tran Thi Trang , Tran Vu Uyen , Le Minh Phong , Do Thi Thanh , Phan Thi Van , Nguyen Hong-Dang Luu , Nguyen Duy Sinh , Cao Van Thinh , Do Thanh-Thuy Thi , Truong Dinh Kiet , Tang Hung Sang , Giang Hoa , Nguyen Hoai-Nghia , Phan Minh-Duy , Tran Le Son
Published: October 2023

Despite their promise, circulating tumor DNA (ctDNA)-based assays for multi-cancer early detection face challenges in test performance, due mostly to the limited abundance of ctDNA and its inherent variability. To address these challenges, published assays to date demanded a very high-depth sequencing, resulting in an elevated price of test. Herein, we developed a multimodal assay called SPOT-MAS (screening for the presence of tumor by methylation and size) to simultaneously profile methylomics, fragmentomics, copy number, and end motifs in a single workflow using targeted and shallow genome-wide sequencing (~0.55×) of cell-free DNA. We applied SPOT-MAS to 738 non-metastatic patients with breast, colorectal, gastric, lung, and liver cancer, and 1550 healthy controls. We then employed machine learning to extract multiple cancer and tissue-specific signatures for detecting and locating cancer. SPOT-MAS successfully detected the five cancer types with a sensitivity of 72.4% at 97.0% specificity. The sensitivities for detecting early-stage cancers were 73.9% and 62.3% for stages I and II, respectively, increasing to 88.3% for non-metastatic stage IIIA. For tumor-of-origin, our assay achieved an accuracy of 0.7. Our study demonstrates comparable performance to other ctDNA-based assays while requiring significantly lower sequencing depth, making it economically feasible for population-wide screening.
Early acquisition of S-specific Tfh clonotypes after SARS-CoV-2 vaccination is associated with the longevity of anti-S antibodies
Authors: Lu Xiuyuan , Hayashi Hiroki , Ishikawa Eri , Takeuchi Yukiko , Dychiao Julian Vincent Tabora , Nakagami Hironori , Yamasaki Sho
Published: October 2023

SARS-CoV-2 vaccines have been used worldwide to combat COVID-19 pandemic. To elucidate the factors that determine the longevity of spike (S)-specific antibodies, we traced the characteristics of S-specific T cell clonotypes together with their epitopes and anti-S antibody titers before and after BNT162b2 vaccination over time. T cell receptor (TCR) αβ sequences and mRNA expression of the S-responded T cells were investigated using single-cell TCR- and RNA-sequencing. Highly expanded 199 TCR clonotypes upon stimulation with S peptide pools were reconstituted into a reporter T cell line for the determination of epitopes and restricting HLAs. Among them, we could determine 78 S epitopes, most of which were conserved in variants of concern (VOCs). After the 2nd vaccination, T cell clonotypes highly responsive to recall S stimulation were polarized to follicular helper T (Tfh)-like cells in donors exhibiting sustained anti-S antibody titers (designated as ‘sustainers’), but not in ‘decliners’. Even before vaccination, S-reactive CD4+ T cell clonotypes did exist, most of which cross-reacted with environmental or symbiotic microbes. However, these clonotypes contracted after vaccination. Conversely, S-reactive clonotypes dominated after vaccination were undetectable in pre-vaccinated T cell pool, suggesting that highly responding S-reactive T cells were established by vaccination from rare clonotypes. These results suggest that de novo acquisition of memory Tfh-like cells upon vaccination may contribute to the longevity of anti-S antibody titers.
The mTOR pathway genes MTOR, Rheb, Depdc5, Pten, and Tsc1 have convergent and divergent impacts on cortical neuron development and function
Authors: Nguyen Lena H , Xu Youfen , Nair Maanasi , Bordey Angelique
Published: October 2023

Brain somatic mutations in various components of the mTOR complex 1 (mTORC1) pathway have emerged as major causes of focal malformations of cortical development and intractable epilepsy. While these distinct gene mutations converge on excessive mTORC1 signaling and lead to common clinical manifestations, it remains unclear whether they cause similar cellular and synaptic disruptions underlying cortical network hyperexcitability. Here, we show that in utero activation of the mTORC1 activator genes, Rheb or MTOR, or biallelic inactivation of the mTORC1 repressor genes, Depdc5, Tsc1, or Pten in the mouse medial prefrontal cortex leads to shared alterations in pyramidal neuron morphology, positioning, and membrane excitability but different changes in excitatory synaptic transmission. Our findings suggest that, despite converging on mTORC1 signaling, mutations in different mTORC1 pathway genes differentially impact cortical excitatory synaptic activity, which may confer gene-specific mechanisms of hyperexcitability and responses to therapeutic intervention.
The mTOR pathway genes mTOR, Rheb, Depdc5, Pten, and Tsc1 have convergent and divergent impacts on cortical neuron development and function
Authors: Nguyen Lena H. , Xu Youfen , Nair Maanasi , Bordey Angelique
Published: October 2023

Brain somatic mutations in various components of the mTOR complex 1 (mTORC1) pathway have emerged as major causes of focal malformations of cortical development and intractable epilepsy. While these distinct gene mutations converge on excessive mTORC1 signaling and lead to common clinical manifestations, it remains unclear whether they cause similar cellular and synaptic disruptions underlying cortical network hyperexcitability. Here, we show that
in utero
activation of the mTORC1 activators,
Rheb
or
mTOR
, or biallelic inactivation of the mTORC1 repressors,
Depdc5
,
Tsc1
, or
Pten
in mouse medial prefrontal cortex leads to shared alterations in pyramidal neuron morphology, positioning, and membrane excitability but different changes in excitatory synaptic transmission. Our findings suggest that, despite converging on mTORC1 signaling, mutations in different mTORC1 pathway genes differentially impact cortical excitatory synaptic activity, which may confer gene-specific mechanisms of hyperexcitability and responses to therapeutic intervention.
Transcriptional control of compartmental boundary positioning during Drosophila wing development
Authors: Aguilar Gustavo , Sickmann Michèle , Bieli Dimitri , Born Gordian , Affolter Markus , Müller Martin
Published: October 2023

The establishment of tissue axes is fundamental during embryonic development. In the Drosophila wing, the anterior/posterior (AP) and the dorsal/ventral (DV) compartment boundaries provide the basic coordinates around which the tissue develops. These boundaries arise as a result of two lineage decisions, the acquisition of posterior fate by the selector gene
engrailed
(
en)
and of dorsal fate by the selector gene
apterous
(
ap
). While
en
expression domain is set up during embryogenesis,
ap
expression only starts during early wing development. Thus, the correct establishment of
ap
expression pattern with respect to
en
must be tightly controlled. Here we have functionally investigated the transcriptional inputs integrated by the “early”
ap
enhancer (apE) and their requirement for correct boundary positioning. Detailed mutational analyses using CRISPR/Cas revealed a role of apE in positioning the DV boundary with respect to the AP boundary, with apE mutants often displaying mirror-image anterior wing duplications. We then accomplished tissue-specific enhancer disruption via dCas9 expression. This approach allowed us to dissect the spatio-temporal requirement of apE function, challenging the mechanism by which apE miss-regulation leads to AP defects. Base-pair resolution analyses of apE uncovered a single HOX binding site essential for wing development, which, when mutated, led to wingless flies. Along these lines, we found that the HOX gene Antennapedia (Antp) is fundamental for
ap
expression. In addition, we demonstrated that the transcription factors Pointed (Pnt), Homothorax (Hth) and Grain (Grn) are necessary for apE function. Together, our results provide a comprehensive molecular basis of early
ap
activation and the developmental consequences of its miss-regulation, shedding light on how compartmental boundaries are be set up during development.
Role of the αC-β4 loop in protein kinase structure and dynamics
Authors: Wu Jian , Jonniya Nisha A , Hirakis Sophia P , Olivieri Cristina , Veglia Gianluigi , Kornev Alexandr P , Taylor Susan S
Published: October 2023

Although the αC-β4 loop is a stable feature of all protein kinases, the importance of this motif as a conserved element of secondary structure, as well as its links to the hydrophobic architecture of the kinase core, has been underappreciated. We first review the motif and then describe how it is linked to the hydrophobic spine architecture of the kinase core, which we first discovered using a computational tool, local spatial Pattern (LSP) alignment. Based on NMR predictions that a mutation in this motif abolishes the synergistic high-affinity binding of ATP and a pseudo substrate inhibitor, we used LSP to interrogate the F100A mutant. This comparison highlights the importance of the αC-β4 loop and key residues at the interface between the N- and C-lobes. In addition, we delved more deeply into the structure of the apo C-subunit, which lacks ATP. While apo C-subunit showed no significant changes in backbone dynamics of the αC-β4 loop, we found significant differences in the side chain dynamics of K105. The LSP analysis suggests disruption of communication between the N- and C-lobes in the F100A mutant, which would be consistent with the structural changes predicted by the NMR spectroscopy.
Beneficial effects of upgrading to His-Purkinje system pacing in patients with pacing-induced cardiomyopathy: a systematic review and meta-analysis
Authors: Tang Nian , Chen Xiaoxiao , Li Hongfei , Zhang Denghong
Published: October 2023

Background

The purpose of this study was to evaluate the effectiveness of His-Purkinje system pacing (HPSP) in the management of patients with pace-induced cardiomyopathy (PICM).

Methods

PubMed, Embase, Web of Science, and the Cochrane Library were searched comprehensively to collect related studies published from the inception of databases to June 1, 2022. R 4.04 software, including the Metafor package, matrix package, and the Meta package, was utilized to conduct the singe-arm meta-analysis. The methodology index for non-randomized studies (MINORS) was used to assess the methodological quality of the included studies.

Results

A total of seven studies were included, involving 164 PICM patients. The meta-analysis showed that HPSP ameliorated the left ventricular ejection fraction (LVEF) by 13.41% (95% CI [11.21–15.61]), improved the New York Heart Association (NYHA) classification by 1.02 (95% CI [−1.41 to −0.63]), and shortened the QRS duration (QRSd) by 60.85 ms (95% CI [−63.94 to −57.75]), resulting in improved cardiac functions in PICM patients. Besides, HPSP reversed the ventricular remodeling, with a 32.46 ml (95% CI [−53.18 to −11.75]) decrease in left ventricular end systolic volume (LVESV) and a 5.93 mm (95% CI [−7.68 to −4.19]) decrease in left ventricular end-diastolic dimension (LVEDD). HPSP also showed stable electrical parameters of pacemakers, with a 0.07 V (95% CI [0.01–0.13]) increase in pacing threshold, a 0.02 mV (95% CI [−0.85 to 0.90]) increase in sensed R-wave amplitude, and a 31.12 Ω reduction in impedance (95% CI [−69.62 to 7.39]). Compared with LBBP, HBP improved LVEF by 13.28% (95% CI [−11.64 to 14.92]) vs 14.43% (95% CI [−13.01 to 15.85]), ameliorated NHYA classification by 1.18 (95% CI [−1.97 to −0.39]) vs 0.95 (95% CI [−1.33 to −0.58]), shortened QRSd by 63.16 ms (95% CI [−67.00 to −59.32]) vs 57.98 ms (95% CI [−62.52 to −53.25]), and decreased LVEDD by 4.12 mm (95% CI [−5.79 to −2.45]) vs 6.26 mm (95% CI [−62.52 to −53.25]). The electrical parameters of the pacemaker were stable in both groups.

Conclusions

This meta-analysis showed that HPSP could significantly improve cardiac function, promote reverse remodeling, and provide stable electrical parameters of pacemakers for PICM patients.
Death and Non-Death Grief Experiences of Filipino College Students
Authors: Pamplona Myla Pilar
Published: October 2023

The experience of grief because of the loss of loved ones during the COVID-19 pandemic and the loss of control resulting from uncertainties and broken relationships were among the concerns experienced by college students in the past two years. The study aims to understand the grief experiences of Filipino young adults and how they can be utilized to help others. An Interpretative Phenomenological Analysis (IPA) was utilized to understand the death and non-death experiences of three Filipino college students experiencing grief. An in-depth interview was conducted, and the steps using the IPA framework were carefully followed, which included reading and rereading, initial noting, developing emergent themes, searching for connections across emergent themes, moving to the following cases, and looking for patterns across issues. A conceptual framework based on the students' experiences was developed, and recommendations were crafted. Themes include roller-coaster emotions and coping, connecting symbols to death, finding meaning to experience, remembering loved ones' wishes, loneliness, and emptiness of missed presence. The recommendation includes creating a Grief Program for Students aligned to their perceived needs.
Uso de las Tecnologías de Información y Comunicación (TIC) en el proceso de Evaluación Formativa, en escuelas que imparten educación primaria y secundaria: una revisión sistemática de literatura
Authors:   , López Stubbs Argenis Elpidio
Published: October 2023

El objetivo de este estudio es describir el uso y aporte que tienen las Tecnologías de Información y Comunicación (TIC), para los docentes de escuelas que imparten educación primaria y secundaria, en la realización de procesos de Evaluación Formativa, en base a la revisión de literatura de los artículos. La metodología utilizada en este trabajo se basó en la revisión de 41 artículos extraídos de 3 plataformas de búsqueda: Web of Science, Scopus y Scielo, utilizando las palabras claves descritas en este trabajo. Luego, estos artículos fueron evaluados de acuerdo con los criterios de inclusión y exclusión establecidos. El paso siguiente consistió en analizar el total de artículos que cumplían con los requerimientos de búsqueda, para luego, realizar una síntesis de los hallazgos encontrados en dichos artículos, permitiendo con esto, sustentar esta investigación. Finalmente, de acuerdo con las conclusiones de los artículos seleccionados en esta revisión, los docentes perciben las herramientas TIC como positivas y atribuyen a las mismas un mejor proceso de evaluación formativa, pues, cuando compararan los resultados del uso de tecnología para evaluar con la forma tradicional, encuentran múltiples ventajas evaluando con TIC, pues brindan dinamismo e innovación en los procesos.