bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence of Vitamin D Deficiency among Patients Attending Tertiary Level Hospitals in Bangladesh: Hospital-Based Cross-Sectional Study
Authors: Islam Majumder Md Mahabubul , Rahman Hafizur , Ahmed Mostaque , Uddin Mohammad Nazim , Ahmed Tarek , Mahadi Ashrafur Rahaman
Published: May 2024

Introduction: Vitamin D (Vit D) is essential for calcium and phosphate homeostasis, critical for bone growth and remodeling. Its deficiency leads to conditions like osteomalacia and rickets, with adverse effects on osteoporosis, growth, and skeletal health. This study aimed to assess Vitamin D Deficiency prevalence among patients in Bangladeshi tertiary-level hospitals. Materials and Methods: A prospective cross-sectional study was conducted from January to December 2019 at Cumilla Medical College Hospital and Central Medical College Hospital. We enrolled 1250 patients meeting inclusion criteria and collected data via a pre-designed questionnaire. Results: Most participants (31.8%) were aged 31-40, with a mean age of 37.31±13.37. Male patients constituted 53.3%, and 46.7% were female. Rural residents accounted for 52.6%, while 25.8% lived in urban areas, and the rest abroad, mainly the Middle East. The majority (88.5%) belonged to middle-class families, and only 1.5% reported sufficient sun exposure. Strikingly, 54.2% were Vitamin D deficient, 40% had insufficient levels, and only 6.4% had adequate Vit D. Conclusion: This study highlights a significant prevalence of Vitamin D deficiency among patients in Bangladeshi tertiary hospitals. The data underscore the urgent need for healthcare authorities to address this public health concern. Policymakers and healthcare providers should be aware of the potential long-term health consequences of Vitamin D deficiency, emphasizing the importance of strategies to promote adequate Vit D levels in the population.
Medicine Today 2023 Vol.36 (1): 17-22
La seguridad jurídica frente al impuesto por utilidades
Authors: Toapanta-Chicaiza Johanna , García-Erazo Erika
Published: May 2024

El impuesto por utilidades es un tributo aplicable a la transferencia de dominio de inmuebles ubicados en el sector urbano. En el Ecuador el cobro de este impuesto forma parte de los ingresos de los gobiernos municipales y metropolitanos a quienes el COOTAD ha provisto de la facultad de modificar su tarifa mediante ordenanza, lo cual ha generado un problema jurídico que vulnera directamente principios como la reserva de ley y la seguridad jurídica. Además, este impuesto que fue reformado en principio únicamente en su denominación con la expedición del COOTAD, ha afectado al objeto mismo del tributo, al abarcar todo tipo de transferencias de dominio, incluidas las de título gratuito como las herencias y donaciones, donde no se evidencia una utilidad real, es decir, el mismo hecho generador. Este trabajo busca analizar críticamente la importancia de la jerarquía normativa y la seguridad jurídica en materia tributaria, a través del reconocimiento del hecho generador para el pago de tributos. La metodología y enfoques aplicados para este estudio son cualitativos conforme a lo establecido por Sampieri. Los resultados demuestran que las normas deben ser claras y de conformidad con la Constitución y principios tributarios para así garantizar el derecho de los contribuyentes.
Diferencias de Burnout entre trabajadores de empresas comerciales, educativas, financieras y de la salud
Authors: Velásquez-Vasquez Erika , Guamán-Castillo Jhon , Mora-Sánchez Norman
Published: May 2024

El burnout es una de las psicopatologías del trabajo de mayor prevalencia en la actualidad y ha sido asociado a diferentes factores, entre ellos la edad y el género. Las empresas de la provincia de El Oro no suelen realizar diagnósticos sobre burnout, por lo tanto, la gestión del talento humano y la productividad están en riesgo. Por lo tanto, para esta investigación se planteó como objetivo realizar un diagnóstico de los niveles de burnout e identificar las diferencias por edad, género y sector. La metodología utilizada es descriptiva de corte transversal y de carácter cuantitativa, se utilizó la técnica de la encuesta para el levantamiento de información primaria y la revisión bibliográfica para la construcción del marco teórico. Se tomó una muestra de 384 trabajadores de los sectores comercial, educativo, financiero y de la salud, a quienes se les aplicó el instrumento MBI-General Survey, y se obtuvo niveles de confiabilidad altos en las tres dimensiones: Agotamiento (α=0,952), Cinismo (α=0,960) y Eficacia laboral (α=0,974). Mediante un análisis MANOVA se observó que las diferencias de burnout respecto a la eficacia profesional percibida entre los trabajadores de los cuatro sectores sí son significativas, siendo aquellos de los sectores comercial, educativo y de la salud los más vulnerables. Respecto a la edad y el género, la primera variable no está relacionada con el burnout, pero la segunda sí cuando interactúa en conjunto al sector donde trabaja una persona.
Calidad De Vida e Intervención del Trabajador Social en Atención a Personas con Tratamiento de Hemodiálisis
Authors: Mendoza-Intriago Dreysi , Moreira-Chica Tatiana
Published: May 2024

La calidad de vida es la interacción constante entre factores económicos, sociales, las necesidades que se presentan en el transcurso de la vida y sobre todo en la incidencia individual que cada individuo tiene en el desarrollo personal, y es en ello donde el Trabajador Social cumple un rol muy imperativo, dispuesto a concentrar procesos, acciones formativas y la participación activa hacia los usuarios que lo necesita. El objetivo de la investigación fue analizar la calidad de vida e intervención del Trabajador Social en atención a personas con tratamiento de hemodiálisis en el prestador de salud RenalPRO C.A Santa Elena. Para el diseño de la investigación se estableció el uso del paradigma mixto, el cual focalizo la aplicabilidad de instrumentos cuantitativos y cualitativos, bajo el procesamiento de datos estadísticos y el desarrollo de evaluación mediante el Alfa de Cronbach que midió la fiabilidad de la calidad de vida. Los resultados indican que las personas tienen una calidad de vida normal, es decir que ejecutan sus actividades normales, y que están dispuestas a seguir avanzando a pesar de las situaciones que se generan en el entorno de diálisis. De acuerdo con la efectividad de resultados se trabajó con una confiabilidad del instrumento del 0,982, de lo cual su margen de error fue mínimo, en esto recaen que los resultados expresados fueron compilados y comprendidos para dar énfasis sobre la calidad de vida, en el caso del personal de Trabajo Social se pudo reconocer que existe el dominio y la comprensión sobre los temas que están relacionados en pacientes con este tratamiento, y que su principal rol está en el direccionamiento y atención al  bienestar el paciente.
Estrategias de marketing digital para cafeterías - restaurantes en Esmeraldas, Ecuador.
Authors: Dueñas-Mendoza Andrea , Zaldumbide-Peralvo David
Published: May 2024

El objeto de estudio de este artículo fue diseñar estrategias de marketing digital que sean ideales para una cafetería – restaurante ubicado en Esmeraldas – Ecuador. La investigación desarrollada nace de un estudio de tipo mixto con un análisis de carácter descriptivo donde se levantó información relevante a través de encuestas y técnica de observación. Se indica que la falta de estrategias de marketing digital en cafeterías restaurantes no ha permitido el alcance de los clientes potenciales siendo estos, parte fundamental para el incremento de sus ventas y futura expansión. Es importante para el desarrollo de una cafetería restaurante contar con un plan de marketing estratégico basado en las necesidades del mercado, el cual debe ser implementado inmediatamente debido a su eficacia para captar nuevos clientes y retener a los que ya se tienen.
The Effect of Smit-Style Training on the CPK Enzyme, Kinetic Response Speed, and Accuracy of the Blocking Skill for Young Volleyball Players
Authors: Jerri Zainab , Radhi Mahmoud , Oleiwi Ahmed
Published: May 2024

The purpose of this paper is to prepare volleyball-style (SMlT) exercises, as well as identify the effect of (SMlT)-style exercises on the CPK enzyme, speed of kinetic response, and accuracy of the blocking skill for young volleyball players. The researchers to use the experimental method because it is compatible with the nature of the research problem, and to design the method of the two equal groups (experimental and control) with pre- and post-tests. The research population was determined by the young players of Al-Daghara Sports Club for the sports season (2023-2024), who numbered (14) players, and the freestyle players, who numbered two players, were excluded because their characteristics did not match the nature of the study. Thus, the total number became (12) players, and the researcher chose them entirely for the experiment, and they were distributed. Two groups were divided equally in a random manner (lottery method), after which the experimental group underwent training (SMlT) method, while the control group remained using the trainer’s normal training curriculum. One of the most important results reached by the researcher is that: The exercises applied by the experimental research group using the SMlT method helped adapt the muscle cells by increasing the activity of the CPK enzyme . One of the most important recommendations recommended by the researchers is that: Researchers recommend adopting specialized exercises using the SMIT method as basic data when training volleyball players.
The Impact of Rehabilitation Exercises and Infrared Device on Knee Osteoarthritis Rehabilitation in Women Over 40 Years
Authors: Abdul Hussein Narges , Abed Hussein Suaad
Published: May 2024

The study aimed to prepare exercises using infrared radiation and identify its effect on the rehabilitation of women with osteoarthritis at the age of (40) women. The researchers assumed that there were statistically significant differences between the results of the rehabilitation tests for women with osteoarthritis (muscular strength, degree of pain, range of motion) pre and post. For the research group, the experimental method was adopted by designing the experimental group on a sample that was intentionally chosen by (100%) of the women suffering from this injury who are attended by the Al-Warith Center for Physiotherapy / affiliated with the Abbasid Shrine, who number (6) injured. The researchers prepared the rehabilitation exercises according to systematic steps that took a period of time to prepare and implement for the period extending from (5/1/2023) until (5/19/2023), with an application rate of (3) consecutive qualifying weeks, each week of which (3) units represented Rehabilitation sessions, bringing the total number of sessions to (9) rehabilitation units. The conclusions are that applying rehabilitative exercises using infrared rays helps rehabilitate women suffering from knee osteoarthritis by developing the strength of the muscles surrounding the joint and thus getting rid of the injury. It was determined that there were significant differences at the p<0.05 level of Muscular strength, Motor range and Degree of pain. The researchers recommend the need for centers to pay attention to Physiotherapy and should develop the expertise of the therapists working in it on how to apply rehabilitative exercises using infrared radiation in light of the findings of this study.
Biomechanical Features of the Double Back Tuck on the Floor Exercises in Gymnastics in Male Artistic Gymnastics
Authors: Naji Jalil Sarmad , Sayah Qasim , Abdulameer Mothna
Published: May 2024

This study aims to identify the characteristics of the takeoff and landing in the round off performance followed by followed by a double back tuck. One gymnast participated in this study, and the data was captured using an camera at a speed of 240 fps and perpendicular to the plane of movement. Data were extracted using the analytical software SkillSpector and Kinovea. The data revealed that the vertical velocity, which was when takeoff (5.9 m/s). This was evident at the maximum height of the center of mass, which was measured (2.3 m). The higher values for the maximum height of the center of mass were the result of a combination of several performance factors, such as the contact angle and the takeoff on the floor with horizontal and faster leg extension. The horizontal velocity at contact was (5.7 m/s) and decreased to (-2.5 m/s) at takeoff. The results of the study indicate that the double back tuck movement involves a reduction in horizontal velocity and an increase in vertical velocity. This is because the horizontal velocity is converted into vertical velocity to raise the body to a great height so that the gymnast can get the time required to execute the skill while flying in the air. The leg muscles also played the dominant role in takeoff and landing through contact angles and takeoff and landing.
Analytical Thinking and its Relationship to the Performance of the Simple Response Skill in Foil Weapon for Students
Authors: Rashid Shahed , Muhalhel Hind , Isawi Iqbal
Published: May 2024

The purpose of this paper is to identifying the level of analytical thinking and its relationship to the skills of response and simple response to the foil weapon for students of the College of Physical Education and Sports Sciences, University of Basra. Achieving the objectives of the research requires the use of a research method, and accordingly, the researchers used the descriptive method using the survey method .The two researchers identified the research community with the students of the third stage - College of Physical Education and Sports Sciences / University of Basra / for the academic year (2021-2022). Their number is (45) students and the two researchers chose the entire research community to represent the research sample. One of the most important results reached by the researcher is that: There is a significant correlation between the student's analytical thinking and the skills of replying and simple replying ,and the research sample individuals have a good level of analytical thinking, which helps them to perform sports skills, including fencing skills. One of the most important recommendations recommended by the researchers is that: Investing in the level of understanding shown by the research sample of the role of analytical thinking in performing skills, fencing lessons and training should include situations that encourage the use of analytical thinking ,and conducting similar studies and research on university students in Iraq.
Literature review of potential materials for the construction of an alternative flat-plate solar collector
Authors: Chichango Fernando , Cristóvão Luís , Nhambiu Jorge , Cumbe Fabião , Mavanga Gil Gabriel
Published: May 2024

Through systematic review method the article presents the potential of existing solar energy in Mozambique for use in water heating with the integration of thermal energy storage systems that are currently being investigated. It emphasizes the need for affordable materials in building solar collectors for Mozambique’s homes, leveraging the country’s solar potential to reduce electricity consumption and environmental impact for sustainable development. It explores current research on thermal energy storage systems for solar water heating and reviews alternative materials for solar collectors based on their properties, cost, and availability. The importance of thermal energy storage in solar collectors for efficiency and load balancing is highlighted., it discusses and list the potential alternative materials for the construction of flat plate solar thermal collectors from roofing material, frame, absorber, pipes, and heat storage material according to their thermophysical properties, costs, and availability in the Mozambican market in the context of industrialization.
RANCANG BANGUN WEB MOBILE HIMPUNAN MAHASISWA TEKNIK INFORMATIKA (HMTI) STMIK PALANGKARAYA
Authors: Rusdiana Lili , Hermawan Heri , Maryamah Siti
Published: May 2024

Organisasi dari Himpunan Mahasiswa Teknik Informatika pada STMIK Palangkaraya belum memiliki website khusus terkait kegiatan yang berhubungan dengan organisasi tersebut. Hal ini membuat kesulitan untuk mengakses dan mengetahui kegiatan yang dilakukan oleh organisasi tersebut. Maka dari itu, perlunya merancang dan membangun web mobile untuk menampung semua aktifitas dari kegiatan organisasi Mahasiswa tersebut. Metode yang digunakan dalam penelitian ini yaitu Research & Development dengan cara studi pendahuluan, pengembangan model, dan pengujian. Tujuan dari penelitian ini yaitu untuk mempemudah dalam mencari informasi kegiatan tentang Mahasiswa di UKM Himpunan Mahasiswa Teknik Informatika melalui Web Mobile. Hasil dari penelitian ini yaitu web dapat diimplementasikan dan diakses secara online berbasis mobile. Web dapat digunakan untuk mengelola informasi terkait kegiatan yang dilakukan pada lembaga kemahasiswaan Himpunan Mahasiswa Teknik Informatika di STMIK Palangkaraya.
Hubungan Antara Kreativitas Dengan Hasil Belajar Agama Islam di SMKN 5 Kabupaten Tangerang
Authors: Huda Syafa'at Ariful
Published: May 2024

Analisis hasil belajar agama islam di SMKN 5 Kabupaten Tangerang. â€œPenelitian ini bertujuan untukâ€ menganalisis hubungan antara kreativitas dengan hasil belajar agama islam.â€ Penelitian ini dilakukan kepada siswa SMKN 5 Kabupaten Tangerang. sampel diambil secara acak sederhana (sample random sampling) dengan mengambil 30 orang siswa yang berasal dari 3 kelas XI yang berjumlah 90. â€œMetode penelitian yang digunakan adalah metode deskriptif kualitatif dengan teknikâ€ korelasi. Variabel bebas (X) adalah kreativitas dan variabel terikat â€œ(Y) adalah hasil belajar agama islam. â€œData yang diperoleh dianalisis terlebih dahulu dengan uji normalitas memakai uji lilliefors, kemudian uji koefisien korelasi dan uji keberartian koefisien korelasi.â€Dari hasil pengujian normalitas untuk variabel bebas didapat Koefisien korelasi variabel X dan Y yang dihitung dengan analisis korelasi product moment, dan diperoleh rxy = 0,40. Selanjutnya menghitung keberartian koefesien dengan uji t-student diperoleh thit = 2,52 (ttab= 2,05) sehingga kesimpulannya adalah terdapat hubungan antara kreativitas dengan hasil belajar agama islam.
Clinical significance of procollagen type III N-terminal peptide in patients with alcoholic liver disease
Authors: Geyvandova N. I. , Bolbat G. K. , Yagoda A. V.
Published: May 2024

Background. Alcoholic liver disease (ALD) – is a disease that leads to the development of liver cirrhosis (LC) with a high mortality rate. N-terminal type lll procollagen peptide (PIIINP) is one of the optimal biomarkers for assessing fibrogenesis.

Objective: to determine the clinical significance of PIIINP blood level in patients with ALD.

Materials and methods. 97 patients with ALD were examined. The age of the patients was 48,5±9,9 years, there were 30 women, 67 men. Steatosis was diagnosed in 12 patients, 11 – alcoholic hepatitis (AH), 74 – LC. In group with LC, 16 patients was diagnosed AH against confirmed cirrhosis. PIIINP blood level determined by ELISA. Control group consisted of 22 healthy volunteers who have not consumed alcohol in hepatotoxic doses.

Results. In all patients, PIIINP blood level was increased. In steatosis PIIINP slightly increased the norm, indicating the beginning of fibrogenesis. In LC, PIIINP blood level was higher than in patients with steatosis, which reflected increasing of fibrosis and progression of the disease. The highest levels of PIIINP were observed in cases with AH. Levels PIIINP in patients with AH but without LC and in patients with AH against the background of the formed LC did not differ. In Maddray index of more than 32 (9 patients), the PIIINP level was higher than in 18 patients with index values <32, which confirmed the role of AH in development of fibrosis and decompensation of liver function.

Conclusion. Determination of PIIINP blood level in patients with ALD will allow predict the activity of fibrogenesis and the severity of subsequent changes in liver tissue. In cases of severe AH, PIIINP may be an additional criterion determining the severity and prognosis of hepatitis outcomes.
Sentido pedagógico de las disciplinas artísticas desde la visión de las y los artistas
Authors: Navarro Gabriela Ibeth , García García Blanca Elba
Published: May 2024

El objetivo fue identificar el sentido pedagógico de las disciplinas artísticas escénicas y visuales en los artistas que las profesan, así como el aprendizaje obtenido de éstas y la manera en que lo transfieren a su cotidianeidad. El sentido pedagógico se construyó a partir de cuatro atributos sustanciales: epistemológico, heurístico, hermenéutico y ontológico. Se realizó un análisis cualitativo con treinta y dos participantes quienes afirmaron que existe un aprendizaje que les permite llegar a formarse como personas y a vivir su propia realidad. Los hallazgos indican que además de los saberes que se alcanzan al estudiar una disciplina, ésta es una herramienta para actuar ante la vida, dado que genera arrobamiento, pasión, sentimiento de libertad. A través del arte, los entrevistados van creando su propia filosofía de vida, fortalecen su sistema axiológico y logran alcanzar un balance de vida.
La exclusión digital como una forma de exclusión social: una revisión crítica del concepto de brecha digital
Authors: Haz-Gómez Francisco Eduardo , López-Martínez Gabriel , Manzanera-Román Salvador
Published: May 2024

La exclusión social se define como un fenómeno cuyos efectos determinan que un individuo o grupo se sitúen en diferentes posiciones sociales. De manera análoga, el desarrollo de las tecnologías de la información y la comunicación en esta tercera década del siglo XXI, con la emergencia de la Cuarta Revolución Industrial, provoca que con el avance de la digitalización se establezcan diferencias estructurales entre quienes tienen acceso y conocimientos en el uso de dispositivos y aplicaciones. En este trabajo se realiza una revisión crítica al concepto de brecha digital, en muchos aspectos más limitado y estático que el término exclusión digital. Este último, análogo al fenómeno de exclusión social, y concepto más versátil y adaptado a los procesos de fragmentación social provocados por la digitalización. Mediante el uso de la Encuesta sobre equipamiento y uso de tecnologías de información y comunicación en los hogares elaborada por el Instituto Nacional de Estadística se realiza un análisis estadístico con el objetivo de validar que, al igual que la exclusión social, la exclusión digital es un fenómeno estructural, dinámico, multifactorial y heterogéneo, además de subjetivo. Simultáneamente, se trata de un fenómeno que alcanzaría a todo grupo poblacional, incluso a los denominados nativos digitales.
Seguimiento fisicoquímico en camas de lombricultura – modelación químico computacional 3D del ácido húmico
Authors:   Universidad de las Fuerzas Armadas ESPE, Santana Romo Fabián Mauricio , Benavides Gutiérrez Henry Roberto ,   Universidad de las Fuerzas Armadas ESPE
Published: May 2024

Como consecución a la implementación de camas de lombricultura, se construyeron dos modelos, unos basado en la literatura, y otro propuesto por la comunidad beneficiaria. Luego de adecuar las cuatro camas con material orgánico, y lombrices californianas (Eisenia foetida), se tomaron mediciones de parámetros fisicoquímicos (conductividad, humedad, temperatura, y pH) a través de un cronograma semanal definido. Se trató estadísticamente los resultados obtenidos con la premisa de entender la correlación que tienen las variables en estudio; se consideró al pH como una de las principales, ya que el ácido húmico producido por el metabolismo de las lombrices aumenta su concentración con respecto al tiempo y condiciones paralelas favorables. Se llegó a obtener una ecuación para su regresión lineal, proveyendo un modelo matemático aplicable para la predicción. Se encontró que el manejo ancestral, conocimiento de los beneficiarios, hay que potenciarlo con datos actuales y adecuación a la realidad local, para obtener mejores resultados. Para complementar el estudio se aplicó conocimiento multidisciplinar, con la química computacional para describir las moléculas químicas presentes en el humus, y modelar la estructura tridimensional del ácido húmico con el fin de reconocer las unidades monoméricas que lo conforman.
Evaluating the use of smartphones for processing computational tasks: "A case study for the annotation of prokaryotic genomes"
Authors: Junior Jamir Nascimento Cardoso , Oliveira Mônica Silva De , Veras Adonney Allan De Oliveira
Published: May 2024

Currently, there is a growing dependence on smartphones in the daily lives of thousands of people, noting that the number of users continues to rise, surpassing the number of computers in use globally. In addition, the performance of smartphone hardware has become an essential factor when choosing these devices, along with price, brand and operating system. Constant innovations in smartphones have made these devices increasingly powerful, even rivaling the performance of many computers. The example of the Samsung S23 5G, which has features comparable to a low-performance notebook, illustrates the advancement of the hardware in these devices. Despite the growing demand for advanced hardware in smartphones, many users may not fully understand the technical specifications of the processors. The article proposes an evaluation of the use of this hardware in the execution of specific tasks, with a focus on the annotation of prokaryotic genomes. The methodology of the study involved selecting popular smartphones from Samsung and Motorola, choosing the Android operating system due to its efficiency in resource management, using the Prokka tool for genomic annotation due to its minimal resource requirements and using Termux, a terminal emulator that allows users to run a full Linux distribution on Android devices. To evaluate performance, the article uses the Linux 'time' command to measure execution time, memory consumption, CPU utilization and other relevant metrics
Sustainability and innovation across the aquaculture value chain
Authors: Aarstad Jarle , Jakobsen Stig-Erik , Fløysand Arnt , Kvitastein Olav Andreas
Published: May 2024

Previous research has shown that Norwegian aquaculture firms strongly emphasize environmental and social sustainability, and this study aims to assess if the pattern is consistent across the value chain and consistent independent of suppliers’ amount of sales to fish farming. Also, it studies if value chain position and sales to fish farming are associated with innovation activities. Empirically, the study compares survey data between firms in the aquaculture industry and other industries as reference groups. The results show that aquaculture firms across the value chain overall emphasize environmental and social sustainability more than actors in the reference industries. For suppliers, the emphasis is strongest for those with high sales to fish farming. Another finding is that aquaculture firms’ innovation activities are relatively strong among firms providing services and input factors, particularly among suppliers with high sales to fish farming.
Amyloid, Crohn’s disease, and Alzheimer’s disease - are they linked?
Authors: Duda-Madej Anna , Stecko Jakub , Szymańska Natalia , Miętkiewicz Agnieszka , Szandruk-Bender Marta
Published: May 2024

Crohn’s disease (CD) is a chronic inflammatory disease that most frequently affects part of the distal ileum, but it may affect any part of the gastrointestinal tract. CD may also be related to systemic inflammation and extraintestinal manifestations. Alzheimer’s disease (AD) is the most common neurodegenerative disease, gradually worsening behavioral and cognitive functions. Despite the meaningful progress, both diseases are still incurable and have a not fully explained, heterogeneous pathomechanism that includes immunological, microbiological, genetic, and environmental factors. Recently, emerging evidence indicates that chronic inflammatory condition corresponds to an increased risk of neurodegenerative diseases, and intestinal inflammation, including CD, increases the risk of AD. Even though it is now known that CD increases the risk of AD, the exact pathways connecting these two seemingly unrelated diseases remain still unclear. One of the key postulates is the gut-brain axis. There is increasing evidence that the gut microbiota with its proteins, DNA, and metabolites influence several processes related to the etiology of AD, including β-amyloid abnormality, Tau phosphorylation, and neuroinflammation. Considering the role of microbiota in both CD and AD pathology, in this review, we want to shed light on bacterial amyloids and their potential to influence cerebral amyloid aggregation and neuroinflammation and provide an overview of the current literature on amyloids as a potential linker between AD and CD.
Pharmacogenomic analysis in adrenocortical carcinoma reveals genetic features associated with mitotane sensitivity and potential therapeutics
Authors: Zhang Jie , Wu Luming , Su Tingwei , Liu Haoyu , Jiang Lei , Jiang Yiran , Wu Zhiyuan , Chen Lu , Li Haorong , Zheng Jie , Sun Yingkai , Peng Hangya , Han Rulai , Ning Guang , Ye Lei , Wang Weiqing
Published: May 2024

Background

Adrenocortical carcinoma (ACC) is an aggressive endocrine malignancy with limited therapeutic options. Treating advanced ACC with mitotane, the cornerstone therapy, remains challenging, thus underscoring the significance to predict mitotane response prior to treatment and seek other effective therapeutic strategies.

Objective

We aimed to determine the efficacy of mitotane via an in vitro assay using patient-derived ACC cells (PDCs), identify molecular biomarkers associated with mitotane response and preliminarily explore potential agents for ACC.

Methods

In vitro mitotane sensitivity testing was performed in 17 PDCs and high-throughput screening against 40 compounds was conducted in 8 PDCs. Genetic features were evaluated in 9 samples using exomic and transcriptomic sequencing.

Results

PDCs exhibited variable sensitivity to mitotane treatment. The median cell viability inhibition rate was 48.4% (IQR: 39.3-59.3%) and -1.2% (IQR: -26.4-22.1%) in responders (n=8) and non-responders (n=9), respectively. Median IC50 and AUC were remarkably lower in responders (IC50: 53.4 µM vs 74.7 µM, P<0.0001; AUC: 158.0 vs 213.5, P<0.0001). Genomic analysis revealed CTNNB1 somatic alterations were only found in responders (3/5) while ZNRF3 alterations only in non-responders (3/4). Transcriptomic profiling found pathways associated with lipid metabolism were upregulated in responder tumors whilst CYP27A1 and ABCA1 expression were positively correlated to in vitro mitotane sensitivity. Furthermore, pharmacologic analysis identified that compounds including disulfiram, niclosamide and bortezomib exhibited efficacy against PDCs.

Conclusion

ACC PDCs could be useful for testing drug response, drug repurposing and guiding personalized therapies. Our results suggested response to mitotane might be associated with the dependency on lipid metabolism. CYP27A1 and ABCA1 expression could be predictive markers for mitotane response, and disulfiram, niclosamide and bortezomib could be potential therapeutics, both warranting further investigation.
HIV immunological non-responders are characterized by extensive immunosenescence and impaired lymphocyte cytokine production capacity
Authors: Vos Wilhelm A. J. W. , Navas Adriana , Meeder Elise M. G. , Blaauw Marc J. T. , Groenendijk Albert L. , van Eekeren Louise E. , Otten Twan , Vadaq Nadira , Matzaraki Vasiliki , van Cranenbroek Bram , Brinkman Kees , van Lunzen Jan , Joosten Leo A. B. , Netea Mihai G. , Blok Willem L. , van der Ven Andre J. A. M. , Koenen Hans J. P. M. , Stalenhoef Janneke E.
Published: May 2024

Introduction

Immunological non-responders (INR) are people living with HIV (PLHIV) who fail to fully restore CD4+ T-cell counts despite complete viral suppression with antiretroviral therapy (ART). INR are at higher risk for non-HIV related morbidity and mortality. Previous research suggest persistent qualitative defects.

Methods

The 2000HIV study (clinical trials NTC03994835) enrolled 1895 PLHIV, divided in a discovery and validation cohort. PLHIV with CD4 T-cell count <350 cells/mm3 after ≥2 years of suppressive ART were defined as INR and were compared to immunological responders (IR) with CD4 T-cell count >500 cells/mm3. Logistic and rank based regression were used to analyze clinical data, extensive innate and adaptive immunophenotyping, and ex vivo monocyte and lymphocyte cytokine production after stimulation with various stimuli.

Results

The discovery cohort consisted of 62 INR and 1224 IR, the validation cohort of 26 INR and 243 IR. INR were older, had more advanced HIV disease before starting ART and had more frequently a history of non-AIDS related malignancy. INR had lower absolute CD4+ T-cell numbers in all subsets. Activated (HLA-DR+, CD38+) and exhausted (PD1+) subpopulations were proportionally increased in CD4 T-cells. Monocyte and granulocyte immunophenotypes were comparable. INR lymphocytes produced less IL-22, IFN-γ, IL-10 and IL-17 to stimuli. In contrast, monocyte cytokine production did not differ. The proportions of CD4+CD38+HLA-DR+ and CD4+PD1+ subpopulations showed an inversed correlation to lymphocyte cytokine production.

Conclusions

INR compared to IR have hyperactivated and exhausted CD4+ T-cells in combination with lymphocyte functional impairment, while innate immune responses were comparable. Our data provide a rationale to consider the use of anti-PD1 therapy in INR.
Plasminogen activator inhibitor-1 promotes immune evasion in tumors by facilitating the expression of programmed cell death-ligand 1
Authors: Ibrahim Abd Aziz , Fujimura Taku , Uno Tomoko , Terada Tomoya , Hirano Ken-ichi , Hosokawa Hiroyuki , Ohta Akio , Miyata Toshio , Ando Kiyoshi , Yahata Takashi
Published: May 2024

Background

Increased levels of plasminogen activator inhibitor-1 (PAI-1) in tumors have been found to correlate with poor clinical outcomes in patients with cancer. Although abundant data support the involvement of PAI-1 in cancer progression, whether PAI-1 contributes to tumor immune surveillance remains unclear. The purposes of this study are to determine whether PAI-1 regulates the expression of immune checkpoint molecules to suppresses the immune response to cancer and demonstrate the potential of PAI-1 inhibition for cancer therapy.

Methods

The effects of PAI-1 on the expression of the immune checkpoint molecule programmed cell death ligand 1 (PD-L1) were investigated in several human and murine tumor cell lines. In addition, we generated tumor-bearing mice and evaluated the effects of a PAI-1 inhibitor on tumor progression or on the tumor infiltration of cells involved in tumor immunity either alone or in combination with immune checkpoint inhibitors.

Results

PAI-1 induces PD-L1 expression through the JAK/STAT signaling pathway in several types of tumor cells and surrounding cells. Blockade of PAI-1 impedes PD-L1 induction in tumor cells, significantly reducing the abundance of immunosuppressive cells at the tumor site and increasing cytotoxic T-cell infiltration, ultimately leading to tumor regression. The anti-tumor effect elicited by the PAI-1 inhibitor is abolished in immunodeficient mice, suggesting that PAI-1 blockade induces tumor regression by stimulating the immune system. Moreover, combining a PAI-1 inhibitor with an immune checkpoint inhibitor significantly increases tumor regression.

Conclusions

PAI-1 protects tumors from immune surveillance by increasing PD-L1 expression; hence, therapeutic PAI-1 blockade may prove valuable in treating malignant tumors.
The single-dose Janssen Ad26.COV2.S COVID-19 vaccine elicited robust and persistent anti-spike IgG antibody responses in a 12-month Ugandan cohort
Authors: Serwanga Jennifer , Kato Laban , Oluka Gerald Kevin , Ankunda Violet , Sembera Jackson , Baine Claire , Kitabye Isaac , Namuyanja Angela , Opio Solomon , Katende Joseph Ssebwana , Ejou Peter ,   The COVID-19 Immunoprofiling Team, Kaleebu Pontiano
Published: May 2024

Introduction

The study investigation examined the immune response to the Janssen Ad26.COV2.S COVID-19 vaccine within a Ugandan cohort, specifically targeting antibodies directed against spike (S) and nucleocapsid (N) proteins. We aimed to examine the durability and robustness of the induced antibody response while also assessing occurrences of breakthrough infections and previous anti-Spike seropositivity to SARS-CoV-2.

Methods

The study included 319 specimens collected over 12 months from 60 vaccinees aged 18 to 64. Binding antibodies were quantified using a validated ELISA method to measure SARS-CoV-2-specific IgG, IgM, and IgA levels against the S and N proteins.

Results

The results showed that baseline seropositivity for S-IgG was high at 67%, increasing to 98% by day 14 and consistently stayed above 95% for up to 12 months. However, S-IgM responses remained suboptimal. A raised S-IgA seropositivity rate was seen that doubled from 40% at baseline to 86% just two weeks following the initial vaccine dose, indicating sustained and robust peripheral immunity. An increase in N-IgG levels at nine months post-vaccination suggested breakthrough infections in eight cases. Baseline cross-reactivity influenced spike-directed antibody responses, with individuals harbouring S-IgG antibodies showing notably higher responses.

Discussion

Robust and long lasting vaccine and infection-induced immune responses were observed, with significant implications for regions where administering subsequent doses poses logistical challenges.
A review of lactate-lactylation in malignancy: its potential in immunotherapy
Authors: Zha Jinhui , Zhang Junan , Lu Jingfen , Zhang Guangcheng , Hua Mengzhan , Guo Weiming , Yang Jing , Fan Gang
Published: May 2024

Lactic acid was formerly regarded as a byproduct of metabolism. However, extensive investigations into the intricacies of cancer development have revealed its significant contributions to tumor growth, migration, and invasion. Post-translational modifications involving lactate have been widely observed in histone and non-histone proteins, and these modifications play a crucial role in regulating gene expression by covalently attaching lactoyl groups to lysine residues in proteins. This discovery has greatly enhanced our comprehension of lactic acid’s involvement in disease pathogenesis. In this article, we provide a comprehensive review of the intricate relationship between lactate and tumor immunity, the occurrence of lactylation in malignant tumors, and the exploitation of targeted lactate-lactylation in tumor immunotherapy. Additionally, we discuss future research directions, aiming to offer novel insights that could inform the investigation, diagnosis, and treatment of related diseases.
FASTMAP—a flexible and scalable immunopeptidomics pipeline for HLA- and antigen-specific T-cell epitope mapping based on artificial antigen-presenting cells
Authors: Weisbrod Luisa , Capriotti Luigi , Hofmann Marco , Spieler Valerie , Dersch Herbert , Voedisch Bernd , Schmidt Peter , Knake Susanne
Published: May 2024

The study of peptide repertoires presented by major histocompatibility complex (MHC) molecules and the identification of potential T-cell epitopes contribute to a multitude of immunopeptidome-based treatment approaches. Epitope mapping is essential for the development of promising epitope-based approaches in vaccination as well as for innovative therapeutics for autoimmune diseases, infectious diseases, and cancer. It also plays a critical role in the immunogenicity assessment of protein therapeutics with regard to safety and efficacy concerns. The main challenge emerges from the highly polymorphic nature of the human leukocyte antigen (HLA) molecules leading to the requirement of a peptide mapping strategy for a single HLA allele. As many autoimmune diseases are linked to at least one specific antigen, we established FASTMAP, an innovative strategy to transiently co-transfect a single HLA allele combined with a disease-specific antigen into a human cell line. This approach allows the specific identification of HLA-bound peptides using liquid chromatography–tandem mass spectrometry (LC-MS/MS). Using FASTMAP, we found a comparable spectrum of endogenous peptides presented by the most frequently expressed HLA alleles in the world’s population compared to what has been described in literature. To ensure a reliable peptide mapping workflow, we combined the HLA alleles with well-known human model antigens like coagulation factor VIII, acetylcholine receptor subunit alpha, protein structures of the SARS-CoV-2 virus, and myelin basic protein. Using these model antigens, we have been able to identify a broad range of peptides that are in line with already published and in silico predicted T-cell epitopes of the specific HLA/model antigen combination. The transient co-expression of a single affinity-tagged MHC molecule combined with a disease-specific antigen in a human cell line in our FASTMAP pipeline provides the opportunity to identify potential T-cell epitopes/endogenously processed MHC-bound peptides in a very cost-effective, fast, and customizable system with high-throughput potential.
Sterile inflammation of peritoneal membrane caused by peritoneal dialysis: focus on the communication between immune cells and peritoneal stroma
Authors: Su Hongyong , Zou Rong , Su Jinqi , Chen Xiaocui , Yang Haijuan , An Ning , Yang Chen , Tang Jixin , Liu Huafeng , Yao Cuiwei
Published: May 2024

Peritoneal dialysis is a widely used method for treating kidney failure. However, over time, the peritoneal structure and function can deteriorate, leading to the failure of this therapy. This deterioration is primarily caused by infectious and sterile inflammation. Sterile inflammation, which is inflammation without infection, is particularly concerning as it can be subtle and often goes unnoticed. The onset of sterile inflammation involves various pathological processes. Peritoneal cells detect signals that promote inflammation and release substances that attract immune cells from the bloodstream. These immune cells contribute to the initiation and escalation of the inflammatory response. The existing literature extensively covers the involvement of different cell types in the sterile inflammation, including mesothelial cells, fibroblasts, endothelial cells, and adipocytes, as well as immune cells such as macrophages, lymphocytes, and mast cells. These cells work together to promote the occurrence and progression of sterile inflammation, although the exact mechanisms are not fully understood. This review aims to provide a comprehensive overview of the signals from both stromal cells and components of immune system, as well as the reciprocal interactions between cellular components, during the initiation of sterile inflammation. By understanding the cellular and molecular mechanisms underlying sterile inflammation, we may potentially develop therapeutic interventions to counteract peritoneal membrane damage and restore normal function.
BacScan: a novel genome-wide strategy for uncovering broadly immunogenic proteins in bacteria
Authors: Dong Junhua , Zhang Qian , Yang Jinyue , Zhao Yacan , Miao Zhuangxia , Pei Siyang , Qin Huan , Jing Changwei , Wen Guoyuan , Zhang Anding , Tao Pan
Published: May 2024

In response to the global threat posed by bacterial pathogens, which are the second leading cause of death worldwide, vaccine development is challenged by the diversity of bacterial serotypes and the lack of immunoprotection across serotypes. To address this, we introduce BacScan, a novel genome-wide technology for the rapid discovery of conserved highly immunogenic proteins (HIPs) across serotypes. Using bacterial-specific serum, BacScan combines phage display, immunoprecipitation, and next-generation sequencing to comprehensively identify all the HIPs in a single assay, thereby paving the way for the development of universally protective vaccines. Our validation of this technique with Streptococcus suis, a major pathogenic threat, led to the identification of 19 HIPs, eight of which conferred 20-100% protection against S. suis challenge in animal models. Remarkably, HIP 8455 induced complete immunity, making it an exemplary vaccine target. BacScan’s adaptability to any bacterial pathogen positions it as a revolutionary tool that can expedite the development of vaccines with broad efficacy, thus playing a critical role in curbing bacterial transmission and slowing the march of antimicrobial resistance.
The shape of fringing tidal flats in engineered estuaries
Authors: Hanssen Jill L. J. , van Prooijen Bram C. , van Maren Dirk S.
Published: May 2024

For the management of estuaries and the preservation of tidal flats it is crucial to understand the tidal flat shape and development. Previous work focused predominantly on the quasi-equilibrium shape of tidal flats along open coasts with a dominant cross-shore flow and wave exposure. This paper evaluates the shape of fringing tidal flats in engineered estuaries, where longshore velocities generally dominate. Using a long-term (20 years) topographic data set of an anthropogenically modified estuary in the Netherlands (the Western Scheldt estuary), we relate key profile shape parameters and changes over time to natural and anthropogenic processes. In an engineered estuary, the tidal flat shape depends on the estuary geometry, hydrodynamic forcings and human interventions. In contrast to open coast tidal flats, the presence of the channel and dominant longshore flow determines the available cross-shore length (accommodation space) of the tidal flat and the shape of the tidal flat. This accommodation space defines the maximum tidal flat height and opportunity for marsh development. We propose the use of the Index of Development, indicating to what extend tidal flats have space to develop. This index is not only influenced by longshore and cross-shore flow, but also (or even more) by hydraulic structures, dike realignments and channel migration. Especially the latter two strongly influence the accommodation space and thereby the maximum tidal flat height and the opportunity for marsh development. For large stretches of the Western Scheldt, the accommodation space is too small, and the majority of the tidal flats do not vertically extent to mean high water. The success of tidal flat and marsh restoration projects depends on the accommodation space.
A low-cost, easy-to-use prototype bioreactor model for the investigation of human gut microbiota: validation using a prebiotic treatment
Authors: Agrinier Anne-Laure , Pilon Geneviève , Marette André
Published: May 2024

In vitro gut models allow for the study of the impact of molecules on human gut microbiota composition and function without the implication of the host. However, current models, such as the Simulator of Human Intestinal Microbial Ecosystem (SHIME®), are expensive, time-consuming, and require specialized personnel. Homemade in vitro models that lessen these issues have limited evidence of their humanlike functionality. In this study, we present the development of a low-cost and easy-to-use bioreactor with the proven functionality of human microbiota. In our model, we evaluated the capability of replicating human gut microbiota growth and the response of the human bacterial community to a prebiotic, resistant starch, particularly resistant starch type 2 (RS2). Our bioreactor produced an environment that was stable for pH, temperature, and anaerobic conditions. The bioreactor consistently cultivated bacterial communities over a 48 h time period, replicating the composition of the gut microbiota and the associated metabolite production response to RS2, in line with prior human studies. In response to the RS2 prebiotic, we observed an increase in Bifidobacterium adolescentis and Bifidobacterium faecale and an increase in the production of the short-chain fatty acids such as acetate, propionate, and isobutyrate. Taken together, these data demonstrate that our low-cost and user-friendly prototype bioreactor model provides a favorable environment for the growth of human gut microbiota and can mimic its response to a prebiotic.