bluuebunny/crossref_metadata_2025 huggingface dataset:
Shape and Height of Human Duodenal Villi
Authors: Sayeed Sharmina , Ara Shamim , Reza Rumana , Rahman Sadia , Kashem Kanetarin , Paul Uttam Kumar
Published: April 2024

Context: Villus atrophy of the small intestine is one of the causes of chronic diarrhoea. The etiology of villus atrophy of the small intestine includes celiac disease, tropical sprue, Giardiasis etc. The knowledge of villus shape and height of duodenum in Bangladeshi people can help the gastroenterologist to diagnosis and provide better treatment.

Materials & Methods: A Cross sectional, analytical type of study was performed in the Department of Anatomy of Dhaka Medical College, Dhaka from July 2010 to June 2011 on histological slides of 19 human duodenums of Bangladeshi people. The sample was divided into 5 different age groups, group A (20-29 years), group B (30-39 years), group C (40-49 years), group D (50-59 years) and group E (60-69 years). From group A, B and C five duodenums and from group D and E two duodenums were stained with Harris’ Haematoxylin and Eosin stains. From each four parts of duodenum four paraffin blocks were prepared and best 76 slides were taken. The shape of villi in each four parts of the duodenum was observed and noted. The height of villi was measured by using a stage micrometer and ocular micrometer.

Results: The shape of the villi were broader & shorter in age group E (60-69 years). Villi were found finger sharped in all age groups. The mean difference in height of villi in different parts of duodenum between group A and B, group B and C, group B and D, group C and D, group C and E, group D and E were statistically not significant. But the difference between height of villi of the first part of the duodenum in group A and C, group A and D, group A and E, group B and E found statistically significant (p< 0.05) and the difference between height of villi of fourth part of the duodenum in group A and C, group A and D, group A and E found statistically significant (p < 0.05).­­­

Bangladesh J. Anat. 2015; 13(1) : 1-7
Ischemic and Inflammatory Ocular Adverse Events Following Different Types of Vaccination for COVID-19 and Their Incidence Analysis
Authors: Seo Eoi Jong , Jung Moon Sun , Lee Kibum , Kim Kyung Tae , Choi Mi Young
Published: April 2024

Purpose: To evaluate the ocular adverse event (OAE) and the incidence rate that can occur after the COVID-19 vaccination.Methods: Patients who visited with an ophthalmologic diagnosis within a month of COVID-19 vaccination were retrospectively analyzed. OAEs were categorized as ischemia and inflammation by their presumed pathogenesis and were compared by types of vaccine: messenger RNA (mRNA) and viral vector vaccine. The crude incidence rate was calculated using data from the Korea Disease Control and Prevention Agency.Results: Twenty-four patients with OAEs after COVID-19 vaccination were reviewed: 10 patients after mRNA and 14 after viral vector vaccine. Retinal vein occlusion (nine patients) and paralytic strabismus (four patients) were the leading diagnoses. Ischemic OAE was likely to occur after viral vector vaccines, while inflammatory OAE was closely related to mRNA vaccine (p = 0.017). The overall incidence rate of OAE was 5.8 cases per million doses: 11.5 per million doses in viral vector vaccine and 3.4 per million doses in mRNA vaccine.Conclusions: OAEs can be observed shortly after the COVID-19 vaccination, and their category was different based on the types of vaccine. The information and incidence of OAE based on the type of vaccine can help monitor patients who were administered the COVID-19 vaccine.
Exploring Indicators Impacting Gross Domestic Product: A Case of the Gulf Cooperation Council Members
Authors: Alharthi Majed
Published: April 2024

This study investigates the factors that influenced the economic growth of the six Gulf Cooperation Council (GCC) members from 1990 to 2021. The study employed statistical methods such as ordinary least squares (OLS), fixed-effects model (FEM), and generalized method of moments (GMM) regressions to arrive at its findings. The World Bank and International Monetary Fund (IMF) databases provided the data for this paper. The six Gulf Cooperation Council members are the United Arab Emirates (UAE), the Kingdom of Saudi Arabia, the State of Qatar, the Sultanate of Oman, the State of Kuwait, and the Kingdom of Bahrain. In fact, the economies of Gulf Cooperation Council members (countries) are highly dependent on the oil sector. Therefore, one of the main positive indicators of gross domestic product in the Gulf Cooperation Council countries is oil prices. In addition, inflation plays a significant and positive role in supporting the gross domestic product in the Gulf Cooperation Council area. In contrast, unemployment rates and the COVID-19 pandemic impacted the gross domestic product in the Gulf Cooperation Council region significantly and negatively. The implications of this study help policymakers make the right decisions and implement policies to increase economic growth in Gulf Cooperation Council countries. Furthermore, this study supports economists and academics in conducting their research in the same field.
PENYUSUNAN STANDAR PELAYANAN PADA DINAS PENANAMAN MODAL DAN PELAYANAN TERPADU SATU PINTU (DPMPTSP) KABUPATEN TAKALAR
Authors: Sayuti Nuraeni , Nasir Abd Wahid
Published: April 2024

Setiap negara yang ada di dunia memiliki kewajiban untuk memberikan layanan kepada masyarakatnya. Terkhusus Negara Indonesia yang memiliki luas wilayah berbentuk kepulauan menyebabkan masyarakat yang tersebar luas. Negara Indonesia memperkenalkan otonomi daerah untuk memenuhi semua kebutuhan dasar. Hal ini merupakan hak setiap warga negara untuk melaksanakan pelayanan administrasi yang diperoleh dari pemerintah sebagai penyedia pelayanan publik. Instansi Pemerintah Daerah merupakan instansi dengan tingkat keluhan terbanyak di Indonesia dan terkhusus di Sulawesi Selatan menduduki posisi keempat sebagai provinsi dengan keluhan pelayanan terbanyak. DPMPTS Kabupaten Takalar yang telah menduduki zona kuning dalam pelayanan masih menghadapi beberapa hambatan dalam pelayanan publik seperti belum adanya prosedur layanan yang dipublikasi dalam standar pelayanan sehingga perlu dilakukan pengembangan dalam standar pelayanannya. Penelitian ini menggunakan teknik wawancara, observasi dan telaah dokumen. Hasil akhir dari penelitian ini yakni standar pelayanan yang disusun berdasarkan pedoman penyusunan standar pelayanan  dari PERMENPAN RB nomor 15 tahun 2014. Karya ini merupakan solusi untuk mengatasi permasalahan yang muncul.
PERANCANGAN WEBSITE KEMITRAAN DALAM MENUNJANG PROGRAM KEMITRAAN DAN BINA LINGKUNGAN PT ANGKASA PURA I
Authors: Al Adawiah Fitrah Rabiah , Chairunisa Frida
Published: April 2024

PT Angkasa Pura I merupakan BUMN yang bergerak dalam bidang bisnis kebandarudaraan. Salah satu program wajib yang wajib dilaksanakan oleh setiap BUMN adalah Program Kemitraan dan Bina Lingkungan. Dalam pelaksanaan Program Kemitraan ini PT Angkasa Pura I cabang Sultan Hasanuddin masih secara konvensional. Berdasarkan permasalahan tesebut, penelitian ini bertujuan untuk mempermudah baik itu calon mitra binaan maupun masyarakat umum untuk mengakses informasi mengenai program ini dan juga memudahkan proses pendaftaran calon mitra binaan. Penelitian ini menggunakan metode kualiatif. Peneliti menggunakan reduksi data, penyajian data, dan penarikan kesimpulan sebagai metodologi analisis data. Data primer dan data sekunder adalah dua jenis sumber data yang digunakan dalam penelitian ini dan menggunakan membercheck sebagai validasi data. Hasil penelitian berupa rancangan website yang berguna sebagai media informasi dan media pendaftaran calon mitra binaan. Dalam proses perancangan webstie, peneliti menggunakan lima komponen sistem informasi yang diantaranya hardware, software, data, prosedur, dan manusia. Rancangan webstie yang akan memudahkan baik dari sisi mitra binaan maupun CSR officer guna pelaksanaan program kemitraan dan bina lingkungan. Adapun fitur yang terdapat pada rancangan website ini yaitu fitur pendaftaran, katalog, tentang program, pengumuman dan informasi terkait program kemitraan ini.
EVALUASI KINERJA PELAYANAN PEGAWAI PERPUSTAKAAN DI KANTOR DINAS KEARSIPAN DAN PERPUSTAKAAN PROVINSI GORONTALO
Authors: Manangin Yulmi
Published: April 2024

Penelitian ini bertujuan untuk menganalisis & mendeskripsikan kinerja pegawai dalam pelayanan perpustakaan di Kantor Dinas Kearsipan dan Perpustakaan Provinsi Gorontalo dikaji dari perspektif  produktivitas, kualitas layanan, responsifitas, responsibilitas, dan akuntabilitas. Dengan menggunakan pendekatan metode penelitian deskriptif kualitatif. Dari hasil temuan penelitian dapat disimpulkan bahwa kinerja pegawai dalam pelayanan perpustakaan di Kantor Dinas Kearsipan dan Perpustakaan Provinsi Gorontalo ditinjau dari indikator kualitas layanan dan responsibilitasnya telah berjalan dengan optimal secara menyeluruh. Meskipun demikian, kinerja pegawai ditinjau dari perspektif indikator produktivitas terdapat kekurangan dalam jumlah personil pegawai, alokasi anggaran yang terbatas, dan ketersediaan koleksi buku yang tidak mencukupi standar yang ditetapkan mengakibatkan produktivitas pegawai yang kurang efektif. Indikator responsivitas menunjukkan bahwa beberapa pegawai masih kurang responsif terhadap kebutuhan pengunjung, sehingga mempengaruhi kualitas pelayanan yang diberikan dengan maksimal. Sementara indikator akuntabilitas menunjukkan bahwa tidak semua pegawai di bidang yang sama memiliki kompetensi dalam memberikan layanan informasi dan bimbingan pemustaka kepada pengunjung, menyebabkan ketidaksempurnaan dalam kedua layanan tersebut.
A New Method for Treating Pododermatitis in Cows
Authors: Akhundzade H. , Rustamova S. , Mekhtiyev A. , Bagirov Yu.
Published: April 2024

Hoof disease in cattle has a negative impact on their productivity. There are many causes of the disease. Thus, as a result of unsatisfactory feeding and maintenance conditions, untimely implementation of preventive veterinary and sanitary measures, complications of infectious diseases, as well as improper hoof care, pododermatitis occurs in animals. There are various methods for treating claw diseases in animals. However, despite this, our new treatment method is different from other treatments. As a result of the disease, heat shock proteins (HSP70) with a molecular weight of 70 kilodaltons were obtained, which restore the damaged structure of proteins in the body and were used to treat pododermatitis in cattle and small cattle. Many scientists have conducted research and obtained good results using dihydropyrimidinase-like protein 2 (DPB2) to produce this HSP70 in the body to treat various diseases.
Potential for Scientific Collaboration between Russian Think Tanks and the Global South
Authors: Vavilova Lyudmila
Published: April 2024

Introduction. This article analyses expert survey data conducted among Russian think tank employees and is aimed to assess the current level of scientific cooperation between Russia and new partners amidst Russia's geopolitical shift, analyses the potential for such cooperation, and answers what problematic agenda can unify and provide a cumulative effect to international scientific cooperation. The article also gives the main challenges that think tanks face when establishing scientific cooperation with colleagues from the Global South. The article addresses whether think tanks cooperate with EAEU countries and the Global South, in which areas the cooperation takes place and with which countries, whether the intensity of international communications has changed in the last 2 years, and what social and political agenda is prioritised in the scientific community's work. Methods. Both general theoretical and empirical methods were used to solve the research tasks: systematisation and generalisation; an expert survey, which results allowed for the assessment of the current level of scientific cooperation and the identification of priority areas for scientific diplomacy. Results and Discussion. Based on an expert survey among leading Russian think tanks, the current level of scientific communication was determined, countries were ranked by the intensity of scientific contacts, main forms of scientific cooperation were identified, and the problematic agenda of the Russian scientific community was analysed. Conclusion. Russia has significant potential for scientific cooperation with Global South countries, based on existing experience and similar problem agendas faced by the scientific communities of Russia and the Global South.
Temporal regulation of the Mediator complex during muscle proliferation, differentiation, regeneration, aging, and disease
Authors: Kolonay Dominic W. , Sattler Kristina M. , Strawser Corinne , Rafael-Fortney Jill , Mihaylova Maria M. , Miller Katherine E. , Lepper Christoph , Baskin Kedryn K.
Published: April 2024

Genesis of skeletal muscle relies on the differentiation and fusion of mono-nucleated muscle progenitor cells into the multi-nucleated muscle fiber syncytium. The temporally-controlled cellular and morphogenetic changes underlying this process are initiated by a series of highly coordinated transcription programs. At the core, the myogenic differentiation cascade is driven by muscle-specific transcription factors, i.e., the Myogenic Regulatory Factors (MRFs). Despite extensive knowledge on the function of individual MRFs, very little is known about how they are coordinated. Ultimately, highly specific coordination of these transcription programs is critical for their masterfully timed transitions, which in turn facilitates the intricate generation of skeletal muscle fibers from a naïve pool of progenitor cells. The Mediator complex links basal transcriptional machinery and transcription factors to regulate transcription and could be the integral component that coordinates transcription factor function during muscle differentiation, growth, and maturation. In this study, we systematically deciphered the changes in Mediator complex subunit expression in skeletal muscle development, regeneration, aging, and disease. We incorporated our in vitro and in vivo experimental results with analysis of publicly available RNA-seq and single nuclei RNA-seq datasets and uncovered the regulation of Mediator subunits in different physiological and temporal contexts. Our experimental results revealed that Mediator subunit expression during myogenesis is highly dynamic. We also discovered unique temporal patterns of Mediator expression in muscle stem cells after injury and during the early regeneration period, suggesting that Mediator subunits may have unique contributions to directing muscle stem cell fate. Although we observed few changes in Mediator subunit expression in aging muscles compared to younger muscles, we uncovered extensive heterogeneity of Mediator subunit expression in dystrophic muscle nuclei, characteristic of chronic muscle degeneration and regeneration cycles. Taken together, our study provides a glimpse of the complex regulation of Mediator subunit expression in the skeletal muscle cell lineage and serves as a springboard for mechanistic studies into the function of individual Mediator subunits in skeletal muscle.
Atrial fibrillation and COVID-19: an analysis of the ambulatory database
Authors: Sizova Zhanna M. , Zakharova Valeria L. , Shindryaeva Natalya N. , Lapidus Natalia I. , Melnik Mariya V. , Shikh Evgenia V. , Grebenshchikova Ludmila Y. , Beloborodova Alexandra V. , Polovikov Ivan P.
Published: April 2024

Atrial fibrillation (AF) is the most common heart rhythm disorder in clinical practice. It worsens the quality of life of patients, leads to an increase in the mortality rate because of its association with a high risk of thromboembolic complications. The current pandemic of a new coronavirus infection, which began in March 2020, was marked by an increase in cardiovascular diseases, including an increase in the number of patients with AF. That is why it is extremely relevant to find answers to questions about the association and mutual influence of AF and coronavirus infection to reduce the risk of vascular complications. However, most research in this area has focused on hospital patients. In this study, an electronic database of outpatients with AF, including patients with a history of COVID-19 infection was analyzed in order to assess the most significant risk factors for complications.
The method for precise seismic detection of geological structures in underground coal mines and application
Authors: Xie Liujun , Wang Bo , Wang Yifan , Fang Jinwei , Zeng Linfeng , Xin Guoxu , Shen Sihongren , She Zilong
Published: April 2024

The occurrence of major accidents such as water inrush in coal mines and coal-gas outbursts is closely correlated with the unclear exploration of underground geological structures. Seismic exploration in underground coal mines is not limited by ground conditions and close to the detected target, so it has advantages with respect to the detection of underground geological structures. However, the geological structures leading to accidents are usually characterized by small size and diverse combinations, making it difficult to detect. In coal mine working faces, the use of transmission observation systems, combined with full waveform inversion methods, represents a new attempt at finely detecting geological structures. Therefore, a three-dimensional numerical model of an abnormal combination of faults and collapse columns was established, a physical simulation model of a multi-collapse column combination was built, and transmission and detection experiments were carried out. The results show that the morphology and locations of 1 fault and 4 collapse columns obtained by the FWI algorithm are consistent with the data from the actual numerical model. According to physical simulation results, the background velocity of the model after inversions and the velocity of 5 anomalies are consistent with the actual values. Field experiments were conducted in the actual underground coal mines. After verification, the average error ratios of the long axis, short axis and intersection angle of the 4 collapse columns were 0.19, 0.15 and 0.02. The detection findings and comparison results confirm the feasibility of precise detection of geological structures by transmissive seismic waves based on the FWI method.
Japanese cultural adaptation and validation of the social emotional health survey-secondary for junior high school students
Authors: Iida Junko , Takizawa Yu , Okayasu Tomoko , Furlong Michael J.
Published: April 2024

The Social Emotional Health Survey–Secondary (SEHS-S) assesses adolescents’ psychological dispositions associated with positive psychosocial development. The present study extended SEHS–S research by validating the SEHS-S with a nonwestern sample of Japanese junior high school students (Grades 7–9; N = 1,181) and investigating sex and grade level difference in Covitality and four domains of positive psychological dispositions (Belief-in-Self, Belief-in-Others, Emotional Competence, and Engaged Living). The confirmatory factor analyses supported the internal validity of the SEHS-S with a second-order model. Higher Covitality scores predicted higher life satisfaction, school connectedness, and prosocial behavior and lower emotional symptoms, conduct problems, inattention/hyperactivity, and peer problems, evidence of concurrent validity. Analyses supported the factorial invariance for different sex and grade level. Females reported higher Belief-in-Others and Emotional Competence and lower Belief-in-Self and Engaged Living than males. Grade 9 students reported higher Covitality, Belief-in-Self, Emotional Competence, and Belief-in-Others than Grade 8 students. These results support expanding the use of the SEHS–S as a universal wellness screener in Japanese junior high schools to identify the social–emotional strengths of all students. Further study needs to establish how to use the SEHS–S most effectively with Japanese junior high school students in a culturally sensitive manner.
Children’s learning for sustainability in social studies education: a case study from Taiwanese elementary school
Authors: Shih Yi-Huang
Published: April 2024

Introduction

The primary aim of social studies education is to convey knowledge about cultural and social systems while fostering inquiry, participation, practice, reflection, and innovation. Social studies education plays a pivotal role in raising awareness about various ethnic groups, societies, localities, countries, and the world at large. Furthermore, it instills in students a sense of responsibility, leading them to embrace diversity, value human rights, and promote global sustainability. The current elementary social studies curriculum in Taiwan strongly aligns with these principles and is a vehicle for sustainable development in society.

Methods

The researcher used qualitative research methods and adopted a case study design to review the pedagogical design of the elementary social studies curriculum in Taiwan as a means of sustainability education and enriching children’s cultural learning in the context of sustainability. Children’s learning related to sustainability in an elementary school was investigated, and a social studies teaching design was developed. Finally, the developed teaching approach was implemented in a classroom setting.

Results and discussion

The study yielded the following findings: (1) The social studies curriculum development in Taiwan is connected to the pulse of life, a sense of care for local communities, and cultivation of local thinking. (2) This social studies curriculum adopts a child-centered and problem-oriented approach and integrates students’ interests and the local environment into the learning process. (3) It effectively enhances students’ sustainability-related competencies and skills. These findings offer valuable insights for teachers and can enable them to shape the direction of their social studies courses and cultivate children’s concept of sustainable development for their living environment.
The multifaceted role of autophagy in skin autoimmune disorders: a guardian or culprit?
Authors: Lin Yi , Wu Xiuyi , Yang Yiwen , Wu Yue , Xiang Leihong , Zhang Chengfeng
Published: April 2024

Autophagy is a cellular process that functions to maintain intracellular homeostasis via the degradation and recycling of defective organelles or damaged proteins. This dynamic mechanism participates in various biological processes, such as the regulation of cellular differentiation, proliferation, survival, and the modulation of inflammation and immune responses. Recent evidence has demonstrated the involvement of polymorphisms in autophagy-related genes in various skin autoimmune diseases. In addition, autophagy, along with autophagy-related proteins, also contributes to homeostasis maintenance and immune regulation in the skin, which is associated with skin autoimmune disorders. This review aims to provide an overview of the multifaceted role of autophagy in skin autoimmune diseases and shed light on the potential of autophagy-targeting therapeutic strategies in dermatology.
The interleukin-4/interleukin-13 pathway in type 2 inflammation in chronic rhinosinusitis with nasal polyps
Authors: Bachert Claus , Hicks Alexandra , Gane Simon , Peters Anju T. , Gevaert Philippe , Nash Scott , Horowitz Julie E. , Sacks Harry , Jacob-Nara Juby A.
Published: April 2024

Chronic rhinosinusitis with nasal polyps (CRSwNP) is predominantly a type 2 inflammatory disease associated with type 2 (T2) cell responses and epithelial barrier, mucociliary, and olfactory dysfunction. The inflammatory cytokines interleukin (IL)-4, IL-13, and IL-5 are key mediators driving and perpetuating type 2 inflammation. The inflammatory responses driven by these cytokines include the recruitment and activation of eosinophils, basophils, mast cells, goblet cells, M2 macrophages, and B cells. The activation of these immune cells results in a range of pathologic effects including immunoglobulin E production, an increase in the number of smooth muscle cells within the nasal mucosa and a reduction in their contractility, increased deposition of fibrinogen, mucus hyperproduction, and local edema. The cytokine-driven structural changes include nasal polyp formation and nasal epithelial tissue remodeling, which perpetuate barrier dysfunction. Type 2 inflammation may also alter the availability or function of olfactory sensory neurons contributing to loss of sense of smell. Targeting these key cytokine pathways has emerged as an effective approach for the treatment of type 2 inflammatory airway diseases, and a number of biologic agents are now available or in development for CRSwNP. In this review, we provide an overview of the inflammatory pathways involved in CRSwNP and describe how targeting key drivers of type 2 inflammation is an effective therapeutic option for patients.
Self-sufficient primary natural killer cells engineered to express T cell receptors and interleukin-15 exhibit improved effector function and persistence
Authors: van Hees Els P. , Morton Laura T. , Remst Dennis F. G. , Wouters Anne K. , Van den Eynde Astrid , Falkenburg J. H. Frederik , Heemskerk Mirjam H.M.
Published: April 2024

Background

NK cells can be genetically engineered to express a transgenic T-cell receptor (TCR). This approach offers an alternative strategy to target heterogenous tumors, as NK:TCR cells can eradicate both tumor cells with high expression of HLA class I and antigen of interest or HLA class I negative tumors. Expansion and survival of NK cells relies on the presence of IL-15. Therefore, autonomous production of IL-15 by NK:TCR cells might improve functional persistence of NK cells. Here we present an optimized NK:TCR product harnessed with a construct encoding for soluble IL-15 (NK:TCR/IL-15), to support their proliferation, persistence and cytotoxic capabilities.

Methods

Expression of tumor-specific TCRs in peripheral blood derived NK-cells was achieved following retroviral transduction. NK:TCR/IL-15 cells were compared with NK:TCR cells for autonomous cytokine production, proliferation and survival. NK:BOB1-TCR/IL-15 cells, expressing a HLA-B*07:02-restricted TCR against BOB1, a B-cell lineage specific transcription factor highly expressed in all B-cell malignancies, were compared with control NK:BOB1-TCR and NK:CMV-TCR/IL-15 cells for effector function against TCR antigen positive malignant B-cell lines in vitro and in vivo.

Results

Viral incorporation of the interleukin-15 gene into engineered NK:TCR cells was feasible and high expression of the TCR was maintained, resulting in pure NK:TCR/IL-15 cell products generated from peripheral blood of multiple donors. Self-sufficient secretion of IL-15 by NK:TCR cells enables engineered NK cells to proliferate in vitro without addition of extra cytokines. NK:TCR/IL-15 demonstrated a marked enhancement of TCR-mediated cytotoxicity as well as enhanced NK-mediated cytotoxicity resulting in improved persistence and performance of NK:BOB1-TCR/IL-15 cells in an orthotopic multiple myeloma mouse model. However, in contrast to prolonged anti-tumor reactivity by NK:BOB1-TCR/IL-15, we observed in one of the experiments an accumulation of NK:BOB1-TCR/IL-15 cells in several organs of treated mice, leading to unexpected death 30 days post-NK infusion.

Conclusion

This study showed that NK:TCR/IL-15 cells secrete low levels of IL-15 and can proliferate in an environment lacking cytokines. Repeated in vitro and in vivo experiments confirmed the effectiveness and target specificity of our product, in which addition of IL-15 supports TCR- and NK-mediated cytotoxicity.
PCBP1 interacts with the HTLV-1 Tax oncoprotein to potentiate NF-κB activation
Authors: Su Rui , Kang Xue , Niu Yifan , Zhao Tiesuo , Wang Hui
Published: April 2024

Human T-cell leukemia virus type 1 (HTLV-1) is the etiological agent of adult T-cell leukemia/lymphoma. The HTLV-1 Tax constitutively activates nuclear factor-κB (NF-κB) to promote the survival and transformation of HTLV-1-infected T cells. Despite extensive study of Tax, how Tax interacts with host factors to regulate NF-κB activation and HTLV-1–driven cell proliferation is not entirely clear. Here, we showed that overexpression of Poly (rC)–binding protein 1 (PCBP1) promoted Tax-mediated IκB kinase (IKK)–NF-κB signaling activation, whereas knockdown of PCBP1 attenuated Tax-dependent IKK–NF-κB activation. However, Tax activation of HTLV-1 long terminal repeat was unaffected by PCBP1. Furthermore, depletion of PCBP1 led to apoptosis and reduced proliferation of HTLV-1–transformed cells. Mechanistically, PCBP1 interacted and co-localized with Tax in the cytoplasm, and PCBP1 KH3 domain was indispensable for the interaction between PCBP1 and Tax. Moreover, PCBP1 facilitated the assembly of Tax/IKK complex. Collectively, our results demonstrated that PCBP1 may exert an essential effect in Tax/IKK complex combination and subsequent NF-κB activation, which provides a novel insight into the pathogenetic mechanisms of HTLV-1.
Tissue adaptation of CD4 T lymphocytes in homeostasis and cancer
Authors: Pereira Marina V. A. , Galvani Rômulo G. , Gonçalves-Silva Triciana , de Vasconcelo Zilton Farias Meira , Bonomo Adriana
Published: April 2024

The immune system is traditionally classified as a defense system that can discriminate between self and non-self or dangerous and non-dangerous situations, unleashing a tolerogenic reaction or immune response. These activities are mainly coordinated by the interaction between innate and adaptive cells that act together to eliminate harmful stimuli and keep tissue healthy. However, healthy tissue is not always the end point of an immune response. Much evidence has been accumulated over the years, showing that the immune system has complex, diversified, and integrated functions that converge to maintaining tissue homeostasis, even in the absence of aggression, interacting with the tissue cells and allowing the functional maintenance of that tissue. One of the main cells known for their function in helping the immune response through the production of cytokines is CD4+ T lymphocytes. The cytokines produced by the different subtypes act not only on immune cells but also on tissue cells. Considering that tissues have specific mediators in their architecture, it is plausible that the presence and frequency of CD4+ T lymphocytes of specific subtypes (Th1, Th2, Th17, and others) maintain tissue homeostasis. In situations where homeostasis is disrupted, such as infections, allergies, inflammatory processes, and cancer, local CD4+ T lymphocytes respond to this disruption and, as in the healthy tissue, towards the equilibrium of tissue dynamics. CD4+ T lymphocytes can be manipulated by tumor cells to promote tumor development and metastasis, making them a prognostic factor in various types of cancer. Therefore, understanding the function of tissue-specific CD4+ T lymphocytes is essential in developing new strategies for treating tissue-specific diseases, as occurs in cancer. In this context, this article reviews the evidence for this hypothesis regarding the phenotypes and functions of CD4+ T lymphocytes and compares their contribution to maintaining tissue homeostasis in different organs in a steady state and during tumor progression.
Development of polymorphic simple sequences repeats markers from whole gene resequencing data comparison of 68 Oncorhynchus mykiss
Authors: Ma Haibing , Huang Tianqing , Liu Enhui , Wang Gaochao , Gu Wei , Xu Gefeng
Published: April 2024

Rainbow trout (Oncorhynchus mykiss) is a significant cold-water fish farmed in China. Currently, most molecular marker-assisted breeding applications in rainbow trout rely on SSR markers. Although many rainbow trout SSR markers have been developed, methods for mining many polymorphic SSR markers from the genome and identifying them efficiently and rapidly are still lacking. For this reason, this study used in silico simulation method to rapidly develop a large number of polymorphic SSR markers quickly. A total of 354,613 SSR loci with two to six nucleotide repeat motifs were mined from 32 chromosomes of the rainbow trout reference genome using GMATA. The chromosome sequences of the reference genome were then aligned to the whole genome sequencing data (10×) of 68 rainbow trout samples. In silico genotyping was performed using the HipSTR programme to compare and count the variation in the number of repeats of the motifs of the SSR loci in the samples. The loci with high deletion rates and monomorphism were discarded, while those with more than one non-reference allele were kept. The final set of polymorphic SSR loci screened was 78,828. Finally, 4,821 SSR loci were selected with more than 3 alleles and no deletion in all rainbow trout samples and were physically mapped. The average polymorphic information content of these loci was 0.692, indicating high levels of polymorphism. These SSRs were utilized to analyse the genetic diversity and population structure of the 68 rainbow trout samples. The results showed that these 68 samples were divided into two groups. These newly discovered polymorphic SSR markers will provide valuable information for evaluating the construction of rainbow trout family lines for genetic diversity and improvement.
Efficient design of sandwich panels with cellular truss cores and large phononic band gaps using surrogate modeling and global optimization
Authors: Meruane Viviana , Puiggros Ignacio , Fernandez Ruben , Ruiz Rafael O.
Published: April 2024

Recent advancements in additive manufacturing technologies and topology optimization techniques have catalyzed a transformative shift in the design of architected materials, enabling increasingly complex and customized configurations. This study delves into the realm of engineered cellular materials, spotlighting their capacity to modulate the propagation of mechanical waves through the strategic creation of phononic band gaps. Focusing on the design of sandwich panels with cellular truss cores, we aim to harness these band gaps to achieve pronounced wave suppression within specific frequency ranges. Our methodology combines surrogate modeling with a comprehensive global optimization strategy, employing three machine learning algorithms—k-Nearest Neighbors (kNN), Random Forest Regression (RFR), and Artificial Neural Networks (ANN)—to construct predictive models from parameterized finite element (FE) analyses. These models, once trained, are integrated with Particle Swarm Optimization (PSO) to refine the panel designs. This approach not only facilitates the discovery of optimal truss core configurations for targeted phononic band gaps but also showcases a marked increase in computational efficiency over traditional optimization methods, particularly in the context of designing for diverse target frequencies.
Experimental investigation of tungsten–nickel–iron alloy, W95Ni3.5Fe1.5, compared to copper monolithic bullets
Authors: Abhishek T. , Sundeep Dola , Chandrasekhara Sastry C. , Eswaramoorthy K. V. , Kesireddy Gagan Chaitanya , Siva Reddy Bobbili Veera , Verma Rakesh Kumar , Salunkhe Sachin , Cep Robert , Abouel Nasr Emad
Published: April 2024

Introduction:

The demand for improved small arms ammunition has led to exploring advanced materials and manufacturing techniques. This research investigates the machining characteristics of CM and WNF alloy bullets, aiming to enhance ballistic performance and durability.

Methods:

Bullet profile-making trials were conducted to evaluate the impact of machining parameters such as cutting speed and feed. The study also considered variables including surface roughness, cutting temperature, and hardness, alongside a detailed morphological analysis, The evaluation utilized an orthogonal array and MCDM approach, incorporating the TOPSIS method for decision-making processes.

Results:

The findings reveal that WNF alloy bullets exhibit 3.01% to 27.95% lower machining temperatures, 24.88%-61.85% reduced surface roughness, and 19.45%-34% higher microhardness compared to CM bullets. Moreover, CM bullets demonstrated higher machining temperatures, resulting in 47.53% increased tool flank wear. WNF bullets showed a 24.89% reduction in crater wear and a 38.23% decrease in compressive residual stress in bullet profiles, indicating superior machining performance.

Discussion:

The superior machining performance of WNF alloy bullets suggests their potential to improve the ballistic performance and durability of small arms ammunition. The reduced tool wear and favorable machining parameters highlight WNF alloy's advantages for military and defense applications. A ballistic impact analysis using a finite element method (FEM) model in Abaqus software further supports the potential of WNF alloy bullets, providing a solid foundation for future advancements in bullet manufacturing technologies.
Efficacy and safety of the Ayurvedic herbal preparation Maharishi Amrit Kalash: a systematic review of randomized controlled trials
Authors: Koch Anna K. , Patel Manish , Gupta Shivenarain , Wullenkord Ricarda , Jeitler Michael , Kessler Christian S.
Published: April 2024

Background

Maharishi Amrit Kalash (MAK) 4 and 5 are Ayurvedic herbal nutritional supplements that are believed to have beneficial effects on overall health and wellbeing. This study aimed to systematically review all available randomized controlled trials (RCTs) investigating the clinical effects and safety of MAK.

Methods

We included RCTs on therapy, health promotion, and prevention for patients and healthy volunteers of all ages. We systematically searched MEDLINE (via PubMed), EMBASE (via Ovid), the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library), DHARA, Clinicaltrials.gov, the World Health Organization (WHO) International Clinical Trials Registry Platform, and Google Scholar from inception through 7 May 2023, with no time or language restrictions. The risk of bias was assessed using the Cochrane Risk of Bias Tool version 1. The protocol was registered with PROSPERO before conducting the review (CRD42023421655).

Results

Three RCTs with 418 study participants were included. Two studies were on breast cancer patients and one on healthy adults. The two studies on cancer evaluated the efficacy of MAK in reducing the side effects of chemotherapy in women with breast cancer. The study on healthy adults evaluated whether MAK has an effect on an age-related alertness task as an indicator of cognitive aging. Both studies on breast cancer patients found beneficial effects on performance status, anorexia, vomiting, and body weight. One study reported positive effects regarding stomatitis. Regarding visual alertness, results showed that individuals who received MAK improved in performance. None of the three included studies reported adverse events. The risk of bias was mixed. Due to the small number and heterogeneity of the RCTs, no meta-analysis could be performed.

Conclusion

There is evidence that MAK may have supportive effects in chemotherapeutic treatments for breast cancer patients and for healthy individuals regarding visual discrimination. However, it is difficult to verify treatment effects due to the small number of RCTs and the mixed risk of bias. Furthermore, none of the included studies recorded adverse events. Therefore, further high-quality studies are warranted to confirm the potential health benefits of MAK and to determine its optimal dosage and duration of use.

Systematic review registration

PROSPERO, CRD42023421655.
Diagnostic performance of rapid antigen testing for SARS-CoV-2: the COVid-19 AntiGen (COVAG) extension study
Authors: Wertenauer Christoph , Dressel Alexander , Wieland Eberhard , Wertenauer Hans-Jörg , Braitmaier Helmine , Straub Anna , Helfert Stefan , Lützner Nicolas , März Winfried
Published: April 2024

Background

This study is the extension of the COVAG study. We compared two RATs, the Panbio COVID-19 Ag Rapid Test (Abbott) and the SD Biosensor Q SARS-CoV-2 Rapid Antigen Test (Roche), against RT-PCR on the foil of new variants.

Methods

We included 888 all-comers at a diagnostic center between October 20, 2021, and March 18, 2022. RT-PCR-positive samples with a Ct value ≤32 were examined for SARS-CoV-2 variants.

Findings

The sensitivity of the Abbott-RAT and Roche-RAT were 65 and 67%, respectively. For both RATs, lower Ct values were significantly correlated with higher sensitivity. For samples with Ct values ≤25, the sensitivities of the Roche-RAT and of the Abbott-RAT were 96 and 95%, for Ct values 25–30 both were 19%, and for Ct values ≥30 they were 6 and 2%, respectively. The RATs had substantially higher sensitivities in symptomatic than asymptomatic participants (76, 77%, vs. 29, 31%, for Abbott-RAT, Roche-RAT, respectively) and in participants referred to testing by their primary care physician (84, 85%) compared to participants who sought testing due to referral by the health department (55, 58%) or a warning by the Corona-Warn-App (49, 49%). In persons with self-reported previous COVID-19 sensitivities were markedly lower than in patients without previous COVID-19: 27% vs. 75% for Roche-RAT and 27% vs. 73% for Abbott-RAT. We did not find significant correlation between vaccination status and sensitivity. The Omicron variant was detected with a sensitivity of 94 and 92%, the delta variant with a sensitivity of 80 and 80% for Abbott-RAT and Roche-RAT, respectively. This difference is attributable to the lower Ct values of the Omicron samples compared to the Delta samples. When adjusted for the Ct value, a multivariate logistic regression did not show a significant difference between Omicron and Delta. In terms of sensitivity, we found no significant difference between the wild-type and the Omicron and Delta variants, but a significantly lower sensitivity to the alpha variant compared to the other variants.

The specificities were > 99% overall.
Endocrine system-related adverse events associated with PD-1/PD-L1 inhibitors: data mining from the FDA adverse event reporting system
Authors: Shi Hongxia , He Yunhua , Dan Siyuan , Yang Lin , Wang Jing , Chen Li , Chen Zelian
Published: April 2024

Background

Various immune checkpoint inhibitors, such as programmed cell death protein-1 (PD-1) and its ligand (PD-L1), have been approved for use, but they have side effects on the endocrine glands.

Methods

Adverse event reports related to PD-1/PD-L1 inhibitors from the FDA Adverse Event Reporting System (FAERS) from the first quarter of 2019 to the first quarter of 2023 were extracted, and the reported Odds ratio methods (ROR method) and comprehensive standard methods (MHRA methods) were used for data mining and analysis.

Results

A total of 5,322 reports (accounts for 6.68% of the total reports)of AEs in endocrine system were collected, including 1852 of pabolizumab (34.80%), 2,326 of navuliumab (43.71%), 54 of cimipriliumab (1.01%), 800 of atilizumab (15.03%), 222 of duvariumab (4.17%) and 68 of averumab (1.28%). Endocrine system-related AEs were mainly present in men (excluding those treated with pembrolizumab) aged ≥65 years. The ratio of AEs components in the endocrine system for the six drugs was approximately 3–8%. The main endocrine glands involved in AEs were the thyroid (pembrolizumab), pituitary and adrenal (nivolumab), adrenal (cemiplimab, atezolizumab, and avelumab), and thyroid (durvalumab). Most patients experienced AEs between 30 and 365 (mean, 117) days,the median time was 61d. AEs resulted in prolonged hospitalization in >40% and death in >10% of cases after administration of pembrolizumab, nivolumab, or durvalumab.

Conclusion

Men aged ≥65 years should be concerned about endocrine-related AEs. There was a lengthy interval between the use of PD-1/PD-L1 inhibitors and endocrine system-related AEs, but the outcome was serious. Special attention should be given to endocrine system-related AEs when using pembrolizumab, nivolumab, or durvalumab.
SQUID magnetoneurography: an old-fashioned yet new tool for noninvasive functional imaging of spinal cords and peripheral nerves
Authors: Adachi Yoshiaki , Kawabata Shigenori
Published: April 2024

We are engaged in the development and clinical application of a neural magnetic field measurement system that utilizes biomagnetic measurements to observe the activity of the spinal cord and peripheral nerves. Unlike conventional surface potential measurements, biomagnetic measurements are not affected by the conductivity distribution within the body, making them less influenced by the anatomical structure of body tissues. Consequently, functional testing using biomagnetic measurements can achieve higher spatial resolution compared to surface potential measurements. The neural magnetic field measurement, referred to as magnetoneurography, takes advantage of these benefits to enable functional testing of the spinal cord and peripheral nerves, while maintaining high spatial resolution and noninvasiveness. Our magnetoneurograph system is based on superconducting quantum interference devices (SQUIDs) similar to the conventional biomagnetic measurement systems. Various design considerations have been incorporated into the SQUID sensor array structure and signal processing software to make it suitable for detecting neural signal propagation along spinal cord and peripheral nerve. The technical validation of this system began in 1999 with a 3-channel SQUID system. Over the course of more than 20 years, we have continued technological development through medical-engineering collaboration, and in the latest prototype released in 2020, neural function imaging of the spinal cord and peripheral nerves, which could also be applied for the diagnosis of neurological disorders, has become possible. This paper provides an overview of the technical aspects of the magnetoneurograph system, covering the measurement hardware and software perspectives for providing diagnostic information, and its applications. Additionally, we discuss the integration with a helium recondensing system, which is a key factor in reducing running costs and achieving practicality in hospitals.
To analyze the relationship between gut microbiota, metabolites and migraine: a two-sample Mendelian randomization study
Authors: Qu Kang , Li Ming-Xi , Gan Lin , Cui Zi-Ting , Li Jia-Jia , Yang Rong , Dong Ming
Published: April 2024

Background

It has been suggested in several observational studies that migraines are associated with the gut microbiota. It remains unclear, however, how the gut microbiota and migraines are causally related.

Methods

We performed a bidirectional two-sample mendelian randomization study. Genome-wide association study (GWAS) summary statistics for the gut microbiota were obtained from the MiBioGen consortium (n = 18,340) and the Dutch Microbiota Project (n = 7,738). Pooled GWAS data for plasma metabolites were obtained from four different human metabolomics studies. GWAS summary data for migraine (cases = 48,975; controls = 450,381) were sourced from the International Headache Genetics Consortium. We used inverse-variance weighting as the primary analysis. Multiple sensitivity analyses were performed to ensure the robustness of the estimated results. We also conducted reverse mendelian randomization when a causal relationship between exposure and migraine was found.

Results

LachnospiraceaeUCG001 (OR = 1.12, 95% CI: 1.05–1.20) was a risk factor for migraine. Blautia (OR = 0.93, 95% CI: 0.88–0.99), Eubacterium (nodatum group; OR = 0.94, 95% CI: 0.90–0.98), and Bacteroides fragilis (OR = 0.97, 95% CI: 0.94–1.00) may have a suggestive association with a lower migraine risk. Functional pathways of methionine synthesis (OR = 0.89, 95% CI: 0.83–0.95) associated with microbiota abundance and plasma hydrocinnamate (OR = 0.85, 95% CI: 0.73–1.00), which are downstream metabolites of Blautia and Bacteroides fragilis, respectively, may also be associated with lower migraine risk. No causal association between migraine and the gut microbiota or metabolites was found in reverse mendelian randomization analysis. Both significant horizontal pleiotropy and significant heterogeneity were not clearly identified.

Conclusion

This Mendelian randomization analysis showed that LachnospiraceaeUCG001 was associated with an increased risk of migraine, while some bacteria in the gut microbiota may reduce migraine risk. These findings provide a reference for a deeper comprehension of the role of the gut–brain axis in migraine as well as possible targets for treatment interventions.