bluuebunny/crossref_metadata_2025 huggingface dataset:
The impact of changes in scale configuration on the gangsa instrument of the Bhavana Ethnic Mataram as an Indonesian music innovation
Authors: Agus Mega Saputra Gde , Suryadmaja Galih , Puspita Ningsih Dewi
Published: July 2024

The use of traditional instruments in Bhavana Ethnic's musical compositions is one of the innovative aspects of Indonesian music offered. This Indonesian authenticity emerges through the characteristic sounds and drumming patterns that are presented in composing the harmony of the musical works. The innovation in question is the group's efforts to change the composition and configuration of the notes and scales on the gangsa  instrument. An instrument adopted from the Balinese gamelan ensemble. Making adjustments to the reality of traditional music in the creative process. The aim of this research is to explain the importance of innovation in the creative (music) process. Seeing how the Bhavana Ethnic group's perspective understands the reality of tradition in gangsa  instruments, the idea emerged to change the composition and configuration of the notes in an effort to meet the aesthetic needs in the work. This research was conducted using qualitative methods. Researchers as the main instrument to understand the impact of changes in the tone composition and scale configuration of bronze instruments in natural conditions. The research results are that changes in aspects of the instrument's pitch configuration have implications for changes in the number of tones, pitch range, rules, melodic pattern system, and instrument function in the ensemble. The result of the musical innovation process carried out is that there is a tendency for interval patterns in the selection of tones in each musical creation process. The tendencies for interval patterns in question include the 2- ½ -1- 2 -½ pattern on the major scale, and 1-1- 1½ -1 -1½ on the minor scale.
Javanese wayang system of signs in batik logo and its role in creating visual brand identity
Authors: Pangestu Melinia Enggal , Murtono Taufik , Kurniawan Rendya Adi
Published: July 2024

Batik was one of Indonesia's cultural heritages that had been recognized worldwide. Batik in Indonesia was diverse in terms of products and producing regions. One of the Batik-producing areas in Indonesia was Masaran in Sragen Regency. Batik producers in Kliwonan had their business names complete with logos as trademarks. One form of this was using names and images of wayang characters in trademarks, which had been done for a long time. This study analyzed four Batik company logos in Kliwonan Village, Masaran District, Sragen Regency, which were found using images of puppet figures, namely Janoko Kembar Batik, Sadewa Batik, Dewi Brotojoyo Batik, and Dewa Rama Batik. The research phase begins with data collection in the form of visual logos and literature related to the meaning of puppet figures. Data analysis is carried out by identifying the visual elements of the logo, including colors, illustrative images, typography, and layout as the first sign system (denotation). The denotational data is then read using a second sign system (connotation), which involves analyzing the characters of the puppet characters. The character of the puppet character that is understood is then discussed in a cultural context (myth). Roland Barthes' semiotic analysis is used to describe signs through first-order meaning (denotative), second-order meaning (connotative), and interpretation of meaning in cultural contexts (myth) The reading of the logo sign system was confirmed by interviews with the Batik entrepreneurs. The research results described the system of signs in denotation, connotation, and mythical meaning in the logos studied, which was in line with the application of visual elements and design principles. This research concluded that wayang could be used to discover self-identity for brand owners. The visual formation of brand identity in this study occurs through the selection of illustrations of images, colors, typography, and personal layout by brand owners. Illustrations of puppet characters are selected from the types of knights and princesses that give good character meaning. The selection of knight and princess characters can be a logo design model that uses puppet characters.
Los museos universitarios como guardianes del patrimonio académico
Authors: Martínez González Andrea
Published: July 2024

Texto para el debate “Universidad, museo y patrimonio ¿un ámbito cultural inexplorado o aún infravalorado?”. Los museos universitarios son espacios fundamentales para la preservación y difusión del conocimiento cultural, por ello es importante conocer sus aspectos clave o las tecnologías que los mantienen activos. En este breve texto se pretende mostrar una aproximación a los museos universitarios y su valor.
Peningkatkan Kesejahteraan Mental dan Pola Hidup Sehat Lansia di Panti Werdha X
Authors: Purnomo Hari , A.P. Rezki Amelia Aminuddin
Published: July 2024

Decreased cognitive abilities and physical and motor activities are often experienced by the elderly. This research aims to explore the effectiveness of a multidimensional intervention program, which includes healthy lifestyle patterns, cognitive ergonomics training, and mental health education in improving older adults' physical and mental well-being at Nursing Home X. The research method used was a survey involving older adults as respondents. The research results showed a significant positive impact on the well-being of the elderly, namely an 80% increase in sleep quality, a reduction in stress and depression levels by 30% and 20%, respectively, an increase in cognitive abilities by 65%, and an increase in social relationships by 70%. Overall, these programs effectively improve seniors' physical and mental well-being at Nursing Home X, providing a solid foundation for improving healthcare services for seniors in the future.ABSTRAKPenurunan kemampuan kognitif, fisik dan aktivitas motorik seringkali dialami oleh lansia. Penelitian ini bertujuan untuk mengeksplorasi efektivitas program intervensi multidimensi yang mencakup pola hidup sehat, pelatihan ergonomi kognitif, dan penyuluhan kesehatan mental dalam meningkatkan kesejahteraan fisik dan mental lansia di Panti Werdha X. Metode penelitian yang digunakan adalah survei dengan melibatkan lansia sebagai responden. Hasil penelitian menunjukkan dampak positif yang signifikan bagi kesejahteraan lansia yaitu terjadi peningkatan 80% kualitas tidur, penurunan tingkat stress dan depresi masing-masing sebesar 30% dan 20%, peningkatan kemampuan koginitif sebesar 65%, dan peningkatan hubungan sosial sebesar 70%. Secara keseluruhan, program-program ini efektif dalam peningkatan kesejahteraan fisik dan mental lansia di Panti Werdha X, memberikan dasar yang kuat bagi peningkatan layanan perawatan kesehatan bagi lansia di masa mendatang.
Pengolahan Sampah Plastik Menjadi Eco Paving Block di Desa Pekauman Bondowoso
Authors: Juwita Oktalia , Aprilianti Noviana Dwi , Wibowo Krisna , Najib Muhammad Fikri
Published: July 2024

PPM activities with the theme Caring for the Environment, located in Pekauman Village, aim to increase community awareness of the environment and entrepreneurial spirit. This activity was carried out with the aim of helping the community find solutions, one of which is managing waste and plastic waste. Observations began by looking at data via the Ministry of Village data website, surveys and interviews in Pekauman Village. The people of Pekauman Village still do not care and have minimal waste management, resulting in large piles of waste. This has negative consequences for health and also environmental sustainability, including residential areas, rivers and rice fields. The method used in this activity is providing counseling, assistance and training about the process of collecting plastic waste and managing plastic waste. Making eco paving blocks is an effort to utilize plastic waste in Pekauman Village. This effort received a very good response and enthusiasm from the community and village officials. The results of this activity can be seen from the awareness of the people of Pekauman Village who are starting to actively participate in the waste bank and sort plastic waste to be processed into eco paving blocks. The selling price of plastic waste is around Rp. 10,000/kg and the selling price of eco paving blocks is around Rp. 70,000 to Rp. 80,000 per m2. This activity will be followed up and continued by village youth and village officials.ABSTRAKKegiatan PPM dengan tematik Peduli Lingkungan yang berlokasi di Desa Pekauman bertujuan untuk meningkatkan kepeduliaan masyarakat terhadap lingkungan dan jiwa kewirausahaan. Kegiatan tersebut dilakukan dengan tujuan membantu masyarakat dalam menemukan solusi, salah satunya yaitu pengelolaan sampah dan limbah plastik. Observasi diawali dengan melihat data melalui web data kemendesa, survei, dan wawancara di Desa Pekauman. Masyarakat Desa Pekauman masih kurang peduli dan minim pengelolaan sampah sehingga banyak timbunan limbah sampah. Hal tersebut memiliki konsekuensi negatif terhadap kesehatan dan juga kelestarian lingkungan baik lingkungan permukiman, sungai dan persawahan. Metode yang digunakan dalam kegiatan ini yaitu memberikan penyuluhan, pendampingan dan pelatihan tentang proses pengumpulan limbah plastik serta pengelolaan limbah plastik. Pembuatan eco paving blok merupakan upaya pemanfaatan limbah plastik di Desa Pekauman. Upaya tersebut mendapatkan respon dan antusias yang sangat baik dari masyarakat serta perangkat desa. Hasil dari kegiatan ini dapat dilihat dari kesadaran masyarakat Desa Pekauman yang mulai aktif ikut serta pada bank sampah dan memilah sampah plastik untuk diolah menjadi eco paving block. Harga jual sampah plastik adalah sekitar Rp. 10.000/kg dan harga jual eco paving block aadalah sekitar Rp. 70.000 s/d Rp. 80.000 per m2. Kegiatan ini akan ditindaklanjuti dan diteruskan oleh pemuda desa dan juga perangkat desa.
Changes in Astigmatism after Surgery in Pediatric Patients with Limbal Dermoid
Authors: Kim Si Young , Lee Ju-Yeun , Kwon Ji-Won
Published: July 2024

Purpose: To analyze changes in astigmatism and visual acuity in pediatric patients with limbal dermoid before and after surgery.Methods: Twenty-five pediatric patients (7 male, 18 female) diagnosed with limbal dermoid from March 2018 to February 2022 were included. We analyzed best corrected visual acuity and astigmatism using cycloplegic refraction, automated keratometry, and topography before and after surgery.Results: In cycloplegic refraction and automated keratometry, postoperative astigmatism did not decrease significantly (p = 0.53 and p = 0.38, respectively). Topography showed a significant decrease in corneal astigmatism from 3.6 ± 2.8 diopters (D) to 2.7 ± 1.8 D (p < 0.05) and in irregular astigmatism from 3.7 ± 2.2 D to 2.5 ± 1.5 D (p < 0.001). Significant decreases were observed in the corneal irregularity index from 0.14 ± 0.10 mm to 0.08 ± 0.47 mm (p < 0.001) and in the index of surface variance from 60.56 ± 41.02 to 35.00 ± 16.00 (p < 0.001). There was a statistically significant improvement in best corrected visual acuity from logarithm of minimal angle of resolution (logMAR) 0.18 to logMAR 0.07 (p < 0.05).Conclusions: Surgery for limbal dermoid significantly reduced irregular astigmatism and improved best-corrected visual acuity. It is suggested that achieving visual development through active amblyopia treatment after surgery is important.
Orbital Myositis Leading to Compressive Optic Neuropathy after COVID-19 mRNA Vaccination: A Case Report
Authors: Choi Ji Youn , Woo Kyung In
Published: July 2024

Purpose: We present a case of bilateral compressive optic neuropathy secondary to orbital myositis after COVID-19 messenger ribonucleic acid (mRNA) vaccination.Case summary: A 51-year-old man developed acute bilateral visual loss and painful ophthalmoplegia shortly after receiving the second dose of the BNT162b2 COVID-19 mRNA vaccine (Comirnaty, Pfizer®, New York, NY, USA). His best-corrected visual acuity was counting fingers at 30 cm and 50 cm in the right and left eyes, respectively. Bilateral eyelid swelling, erythema, conjunctival injection, and color vision deficit were observed. Orbital magnetic resonance imaging revealed diffuse enhancement and hypertrophy of the bilateral extraocular muscles. The patient had no significant ophthalmic history and systemic work-up revealed no evidence of underlying inflammatory disease. Based on the clinical presentation and imaging findings, he was tentatively diagnosed with bilateral compressive optic neuropathy secondary to orbital myositis after COVID-19 mRNA vaccination. He was treated with intravenous corticosteroids for 3 days followed by low-dose oral corticosteroids. One month later, his visual acuity and color vision improved; moreover, the inflammatory signs in the eyelids, conjunctiva, and extraocular muscles resolved. However, after developing COVID-19, he experienced a recurrence of symptoms and was retreated with corticosteroids. Radiotherapy was administered to address persistent color vision deficit in the right eye and recurrent eyelid edema, erythema, and conjunctival injection. This treatment effectively resolved all inflammatory signs and color vision deficits, without signs of recurrence.Conclusions: Acute fulminant orbital myositis with associated compressive optic neuropathy can manifest after COVID-19 mRNA vaccination and onset of COVID-19. Anti-inflammatory treatment measures can effectively control these manifestations.
Perbedaan Pengaruh Pursed Lips Breathing dan Diaphragmatic Breathing Terhadap Penurunan Sesak Napas Penyakit Paru Obstruktif Kronik
Authors: Puspita Mita , Khotimah Siti
Published: July 2024

Individu yang mengalami kesulitan dalam pernapasan atau mengalami sesak napas akan merasakan adanya ketidaknyamanan dalam melakukan aktivitas sehingga individu tersebut akan membatasi kegiatan. Mekanisme sesak napas pada PPOK karena meningkatnya ventilasi saluran pernapasan, obstruksi jalan napas, hipoksemia, produksi sputum berlebih, gangguan otot dinding pernapasan, peradangan akut jaringan paru, dan menurunnya kemampuan fungsi otot-otot pernapasan. Subjek perlakuan sebanyak 32 responden, dengan kelompok PLB sebanyak 16 responden dan kelompok DB sebanyak 16 responden.  Tujuan penelitian ini untuk mengetahui perbedaan pengaruh pursed lips breathing dan diaphragmatic breathing terhadap penurunan sesak napas pasien penyakit paru obstruktif kronik (PPOK). Penelitian ini menggunakan metode quasi experimental dengan pre test and post test two design group dimana kelompok perlakuan pursed lips breathing diberikan dosis 6 sesi latihan dalam 20 menit. Dalam 1 sesi latihan dilakukan 8 kali pengulangan dengan waktu istirahat selama 2 menit dan kelompok perlakuan diaphragmatic breathing diberikan 5 sesi latihan dalam 20 menit. Dalam 1 sesi latihan dilakukan 8 kali pengulangan dengan waktu istirahat selama 2 menit, masing-masing kelompok perlakuan diberikan latihan sebanyak 2x dalam seminggu selama 4 minggu. Alat ukur sesak napas menggunakan Visual Analog Scale (VAS). Hasil penelitian menggunakan uji independent sample t-test nilai p = 0,505 (p>0,05) menunjukkan bahwa tidak ada perbedaan pengaruh pursed lips breathing dan diaphragmatic breathing terhadap penurunan sesak napas pasien PPOK.
Pemberian Ultrasound Terapi dan Mobilisasi Saraf dalam Mengurangi Nyeri dan Meningkatkan Lingkup Gerak Sendi pada pasien carpal tunnel syndrome
Authors: Mamuaja Filly , Posumah Margaretha Eugenie
Published: July 2024

Carpal tunnel syndrome (CTS) atau sindrom terowongan karpal merupakan penyakit yang muncul dikarenakan terjepitnya saraf medianus di dalam terowongan karpal yang terdapat pada sendi pergelangan tangan. CTS menimbulkan rasa tidak nyaman hingga menyebabkan nyeri yang terasa pada pergelangan tangan. Gejala yang ditimbulkan berupa rasa kram, rasa baal, rasa nyeri bahkan sampai hilang rasa, hingga dapat menyebabkan atrofi otot. Gangguan aktivitas yang bisa terjadi akibat CTS antara lain pasien akan kesulitan dalam melakukan aktivitas pada pergelangan tangan berupa menggenggam, mengetik dan atau melakukan pekerjaan yang berulang pada area tangan. Penerapan ultrasound terapi dan mobilisasi saraf bertujuan mengurangi nyeri dan meningkatkan lingkup gerak sendi pada pasien CTS. Metode penelitian melalui studi kasus pada seorang responden berumur 55 tahun dengan keluhan nyeri dan keterbatasan lingkup gerak sendi diarea pergelangan tangan. Setelah dilakukan intervensi menggunakan ultrasound terapi dan mobilisasi saraf sebanyak 6 kali pengobatan terjadi perubahan yang signifikan yaitu nyeri berkurang, dan peningkatan lingkup gerak sendi pada kedua pergelangan tangan. Dengan demikian penerapan ultrasound terapi dan mobilisasi saraf pada pasien CTS memberikan pengaruh pada penurunan nyeri dan peningkatan lingkup gerak sendi pada pergelangan tangan.
Note for the P versus NP Problem (II)
Authors: Vega Frank
Published: July 2024

One of the biggest unsolved mysteries in computer science is the P versus NP problem. It asks a simple question: can every problem whose solution can be quickly verified be solved just as quickly (Here, "quickly" means in polynomial time)? While the question itself was hinted at in a 1955 letter from John Nash, a formalization of the problem is credited to Stephen Cook and Leonid Levin. Despite decades of effort, no one has been able to definitively answer it. Closely related is the concept of NP-completeness. If even one NP-complete problem can be solved efficiently (in polynomial time), then it implies P equals NP. This work proposes that a specific NP-complete problem, ONE-IN-THREE 3SAT, can be solved efficiently. In this way, we prove that P is equal to NP.
Representation of the Euler Product for the Riemann Zeta Function
Authors: Annamalai Chinnaraji
Published: July 2024

The Riemann zeta function is the important special function in the large family of zeta functions. The Euler product is an infinite product of many functions in the multiplicative number theory. A completely multiplicative function gives the Euler product representation of the Riemann zeta function. In this article, the author proves the Euler product for the Riemann zeta function and also derives the Euler product from the Riemann zeta Function.
El hilo de Ariadna
Authors: De Camargo Coronato Vivian
Published: July 2024

O chamado desse volume encorajou-nos a adentrar, mais uma vez, após nosso doutoramento, nos labirintos criados pelo grupo Teatro de los Sentidos, grupo internacional sediado em Barcelona. O grupo, em seus mais de vinte anos de existência, investiga o que denomina a Poética dos Sentidos e a relação das linguagens sensoriais com a criação artística. Nosso desafio, sabido inalcançável, é tentar dizer o indizível, descrevendo o percurso labiríntico da primeira obra do grupo, a primeira máquina de imaginar criada pelo diretor Enrique Vargas, denominada El Hilo de Ariadna. Para tanto, buscamos relatos de espectadores, transformados em viajantes/imaginantes pelo grupo, de diversas montagens e versões da obra. Em seguida, traçamos um paralelo entre a estrutura labiríntica da obra e a jornada do herói aventada por Joseph Campbell (1997). Por fim, discorremos sobre alguns elementos da Poética do grupo, colocando enfoque na relação entre curiosidade, escuridão e imaginação, tecendo fios com o pensamento de autores como Gaston Bachelard, Paul Virilo, Michel Serres e Georges Didi-Huberman.
Formação de professores para a EJA
Authors: De Freitas Negrello Thais Caroline , Ribas Machado Érico
Published: July 2024

Este artigo traz como tema a formação de professores para atuação na Educação de Jovens e Adultos (EJA). O objetivo geral da pesquisa é identificar qual a concepção de formação de professores para a EJA presente nas pesquisas publicadas no GT 18 da Associação Nacional de Pós-graduação e Pesquisa em Educação (ANPED), entre 2011 a 2021. Os objetivos específicos são: analisar o histórico da EJA, bem como suas legislações, desde sua origem até a atualidade; vislumbrar quem são os professores e alunos desta modalidade de ensino; mapear a concepção de formação de professores para a EJA que trazem as pesquisas publicadas na ANPED. A pesquisa possui abordagem qualitativa e configura-se como bibliográfica. A partir da análise dos dados obtidos, não se identificam menções a respeito de uma formação inicial docente específica para atuação na EJA, assim como, muitas vezes, a mesma também não tem espaço de reflexão e discussão no curso de Licenciatura em Pedagogia, o que pode gerar fragilidades no processo formativo desse profissional. Constata-se que a formação continuada se torna de grande relevância por ser, muitas vezes, a única formação específica de educadores que podem atuar na Educação de Jovens e Adultos.
Dynamic study of the duopoly market stability based on open innovation rate integration and intellectual property
Authors: Elmire Aziz , Bassou Aziz Ait , Hlyal Mustapha , El Alami Jamila
Published: July 2024

In this paper, we present a model detailing the benefits of two competing firms in a duopoly market, where profit maximization is linked to their production levels using the Cournot method. Our primary objective is to develop a collaborative strategy within the framework of open innovation to optimize their profits. Furthermore, we analyze how these firms can integrate an additional source of revenue in the form of intellectual property, without negatively impacting their open innovation strategies. To achieve this, we conducted a dynamic study of these strategies by introducing this intellectual property, to assess the impact of its components, such as patent licensing fees and royalties, on the equilibrium of strategies adopted by these firms. Our aim is to provide recommendations for optimal management of this intellectual property, thus enabling firms to fully leverage its benefits while preserving their competitive position in the market.
The chemistry of Formycin biosynthesis
Authors: Richards Nigel G. J. , Naismith James H.
Published: July 2024

Remarkable progress has been made to elucidate the structural and mechanistic enzymology of the biosynthetic pathways that give rise to naturally occurring C-nucleosides. These compounds are generally cytotoxic and exhibit interesting antiviral, antibiotic and anti-parasitic activity. Here we review current knowledge concerning formycin biosynthesis and highlight deficiencies in our understanding of key chemical transformations in the pathway.
Development of a versatile [68Ga]Ga-FAPI-46 automated synthesis suitable to multi-elutions of germanium-68/gallium-68 generators
Authors: Paty Louis-Paul , Degueldre Simon , Provost Claire , Schmitt Camille , Trump Laura , Fouque Julien , Vriamont Charles , Valla Frank , Gendron Thibault , Madar Olivier
Published: July 2024

Gallium-68-labeled FAPI-46 has recently been proposed as a novel positron emission tomography imaging probe to diagnose and monitor a wide variety of cancers. Promising results from several ongoing clinical trials have led to a soaring demand for this radiotracer. Typical [68Ga]Ga-FAPI-46 labeling protocols do not cope with multiple generator elutions, leaving radiopharmacies unable to scale-up the production and meet the demand. Here, we propose a robust and efficient automated radiosynthesis of [68Ga]Ga-FAPI-46 on the Trasis miniAllinOne synthesizer, featuring a prepurification step which allows multiple generator elutions and ensures compatibility with a wide range of gallium-68 generators. Our approach was to optimize the prepurification step by first testing five different cationic cartridge chemistries. Only the strong cationic exchange (SCX) cartridges tested had sufficient affinities for quantitative trapping of >99.9%, while the weak cationics did not exceed 50%. Packaging, rinsing, or flowing of the selected SCX cartridges was not noticeable, but improvements in fluidics managed to save time. Based on our previous development experience of [68Ga]Ga-FAPI-46, radiolabeling optimization was also carried out at different temperatures during 10 min. At temperatures above 100°C, radiochemical yield (RCY) > 80% was achieved without significantly increasing the chemical impurities (<5.5 μg mL-1). The optimized sequence was reproducibly conducted with three different brands of widely used generators (RCY >88%). A comparison with radiosyntheses carried out without prepurification steps was also conclusive in terms of RCY, radiochemical yield, and chemical purity. Finally, high-activity tests using elutions from three generators were also successful for these parameters. [68Ga]Ga-FAPI-46 was consistently obtained in good radiochemical yields (>89%, n = 3), and the final product quality was compliant with internal specifications based on European Pharmacopoeia. This process is suitable for GMP production and allows scaling-up of routine productions, higher throughput, and, ultimately, better patient care.
Frontiers in premature beats research: a bibliometric analysis
Authors: Wu Dan , Xia Xiaojing
Published: July 2024

Background

This study aimed to assess the scientific results and activities of premature beats research from a global perspective.

Methods

Publications related to premature beats published between 2003 and 2024 were identified and selected from the Web of Science core collection. VOSviewer was used to conduct co-authorship, co-citation, and co-occurrence analyses of the authors, organizations, countries/regions, references, sources, cited authors, and keywords.

Results

In total, 5,283 publications on the topic of premature beats were identified from the Web of Science core collection. The number of publications on this topic has steadily grown since 2003. Fred Morady, Frank Bogun and Krit Jongnarangsin were the top three researchers with the strongest total link strengths. The University of Washington, Johns Hopkins University, and the University of Minnesota are the top three organizations with the strongest total link strengths. The United States has made the greatest contributions to the field of premature beats. Haïssaguerre, M et al.'s publication in The New England Journal of Medicine in 1998 entitled “Spontaneous initiation of atrial fibrillation by ectopic beats originating in the pulmonary veins” is the most cited reference. The most cited references come from the journal named Circulation. Haïssaguerre, M has the highest number of citations. The keywords for all current publications can be divided into four categories: “mortality rate,” “risk and prevention,” “mechanism,” and “classification and treatment.”

Conclusions

This bibliometric study provides insights into the current status and research trends in premature beats over more than 20 years. Future research will focus on an in-depth exploration of the nature of premature beats, especially ventricular premature beats, mastering the development law of premature beats, and optimizing existing detection methods.
The emerging role of oxidative stress in inflammatory bowel disease
Authors: Muro Peter , Zhang Li , Li Shuxuan , Zhao Zihan , Jin Tao , Mao Fei , Mao Zhenwei
Published: July 2024

Inflammatory bowel disease (IBD) is a chronic immune-mediated condition that affects the digestive system and includes Crohn’s disease (CD) and ulcerative colitis (UC). Although the exact etiology of IBD remains uncertain, dysfunctional immunoregulation of the gut is believed to be the main culprit. Amongst the immunoregulatory factors, reactive oxygen species (ROS) and reactive nitrogen species (RNS), components of the oxidative stress event, are produced at abnormally high levels in IBD. Their destructive effects may contribute to the disease’s initiation and propagation, as they damage the gut lining and activate inflammatory signaling pathways, further exacerbating the inflammation. Oxidative stress markers, such as malondialdehyde (MDA), 8-hydroxy-2’-deoxyguanosine (8-OHdG), and serum-free thiols (R-SH), can be measured in the blood and stool of patients with IBD. These markers are elevated in patients with IBD, and their levels correlate with the severity of the disease. Thus, oxidative stress markers can be used not only in IBD diagnosis but also in monitoring the response to treatment. It can also be targeted in IBD treatment through the use of antioxidants, including vitamin C, vitamin E, glutathione, and N-acetylcysteine. In this review, we summarize the role of oxidative stress in the pathophysiology of IBD, its diagnostic targets, and the potential application of antioxidant therapies to manage and treat IBD.
Association between serum osmolality and 28-day all-cause mortality in patients with heart failure and reduced ejection fraction: a retrospective cohort study from the MIMIC-IV database
Authors: Zou Qi , Li Jiazheng , Lin Pengyang , Ma Jialiang , Wei Zhiliang , Tao Ting , Han Guodong , Sun Shougang
Published: July 2024

Background

Previous studies have not thoroughly explored the impact of serum osmolality levels on early mortality in heart failure and reduced ejection fraction (HFrEF) patients. The purpose of this study was to investigate the relationship between serum osmolality levels and early all-cause mortality in patients with HFrEF.

Methods

The open access MIMIC-IV database was the source of data for our study. We collected demographic data, vital signs, laboratory parameters, and comorbidities of the included patients and divided them into 3 groups based on their initial serum osmolality on admission, with the primary outcome being all-cause mortality within 28 days of admission. Smoothing Spline Fitting Curve, the Kaplan-Meier survival curve, and Threshold effect analysis were used to assess the relationship between serum osmolality and early mortality in HFrEF patients.

Results

A total of 6228 patients (55.31% male) were included. All-cause mortality within 28 days on admission was 18.88% in all patients. After adjusting for confounders, higher serum osmolality levels were independently associated with an increased risk of 28-days all-cause mortality compared with the reference group (Reference group Q2: 290–309 mmol/L, Q4: HR, 1.82 [95% CI 1.19–2.78] P<0.05, Q5: HR, 1.99 [95% CI 1.02–3.91] P<0.05). Smooth spline fitting revealed a U-shaped association between serum osmolality and 28-days all-cause mortality. Further threshold effect analysis results suggested that each unit increase in serum osmolality level was associated with a 2% increase in 28-days all-cause mortality when serum osmolality levels were ≥ 298.8 mmol/L (HR, 1.019 [95% CI 1.012–1.025] P<0.05).

Conclusion

A U-shaped correlation between initial serum osmolality and 28-days all-cause mortality in HFrEF patients was identified, revealing higher osmolality levels significantly increase mortality risk. These results underscore serum osmolality’s critical role in early mortality among HFrEF patients, highlighting the need for further, larger-scale studies for validation.
Association between serum uric acid levels and diabetic peripheral neuropathy in type 2 diabetes: a systematic review and meta-analysis
Authors: Zhang Xieyu , Zhang Xinwen , Li Xiaoxu , Zhao Xin , Wei Guangcheng , Shi Jinjie , Yang Yue , Fan Su , Zhao Jiahe , Zhu Ke , Du Jieyang , Guo Junyi , Cao Wei
Published: July 2024

Background

The evidence supporting a connection between elevated serum uric acid (SUA) levels and diabetic peripheral neuropathy (DPN) is controversial. The present study performed a comprehensive evaluation of this correlation by conducting a systematic review and meta-analysis of relevant research.

Method

PubMed, Web of Science (WOS), Embase, and the Cochrane Library were searched for published literature from the establishment of each database to January 8, 2024. In total, 5 cohort studies and 15 cross-sectional studies were included, and 2 researchers independently screened and extracted relevant data. R 4.3.0 was used to evaluate the included literature. The present meta-analysis evaluated the relationship between SUA levels and the risk of DPN in type 2 diabetes (T2DM) by calculating the ratio of means (RoM) and 95% confidence intervals (CIs) using the method reported by JO Friedrich, and it also analyzed continuous outcome measures using standardized mean differences (SMDs) and 95% CIs to compare SUA levels between DPN and non-DPN groups. Funnel plot and Egger’s test were used to assess publication bias. Sensitivity analysis was conducted by sequentially removing each study one-by-one.

Results

The meta-analysis included 20 studies, with 12,952 T2DM patients with DPN and 16,246 T2DM patients without DPN. There was a significant correlation between SUA levels and the risk of developing DPN [odds ratio (OR) = 1.23; 95% CI: 1.07-1.41; p = 0.001]. Additionally, individuals with DPN had higher levels of SUA compared to those without DPN (SMD = 0.4; 95% CI: -0.11-0.91; p < 0.01).

Conclusion

T2DM patients with DPN have significantly elevated SUA levels, which correlate with a heightened risk of peripheral neuropathy. Hyperuricemia (HUA) may be a risk indicator for assessing the risk of developing DPN in T2DM patients.

Systematic review registration

https://www.crd.york.ac.uk/PROSPERO, identifier CRD42024500373.
The role of product market competition and analyst attention in modulating the link between equity pledges and classification shifting
Authors: Xue Ruixiang , Lu Jiao
Published: July 2024

This study investigates the association between equity pledges and classification shifting earnings management in Chinese listed firms, spanning the period from 2016 to 2022. Additionally, it explores the moderating influence of product market competition (PMC) and analyst attention on this relationship. By analyzing a sample comprising 12,583 firm-year observations, several notable findings are observed. The regression results reveal a positive and statistically significant relationship between equity pledges and classification shifting earnings management (coefficient = 0.00234, p < 0.01). Moreover, this positive impact is further magnified when specifically considering downward classification shifting (coefficient = 0.00368, p < 0.01). Regarding the moderating factors, the results demonstrate a positive moderating effect of PMC on the relationship between equity pledges and classification shifting, with an interaction coefficient of 0.0165 (p < 0.01). This moderating effect is particularly pronounced in the context of downward classification shifting, with an interaction coefficient of 0.0142 (p < 0.01). Similarly, analyst attention also positively moderates the relationship, as indicated by an interaction coefficient of 0.00144 (p < 0.05), with a stronger effect observed in the case of downward classification shifting, with an interaction coefficient of 0.00329 (p < 0.01). Furthermore, additional tests reveal that leverage strengthens the aforementioned moderating effects. The three-way interaction involving debt, PMC, and equity pledges significantly influences classification shifting, with a coefficient of 0.0415 (p < 0.05). Specifically, debt exacerbates the moderating impact of competition on highly leveraged firms that engage in downward classification shifting, as evidenced by a coefficient of 0.0599 (p < 0.05). Similarly, debt reinforces the moderating role of analyst attention (coefficient = 0.00820, p < 0.05), especially for downward classification shifting (coefficient = 0.00902, p < 0.1). Propensity score matching and robustness tests validate the findings. Therefore, this research contributes to the understanding of the economic implications of equity pledge by focusing on earnings manipulation through classification shifting. It also examines this relationship within different competitive environments and external regulatory frameworks, aiming to promote the long-term viability of companies.
The obese inflammatory microenvironment may promote breast DCIS progression
Authors: Habanjar Ola , Nehme Rawan , Goncalves-Mendes Nicolas , Cueff Gwendal , Blavignac Christelle , Aoun Jessy , Decombat Caroline , Auxenfans Céline , Diab-Assaf Mona , Caldefie-Chézet Florence , Delort Laetitia
Published: July 2024

Introduction

Ductal carcinoma in situ (DCIS), characterized by a proliferation of neoplastic cells confined within the mammary ducts, is distinctly isolated from the surrounding stroma by an almost uninterrupted layer of myoepithelial cells (MECs) and by the basement membrane. Heightened interactions within the adipose microenvironment, particularly in obese patients, may play a key role in the transition from DCIS to invasive ductal carcinoma (IDC), which is attracting growing interest in scientific research. Adipose tissue undergoes metabolic changes in obesity, impacting adipokine secretion and promoting chronic inflammation. This study aimed to assess the interactions between DCIS, including in situ cancer cells and MECs, and the various components of its inflammatory adipose microenvironment (adipocytes and macrophages).

Methods

To this end, a 3D co-culture model was developed using bicellular bi-fluorescent DCIS-like tumoroids, adipose cells, and macrophages to investigate the influence of the inflammatory adipose microenvironment on DCIS progression.

Results

The 3D co-culture model demonstrated an inhibition of the expression of genes involved in apoptosis (BAX, BAG1, BCL2, CASP3, CASP8, and CASP9), and an increase in genes related to cell survival (TP53, JUN, and TGFB1), inflammation (TNF-α, PTGS2, IL-6R), invasion and metastasis (TIMP1 and MMP-9) in cancer cells of the tumoroids under inflammatory conditions versus a non-inflammatory microenvironment. On the contrary, it confirmed the compromised functionality of MECs, resulting in the loss of their protective effects against cancer cells. Adipocytes from obese women showed a significant increase in the expression of all studied myofibroblast-associated genes (myoCAFs), such as FAP and α-SMA. In contrast, adipocytes from normal-weight women expressed markers of inflammatory fibroblast phenotypes (iCAF) characterized by a significant increase in the expression of LIF and inflammatory cytokines such as TNF-α, IL-1β, IL-8, and CXCL-10. These changes also influenced macrophage polarization, leading to a pro-inflammatory M1 phenotype. In contrast, myoCAF-associated adipocytes, and the cancer-promoting microenvironment polarized macrophages towards an M2 phenotype, characterized by high CD163 receptor expression and IL-10 and TGF-β secretion.

Discussion

Reciprocal interactions between the tumoroid and its microenvironment, particularly in obesity, led to transcriptomic changes in adipocytes and macrophages, may participate in breast cancer progression while disrupting the integrity of the MEC layer. These results underlined the importance of adipose tissue in cancer progression.
Immune infiltration-related genes regulate the progression of AML by invading the bone marrow microenvironment
Authors: Yu Shuangmei , Jiang Jiquan
Published: July 2024

In this study, we try to find the pathogenic role of immune-related genes in the bone marrow microenvironment of AML. Through WGCNA, seven modules were obtained, among which the turquoise module containing 1793 genes was highly correlated with the immune infiltration score. By unsupervised clustering, the turquoise module was divided into two clusters: the intersection of clinically significant genes in the TCGA and DEGs to obtain 178 genes for mutation analysis, followed by obtaining 17 genes with high mutation frequency. Subsequently, these 17 genes were subjected to LASSO regression analysis to construct a riskscore model of 8 hub genes. The TIMER database, ImmuCellAI portal website, and ssGSEA elucidate that the hub genes and risk scores are closely related to immune cell infiltration into the bone marrow microenvironment. In addition, we also validated the relative expression levels of hub genes using the TCGA database and GSE114868, and additional expression levels of hub genes in AML cell lines in vitro. Therefore, we constructed an immune infiltration-related gene model that identify 8 hub genes with good risk stratification and predictive prognosis for AML.
SOX combined with apatinib and camrelizumab in the treatment of resectable locally advanced gastric cancer: a case report
Authors: Hu JiKe , Li Xuemei , Wang Yunpeng , Xu Bo , He Puyi , Wang Zhuanfang , He Lijuan , Chen Hao
Published: July 2024

Gastric cancer is highly prevalent in China, yet early diagnosis and overall survival rates are low. The primary treatment strategy is comprehensive therapy centered on surgery. Studies indicate that neoadjuvant chemotherapy can enhance radical resection rates and extend survival in locally advanced gastric cancer. Combining VEGFR inhibitors with chemotherapy improves efficacy in digestive system tumors, while PD-1/PD-L1 inhibitors combined with anti-angiogenesis agents or chemotherapy show synergistic effects. This report presents a case of gastric adenocarcinoma (cT3N1M0) treated with SOX, apatinib mesylate, and camrelizumab as neoadjuvant therapy, followed by D2 distal gastrectomy and postoperative adjuvant therapy with the same regimen. The patient completed all treatment cycles successfully. Post-neoadjuvant therapy, only focal residual cancer cells were found in the lamina propria (pT1a). During postoperative adjuvant therapy follow-up, gastroscopic biopsy indicated a pathological complete response with no recurrence or metastasis. The patient primarily experienced dyspepsia, oropharyngeal pain, capillary proliferation, mild bone marrow suppression, nausea, and vomiting as side effects. Therefore, SOX combined with apatinib mesylate and camrelizumab shows promise for treating resectable locally advanced gastric cancer.
Centralized care model for hereditary angioedema overcomes geographical barriers
Authors: Holmes Ashley , Srinivasan Cindy , Borle Jack , Blain Heather , Ritchie Bruce , Adatia Adil
Published: July 2024

Hereditary angioedema due to C1 inhibitor deficiency (HAE) is a rare inborn error of immunity that presents with episodic swelling. Management is multifaceted and includes on-demand treatment of swelling episodes, short-term prophylaxis to prevent swelling episodes from procedures, and long-term prophylaxis (LTP) to prevent angioedema on an ongoing basis. All approved on-demand therapies are parenteral, necessitating patient training for home administration, particularly intravenous C1 inhibitor. These complexities can result in care gaps for rural HAE patients. We conducted a cross-sectional study at our Angioedema Center of Reference and Excellence to assess the care provided to urban and rural patients. The proportion of patients receiving LTP, proportion of patients diagnosed as children, and disease control measured using the Angioedema Control Test (AECT) were collected. Logistic and Poisson regression models adjusted for age and sex were used to compare the two groups. The proportion using LTP was similar at 62% and 61% in urban and rural patients, respectively (odds ratio [OR] 1.01 (CI 95% 0.34-2.99)). Among urban patients, 52% were diagnosed as children compared to 60% among rural residents (1.43 (0.37-5.56)). The mean (IQR) AECT score was 14.0 (8.5-15.5) in urban patients and 13.0 (10.0-14.0) in rural patients (Poisson β -0.001 (-0.23-0.23). These data indicate that rural patients received similar high-quality care. We attribute these findings to the centralized care model employed in which HAE patients in the region are seen at a single comprehensive care clinic.
Regulatory T cell homing and activation is a signature of neonatal sepsis
Authors: Sossou Darius , Ezinmegnon Sem , Agbota Gino , Gbedande Komi , Accrombessi Manfred , Massougbodji Achille , d’Almeida Marceline , Alao Jules M. , Dossou-Dagba Ida , Pachot Alexandre , Vachot Laurence , Brengel-Pesce Karen , Cottrell Gilles , Yessoufou Akadiri , Briand Valérie , Tissières Pierre , Fievet Nadine
Published: July 2024

Regulatory T cells (Treg) play a prominent role in utero tolerating non-inherited maternal antigens and in regulating immune responses against pathogens at birth. This study investigates Treg immunity in newborns in West Africa, where sepsis remains a major public health problem. Treg phenotypes on neonates subgroups with early-onset sepsis (EOS), presumed sepsis, and healthy newborn with and without prenatal risk factors were evaluated. Treg phenotypes varied according to prenatal conditions, with increase in Treg frequency and Foxp3 expression in healthy newborns with prenatal risk factors compared to those with none risk. Compared to healthy newborns with prenatal risk factors, EOS neonates had a significantly reduced frequency of Treg and Foxp3 expression. In the Treg pool, higher frequency of activated Treg was observed in EOS neonates, suggesting an in-utero activation upstream of the sepsis onset. Their migration to the infection site may explain the reduced frequency of circulating Integrin α4β1+ Treg suggestive of homing to the endothelial tissue. EOS neonates show increases expression of CTLA-4, PD-1 and CD39 on Treg, which negatively regulate the activation of effector T cells (Teff) corroborating by the lower frequency of Teff in EOS neonates. The higher frequency of CD39+ Treg and the lower frequency of integrinα4β1+ Treg in EOS non-survivor suggests that Treg exhaustement and endothelial homing are associated with outcome severity. Neonates developing EOS are born with an altered Treg phenotypic profile. Treg expression of CTLA-4, PD-1, CD39, and integrinα4β1 cell markers can be considered as early warning or diagnostic markers of EOS.
Case report: PCA-2-associated encephalitis with different clinical phenotypes: a two-case series and literature review
Authors: Li Xiaona , Lang Yue , Ma Di , Bai Jing , Shen Pingping , Wang Xinyu , Cui Li
Published: July 2024

Purkinje cell cytoplasmic antibody type 2 (PCA-2), identified in 2000, targets the widely distributed microtubule-associated protein 1B in the central and peripheral nervous systems, leading to diverse clinical phenotypes of neurological disorders. We report two cases of PCA-2-associated encephalitis, each presenting with distinct onset forms and clinical manifestations, thereby illustrating the phenotypic variability of PCA-2-related diseases. The first patient was diagnosed with PCA-2-associated autoimmune cerebellitis and undifferentiated small cell carcinoma with metastasis in mediastinal lymph nodes of unknown primary origin. The second patient was diagnosed with PCA-2-associated limbic encephalitis. Our findings underscore the superior sensitivity of positron emission tomography-computed tomography over brain magnetic resonance imaging in the early detection of PCA-2-associated encephalitis. Given the high risk of relapse and suboptimal response to traditional immunotherapy in PCA-2-related neurological disorders, this study highlights the need for a deeper understanding of their pathogenesis to develop more effective treatments to control symptoms and improve patient prognosis.
Ferroptosis and endoplasmic reticulum stress in rheumatoid arthritis
Authors: Ao Qin , Hu Huan , Huang Ying
Published: July 2024

Ferroptosis is an iron-dependent mode of cell death distinct from apoptosis and necrosis. Its mechanisms mainly involve disordered iron metabolism, lipid peroxide deposition, and an imbalance of the antioxidant system. The endoplasmic reticulum is an organelle responsible for protein folding, lipid metabolism, and Ca2+ regulation in cells. It can be induced to undergo endoplasmic reticulum stress in response to inflammation, oxidative stress, and hypoxia, thereby regulating intracellular environmental homeostasis through unfolded protein responses. It has been reported that ferroptosis and endoplasmic reticulum stress (ERS) have an interaction pathway and jointly regulate cell survival and death. Both have also been reported separately in rheumatoid arthritis (RA) mechanism studies. However, studies on the correlation between ferroptosis and ERS in RA have not been reported so far. Therefore, this paper reviews the current status of studies and the potential correlation between ferroptosis and ERS in RA, aiming to provide a research reference for developing treatments for RA.