bluuebunny/crossref_metadata_2025 huggingface dataset:
Analisis Determinan Struktur Modal pada Perusahaan Property dan Real Estate
Authors: Sihombing Febie Tania , Kristanti Farida Titik
Published: June 2024

The aim of this research is to determine the influence of asset tangibility, liquidity, non-debt tax shield, business risk, growth and firm size on the capital structure of property and real estate sector companies listed on the Indonesia Stock Exchange in 2014-2021. A dynamic panel data regression model with the Generalized Method of Moment (GMM) estimator is applied in this research. The results show that determinants simultaneously influence capital structure. Asset tangibility, growth and firm size partially have a significant effect on capital structure, while liquidity, non-debt tax shield and business risk partially have no effect on capital structure. Therefore, the formation of an optimal capital structure is expected to take into account tangible assets, growth rate and company size in order to maximize company value.
Pengaruh Pengungkapan Corporate Social Responsibility, Profitabilitas, Leverage, dan Ukuran Perusahaan terhadap Nilai Perusahaan
Authors: Valentino Ardivan Dicha , Setiawan Putu Ery
Published: June 2024

The aim of this research is to obtain empirical evidence on how corporate social responsibility (CSR) disclosure, profitability, leverage, and firm size influence firm value. Firm value is an indicator that shows company performance through stock price movements. This study was conducted on SRI-KEHATI indexed companies during the 2020-2022 period. The data collection method uses non-participant observation. The sampling method uses non-probability sampling with purposive technique. The collected data was analyzed using multiple linear regression. The research results show that CSR disclosure has no influence on firm value, profitability and leverage have a positive influence on firm value, and firm size has a negative influence on firm value
Kesejahteraan Pekerja, Analisis dari Status Pekerjaan dan Modal Sosial melalui Pasar Kerja
Authors: Rohmah Rosyida Izzati , Rusdjijati Retno , Murniningsih Rochiyati
Published: June 2024

The research aims to examine the influence of informal work and social capital on welfare mediated by the labor market. The cluster random sampling method was used to determine the sample, and 750 respondents were obtained. Research data was processed using SPSS and SmartPLS. The results show that informal workers and social capital have a simultaneous effect on well-being, while informal work is not proven to have an effect. Social capital is proven to have a positive effect on the labor market, and the labor market has a positive effect on welfare. The results of the indirect effect prove that informal work has a negative effect on well-being, while social capital has a positive effect on well-being.
Pengaruh E-Commerce Marketing Stimuli terhadap Trust, Customer Satisfaction, dan Customer Loyalty
Authors: Sakinah Maraya , Heruwasto Ignatius
Published: June 2024

Consumer behavior conceptually begins with marketing stimuli which then ends with purchasing decisions. This research analyzes the influence of e-service quality, reputation, web design and price on trust, customer satisfaction and customer loyalty. Survey data from 370 respondents obtained through an online questionnaire was then processed using structural equation modeling (SEM). The results of this research show that e-service quality, trust, and price influence customer satisfaction. Furthermore, if e-commerce can respond to customer complaints and provide services that are personally tailored to meet customer needs, customer satisfaction will be created.
Faktor-Faktor yang Mempengaruhi Kinerja Keuangan Perusahaan Perbankan dengan Struktur Modal sebagai Variabel Moderasi
Authors: Hutasoit Rama , Tarigan Nelly Agustina BR
Published: June 2024

This research aims to analyze the influence of good corporate governance (GCG), capital adequacy ratio (CAR), interest rates of Bank Indonesia, liquidity and operational efficiency on the financial performance of banking companies listed on the BEI for the 2020-2022 period, as well as testing the role of capital structure as a moderating variable. The results show that GCG and operational efficiency have a positive and significant effect on financial performance; liquidity has a positive and insignificant effect on financial performance; and, CAR and interest rates of Bank Indonesia have a negative and insignificant effect on financial performance. Other results stated that capital structure was proven to be able to moderate the relationship between GCG and operational efficiency on banking financial performance, but was unable to moderate the relationship between CAR, interest rates of Bank Indonesia, and liquidity on banking financial performance.
Studies on the aphids (Homoptera; Aphididae) from Eastern India XXXIV. Two Genera, Three New Subgenera, One new species and Some New Records from Northeast India
Authors: Basu R.C. , Ghosh M.R. , Raychaudhuri D. N.
Published: June 2024

Two genera viz., Neohyalomyzus and Scleromyzus, three new subgenera viz., Anacyrthosiphon, Neomacrosiphum, and Paraneomyzus one new species viz., Xenomyzus Scabripes are described further the genus Xenomyzus and the species Dactynotus (Urontelan) gobonis are reported for the first time from India.
PKM Penerapan Teknologi Aplikasi Zakat Berbasis Mobile Application Pada Masjid Raudhotul Jannah Komplek Taman Cipulir Estate
Authors: Hamdani Agus Umar , Indra Indra , Rani Puspita , Wulan Riskiana
Published: June 2024

Optimalisasi pengelolaan dana zakat dapat dimanfaatkan untuk pemberdayaan ekonomi warga miskin sehingga dapat menurunkan tingkat kemiskinan. Pengurus zakat Masjid Roudhotul Jannah Taman Cipulir Estate diberikan tugas untuk mengelola dana zakat dari jamaah masjid. Layanan tersebut dilakukan dengan cara menulis di buku dan menginput dana zakat melalui website manajemen zakat. Adapun kelemahan dari pengelolaan zakat yang ada saat ini adalah proses pendataan muzakki dan mustahiq masih dilakukan secara manual dan calon muzakki yang berada di luar lingkungan masjid belum dapat ditangani dengan baik. Berdasarkan kondisi diatas, maka diperlukan pelatihan dan pendampingan dalam mengelola zakat kepada pengurus zakat agar dapat menciptakan layanan yang optimal. Metode yang digunakan dalam kegiatan ini adalah pelatihan dan pendampingan. Kegiatan tersebut berupa pelatihan penggunaan aplikasi manajemen zakat berbasis mobile application kepada pengurus zakat. Berdasarkan evaluasi pelaksanaan kegiatan pengabdian masyarakat ini diperoleh prosentase kepuasan mitra sebesar 88% dan prosentase penerimaan aplikasi manajemen zakat berbasis mobile application sebesar 96%.
Development of a Digital Marketing Based Business Model at the Kurdut Garage Workshop in Pematangsiantar City
Authors: Sembiring Lenny Dermawan , Indajang Kevin , Arshandy Eliza , Putri Juan Anastasia , Halim Fitria , Sudirman Acai
Published: June 2024

The development of a digital marketing-based business model at the Kurdut Garage Workshop in Pematangsiantar has a very important urgency in facing the ever-growing era of digitalization. The method used in implementing this activity is through lectures and FGD (group discussion forum). The stages of implementing this event include explaining the fundamentals of being an entrepreneur, explaining several problems that entrepreneurs often face, then continuing with discussions related to developing new businesses. After the service activities are completed, follow-up interviews are conducted regarding the impact of implementing the service activities. By the results of the interview, it is known that the understanding of Kurdut Garage Workshop business owners regarding knowledge of the use of digital marketing has increased by 90%. The use of digital media is useful and can increase understanding and skills for partners. Therefore, it is recommended that sustainable methods of mentoring partners can be used as a solution to increase business size and also function as a means of company adaptation to increase business scale.
Inspirasi Konservasi Lingkungan Melalui Kegiatan Penghijauan di Sekitar Batalyon Infanteri 761/Ka Warmare Distrik Warmare Kabupaten Manokwari
Authors: Tanur Evelin A. , Marwa Jonni , Beljai Matheus , Prasetyawan Herik , Wijaya Deddy S. , May Nunang L. , Worabai Descarlo , Mofu Wolfram Y. , Rahmadaniarti Aditya , Anggrianto Rusdi
Published: June 2024

Peranan hutan sebagai pemelihara keseimbangan ekologi sangatlah penting, namun demikian kondisi ini selalu dipengaruhi ancaman deforestasi dan degradasi. Keduanya merupakan masalah lingkungan yang menjadi tantangan bagi semua wilayah di Pulau Papua termasuk hutan Distrik Warmare di Kabupaten Manokwari. Ancaman dan tantangan deforestasi maupun degradasi hutan di wilayah Warmare dapat meluas secara signifikan jika tidak ditanggulangi secara baik. Sebab itu, perlu upaya penghijauan untuk meminimalisir permasalahan tersebut. Kegiatan penghijauan dilakukan di Kompleks TNI Angkatan Darat Batalyon Infanteri 761/KA Warmare Distrik Warmare Kabupaten Manokwari. Metode demonstrasi digunakan dalam kegiatan ini yaitu penanaman bibit tanaman pada lokasi yang telah disiapkan sebanyak 1035 dari 9 jenis. Peserta dalam kegiatan ini sebanyak 22 orang berasal dari Fakultas Kehutanan dan TNI Angkatan Darat Batalyon Infanteri 761/KA Warmare. Kegiatan penghijauan berjalan dengan baik dan lancar karena semua peserta dapat berpartisipasi dan terlibat secara aktif.
Türkiye’de Yapılan Metin Tenkidi Araştırmaları Kaynakçası ve Değerlendirilmesi
Authors: Çalgan Mehmet Ali
Published: June 2024

Hadiste metin tenkidi konusu güncelliğini korumakta, ülkemizde ve İslam dünyasında bu sahada yapılan akademik çalışmalar hızla artmakta ve bu sebeple bu çalışmaların takibi zorlaşmaktadır. Bu makalenin amacı hadis sahasında metin tenkidine dair bugüne kadar hazırlanmış olan akademik nitelikli makale, tez ve kitapların bir listesini sunmak ve genel bir değerlendirmesini yapmaktır. Tespitimize göre metin tenkidi konusunda toplam 341 çalışma yapılmış olup bunların 194’ü makale, 35’i doktora tezi, 52’si yüksek lisans tezi ve 60’ı kitaptır. Çalışmamızda bu eserler birincil seviyede şu ana başlıklara göre tasnif edilmiştir: Günümüzde Yapılan Metin Tenkitleri, Genel ve Teorik Konular, Metin Tenkidinin Kıstasları, Muhaddislerin Geçmişteki Metin Tenkidi Tatbikatı, Metin Tenkidinin Öncülleri, Metin Tenkidinin Sorunları, Ravi Tasarrufları, Metin Tenkidiyle İlgili Diğer Konular. Metin tenkidi çalışmalarının bu ana başlıklara göre dağılımına bakıldığında en fazla çalışmanın “Günümüzde Yapılan Metin Tenkitleri” başlığında olduğu görülmektedir. Kanaatimizce bu dağılımda daha fazla öncelik hak eden bazı konular arka planda kalmıştır. Zira ravi tasarrufları, metin tenkidinin sorunları, öncülleri, kıstasları ve genel mahiyeti gibi meseleler hakkında yeterli seviyede araştırma yapılarak güçlü bir teorik ve metodolojik zemin hazırlanmadan metin tenkidine yönelinmesi isabetli sonuçlar alınmasını zorlaştıracaktır. Ayrıca, muhaddislerin metin tenkidi tatbikatı konusunun da yine teorik arka plan çalışmaları yapıldıktan sonra daha fazla incelenmesi gerektiğini düşünmekteyiz.
PENGARUH MODIFIKASI CYLINDER HEAD SEPEDA MOTOR SUPRA X 125 TERHADAP DAYA DAN TORSI
Authors: Muhamad Ramli Adi Wardana  , Mohammad Munib Rosadi
Published: June 2024

Untuk meningkatkan performa motor yang lebih baik dari sebelumnya maka penulis ingin mengembangkan dan meneliti pengaruh modifikasi cylinder head terhadap daya dan torsi sepeda motor supra x 125. Tujuani penelitian inii antarai laini adalah untuki mengetahuii perbandingani modifikasi cylinder head terhadap daya dan torsi motor Honda Supra X 125. Variabel Bebas dalam penelitian ini adalah modifikasi pembesaran cylinder head dengan ukuran piston diameter 65, 5 mm dan modifikasi katup in ex adalah in 31, 5 mm dan ex 27 mm. Variabel terikat di penelitian ini ialah efisiensi motor yaitu Daya dan Torsi. Variabel kontrol dalam penelitiani ini adalah putaran mesin/rpm, unit sepeda motor, bahan bakar, transmisi standart, sasis standar dan celah katup 0, 05 mm katup In dan Ex. Untuk hasil dan pembahasan daya max pada mesin modifkasi ialah 16.53 Hp di Rpm = 7.365 di waktu 1.6 Detik, Sedangkan torsi max ialah 18.443 N.m di Rpm = 5.447 Rpm diwaktu 0.5 detik.
Predictive modeling of rocking-induced settlement in shallow foundations using ensemble machine learning and neural networks
Authors: Gajan Sivapalan
Published: June 2024

Introduction

The objective of this study is to develop predictive models for rocking-induced permanent settlement in shallow foundations during earthquake loading using stacking, bagging and boosting ensemble machine learning (ML) and artificial neural network (ANN) models.

Methods

The ML models are developed using supervised learning technique and results obtained from rocking foundation experiments conducted on shaking tables and centrifuges. The overall performance of ML models are evaluated using k-fold cross validation tests and mean absolute percentage error (MAPE) and mean absolute error (MAE) in their predictions.

Results

The performances of all six nonlinear ML models developed in this study are relatively consistent in terms of prediction accuracy with their average MAPE varying between 0.64 and 0.86 in final k-fold cross validation tests.

Discussion

The overall average MAE in predictions of all nonlinear ML models are smaller than 0.006, implying that the ML models developed in this study have the potential to predict permanent settlement of rocking foundations with reasonable accuracy in practical applications.
Antifungal, anti-biofilm, and anti-hyphal properties of N-substituted phthalimide derivatives against Candida species
Authors: Shaik Shamshe , Lee Jin-Hyung , Kim Yong-Guy , Lee Jintae
Published: June 2024

Candida species comprise a ubiquitous pathogenic fungal genus responsible for causing candidiasis. They are one of the primary causatives of several mucosal and systemic infections in humans and can survive in various environments. In this study, we investigated the antifungal, anti-biofilm, and anti-hyphal effects of six N-substituted phthalimides against three Candida species. Of the derivatives, N-butylphthalimide (NBP) was the most potent, with a minimum inhibitory concentration (MIC) of 100 µg/ml and which dose-dependently inhibited biofilm at sub-inhibitory concentrations (10–50 µg/ml) in both the fluconazole-resistant and fluconazole-sensitive Candida albicans and Candida parapsilosis. NBP also effectively inhibited biofilm formation in other pathogens including uropathogenic Escherichia coli, Staphylococcus epidermidis, Staphylococcus aureus, and Vibrio parahaemolyticus, along with the polymicrobial biofilms of S. epidermidis and C. albicans. NBP markedly inhibited the hyphal formation and cell aggregation of C. albicans and altered its colony morphology in a dose-dependent manner. Gene expression analysis showed that NBP significantly downregulated the expression of important hyphal- and biofilm-associated genes, i.e., ECE1, HWP1, and UME6, upon treatment. NBP also exhibited mild toxicity at concentrations ranging from 2 to 20 µg/ml in a nematode model. Therefore, this study suggests that NBP has anti-biofilm and antifungal potential against various Candida strains.
Development of system-based digital decision support (“Pocket Ark”) for post-flood enhanced response coordination and worker safety: an Intervention Mapping approach
Authors: Perkison William Brett , Shegog Ross , Lai Dejian , Upadhyay Saswati , Yalavarthy Geethika , Guerrero-Luera Rosalia , Mathews Patenne D. , Rios Janelle , Mehta Ritesh , McLaughlin Jeffery , Nabeel Ismail
Published: June 2024

Background

The health and safety of workers who work in areas severely damaged by natural weather events (reconstruction workers) is becoming an increasingly important health problem as these disasters increase in intensity and frequency. An evidence-based, innovative e-learning tool, Pocket Ark, has been developed to meet this need.

Methods

Intervention Mapping, an iterative public health programming methodology, was used to create strategies designed to support the development and implementation of the Pocket Ark application for the health and safety of reconstruction workers before, after, and during natural disasters.

Discussion

The development of an evidence-based application, Pocket Ark, uses the concept of the Intervention Mapping planning framework. It can be an effective bridge of pre-deployment education, deployment health, and safety support for the reconstruction work in the immediate post-disaster environment.
Further knowledge and developments in resistance mechanisms to immune checkpoint inhibitors
Authors: Berland Léa , Gabr Zeina , Chang Michelle , Ilié Marius , Hofman Véronique , Rignol Guylène , Ghiringhelli François , Mograbi Baharia , Rashidian Mohamad , Hofman Paul
Published: June 2024

The past decade has witnessed a revolution in cancer treatment, shifting from conventional drugs (chemotherapies) towards targeted molecular therapies and immune-based therapies, in particular immune-checkpoint inhibitors (ICIs). These immunotherapies release the host’s immune system against the tumor and have shown unprecedented durable remission for patients with cancers that were thought incurable, such as metastatic melanoma, metastatic renal cell carcinoma (RCC), microsatellite instability (MSI) high colorectal cancer and late stages of non-small cell lung cancer (NSCLC). However, about 80% of the patients fail to respond to these immunotherapies and are therefore left with other less effective and potentially toxic treatments. Identifying and understanding the mechanisms that enable cancerous cells to adapt to and eventually overcome therapy can help circumvent resistance and improve treatment. In this review, we describe the recent discoveries on the onco-immunological processes which govern the tumor microenvironment and their impact on the resistance to PD-1/PD-L1 checkpoint blockade.
Dendritic cell subsets and implications for cancer immunotherapy
Authors: Chen Michael Y. , Zhang Felicia , Goedegebuure Simon Peter , Gillanders William E.
Published: June 2024

Dendritic cells (DCs) play a central role in the orchestration of effective T cell responses against tumors. However, their functional behavior is context-dependent. DC type, transcriptional program, location, intratumoral factors, and inflammatory milieu all impact DCs with regard to promoting or inhibiting tumor immunity. The following review introduces important facets of DC function, and how subset and phenotype can affect the interplay of DCs with other factors in the tumor microenvironment. It will also discuss how current cancer treatment relies on DC function, and survey the myriad ways with which immune therapy can more directly harness DCs to enact antitumor cytotoxicity.
Strategic environmental assessment in areas beyond national jurisdiction: existing regimes, challenges, and prospects
Authors: Song Yuanming , Mao Zhengkai , Zhang Zhijun
Published: June 2024

As a system based on domestic law, strategic environmental assessment (SEA) can take environmental factors into consideration in the formulation of policies, plans, and programmes, and has received much attention in the field of environmental governance of areas beyond national jurisdiction (ABNJ). The recently adopted “Agreement under the United Nations Convention on the Law of the Sea on the Conservation and Sustainable Use of Marine Biological Diversity of Areas beyond National Jurisdiction” (BBNJ Agreement) incorporates SEA into its text, but the BBNJ Agreement has not yet entered into force. Of other existing schemes governing ABNJ, some lack provisions on SEA, and some do not set SEA as a binding legal obligation. Conducting SEA in ABNJ faces several challenges, including fragmented rules and reluctance on the part of countries, which lead to unsatisfactory results. Therefore, this study suggests that the BBNJ Agreement should collaborate with regional treaties and international organizations in the future to complement and reinforce current systems and regulations, improving compatibility among them. At the same time, consideration should be given to identifying the protection of BBNJ as a common concern of humankind (CCH) to strengthen the implementation of future SEAs.
Recommendations for advancing mixoplankton research through empirical-model integration
Authors: Millette Nicole C. , Leles Suzana G. , Johnson Matthew D. , Maloney Ashley E. , Brownlee Emily F. , Cohen Natalie R. , Duhamel Solange , Poulton Nicole J. , Princiotta Sarah D. , Stamieszkin Karen , Wilken Susanne , Moeller Holly V.
Published: June 2024

Protist plankton can be divided into three main groups: phytoplankton, zooplankton, and mixoplankton. In situ methods for studying phytoplankton and zooplankton are relatively straightforward since they generally target chlorophyll/photosynthesis or grazing activity, while the integration of both processes within a single cell makes mixoplankton inherently challenging to study. As a result, we understand less about mixoplankton physiology and their role in food webs, biogeochemical cycling, and ecosystems compared to phytoplankton and zooplankton. In this paper, we posit that by merging conventional techniques, such as microscopy and physiological data, with innovative methods like in situ single-cell sorting and omics datasets, in conjunction with a diverse array of modeling approaches ranging from single-cell modeling to comprehensive Earth system models, we can propel mixoplankton research into the forefront of aquatic ecology. We present eight crucial research questions pertaining to mixoplankton and mixotrophy, and briefly outline a combination of existing methods and models that can be used to address each question. Our intent is to encourage more interdisciplinary research on mixoplankton, thereby expanding the scope of data acquisition and knowledge accumulation for this understudied yet critical component of aquatic ecosystems.
Microbial respiration in contrasting ocean provinces via high-frequency optode assays
Authors: Cohn Melanie R. , Stephens Brandon M. , Meyer Meredith G. , Sharpe Garrett , Niebergall Alexandria K. , Graff Jason R. , Cassar Nicolas , Marchetti Adrian , Carlson Craig A. , Gifford Scott M.
Published: June 2024

Microbial respiration is a critical component of the marine carbon cycle, determining the proportion of fixed carbon that is subject to remineralization as opposed to being available for export to the ocean depths. Despite its importance, methodological constraints have led to an inadequate understanding of this process, especially in low-activity oligotrophic and mesopelagic regions. Here, we quantify respiration rates as low as 0.2 µmol O2 L-1 d-1 in contrasting ocean productivity provinces using oxygen optode sensors to identify size-fractionated respiration trends. In the low productivity region of the North Pacific Ocean at Station Papa, surface whole water microbial respiration was relatively stable at 1.2 µmol O2 L-1 d-1. Below the surface, there was a decoupling between respiration and bacterial production that coincided with increased phytodetritus and small phytoplankton. Size-fractionated analysis revealed that cells <5 µm were responsible for the majority of the respiration in the Pacific, both at the surface and below the mixed layer. At the North Atlantic Porcupine Abyssal Plain, surface whole water microbial respiration was higher (1.7 µmol O2 L-1 d-1) than in the Pacific and decreased by 3-fold below the euphotic zone. The Atlantic size-fraction contributions to total respiration shifted on the order of days during the evolution of a phytoplankton bloom with regular storm disturbances. The high-resolution optode method used in the Atlantic captured these significant shifts and is consistent with coinciding stain-based respiration methods and historical site estimates. This study highlights the dynamic nature of respiration across vertical, temporal, and size-fractionated factors, emphasizing the need for sensitive, high-throughput techniques to better understand ocean ecosystem metabolism.
From apparent attenuation towards physics-based source terms – a perspective on spectral wave modeling in ice-covered seas
Authors: Herman Agnieszka
Published: June 2024

Numerical modeling of waves in sea ice covered regions of the oceans is important for many applications, from short-term forecasting and ship route planning up to climate modeling. In spite of a substantial progress in wave-in-ice research that took place in recent years, spectral wave models – the main tool for wave modeling at regional and larger scales – still don’t capture the underlying physics and have rather poor predictive skills. This article discusses recent developments in wave observations and spectral wave modeling in sea ice, identifies problems and shortcomings of the approaches used so far, and sketches future directions that, in the opinion of the author, have the potential to improve the performance of wave-in-ice models.
Effect of photobiomodulation in the balance between effector and regulatory T cells in an experimental model of COPD
Authors: Brito Auriléia Aparecida de , Herculano Karine Zanella , de Alvarenga-Nascimento Cristiano Rodrigo , Estefano-Alves Cintia , Duran Cinthya Cosme Gutierrez , Marcos Rodrigo Labat , Silva Junior José Antonio , Chavantes Maria Cristina , Zamuner Stella Regina , Aimbire Flávio , Lladó-Pelfort Laia , Gubern Albert , Fàbrega Anna , da Palma Renata Kelly , Ligeiro de Oliveira Ana Paula
Published: June 2024

Introduction

Currently, Chronic Obstructive Pulmonary Disease (COPD) has a high impact on morbidity and mortality worldwide. The increase of CD4+, CD8+ cells expressing NF-κB, STAT4, IFN-γ and perforin are related to smoking habit, smoking history, airflow rate, obstruction and pulmonary emphysema. Furthermore, a deficiency in CD4+CD25+Foxp3+ regulatory T cells (Tregs) may impair the normal function of the immune system and lead to respiratory immune disease. On the other hand, the anti-inflammatory cytokine IL-10, produced by Treg cells and macrophages, inhibits the synthesis of several pro-inflammatory cytokines that are expressed in COPD. Therefore, immunotherapeutic strategies, such as Photobiomodulation (PBM), aim to regulate the levels of cytokines, chemokines and transcription factors in COPD. Consequently, the objective of this study was to evaluate CD4+STAT4 and CD4+CD25+Foxp3+ cells as well as the production of CD4+IFN- γ and CD4+CD25+IL-10 in the lung after PBM therapy in a COPD mice model.

Methods

We induced COPD in C57BL/6 mice through an orotracheal application of cigarette smoke extract. PMB treatment was applied for the entire 7 weeks and Bronchoalveolar lavage (BAL) and lungs were collected to study production of IFN- γ and IL-10 in the lung. After the last administration with cigarette smoke extract (end of 7 weeks), 24 h later, the animals were euthanized. One-way ANOVA followed by NewmanKeuls test were used for statistical analysis with significance levels adjusted to 5% (p < 0.05).

Results

This result showed that PBM improves COPD symptomatology, reducing the number of inflammatory cells (macrophages, neutrophils and lymphocytes), the levels of IFN-γ among others, and increased IL-10. We also observed a decrease of collagen, mucus, bronchoconstriction index, alveolar enlargement, CD4+, CD8+, CD4+STAT4+, and CD4+IFN-γ+ cells. In addition, in the treated group, we found an increase in CD4+CD25+Foxp3+ and CD4+IL-10+ T cells.

Conclusion

This study suggests that PBM treatment could be applied as an immunotherapeutic strategy for COPD.
Contrast agent-free functional magnetic resonance imaging with matrix pencil decomposition to quantify abnormalities in lung perfusion and ventilation in patients with cystic fibrosis
Authors: Doellinger Felix , Bauman Grzegorz , Roehmel Jobst , Stahl Mirjam , Posch Helena , Steffen Ingo G. , Pusterla Orso , Bieri Oliver , Wielpütz Mark O. , Mall Marcus A.
Published: June 2024

Background

Previous studies showed that contrast-enhanced (CE) morpho-functional magnetic resonance imaging (MRI) detects abnormalities in lung morphology and perfusion in patients with cystic fibrosis (CF). Novel matrix pencil decomposition MRI (MP-MRI) enables quantification of lung perfusion and ventilation without intravenous contrast agent administration.

Objectives

To compare MP-MRI with established morpho-functional MRI and spirometry in patients with CF.

Methods

Thirty-nine clinically stable patients with CF (mean age 21.6 ± 10.7 years, range 8–45 years) prospectively underwent morpho-functional MRI including CE perfusion MRI, MP-MRI and spirometry. Two blinded chest radiologists assessed morpho-functional MRI and MP-MRI employing the validated chest MRI score. In addition, MP-MRI data were processed by automated software calculating perfusion defect percentage (QDP) and ventilation defect percentage (VDP).

Results

MP perfusion score and QDP correlated strongly with the CE perfusion score (both r = 0.81; p < 0.01). MP ventilation score and VDP showed strong inverse correlations with percent predicted FEV1 (r = −0.75 and r = −0.83; p < 0.01). The comparison of visual and automated parameters showed that both MP perfusion score and QDP, and MP ventilation score and VDP were strongly correlated (r = 0.74 and r = 0.78; both p < 0.01). Further, the MP perfusion score and MP ventilation score, as well as QDP and VDP were strongly correlated (r = 0.88 and r = 0.86; both p < 0.01).

Conclusion

MP-MRI detects abnormalities in lung perfusion and ventilation in patients with CF without intravenous or inhaled contrast agent application, and correlates strongly with the well-established CE perfusion MRI score and spirometry. Automated analysis of MP-MRI may serve as quantitative noninvasive outcome measure for diagnostic monitoring and clinical trials.
Relationship between Life’s Essential 8 and metabolic syndrome among older Americans (NHANES, 2007–2010): navigating biological aging and inflammation
Authors: Gou Ruoyu , Xiong Si , Liang Xudong , Wu Hao , Qin Shuitao , Li Bing , Luo Changjun , Chen Junan
Published: June 2024

Background

Metabolic syndrome (MetS) is a global health concern, and it is particularly harmful to middle-aged and elderly individuals. Life Element Eight (LE8), a measure to improve cardiovascular health, may offer benefits for MetS. Herein, we examined the relationship between LE8 and MetS among middle-aged and elderly individuals, and elucidated the role of biological aging and inflammation in this process.

Methods

We obtained the LE8 scores of 2,901 Americans, along with their biological aging indicators (Biological age, Phenotypic age, Serum Klotho), and computed their inflammatory indicators SII, DII. Using logistic regression model, we assessed the association among inflammatory markers, Biological aging, LE8 and MetS. Additionally, we generated restricted cubic spline (RCS) plots to display trends in significant variables in logistic regression. Using parallel mediation analysis, we evaluated the possible mediating role of various factors in the risk relationship between LE8 and MetS.

Results

Our examination revealed that higher LE8 scores were associated with a lower incidence of MetS in a fully adjusted model. The high LE8 subgroup had a 79.73% reduction in the risk of MetS compared to the low subgroup with an OR = 0.2027 (95% Cl 0.0871, 0.4714), with similar correlations between health factor scores and MetS risk. Biological aging mediated the associations between LE8, health behaviors and health factor scores and MetS risk.

Conclusion

A rise in the LE8 score among middle-aged and elderly individuals is a protective factor for MetS, and this association may be partially mediated by biological aging, suggesting that LE8 may reduce the risk of MetS by ameliorating aging.
Clinical development and marketing application review times for novel orphan-designated drugs
Authors: Demirci Ebru , Knicley Jennifer , Fiorentino Lori
Published: June 2024

Development of an orphan-designated drug has been more challenging and financially less attractive than that of other drugs due to low prevalence of the condition, poorly defined biomarkers and lack of experience of healthcare providers in diagnosing and treating the condition. Guidance and incentives in some countries support the sponsors in developing orphan-designated drugs despite the challenges. Expedited regulatory programs as offered by the United States (US) Food and Drug Administration (FDA) and the European Medicines Agency (EMA) support the development of drugs, provide shorter marketing application review times or provide preliminary approval. In this study, we analyze marketing application review times in the US and in the European Union (EU) and clinical development times for novel, i.e., containing new molecular entity, orphan-designated drugs that were approved in the US between 1 June 2020 and 31 May 2023, and their correlation with expedited regulatory programs. Seventy-three marketing applications for novel orphan-designated drugs were approved by the FDA, and 39 also received a positive opinion from the EMA. The marketing application review time by the FDA for the 73 novel orphan-designated drugs approved in the US was 244 days (n = 73, median), and the marketing application review time by the EMA for the 39 drugs that were also approved in the EU was 353 days (n = 39, median). The typical clinical development time for a novel orphan-designated drug was 7.2 years (n = 72).
Comparing quantitative image parameters between animal and clinical CT-scanners: a translational phantom study analysis
Authors: Vellala Abhinay , Mogler Carolin , Haag Florian , Tollens Fabian , Rudolf Henning , Pietsch Friedrich , Wängler Carmen , Wängler Björn , Schoenberg Stefan O. , Froelich Matthias F. , Hertel Alexander
Published: June 2024

Purpose

This study compares phantom-based variability of extracted radiomics features from scans on a photon counting CT (PCCT) and an experimental animal PET/CT-scanner (Albira II) to investigate the potential of radiomics for translation from animal models to human scans. While oncological basic research in animal PET/CT has allowed an intrinsic comparison between PET and CT, but no 1:1 translation to a human CT scanner due to resolution and noise limitations, Radiomics as a statistical and thus scale-independent method can potentially close the critical gap.

Methods

Two phantoms were scanned on a PCCT and animal PET/CT-scanner with different scan parameters and then the radiomics parameters were extracted. A Principal Component Analysis (PCA) was conducted. To overcome the limitation of a small dataset, a data augmentation technique was applied. A Ridge Classifier was trained and a Feature Importance- and Cluster analysis was performed.

Results

PCA and Cluster Analysis shows a clear differentiation between phantom types while emphasizing the comparability of both scanners. The Ridge Classifier exhibited a strong training performance with 93% accuracy, but faced challenges in generalization with a test accuracy of 62%.

Conclusion

These results show that radiomics has great potential as a translational tool between animal models and human routine diagnostics, especially using the novel photon counting technique. This is another crucial step towards integration of radiomics analysis into clinical practice.
Polyextremophile engineering: a review of organisms that push the limits of life
Authors: Caro-Astorga Joaquin , Meyerowitz Joseph T. , Stork Devon A. , Nattermann Una , Piszkiewicz Samantha , Vimercati Lara , Schwendner Petra , Hocher Antoine , Cockell Charles , DeBenedictis Erika
Published: June 2024

Nature exhibits an enormous diversity of organisms that thrive in extreme environments. From snow algae that reproduce at sub-zero temperatures to radiotrophic fungi that thrive in nuclear radiation at Chernobyl, extreme organisms raise many questions about the limits of life. Is there any environment where life could not “find a way”? Although many individual extremophilic organisms have been identified and studied, there remain outstanding questions about the limits of life and the extent to which extreme properties can be enhanced, combined or transferred to new organisms. In this review, we compile the current knowledge on the bioengineering of extremophile microbes. We summarize what is known about the basic mechanisms of extreme adaptations, compile synthetic biology’s efforts to engineer extremophile organisms beyond what is found in nature, and highlight which adaptations can be combined. The basic science of extremophiles can be applied to engineered organisms tailored to specific biomanufacturing needs, such as growth in high temperatures or in the presence of unusual solvents.
Prodigiosin: unveiling the crimson wonder – a comprehensive journey from diverse bioactivity to synthesis and yield enhancement
Authors: Lu Yonglin , Liu Derun , Jiang Renhui , Li Ziyun , Gao Xueyan
Published: June 2024

Prodigiosin (PG) is a red tripyrrole pigment from the prodiginine family that has attracted widespread attention due to its excellent biological activities, including anticancer, antibacterial and anti-algal activities. The synthesis and production of PG is of particular significance, as it has the potential to be utilized in a number of applications, including those pertaining to clinical drug development, food safety, and environmental management. This paper provides a systematic review of recent research on PG, covering aspects like chemical structure, bioactivity, biosynthesis, gene composition and regulation, and optimization of production conditions, with a particular focus on the biosynthesis and regulation of PG in Serratia marcescens. This provides a solid theoretical basis for the drug development and production of PG, and is expected to promote the further development of PG in medicine and other applications.
Strong delayed negative feedback
Authors: Erneux Thomas
Published: June 2024

In this paper, we analyze the strong feedback limit of two negative feedback schemes which have proven to be efficient for many biological processes (protein synthesis, immune responses, breathing disorders). In this limit, the nonlinear delayed feedback function can be reduced to a function with a threshold nonlinearity. This will considerably help analytical and numerical studies of networks exhibiting different topologies. Mathematically, we compare the bifurcation diagrams for both the delayed and non-delayed feedback functions and show that Hopf classical theory needs to be revisited in the strong feedback limit.
The effect of inadvertent systemic hypothermia after mechanical thrombectomy in patients with large-vessel occlusion stroke
Authors: auf dem Brinke Kristina , Kück Fabian , Jamous Ala , Ernst Marielle , Kunze-Szikszay Nils , Psychogios Marios-Nikos , Maier Ilko L.
Published: June 2024

Background and aims

Postinterventional hypothermia is a frequent complication in patients with large-vessel occlusion strokes (LVOS) after mechanical thrombectomy (MT). This inadvertent hypothermia might potentially have neuroprotective but also adverse effects on patients’ outcomes. The aim of the study was to determine the rate of hypothermia in patients with LVOS receiving MT and its influence on functional outcome.

Methods

We performed a monocentric, retrospective study using a prospectively derived databank, including all LVOS patients receiving MT between 2015 and 2021. Predictive values of postinterventional body temperature and body temperature categories (hyperthermia (≥38°C), normothermia (35°C–37.9°C), and hypothermia (<35°C)) on functional outcome were analyzed using multivariable Bayesian logistic regression models. Favorable outcome was defined as modified Rankin Scale (mRS) ≤3.

Results

Of the 480 included LVOS patients with MT (46.0% men; mean ± SD age 73 ± 12.9 years), 5 (1.0%) were hyperthermic, 382 (79.6%) normothermic, and 93 (19.4%) hypothermic. Postinterventional hypothermia was significantly associated with unfavorable functional outcome (mRS > 3) after 90 days (OR 2.06, 95% CI 1.01–4.18, p = 0.045). For short-term functional outcome, patients with hypothermia had a higher discharge NIHSS (OR 1.38, 95% CI 1.06 to 1.79, p = 0.015) and a higher change of NIHSS from admission to discharge (OR 1.35, 95% CI 1.03 to 1.76, p = 0.029).

Conclusion

Approximately a fifth of LVOS patients in this cohort were hypothermic after MT. Hypothermia was an independent predictor of unfavorable functional outcomes. Our findings warrant a prospective trial investigating active warming during MT.
Guillain–Barre syndrome and link with COVID-19 infection and vaccination: a review of literature
Authors: Valaparla Vijaya Lakshmi , Rane Schweta P. , Patel Chilvana , Li Xiangping
Published: June 2024

Background

Guillain–Barré syndrome (GBS) is an autoimmune disease associated with significant morbidity. A wide variety of infectious and non-infectious triggers have been identified to be associated with GBS. COVID-19 has gained attention in recent years for its role in GBS pathogenesis. Our study aims to review the literature on GBS and its epidemiological and pathophysiological association with COVID-19.

Description

Recent literature on GBS associated with COVID-19 infections, such as case reports, case series, systematic reviews, and large-scale epidemiological studies, were reviewed. We also reviewed studies that included vaccines against COVID-19 in association with GBS. Studies that focused on understanding the pathobiology of GBS and its association with infectious agents including COVID-19 were reviewed.

Conclusion

Despite a lack of consensus, GBS is strongly associated with COVID-19 infection. The exact pathophysiological mechanism regarding COVID-19 as a causative agent of GBS is unknown. Mechanisms, such as the proinflammatory state, triggering of autoimmunity, and direct viral invasion, are postulated and remain to be investigated. Adenovirus vector vaccines are most likely associated with GBS, and the consensual reports clearly suggest mRNA vaccines are associated with low risk and may be protective against GBS by reducing the risk of COVID-19 infection.
Risk of epilepsy after traumatic brain injury: a nationwide Norwegian matched cohort study
Authors: Sødal Hild Flatmark , Nordseth Trond , Rasmussen Anders Johan Orland , Rosseland Leiv Arne , Stenehjem Jo Steinson , Gran Jon Michael , Helseth Eirik , Taubøll Erik
Published: June 2024

Background

Post-traumatic epilepsy (PTE) is a well-known complication of traumatic brain injury (TBI). Although several risk factors have been identified, prediction of PTE is difficult. Changing demographics and advances in TBI treatment may affect the risk of PTE. Our aim was to provide an up-to-date estimate of the incidence of PTE by linking multiple nationwide registers.

Methods

Patients with TBI admitted to hospital 2015–2018 were identified in the Norwegian Trauma Registry and matched to trauma-free controls on sex and birth year according to a matched cohort design. They were followed up for epilepsy in nationwide registers 2015–2020. Cumulative incidence of epilepsy in TBI patients and controls was estimated taking competing risks into account. Analyses stratified by the Abbreviated Injury Scale (AIS) severity score, Glasgow Coma Scale score and age were conducted for the TBI group. Occurrence of PTE in different injury types was visualized using UpSet plots.

Results

In total, 8,660 patients and 84,024 controls were included in the study. Of the patients, 3,029 (35%) had moderate to severe TBI. The cumulative incidence of epilepsy in the TBI group was 3.1% (95% Confidence Interval [CI] 2.8–3.5%) after 2 years and 4.0% (3.6–4.5%) after 5 years. Corresponding cumulative incidences in the control group were 0.2% (95% CI 0.2–0.3%) and 0.5% (0.5–0.6%). The highest incidence was observed in patients with severe TBI according to AIS (11.8% [95% CI 9.7–14.4%] after 2 years and 13.2% [10.8–16.0%] after 5 years) and in patients >40 years of age.

Conclusion

Patients with TBI have significantly higher risk of developing epilepsy compared to population controls. However, PTE incidence following moderate–severe TBI was notably lower than what has been reported in several previously published studies.
The effects of vitamin D supplementation on serum lipid profiles in people with type 2 diabetes: a systematic review and meta-analysis of randomized controlled trials
Authors: Lu Qingyang , Liang Qingyue , Xi Yue
Published: June 2024

Introduction

People with type 2 diabetes (T2D) are highly susceptible to the development of cardiovascular diseases. Previous studies have suggested that the application of vitamin D may offer potential benefits in improving lipid profiles, but these effects remain controversial.

Methods

This systematic review and meta-analysis focused on the effects of vitamin D supplementation on serum lipid profiles in people with T2D. Randomized controlled trials (RCTs) assessing the effects of vitamin D supplementation on lipid profiles and published before September 19th, 2023, were identified in PubMed, Embase, and Cochrane Library. This review protocol was registered in the PROSPERO (CRD42023461136). The random-effects model was employed to estimate unstandardized mean differences (MD) and 95% confidence intervals (CIs). The quality of studies was assessed by the Cochrane Risk of Bias tool 2.

Results

Overall, 20 RCTs involving 1711 participants were included. Results indicated that vitamin D supplementation significantly improves serum high-density lipoprotein (HDL) (MD: 1.63 mg/dL, 95% CI: 0.19 to 3.08, P = 0.03), and triglyceride (TG) levels (MD: -8.56 mg/dL, 95% CI: -15.23 to -1.89, P = 0.01). However, vitamin D supplementation failed to improve low-density lipoprotein (LDL) levels and total cholesterol (TC) levels. Subgroup analyses and meta-regressions suggested that higher doses of vitamin D supplementation and shorter duration of intervention were more likely to have favorable effects on lipid profiles. Moreover, participants with lower baseline BMI and higher serum 25-hydroxy vitamin D levels exhibited greater improvements in lipid profiles following vitamin D supplementation.

Conclusions

This meta-analysis highlighted the effects of vitamin D supplementation on improving serum HDL and TG levels while not exhibiting significant improvements in LDL and TC levels. Further long-term and high-quality studies are still needed to draw more precise conclusions.

Systematic review registration

https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=461136.
Plasma exchange treatment of a diabetic ketoacidosis child with hyperlipidemia to avoid pancreatitis: a case report
Authors: Huang Shuyue , Song Fuying , Gao Kang , Song Yi , Chen Xiaobo
Published: June 2024

Type 1 diabetes mellitus (T1DM) is a metabolic disorder characterized by an absolute deficiency of insulin due to pancreatic failure. Diabetes ketoacidosis (DKA) has emerged as one of the most common complications of T1DM. Although exceedingly rare, the onset of T1DM with DKA may result in lipemia secondary to severe hypertriglyceridemia (HTG), accounting for several cases in the pediatric population. Along this line, plasma exchange treatment in children with DKA and severe hyperlipidemia has only been reported in some cases. In this case report, the diagnosis of an 11-year-old girl with diabetes ketoacidosis accompanied by severe HTG, along with subsequent plasma exchange treatment, is presented. Initially, the patient received initial management with crystalloid fluid bolus and intravenous insulin therapy. Despite rapid correction of acidosis, persistent HTG subsequently prompted the plasma exchange treatment. A total of three sessions were administered over 2 days, leading to a significant reduction in the triglyceride levels and corneal opacity resolution, indicating a successful therapeutic intervention.