bluuebunny/crossref_metadata_2025 huggingface dataset:
Pemberdayaan Desa Nelayan Melalui Literasi Ekonomi Digital Untuk Mendukung Ekonomi Produktif Masyarakat Pulau Arar
Authors: Al Jumroh Siti Fatihaturrahmah , Nurteteng Nurteteng , Matahari Matahari , Witdianti Yeni , Ihram Ihram
Published: September 2024

Desa nelayan kampung Arar sebagian masyarakatnya berpenghasilan sebagai nelayan dan pedagang hasil laut. Permasalahan prioritas dalam kegiatan ini adalah 1) Hasil laut yang diperdagangkan tidak laku terjual dan membusuk, 2) Pendapatan pedagang semakin memburuk, 3) Tidak adanya kemampuan dalam ekonomi digital, dan 4) Belum diterapkan inovasi teknologi informasi. Masyarakat kampung Arar belum menemukan solusi untuk mengatasi permasalahan-permasalan tersebut. Selain itu masyarakat juga terkendala pada masalah teknologi yaitu kurangnya pemahaman nelayan terhadap sistem teknologi informasi, sebagian besar nelayan belum memiliki smartphone, dan keterbatasan jaringan internet bukan berarti tidak memiliki akses jaringan internet. Mestinya pada masa ini pemanfaatan teknologi merupakan hal yang sudah lazim pada semua aspek kehidupan. Oleh karena itu, tim pengabdi berinisiatif membuat perubahan yang inovatif dalam bentuk teknologi informasi untuk mengatasi permasalahan tersebut, yakni dengan memberikan pendampingan dalam memasarkan hasil laut melalui teknologi digital. Dari hasil kuesioner evaluasi kegiatan diketahui bahwa peserta pelatihan dari jumlah total peserta 15 terdapat 9 orang peserta yang menyatakan pelatihan mengenai digital marketing ini mudah, 3 orang peserta yang menyatakan sedang, dan tidak ada peserta yang menyatakan sulit. Kegiatan menunjukkan bahwa pelatihan digital marketing ini mudah dipahami oleh masyarakat pulau Arar khususnya yang tergabung dalam BUMDES. Berdasarkan hasil pendampingan yang dilakukan dengan adanya beberapa kendala, maka perlu adanya tindak lanjut bentuk pengabdian yang dilakukan di kampung Arar ini, yakni berupa akses internet yang memadai.
Mengenal Budaya Lamongan Melalui Literasi Digital Berbasis Game Education Di Sekolah Dasar
Authors: Pramusinta Yulia , Viyanti Pratiwi , Fitriani Ayu Novi
Published: September 2024

Pergeseran paradigma budaya lokal yang mulai luntur disebabkan oleh globalisasi mengakitbatkan budaya lokal tersisihkan dan terlupakan. Banyaknya siswa madrasah yang belum mengenal budaya lokal dan rendahnya kemampuan literasi siswa menjadi sebuah masalah yang harus segera diatasi. Pengenalan budaya lokal melalui literasi digital yang dikemas dengan games pembelajaran akan lebih menarik dan efisien dalam memecahkan masalah pembelajaran tersebut. Sasaran kegiatan ini ada siswa kelas 5 dan kelas 6 di MI Narative Quran Lamongan. Kegiatan pengabdian terdiri dari 4 tahapan yakni, analisis kebutuhan, persiapan, pelaksanaan, dan evaluasi. Kegiatan pengabdian ini melalui beberapa rangkaian kegiatan, antara lain 1) pada tahap analisis kebutuhan tim pengabdian melakukan wawancara dan observasi sekolah, 2) pada tahap perisiapan tim pengabdian membuat soal dan modul ajar bertema kearifan lokal Lamongan, 3) pada tahap pelaksanaan tim pengabdian mengimplementasikan pembelajaran berbasis kearifan lokal Lamongan melalui games education, dan 4) pada tahap evaluasi tim pengabdian mengevaluasi nilai games education siswa dan di dapatkan hasil nilai siswa pada kategori tinggi.
Pendampingan Pengaplikasian Hasil Desain Pada Kelompok Remaja Jimpitan Kelurahan Batu Jaya, Kota Tangerang
Authors: Pangestu Ilham Aji , Suseno Ari , Fadhlillah Muhammad Rizqi , Kurniawan Irvan Arif
Published: September 2024

Kegiatan Pengabdian Kepada Masyarakat ini merupakan kegiatan tahap 2 (dua) berdasarkan roadmap kegiatan Pengabdian Kepada Masyarakat pada kelompok remaja Jimpitan. Kelompok remaja Jimpitan dalam hal ini terhimpun dalam Pusat Informasi, Konseling, Komunikasi Remaja (PIKKR). Tujuan dari kegiatan Pengabdian Kepada Masyarakat tahap 2 (dua) ini adalah kelompok remaja PIKKR dapat mengaplikasikan hasil desain yang sudah disusun kedalam suatu media tertentu. Metode yang digunakan pada Pengabdian Kepada Masyarakat tahap 2 (dua) ini menggunkan metode pelatihan. Dengan metode pelatihan, peserta dalam hal ini kelompok remaja PIKKR diberikan materi mengenai dasar-dasar desain, aplikasi yang digunakan serta pemahaman dalam mengaplikasikan kedalam suatu media tertentu. Materi-materi tersebut selain diberikan secara teori, juga dilaksanakan melalui praktik. Berdasarkan kegiatan Pengabdian Kepada Masyarakat tahap 2 (dua) yang sudah dilaksanakan, tujuan utama dari kegiatan ini belum tercapai. Hal tersebut dipengaruhi oleh beberapa faktor kendala. Faktor-faktor kendala tersebut diantaranya, pertama yaitu kendala dalam hal instal aplikasi adobe illustrator. Kedua, tidak seluruhnya anggota kelompok remaja PIKKR memiliki laptop. Ketiga, kurangnya intensitas pendampingan kepada kelompok remaja PIKKR. Untuk kedepannya, saran yang diberikan diantaranya pertama, memperkuat intensitas pendampingan dan monitoring, baik dilakukan secara formal ataupun non formal. Kedua, memperkuat komunikasi dengan kelompok remaja PIKKR, dan ketiga, mengalokasikan laptop yang khusus digunakan oleh kelompok remaja PIKKR.
Peningkatan Kualitas UMKM Dalam Pemasaran Teh Telang Berbasis Digital Di Desa Wage, Kecamatan Taman
Authors: Kurniawan Bagus Ananda , Prasetyo Farrel Eko , Halawa Tita Vestalenti
Published: September 2024

Warga RW 13 Desa Wage di Kecamatan Taman Kabupaten Sidoarjo, Jawa Timur, membudidayakan bunga telang di halaman rumah. Masyarakat menganggap bunga telang adalah tanaman rambat biasa. Oleh karena itu, untuk mengetahui keuntungan bunga telang, pemberdayaan masyarakat harus dilakukan. Kehidupan masyarakat RW 13 Desa Wage Kecamatan Taman memiliki beragam UMKM hasil olahan bunga telang. Usaha olahan produk ini adalah mata pencaharian utama dan memiliki kebun kecil bunga telang di wilayah asrama polisi RW 13 Desa Wage dan sekitar wilayah Desa Wage RW 13 ini salah satu tempat sebagai pengembangan usaha teh telang dan memiliki UMKM hasil olahan bunga telang berupa teh telang dan serbuk teh telang. RW 13 Desa wage ini sebagai tempat kegiatan pengabdian kepada masyarakat mandiri yang dilaksanakan oleh Tim Dosen bidang pengabdian masyarakat dan kelompok 1 KKN gelombang 2. Adapun yang menjadi mitra kegiatan pengabdian kepada masyarakat mandiri  ini adalah Kelompok Kuliah Kerja Nyata (KKN), para warga beserta pengurus Rukun Warga (RW) 3, dan UMKM Asmantoga RW 13 Teh telang Desa Wage Kecamatan Taman. Kegiatan pengabdian kepada masyarakat mandiri ini dilaksanakan dengan metode pelatihan dan pendampingan. Pelatihan dilaksanakan dalam sebuah workshop yang memberikan pendalaman materi tentang pentingnya penghijauan dan menumbuhkan kepedulian penghijauan, mendesain label produk, digital marketing e-commerce dalam memasarkan komoditi teh telang, menambahkan konten berita artikel di website resmi Desa Wage, mengadakan lomba mengaji untuk meningkatkan literasi anak usia dini.
Pharmacokinetics of a new drug based on polysaccharide from acorus calamus in an experiment on laboratory animals
Authors: Krivoshchekov S. V. , Yanovskaya E. A. , Gurto R. V. , Bryushinina O. S. , Isakov D. A. , Zykova A. V. , Zyuz’kova Yu. G. , Guryev A. M. , Udut V. V. , Belousov M. V.
Published: September 2024

Introduction. α(1,2)-L-rhamno-α(1,4)-D-galactopyranosyluronane is a water-soluble heteropolysaccharide isolated from the rhizomes of calamus marsh (Acorus calamus L.) and has antitumor, antimetastatic, immunomodulatory and hepatoprotective effects, protective effect on hematopoiesis suppressed during cytostatic treatment.

Aim. Validation of the bioanalytical method for the determination of α(1,2)-L-rhamno-α(1,4)-D-galactopyranosyluronane Acorus calamus L. and the study of the pharmacokinetic parameters of a new drug based on it after a single administration of 120 mg/kg to rats and 24, 30, 42 mg/kg to rabbits.

Materials and methods. In the study, 8 male rats (average weight – 300 g) were used as the main animals. 6 male rabbits (average body weight – 2.5 kg) were used as an additional animal species. The dose assessment experiment was carried out on 24 rabbits (body weight – 2.3–2.5 kg). The quantitative determination of α(1,2)-L-rhamno-α(1,4)-D-galactopyranosyluronane Acorus calamus L. in the blood plasma of animals was carried out by HPLC-MS/MS, the analytical form was galacturonic acid. The method of sample preparation of biological samples included the stage of enzymatic hydrolysis of α(1,2)-L-rhamno-α(1,4)-D-galactopyranosyluronane Acorus calamus L. with a solution of pectinase for the formation of galacturonic acid.

Results and discussions. The pharmacokinetics of the new drug α(1,2)-L-rhamno-α(1,4)-D-galactopyranosyluronane Acorus calamus L. was studied after a single dose of 120 mg/kg to rats and 24, 30, 42 mg/kg to rabbits. The average residence time of the drug in the rabbit's body was 1.0 ± 0.21 hours, the half-life was 0.7 ± 0.15 hours. The average residence time of the drug in the rat body was 1.16 hours, the half-life T1/2 was 0.80 hours. After a single intravenous administration to rabbits of 24, 30 and 42 mg/kg, the maximum concentration in the systemic bloodstream is reached 5 minutes after administration and averages 133.95 ± 27.04, 145.86 ± 40.90 and 226.13 ± 41.27 µg/ml, respectively, the half-life ranged from 0.22 to 0.26 h, the half-life from 3.52 to 3.96 hours.

Conclusion. The pharmacokinetic parameters of α(1,2)-L-rhamno-α(1,4)-D-galactopyranosyluronane Acorus calamus L. were evaluated in animals based on the use of the method of quantitative determination of galacturonic acid by HPLC-MS/MS.
Stress Level Instrument in Disabled Athletes: A Bibliography Analysis in Database Scopus, Pubmed, and Crossref 2018-2024
Authors: Burhaeın Erick , Phytanza Diajeng Tyas Pinru , Abror Muchlas , Hadiwiyanti Rizka , Marfu'atun Elya
Published: September 2024

The study of theoretical analysis of stress measurement instruments in athletes with disabilities has high urgency in the context of sports science and practice. Athletes with disabilities face unique challenges that are different from non-disabled athletes, both physically, psychologically, and socially. This study chose the Scopus, PubMed, dan Crossref database (the leading databases in the world) as the research sample and data source to be used in bibliometric analysis, covering the spectrum of publications from 2018 to 2024. Through this meticulous process, a subset was screened until finally 552 papers were selected, representing the pinnacle of rigorous research methodology and the basis for subsequent analysis and interpretation. To explore and identify key thematic areas as well as emerging topics using keyword co-emergence analysis. To support the process of visualization and analysis of the data obtained, the Vosviewer application is used. The findings in bibiometric analysis showed that these five clusters, namely: (1) athlete; (2) disability; (3) instrument; (4) patient; (5) stress level. One of them is the keyword "stress level" found in cluster 5. If the keyword is focused on networking, connections will appear on other keywords across the cluster. It can be seen that there is no connection to the keyword "athletes of disability", so this is a novelty and even a new finding in research in the present and the years to come.
Trophic ecology, based on stable isotope values, of long-finned pilot whales Globicephala melas stranded on the Icelandic coast
Authors: Samarra FIP , Borrell A , Selbmann A , Chosson V , Chicco C , Haas CE , Basran CJ , Smith A , Ovide BG , Einarsson GÞ , Halldórson SD , O’Brien ES , Eleman A , Sigurðsson GM , Aguilar A
Published: September 2024

In Iceland, occurrences of long-finned pilot whales Globicephala melas and strandings in coastal waters are irregular and thought to be related to prey movements; however, little is known about the population’s trophic ecology, making it difficult to assess its role in the regional ecosystem. To investigate the trophic niche of the species, we measured δ13C and δ15N values from skin and muscle samples collected from 16 strandings (12 single and 4 mass strandings) spanning 33 yr (1988-2021). We tested the effects of sex, age class and body length on δ13C and δ15N values within the species. We found that δ13C values did not differ between sexes or age classes, nor did they vary with body length. Values of δ15N did not vary with sex or body length, but varied slightly between adults and juveniles, albeit not sufficiently to support a difference in trophic levels. Whales from different mass stranding events showed similar stable isotope niche widths (approximately 0.20‰2) and overlapping isotope niches (generally >45% of the standard ellipse area corrected for small sample size). Overall, pilot whales in this region showed a narrow isotopic niche width and low intraspecific variation in isotopic niche. Future analyses using complementary chemical tracers and stomach contents will be important to identify the factors driving these patterns. The first measurements of the stable isotope niche of pilot whales presented here provide a baseline for future studies to determine niche overlap between cetaceans in Iceland, contributing to their management and conservation.
Civic Learning through active citizenship in diverse societies
Authors: Kukovetz Brigitte , Sprung Annette , Wlasak Petra
Published: September 2024

In response to the growing heterogenous populations in urban areas, and the important role of civic engagement and active citizenship for the promotion of democratic processes, this paper discusses the active participation of resident foreign citizens and/or persons with a history of migration, in urban areas. The theoretical connections between active citizenship, lived citizenship and civic learning are outlined and then linked with the results of an applied research project focused on various aspects of gender. In conclusion, active – lived – citizenship, in particular ‘performative’ acts of citizenship, generate civic learning as subjectification. Public spaces as learning opportunities for active engagement should take into account aspects of diversity as well as inequalities in a diverse society in order to promote inclusion and democracy for as many residents as possible regardless of their citizenship status.
Causal role of immune cells in diabetic nephropathy: a bidirectional Mendelian randomization study
Authors: Wang Shang-Yuan , Yu Yang , Ge Xiao-Li , Pan Shuming
Published: September 2024

Background

Diabetic nephropathy (DN) stands as a pervasive chronic renal disease worldwide, emerging as the leading cause of renal failure in end-stage renal disease. Our objective is to pinpoint potential immune biomarkers and evaluate the causal effects of prospective therapeutic targets in the context of DN.

Methods

We employed Mendelian randomization (MR) analysis to examine the causal associations between 731 immune cell signatures and the risk of DN. Various analytical methods, including inverse-variance weighted (IVW), MR-Egger, weighted median, simple mode, and weighted mode, were employed for the analysis. The primary analytical approach utilized was the inverse-variance weighted (IVW) method. To ensure the reliability of our findings, we conducted comprehensive sensitivity analyses to assess the robustness, heterogeneity, and presence of horizontal pleiotropy in the results. Statistical powers were also calculated. Ultimately, a reverse Mendelian randomization (MR) analysis was conducted to assess the potential for reverse causation.

Results

After Benjamini & Hochberg (BH) correction, four immunophenotypes were identified to be significantly associated with DN risk: HLA DR on Dendritic Cell (OR=1.4460, 95% CI = 1.2904~1.6205, P=2.18×10−10, P.adjusted= 1.6×10−7), HLA DR on CD14+ CD16− monocyte (OR=1.2396, 95% CI=1.1315~1.3580, P=3.93×10−6, P.adjusted = 0.00143). HLA DR on CD14+ monocyte (OR=1.2411, 95% CI=1.12957~1.3637, P=6.97×10−6, P.adjusted=0.0016), HLA DR on plasmacytoid Dendritic Cell (OR=1.2733, 95% CI= 1.1273~1.4382, P= 0.0001, P.adjusted = 0.0183). Significant heterogeneity of instrumental variables was found in the four exposures, and significant horizontal pleiotropy was only found in HLA DR on Dendritic Cell. The bidirectional effects between the immune cells and DN were not supported.

Conclusion

Our research illustrated the intimate association between immune cells and DN, which may contribute to a deeper understanding of the intricate mechanisms underlying DN and aid in the identification of novel intervention target pathways.
Research on reactive power compensation control method for improving the voltage stability of photovoltaic station area
Authors: Zhang Wei , Zhang Zhe , Dai Yuanyi , Dong Chen , Yu Zhijia , Hu Yue
Published: September 2024

In the case of resistance-inductance lines in PV station area, the problem of voltage overstep is easy to occur. This article proposes a reactive power compensation control method to improve the voltage stability in the photovoltaic power plant area, which addresses the problem of voltage at the point of common coupling (PCC) exceeding the upper limit due to resistance circuits and exceeding the lower limit due to relatively insufficient reactive power output when the output active power is high. The idea is to achieve dynamic adjustment of PCC voltage by paralleling a static reactive power generator (SVG) at the grid connection point and using a variable droop control method. In addition, a reactive power optimization method based on improved particle swarm optimization (IPSO) algorithm is proposed to address the changes in power flow caused by photovoltaic integration in the distribution network system. The proposed improvement method not only effectively reduces network losses but also significantly improves voltage stability.
Cloud model-based intelligent controller for load frequency control of power grid with large-scale wind power integration
Authors: Li Dexin , Lv Xiangyu , Zhang Haifeng , Meng Xiangdong , Xu Zhenjun , Chen Chao , Liu Taiming
Published: September 2024

The intermittent and fluctuating nature of active power output from wind power significantly affects the Load Frequency Control (LFC) in a power grid based on active power balance. To address this issue, this paper proposes a cloud-based intelligent PI controller designed to enhance the performance of LFC in smart grids with large-scale wind power integration. By using the error and the rate of change of error as the antecedent inputs of the cloud model-based controller and the tuning values of P and I as the consequent outputs of the cloud model, adaptive online tuning of the PI parameters is achieved. Based on the control rules of LFC in interconnected power grids and considering the uncertainty of wind power’s active power output, the membership cloud parameters are designed, which effectively solves the problems of poor parameter robustness in traditional PI control and significant human influence on membership degrees in Fuzzy PI control. A simulation model of a dual-area interconnected power grid with wind power for LFC was built using Matlab/Simulink. Two typical disturbances, namely random fluctuations in wind power and sudden increases/decreases in load, were simulated. The simulation results demonstrate that the cloud model-based intelligent PI controller designed in this paper can effectively track the frequency variations caused by random fluctuations in wind power and exhibits strong robustness.
Environmental regulation, industrial transformation, and green economy development
Authors: Shao Huimin , Peng Qiong , Zhou Fei , Wider Walton
Published: September 2024

Background

Green development, which is crucial because of the escalating ecological and environmental issues, is largely driven by industrial transformation and environmental legislation.

Purpose

The paper aims to examine the combined effects of environmental regulations and industrial change on the green economy, based on their separate effects.

Methods

We use a fixed-effects regression on panel data covering 30 provinces in China in 2010–2020.

Results

We reach the following conclusions: environmental regulations and rationalization of the industrial structure both support growth in the green economy, but advancement in the industrial structure hinders it. The combined effect of environmental regulations and advancement and rationalization in the industrial structure has a significantly positive impact on growth in the green economy; it is most pronounced in regions with higher resource endowments and economic development.

Discussion

By providing specific empirical facts, this study clarifies the effects of industrial transformation and environmental regulations on growth in the green economy, contributing to enriching the literature and helping to pave the way to sustainable development.
Response of radial growth of Dahurian larch (Larix gmelinii) to climate factors at different altitudes in the northern part of the Greater Khingan Mountains
Authors: Luo Taoran , Wang Zhaopeng , Zhang Dongyou , Li Xiangyou , Wang Xinrui
Published: September 2024

Introduction

To investigate the differences in the response of radial growth of larch (Larix gmelinii) at varying altitude gradients to climatic factors, this study established tree-ring width chronologies of Larix gmelinii at altitudes of 900 m, 1,120 m and 1,300 m based dendroclimatology.

Methods

We also employed R packages including “dplR,” “static” and “moving” to determine the correlation between larch at different altitudes and climatic factors and to explore the sensitivity and stability between radial growth and the climate of larch at different altitudes in the northern part of the Greater Khingan Mountains Range in Northeast China.

Results

The results revealed the radial growth of larch in high altitude areas to exhibit a downward trend due to climate warming, while the growth of trees in intermediate and low altitude areas showed an upward trend. The growth–climate relationship exhibited a significant negative correlation between radial growth in low altitude larch (900 m) and temperatures in the current winter (February and March) and growing season (July, October of the current year, and October of the previous year) (p < 0.05). Moreover, high altitude larch (1,300 m) showed a significant negative correlation with temperature in January, March, and October of the current year (p < 0.05). However, in intermediate altitude areas (1,120 m), the radial growth of trees was significantly positively correlated with the temperature of the growing season (May, June and August). Precipitation in April was observed to promote the radial growth of low-altitude larch. Moving correlation analysis revealed that the inhibitory effect of low temperatures in winter and high temperatures in the growing season on the radial growth of larch at three altitudes gradually strengthened, transitioning from significant negative/positive correlations to significant positive/negative correlations along the altitudinal gradient.

Discussion

Larch trees in high and low altitudes exhibited an increased sensitivity to winter and spring precipitation, while in the intermediate region, the inhibitory effect of growing season precipitation on larch radial growth continued to intensify. The results of the study have an important reference value for the in-depth understanding of the growth dynamics of Larix gmelinii natural forests in the northern part of the Greater Khingan Mountains under climate change.
Comprehensive time-course gene expression evaluation of high-risk beef cattle to establish immunological characteristics associated with undifferentiated bovine respiratory disease
Authors: Scott Matthew A. , Valeris-Chacin Robert , Thompson Alexis C. , Woolums Amelia R. , Karisch Brandi B.
Published: September 2024

Bovine respiratory disease (BRD) remains the leading infectious disease in beef cattle production systems. Host gene expression upon facility arrival may indicate risk of BRD development and severity. However, a time-course approach would better define how BRD development influences immunological and inflammatory responses after disease occurrences. Here, we evaluated whole blood transcriptomes of high-risk beef cattle at three time points to elucidate BRD-associated host response. Sequenced jugular whole blood mRNA from 36 cattle (2015: n = 9; 2017: n = 27) across three time points (n = 100 samples; days [D]0, D28, and D63) were processed through ARS-UCD1.2 reference-guided assembly (HISAT2/Stringtie2). Samples were categorized into BRD-severity cohorts (Healthy, n = 14; Treated 1, n = 11; Treated 2+, n = 11) via frequency of antimicrobial clinical treatment. Assessment of gene expression patterns over time within each BRD cohort was modeled through an autoregressive hidden Markov model (EBSeq-HMM; posterior probability ≥ 0.5, FDR < 0.01). Mixed-effects negative binomial models (glmmSeq; FDR < 0.05) and edgeR (FDR < 0.10) identified differentially expressed genes between and across cohorts overtime. A total of 2,580, 2,216, and 2,381 genes were dynamically expressed across time in Healthy, Treated 1, and Treated 2+ cattle, respectively. Genes involved in the production of specialized resolving mediators (SPMs) decreased at D28 and then increased by D63 across all three cohorts. Accordingly, SPM production and alternative complement were differentially expressed between Healthy and Treated 2+ at D0, but not statistically different between the three groups by D63. Magnitude, but not directionality, of gene expression related to SPM production, alternative complement, and innate immune response signified Healthy and Treated 2+ cattle. Differences in gene expression at D63 across the three groups were related to oxygen binding and carrier activity, natural killer cell-mediated cytotoxicity, cathelicidin production, and neutrophil degranulation, possibly indicating prolonged airway pathology and inflammation weeks after clinical treatment for BRD. These findings indicate genomic mechanisms indicative of BRD development and severity over time.
Radiation immunodynamics in patients with glioblastoma receiving chemoradiation
Authors: Sloan Lindsey , Sen Rupashree , Liu Chunnan , Doucet Michele , Blosser Lee , Katulis Lisa , Kamson David O. , Grossman Stuart , Holdhoff Matthias , Redmond Kristin J. , Quon Harry , Lim Michael , Eberhart Charles , Pardoll Drew M. , Hu Chen , Ganguly Sudipto , Kleinberg Lawrence R.
Published: September 2024

Introduction

This is a prospective, rigorous inquiry into the systemic immune effects of standard adjuvant chemoradiotherapy, for WHO grade 4, glioblastoma. The purpose is to identify peripheral immunologic effects never yet reported in key immune populations, including myeloid-derived suppressor cells, which are critical to the immune suppressive environment of glioblastoma. We hypothesize that harmful immune-supportive white blood cells, myeloid derived suppressor cells, expand in response to conventionally fractionated radiotherapy with concurrent temozolomide, essentially promoting systemic immunity similar what is seen in chronic diseases like diabetes and heart disease.

Methods

16 patients were enrolled in a single-institution, observational, immune surveillance study where peripheral blood was collected and interrogated by flow cytometry and RNAseq. Tumor tissue from baseline assessment was analyzed with spatial proteomics to link peripheral blood findings to baseline tissue characteristics.

Results

We identified an increase in myeloid-derived suppressor cells during the final week of a six-week treatment of chemoradiotherapy in peripheral blood of patients that were not alive at two years after diagnosis compared to those who were living. This was also associated with a decrease in CD8+ T lymphocytes that produced IFNγ, the potent anti-tumor cytokine.

Discussion

These data suggest that, as in chronic inflammatory disease, systemic immunity is impaired following delivery of adjuvant chemoradiotherapy. Finally, baseline investigation of myeloid cells within tumor tissue did not differ between survival groups, indicating immune surveillance of peripheral blood during adjuvant therapy may be a critical missing link to educate our understanding of the immune effects of standard of care therapy for glioblastoma.
Neutrophil-fibroblast crosstalk drives immunofibrosis in Crohn’s disease through IFNα pathway
Authors: Gavriilidis Efstratios , Divolis Georgios , Natsi Anastasia-Maria , Kafalis Nikolaos , Kogias Dionysios , Antoniadou Christina , Synolaki Evgenia , Pavlos Evgenios , Koutsi Marianna A. , Didaskalou Stylianos , Papadimitriou Evangelos , Tsironidou Victoria , Gavriil Ariana , Papadopoulos Vasileios , Agelopoulos Marios , Tsilingiris Dimitrios , Koffa Maria , Giatromanolaki Alexandra , Kouklakis Georgios , Ritis Konstantinos , Skendros Panagiotis
Published: September 2024

Introduction

Crohn’s disease (CD) is characterized by chronic inflammation and intestinal fibrosis leading to lifelong complications. However, the disease pathogenesis remains elusive, and the therapeutic options are limited. Here, we investigated the interaction between neutrophils and intestinal fibroblasts in the development of CD immunofibrosis, a disease mechanism predisposing to inflammatory and fibrotic complications.

Methods

Peripheral neutrophils, enriched neutrophil extracellular traps (eNETs), serum, primary intestinal fibroblasts (PIFs) and intestinal biopsies from CD, ulcerative colitis (UC) patients, and healthy individuals (HI), were studied. Transcriptome analysis of neutrophils, multi-cytokine profiling and cell-based functional assays at mRNA/protein level were performed.

Results

Compared to UC, PIFs from CD patients, independently to the presence of strictures, displayed a distinct pro-fibrotic phenotype characterized by negative Krüppellike Factor-2 (KLF2) and increased cellular communication network factor-2 (CCN2) expression leading to collagen production. In both UC and CD, PIFs-derived IL-8 acted as a culprit chemoattractant for neutrophils in the intestine, where CD neutrophils were accumulated close to fibrotic lesions. Functionally, only CD neutrophils via eNETs induced a CD-like phenotype in HI PIFs, suggesting their fibrotic plasticity. High IFNa in serum and IFΝ-responsive signature in peripheral neutrophils were observed in CD, distinguishing it from UC. Moreover, CD serum stimulated the release of fibrogenic eNETs from neutrophils in an IFNa-dependent manner, suggesting the priming role of IFNa in circulating neutrophils. Inhibition of eNETs or JAK signaling in neutrophils or PIFs prevented the neutrophil-mediated fibrotic effect on PIFs. Furthermore, both serum IFNa levels and mRNA levels of key IFN signaling components in neutrophils were wellcorrelated with CD severity.

Conclusions

This study reveals the important role of the IFNa/neutrophil/fibroblast axis in CD immunofibrosis, suggesting candidate biomarkers and putative therapeutic targets.
Glycolysis-associated lncRNAs in cancer energy metabolism and immune microenvironment: a magic key
Authors: Zhang Xi , Zhang Yunchao , Liu Qiong , Zeng Anqi , Song Linjiang
Published: September 2024

The dependence of tumor cells on glycolysis provides essential energy and raw materials for their survival and growth. Recent research findings have indicated that long chain non-coding RNAs (LncRNAs) have a key regulatory function in the tumor glycolytic pathway and offer new opportunities for cancer therapy. LncRNAs are analogous to a regulatory key during glycolysis. In this paper, we review the mechanisms of LncRNA in the tumor glycolytic pathway and their potential therapeutic strategies, including current alterations in cancer-related energy metabolism with lncRNA mediating the expression of key enzymes, lactate production and transport, and the mechanism of interaction with transcription factors, miRNAs, and other molecules. Studies targeting LncRNA-regulated tumor glycolytic pathways also offer the possibility of developing new therapeutic strategies. By regulating LncRNA expression, the metabolic pathways of tumor cells can be interfered with to inhibit tumor growth and metastasis, thus affecting the immune and drug resistance mechanisms of tumor cells. In addition, lncRNAs have the capacity to function as molecular markers and target therapies, thereby contributing novel strategies and approaches to the field of personalized cancer therapy and prognosis evaluation. In conclusion, LncRNA, as key molecules regulating the tumor glycolysis pathway, reveals a new mechanism of abnormal metabolism in cancer cells. Future research will more thoroughly investigate the specific mechanisms of LncRNA glycolysis regulation and develop corresponding therapeutic strategies, thereby fostering new optimism for the realization of precision medicine.
Unraveling the role of ADAMs in clinical heterogeneity and the immune microenvironment of hepatocellular carcinoma: insights from single-cell, spatial transcriptomics, and bulk RNA sequencing
Authors: Chen Junhong , Yuan Qihang , Guan Hewen , Cui Yuying , Fu Chang , Wei Tianfu , Liu Kai
Published: September 2024

Background

Hepatocellular carcinoma (HCC) is a prevalent and heterogeneous tumor with limited treatment options and unfavorable prognosis. The crucial role of a disintegrin and metalloprotease (ADAM) gene family in the tumor microenvironment of HCC remains unclear.

Methods

This study employed a novel multi-omics integration strategy to investigate the potential roles of ADAM family signals in HCC. A series of single-cell and spatial omics algorithms were utilized to uncover the molecular characteristics of ADAM family genes within HCC. The GSVA package was utilized to compute the scores for ADAM family signals, subsequently stratified into three categories: high, medium, and low ADAM signal levels through unsupervised clustering. Furthermore, we developed and rigorously validated an innovative and robust clinical prognosis assessment model by employing 99 mainstream machine learning algorithms in conjunction with co-expression feature spectra of ADAM family genes. To validate our findings, we conducted PCR and IHC experiments to confirm differential expression patterns within the ADAM family genes.

Results

Gene signals from the ADAM family were notably abundant in endothelial cells, liver cells, and monocyte macrophages. Single-cell sequencing and spatial transcriptomics analyses have both revealed the molecular heterogeneity of the ADAM gene family, further emphasizing its significant impact on the development and progression of HCC. In HCC tissues, the expression levels of ADAM9, ADAM10, ADAM15, and ADAM17 were markedly elevated. Elevated ADAM family signal scores were linked to adverse clinical outcomes and disruptions in the immune microenvironment and metabolic reprogramming. An ADAM prognosis signal, developed through the utilization of 99 machine learning algorithms, could accurately forecast the survival duration of HCC, achieving an AUC value of approximately 0.9.

Conclusions

This study represented the inaugural report on the deleterious impact and prognostic significance of ADAM family signals within the tumor microenvironment of HCC.
Neu1 deficiency and fibrotic lymph node microenvironment lead to imbalance in M1/M2 macrophage polarization
Authors: Escalona Emilia , Olate-Briones Alexandra , Albornoz-Muñoz Sofía , Bonacic-Doric Enzo , Rodríguez-Arriaza Francisca , Herrada Andrés A. , Escobedo Noelia
Published: September 2024

Macrophages play a pivotal role in tissue homeostasis, pathogen defense, and inflammation resolution. M1 and M2 macrophage phenotypes represent two faces in a spectrum of responses to microenvironmental changes, crucial in both physiological and pathological conditions. Neuraminidase 1 (Neu1), a lysosomal and cell surface sialidase responsible for removing terminal sialic acid residues from glycoconjugates, modulates several macrophage functions, including phagocytosis and Toll-like receptor (TLR) signaling. Current evidence suggests that Neu1 expression influences M1/M2 macrophage phenotype alterations in the context of cardiovascular diseases, indicating a potential role for Neu1 in macrophage polarization. For this reason, we investigated the impact of Neu1 deficiency on macrophage polarization in vitro and in vivo. Using bone marrow-derived macrophages (BMDMs) and peritoneal macrophages from Neu1 knockout (Neu1−/−) mice and wild-type (WT) littermate controls, we demonstrated that Neu1-deficient macrophages exhibit an aberrant M2-like phenotype, characterized by elevated macrophage mannose receptor 1 (MMR/CD206) expression and reduced responsiveness to M1 stimuli. This M2-like phenotype was also observed in vivo in peritoneal and splenic macrophages. However, lymph node (LN) macrophages from Neu1−/− mice exhibited phenotypic alterations with reduced CD206 expression. Further analysis revealed that peripheral LNs from Neu1−/− mice were highly fibrotic, with overexpression of transforming growth factor-beta 1 (TGF-β1) and hyperactivated TGF-β signaling in LN macrophages. Consistently, TGF-β1 was found to alter M1/M2 macrophage polarization in vitro. Our findings showed that Neu1 deficiency prompts macrophages towards an M2 phenotype and that microenvironmental changes, particularly increased TGF-β1 in fibrotic tissues such as peripheral LNs in Neu1−/− mice, further influence M1/M2 macrophage polarization, highlighting its sensitivity to the local microenvironment. Therapeutic interventions targeting Neu1 or TGF-β signaling pathways may offer the potential to regulate macrophage behavior across different diseases.
Impact of exercise on cancer: mechanistic perspectives and new insights
Authors: Feng Ye , Feng Xingting , Wan Renwen , Luo Zhiwen , Qu Lijun , Wang Qing
Published: September 2024

This review critically evaluates the substantial role of exercise in enhancing cancer prevention, treatment, and patient quality of life. It conclusively demonstrates that regular physical activity not only reduces cancer risk but also significantly mitigates side effects of cancer therapies. The key findings include notable improvements in fatigue management, reduction of cachexia symptoms, and enhancement of cognitive functions. Importantly, the review elucidates the profound impact of exercise on tumor behavior, modulation of immune responses, and optimization of metabolic pathways, advocating for the integration of exercise into standard oncological care protocols. This refined abstract encourages further exploration and application of exercise as a pivotal element of cancer management.
Use of whole genome sequencing for surveillance and control of foodborne diseases: status quo and quo vadis
Authors: Schadron Tristan , van den Beld Maaike , Mughini-Gras Lapo , Franz Eelco
Published: September 2024

Improvements in sequencing quality, availability, speed and costs results in an increased presence of genomics in infectious disease applications. Nevertheless, there are still hurdles in regard to the optimal use of WGS for public health purposes. Here, we discuss the current state (“status quo”) and future directions (“quo vadis”) based on literature regarding the use of genomics in surveillance, hazard characterization and source attribution of foodborne pathogens. The future directions include the application of new techniques, such as machine learning and network approaches that may overcome the current shortcomings. These include the use of fixed genomic distances in cluster delineation, disentangling similarity or lack thereof in source attribution, and difficulties ascertaining function in hazard characterization. Although, the aforementioned methods can relatively easily be applied technically, an overarching challenge is the inference and biological/epidemiological interpretation of these large amounts of high-resolution data. Understanding the context in terms of bacterial isolate and host diversity allows to assess the level of representativeness in regard to sources and isolates in the dataset, which in turn defines the level of certainty associated with defining clusters, sources and risks. This also marks the importance of metadata (clinical, epidemiological, and biological) when using genomics for public health purposes.
The value of lymphocyte-to-C-reactive protein ratio for predicting clinical outcomes in patients with sepsis in intensive care unit: a retrospective single-center study
Authors: Song Chao , Hu Zhenkui , Zhang Jinhui
Published: September 2024

Background

The lymphocyte-to-C-reactive protein ratio (LCR) was a novel biomarker of inflammation that had been implicated in various diseases. Nevertheless, the role of LCR in the context of sepsis patients admitted to the Intensive Care Unit (ICU) had not been thoroughly elucidated. This study aimed to determine the significance of the LCR in predicting the prognosis of sepsis patients within ICU.

Methods

A sample of sepsis patients requiring ICU care was selected from the Affiliated Hospital of Jiangsu University. These patients were then segmented into four quartiles based on their LCR levels. The primary endpoint of the study was 30-day mortality and the secondary endpoint was the occurrence of Acute Kidney Injury (AKI). Survival analysis, via the Kaplan-Meier method and log-rank test, was conducted to assess survival rates. Cox proportional hazards regression and logistic regression models were employed to investigate the association between LCR and clinical outcomes. Additional subgroup analyses were conducted to evaluate the influence of other confounding factors on the relationship between LCR and patient outcomes.

Results

A total of 1,123 patients were enrolled in this study, with a median age of 75 (65–84) years, and 707 (63.0%) of them were male. The 30-day mortality rate was 28.1%, while the incidence of AKI was 45.6%. A progressive decrease in LCR levels was found to be associated with an increased cumulative incidence of 30-day mortality (log-rank P < 0.001). Multivariable Cox proportional hazards analyses demonstrated that LCR was an independent predictor of 30-day mortality [per 1-unit increase in LCR: HR (95%CI): 0.370 (0.142–0.963); P = 0.042]. Additionally, multivariable logistic regression analysis revealed a significant association between LCR and AKI occurrence [per 1-unit increase in LCR: OR (95%CI): 0.541 (0.307–0.953); P = 0.034]. Furthermore, subgroup analysis indicated a stronger correlation for patients aged over 65 years compared to those aged 65 or younger (p for interaction <0.05) in predicting 30-day mortality or AKI occurrence based on LCR.

Conclusion

A reduction in LCR was notably linked to 30-day mortality and the occurrence of AKI in sepsis patients. These findings suggested that LCR could potentially serve as a valuable tool in identifying sepsis patients at a heightened risk of adverse outcomes.
EBF1 is a potential biomarker for predicting progression from mild cognitive impairment to Alzheimer's disease: an in silico study
Authors: Ju Yanxiu , Li Songtao , Kong Xiangyi , Zhao Qing
Published: September 2024

Introduction

The prediction of progression from mild cognitive impairment (MCI) to Alzheimer's disease (AD) is an important clinical challenge. This study aimed to identify the independent risk factors and develop a nomogram model that can predict progression from MCI to AD.

Methods

Data of 141 patients with MCI were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. We set a follow-up time of 72 months and defined patients as stable MCI (sMCI) or progressive MCI (pMCI) according to whether or not the progression of MCI to AD occurred. We identified and screened independent risk factors by utilizing weighted gene co-expression network analysis (WGCNA), where we obtained 14,893 genes after data preprocessing and selected the soft threshold β = 7 at an R2 of 0.85 to achieve a scale-free network. A total of 14 modules were discovered, with the midnightblue module having a strong association with the prognosis of MCI. Using machine learning strategies, which included the least absolute selection and shrinkage operator and support vector machine-recursive feature elimination; and the Cox proportional-hazards model, which included univariate and multivariable analyses, we identified and screened independent risk factors. Subsequently, we developed a nomogram model for predicting the progression from MCI to AD. The performance of our nomogram was evaluated by the C-index, calibration curve, and decision curve analysis (DCA). Bioinformatics analysis and immune infiltration analysis were conducted to clarify the function of early B cell factor 1 (EBF1).

Results

First, the results showed that 40 differentially expressed genes (DEGs) related to the prognosis of MCI were generated by weighted gene co-expression network analysis. Second, five hub variables were obtained through the abovementioned machine learning strategies. Third, a low Montreal Cognitive Assessment (MoCA) score [hazard ratio (HR): 4.258, 95% confidence interval (CI): 1.994–9.091] and low EBF1 expression (hazard ratio: 3.454, 95% confidence interval: 1.813–6.579) were identified as the independent risk factors through the Cox proportional-hazards regression analysis. Finally, we developed a nomogram model including the MoCA score, EBF1, and potential confounders (age and gender). By evaluating our nomogram model and validating it in both internal and external validation sets, we demonstrated that our nomogram model exhibits excellent predictive performance. Through the Gene Ontology (GO) enrichment analysis, Kyoto Encyclopedia of Genes Genomes (KEGG) functional enrichment analysis, and immune infiltration analysis, we found that the role of EBF1 in MCI was closely related to B cells.

Conclusion

EBF1, as a B cell-specific transcription factor, may be a key target for predicting progression from MCI to AD. Our nomogram model was able to provide personalized risk factors for the progression from MCI to AD after evaluation and validation.
Serum IRAK3 may serve as a prognostic biomarker in acute supratentorial intracerebral hemorrhage: findings from a prospective observational cohort study
Authors: Ma Yijun , Wang Jun , Tang Chao , Li Wei , Lv Xuan , Zhu Suijun
Published: September 2024

Background

Interleukin-1 receptor-associated kinase 3 (IRAK3) modulates neuroinflammation. This study aimed to determine the prognostic role of serum IRAK3 in acute intracerebral hemorrhage (ICH).

Methods

In this prospective observational cohort study, 152 patients with supratentorial ICH, along with 63 healthy controls, were recruited. Serum IRAK3 levels were measured at the time of enrollment for controls, at admission for all patients, and on poststroke days 1, 3, 5, 7, 10, and 15 in a subset of 63 patients. Stroke severity was assessed using the National Institutes of Health Stroke Scale (NIHSS) and hematoma volume. Poststroke 6-month modified Rankin Scale (mRS) scores were registered, with scores of 3–6 representing a poor prognosis. Multivariate models were established to investigate severity correlation and prognosis association.

Results

Serum IRAK3 levels were significantly elevated at the admission of patients, peaked at day 1, plateaued at day 3, gradually declined until day 15, and were substantially higher over the first 15 days poststroke than in controls. Admission serum IRAK3 levels were independently associated with NIHSS scores, hematoma volume, and 6-month mRS scores in a multivariate linear regression model. They were linearly correlated with the risk of poor prognosis in a restricted cubic spline analysis and were independently predictive of poor prognosis in a binary logistic regression model. Additionally, they demonstrated strong prognostic ability in the receiver operating characteristic curve analysis. Using subgroup analysis, no interactions were found between admission serum IRAK3 levels and some routine variables, such as age, gender, hypertension, and diabetes mellitus. Moreover, the model combining admission serum IRAK3, NIHSS scores, and hematoma volume demonstrated stability and clinical value in calibration and decision curve analyses.

Conclusion

A significant increase in serum IRAK3 levels during the early phase after ICH, strongly correlated with disease severity, is independently associated with a poor 6-month prognosis, establishing serum IRAK3 as a valuable prognostic biomarker for ICH.