bluuebunny/crossref_metadata_2025 huggingface dataset:
Geographical Distribution of Small Physical Exercise Enterprises in the Greater Athens Area
Authors: Papanikos Gregory T.
Published: August 2024

The determinants of the geographical distribution of private business exercise centers in a large city, such as the wider area of Athens known as Attica, are the subject matter of this paper. The spatial distribution of any business enterprise, particularly those dealing with physical exercise, is of interest for two reasons. First, the spatial distribution of such businesses highlights the unevenness of health-related activities among the wider population living in a large metropolitan city, where geographical location often indicates uneven wealth distribution. This has certain government policy implications if physical exercise is to be considered a public good to be shared equally by all, rich and poor. Second, the spatial distribution of gym businesses shows whether, given wealth and population, there is an over- or undersupply of gym services. If there is an undersupply, there are opportunities for investment in small physical exercise businesses. This empirical study uses the 58 municipalities of Attica and the geographical distribution of 214 physical exercise businesses to show how wealth and population affect the under- or oversupply of physical exercise enterprises. The empirical evidence shows that, as expected, there is a positive effect of both wealth and population. However, the population effect is linear, while the wealth effect is non-linear; an increase in wealth increases the number of gyms in an area but at a decreasing rate. The study also identifies unexplored opportunities for investing in small physical exercise enterprises as well as areas of oversupply. Keywords: Gyms, population, wealth, SMEs, fitness centers, exercise, geographical distribution, spatial distribution, entrepreneurs, Athens, Attica
SISTEM INFORMASI NILAI AKADEMIK SISWA BERBASIS WEB
Authors: Nasution Raudah , Gamar Muhammad , Butar-butar Belsana
Published: August 2024

Perkembangan teknologi informasi sekarang ini begitu pesat, banyak perusahaan atau instansi  berlomba-lomba merancang sistem informasi yang sistematis dan terstruktur agar memudahkan para pengguna mengakses informasi dengan mudah dan lebih efisien, karena perkembangan teknologi informasi banyak mengubah cara-cara lama yang dilakukan secara manual menjadi terkomputerisasi. Begitupun dengan instansi pendidikan harus mempu mengikuti perkembangan teknologi informasi dengan melakukan perubahan di beberapa proses pengolahan data secara terkomputerisasi , mengelola nilai akademik siswa berbasis web yang diubah dari proses manual ke proses terkomputerisasi diharapkan mampu memudahkan proses pengolahan dan pendataan nilai siswa oleh para guru, dan juga memudahkan para siswa atau orangtua siswa memantau nilai akademik putra-putrinya disekolah. Sistem informasi nilai akademik siswa dilakukan dengan metode pengembangan perangkat lunak prototyping dimana pembuat sistem dan pemakai sistem mengumpulkan informasi kebutuhan dari operasional sistem antara lain  menentukan tujuan dan fungsi dari sistem.
PREDIKSI PENYAKIT DIABETES DENGAN MENGGUNAKAN ALGORITMA C4.5
Authors: Safitri Maryanah , Praba Ardian Dwi
Published: August 2024

Penyakit diabetes merupakan tantangan kesehatan global yang terus meningkat, memerlukan prediksi yang tepat untuk intervensi dini dan manajemen yang efektif. Dalam studi ini, kami menggunakan algoritma C4.5, suatu metode pembelajaran mesin yang terbukti, untuk memproyeksikan risiko diabetes pada kelompok khusus. Analisis mendalam terhadap atribut klinis yang paling penting juga kami lakukan, memberikan wawasan yang lebih rinci tentang profil penyakit dan faktor-faktor yang mempengaruhi. Harapannya, Hasil riset ini dapat menjadi panduan untuk mengembangkan strategi pencegahan yang lebih efektif dan rekomendasi pengobatan individual untuk individu yang menderita diabetes. Dengan menggunakan kumpulan data klinis yang komprehensif, kami berhasil membuat model prediksi yang mampu mengidentifikasi faktor risiko utama dengan tingkat akurasi mencapai 96.16%. Oleh karena itu, riset ini memberikan masukan yang sangat baik dalam upaya global untuk mengurangi prevalensi diabetes dan meningkatkan kualitas hidup pasien.
IMPLEMENTASI RAPID APPLICATION DEVELOPMENT (RAD) STUDI KASUS PENGEMBANGAN SISTEM INFORMASI SEKOLAH YAYASAN AL ABANIYAH
Authors: Mulyati Sri , Herdiansah Arief , Taufiq Rohmat , Prianggodo Dyas Yudi , Bukhori Syaiful
Published: August 2024

Rapid Application Development (RAD) merupakan sebuah metodologi yang berfokus pada pembuatan prototipe sistem informasi dengan cepat dan pengembangan berulang. Metodologi ini menekankan umpan balik pengguna dan waktu pengembangan yang cepat. RAD dapat mengurangi waktu dan biaya pengembangan dengan memprioritaskan keterlibatan dan fleksibilitas pengguna. Metode RAD bermanfaat pada proyek pengembangan sistem informasi yang memerlukan pembaruan rutin dan pengiriman cepat. Penelitian ini mengambil obyek penelitian di Yayasan Al Abaniyah Tangerang yang saat ini mengelola pendidikan ditingkat Pendidikan Anak Usia Dini (PAUD) dan Sekolah Dasar. Penelitian ini dilakukan dengan tujuan membuktikan bahwa pengembangan system informasi RAD dapat menghasilkan sebuah sistem informasi sekolah sesuai dengan kebutuhan pengelola sekolah pada Yayasan Al Abaniyah Tangerang. Sistem Informasi yang dikembangkan diuji menggunakan metode pengujian kotak hitam. Sistem Informasi yang dikembangan telah dapat memberikan manfaat bagi pengguna dalam mensosialisasikan dan meningkatkan layanan pendidikn PAUD dan Sekolah Dasar kepada orang tua dan masyarakat.
SUMBER-SUMBER ILMU PENGETAHUAN DALAM PERSPEKTIF ISLAM DAN BARAT
Authors: Nawazir Safrudin
Published: August 2024

Tujuan dari penulisan ini adalah untuk mengetahui sumber-sumber ilmu pengetahuan dalam perspektif Islam dan Barat. Penelitian ini menggunakan library research. Hasil penelitian menunjukkan bahwa: sumber ilmu pengetahuan dari Islam bersumber dari Al-Qur’an, Assunnah / hadist Nabi Muhammad SAW, Akal, Wahyu, ilham, Panca indra, pengalaman, Intuisi dll. Dalam epistemologi Barat, cara memperoleh pengetahuan dikenal dengan tiga paham: Pertama, pendekatan rasionalisme. Suatu paham bahwa pengetahuan terjadi karena bahan pemberian panca indera dan batin yang diolah oleh “akal”. Kedua, empirisme, yaitu Suatu paham yang berpendapat bahwa pengetahuan yang diperoleh terbatas hanya pada pengalaman. Ketiga, paham dualisme, Paham ini berusaha menggabungkan atau mendamaikan kedua kutub paham yang bersebrangan secara diameteral.
The Impact of Vaginal Dilator Use on the Quality of Life in Women Treated with Adjuvant Radiotherapy for Cervical Cancer
Authors: Shao Liujuan , Chen Xiaoli , Zhang Xiaoyan , Zhu Min , Jin Peijian , Hu Min
Published: August 2024

Background: The aim of the present study was to evaluate the clinical efficacy of a vaginal dilator in patients with cervical cancer after radiotherapy. Methods: A total of 128 patients with cervical cancer (stages I–III) after radical hysterectomy combined with vaginal lengthening surgery were evaluated between January 2018 and January 2021. All eligible patients were told that their radiotherapy treatment resulted in vaginal stenosis and that vaginal dilators may improve this condition. After the patients were informed of the potential benefits, complications, and alternatives, those who agreed to undergo the vaginal dilator manipulation were assigned into Group A (n = 66), while those who refused were included in Group B (n = 62) and received routine treatment. Vaginal diameter and length were measured during the follow-up period and quality of life changes were determined on the basis of the European Organization for Research and Treatment of Cancer (EORTC) Quality-of-Life questionnaire cervical cancer module (EORT QLQ-CX24). Results: Three patients were lost to follow-up over the course of 14 months, while two patients in Group A refused treatment after radical hysterectomy. A total of 123 cases with cervical cancer were analyzed in the course of the study. The vaginal diameter and length were significantly different between the two groups during the follow-up period. Sexual/vaginal function, sexual worry, sexual activity, and sexual enjoyment were also significantly different after radiotherapy in groups A and B (p < 0.05). There were no complication associated with the treatment process. Conclusions: Using a vaginal dilator in cervical cancer patients after radiotherapy is safe and can effectively promote the recovery of patients’ sexual activity and quality of life.
The Impact of Embracing New Antenatal Screening Guidelines on Complications Related to Grand Multiparity in a Jordanian Tertiary Referral Center
Authors: Thekrallah Fida , Muhaidat Nadia , Qatawneh Ayman , Fram Kamil , Al-Husban Naser , Asali Fida
Published: August 2024

Background: Universal screening, including thyroid dysfunction, gestational diabetes, and performing morphology and growth scans, was introduced in the healthcare system to improve perinatal care and pregnancy outcomes. Pregnancy-related complications are usually higher in grand multiparous women and their advanced maternal age. This study aimed to compare the impact of implementing a universal screening strategy protocol versus the selective screening for grand multiparous pregnant women aged ≥35 years on the incidence of adverse pregnancy outcomes and the associated risk factors. Methods: A retrospective cohort study of two groups (n = 89/group) of healthy grand multiparous women aged ≥35 years and who either delivered between 2011–2012 and underwent selective screening, or between 2016–2017 and were universally screened, was conducted at the Department of Obstetrics and Gynecology, Jordan University Hospital. Results: The universal screening protocol detected more cases of women with gestational diabetes, gestational hypertension, and polyhydramnios 7, 4, and 9 more times, respectively, than the selective screening procedure. However, the results of universal screening tests for thyroid function and glucose tolerance were abnormal in only a small number of women. Furthermore, the cesarean section rate was reduced from 45% in the selective screening group to 1% in the universal screening group. No other significant differences in pregnancy or neonatal complications between the two groups were noted. Conclusions: Implementing new perinatal care protocols, including universal screening for thyroid disease and gestational diabetes, morphological and growth scans significantly decreased the rate of cesarean section in grand multiparous women with advanced maternal age, but did not affect pregnancy or neonatal complications. However, larger studies are needed to obtain more representative results among women in high-risk group for gestational diabetes mellitus (GDM) and thyroid dysfunction.
M2 Macrophage-Derived Exosomes Inhibit Atherosclerosis Progression by Regulating the Proliferation, Migration, and Phenotypic Transformation of Smooth Muscle Cells
Authors: Wang Shuo , Wang Xiaokang , Lv Yunhui , Zhang Zhenhao , He Ting , Hao Xiaodong , Wang Shuang , Wang Chunqiang , Meng Jian , Zhong Kejia , Ye Zhen , Chen Tao , Cui Yongchun
Published: August 2024

Background: Vascular smooth muscle cell (VSMC) intimal migration, proliferation, and phenotypic transformation from a contractile to a synthetic state are hallmarks of the progression of atherosclerotic plaques. This study aims to explore the effects of exosomes derived from M2 macrophages (ExoM2) on the pathological changes of VSMCs in atherosclerosis (AS). Methods: Cell Counting Kit-8 (CCK8) and wound healing assays were used to examine the impact of ExoM2 on platelet-derived growth factor-BB (PDGF-BB)-induced VSMC proliferation and migration, respectively. Western blotting was employed to analyze changes in the expression levels of contractile markers (e.g., alpha-smooth muscle actin [α-SMA]) and synthetic ones (e.g., osteopontin [OPN]) in VSMCs with or without ExoM2 treatment. ApoE-⁣/- mice on a high fat diet were utilized to observe the effects of ExoM2 on plaque progression and stability. Serial histopathological analysis was performed to elucidate the cellular mechanisms underlying the atheroprotective effects of ExoM2. Results: Compared with controls, ExoM2 significantly inhibited PDGF-BB-induced VSMC proliferation, migration, and phenotypic transformation in vitro. In ApoE-⁣/- mice, ExoM2 treatment led to a marked reduction in plaque size, necrotic core area, the CD68/α-SMA ratio, and matrix metalloproteinase 9 (MMP9) and OPN levels, while enhancing plaque stability. Conclusions: ExoM2 inhibit AS progression by regulating VSMC proliferation, migration, and phenotypic transformation.
A Novel Molecular-Genetic Approach to the Monitoring of Dynamics of Mitochondrial Function Improvement during Treatment
Authors: Smetanina Mariya A. , Korolenya Valeria A. , Filipenko Maxim L.
Published: August 2024

Making a correct genetically based diagnosis in patients with diseases associated with mitochondrial dysfunction can be challenging both genetically and clinically, as can further management of such patients on the basis of molecular-genetic data assessing the state of their mitochondria. In this opinion article, we propose a novel approach (which may result in a clinical protocol) to the use of a precise molecular-genetic tool in order to monitor the state of mitochondria (which reflects their function) during treatment of certain conditions, by means of not only signs and symptoms but also the molecular-genetic basis of the current condition. This is an example of application of personalized genomic medicine at the intersection of a person’s mitochondrial genome information and clinical care. Advantages of the proposed approach are its relatively low cost (compared to various types of sequencing), an ability to use samples with a low input amount of genetic material, and rapidness. When this approach receives positive outside reviews and gets an approval of experts in the field (in terms of the standards), it may then be picked up by other developers and introduced into clinical practice.
The Synergistic Inhibitory Effect of Combination Drug Treatment of Enteromorpha Prolifera Polysaccaharide and Doxorubicin Hydrochloride on A549 Cell
Authors: Li Yanwei , Liu Li , Xing Yueting , Wang Jiajia , Yin Wei , Huang Yingying , Guo Chun , Zhou Nan
Published: August 2024

Background: As a common drug for tumor therapy, doxorubicin hydrochloride (DOX) is not yet widely used as a clinical solution. This is due to its toxicity and potential drug resistance. Objective: This study investigated the inhibitory effect of enteromorpha prolifera polysaccaharide (EPP) combined with doxorubicin hydrochloride (DOX) on A549 cells, which fall into the cell line of human non-small cell lung cancer (NSCLC). It also explained the attenuated and synergistic effect of enteromorpha acid polysaccharide along with its synergistic effect on DOX. Methods: To evaluate the proliferation inhibitory effect of EPP, DOX and both combined, we monitored cell growth curve and morphology using the real-time cell function analysis and imaging system—xCELLigence RTCA eSight system (eSight system). Flow cytometry was used to monitor cell apoptosis rate and cell cycle distribution. Mitochondrial function was tested by the energy metabolism analysis system. Results: EPP could work with DOX to inhibit the proliferation of A549 cells. Growth curve showed that when 0.4 mg/mL of EPP was mixed with 0.2 µg/mL of DOX for 24 h, the mixure liquid had a significant inhibitory effect on the proliferation of A549 cells (p < 0.0001). The cells had lower cell adhesiveness, shrinking cell membrane, cytoplasmic aggregation, and hyperchromatic nuclei. According to the flow cytometry results, the combined drug of EPP and DOX could significantly increase the apoptosis rate of A549 cells (p < 0.0001), and block the cell cycle in the G1-S phase. Based on the results of the real-time energy metabolism, we found that the combined drug could significantly reduce A549 cells’ ATP production rate and inhibit their mitochondrial respiratory function. Conclusions: The combination of EPP and DOX can block cell cycle, inhibit cell mitochondrial function, promote cell apoptosis, and enhance the killing ability of DOX on tumor cells. This study supports the antitumor activity of enterococcus acid polysaccharide and provides insights on reducing doxorubicin toxicity and drug resistance. It holds great significance for applying traditional Chinese natural medicine in clinical disease treatment.
Investigation of Aberrant Basaloid Cells in a Rat Model of Lung Fibrosis
Authors: Bocchi Emanuela , Pitozzi Vanessa , Pontis Silvia , Caruso Paola L. , Beghi Sofia , Caputi Mariafrancesca , Trevisani Marcello , Ruscitti Francesca
Published: August 2024

Background: Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive interstitial lung disease (ILD) whose cause and pathogenesis are not yet well understood. Until now, no animal model of lung fibrosis succeeds in recapitulating all IPF features, thus the use of different rodent models is essential for the evaluation and development of new effective pharmacological treatments. Recently, the alveolar epithelial dysfunction has been emphasized in the etiopathogenesis context of IPF. Remarkably, the role of an aberrant basaloid cell type, primarily found in humans and confirmed in mice, seems to be crucial in the establishment and progression of the disease/model. Our work aimed to characterize for the first time this cell population in a rat model of lung fibrosis induced by a double bleomycin (BLM) administration, demonstrating the translational value of the model and its potential use in the testing of effective new drugs. Methods: Rats received an intratracheal BLM administration at day 0 and 4. Animals were sacrificed 21 and 28 days post-BLM. The fibrosis evaluation was carried out through histological (Ashcroft score and automatic image analysis) and immunoenzymatic analysis. Immunofluorescence was used for the characterization of the aberrant basaloid cells markers. Results: Lung histology revealed an increase in severe grades of Ashcroft scores and areas of fibrosis, resulting in a rise of collagen deposition at both the analyzed time-points. Immunofluorescence staining indicated the presence of KRT8+ cells in bronchial epithelial cells from both controls (saline, SAL) and BLM-treated animals. Interesting, KRT8+ cells were found exclusively in the fibrotic parenchyma (confirmed by the alpha-smooth muscle actin (α-SMA) staining for myofibroblasts) of BLM-treated animals. Moreover, KRT8+ cells co-expressed markers as Prosurfactant protein C (Pro-SPC) and Vimentin, suggesting their intermediate state potentially originating from alveolar type II (AT2) cells, and participating to the abnormal epithelial–mesenchymal crosstalk. Conclusion: Previous preclinical studies demonstrated the presence of KRT8+ aberrant basaloid-like cells in murine models of lung fibrosis. This work investigated the same cell population in a different rodent (the rat) model of lung fibrosis triggered by a double administration of BLM. Our results provided a further confirmation that, in rats, the intratracheal administration of BLM induced the appearance of a population of cells compatible with the KRT8+ alveolar differentiation intermediate (ADI) cells, as described previously in the mouse. This piece of work enforces previous evidence and further support the use of a rat model of BLM resembling the alveolar epithelial dysfunction to evaluate new clinical candidates for development in IPF.
Inhibiting the NF-κB/DRP1 Axis Affords Neuroprotection after Spinal Cord Injury via Inhibiting Polarization of Pro-Inflammatory Microglia
Authors: Song Chen , Zhang Kaihui , Luo Cheng , Zhao Xiaoyong , Xu Baoshan
Published: August 2024

Background: Spinal cord injury (SCI) is considered a central nervous system (CNS) disorder. Nuclear factor kappa B (NF-κB) regulates inflammatory responses in the CNS and is implicated in SCI pathogenesis. The mechanism(s) through which NF-κB contributes to the neuroinflammation observed during SCI however remains unclear. Methods: SCI rat models were created using the weight drop method and separated into Sham, SCI and SCI+NF-κB inhibitor groups (n = 6 rats per-group). We used Hematoxylin-Eosin Staining (H&E) and Nissl staining for detecting histological changes in the spinal cord. Basso-Beattie-Bresnahan (BBB) behavioral scores were utilized for assessing functional locomotion recovery. Mouse BV2 microglia were exposed to lipopolysaccharide (LPS) to mimic SCI-induced microglial inflammation in vitro. Results: Inhibition of NF-κB using JSH-23 alleviated inflammation and neuronal injury in SCI rats’ spinal cords, leading to improved locomotion recovery (p < 0.05). NF-κB inhibition reduced expression levels of CD86, interleukin-6 (IL-6), IL-1β, and inducible Nitric Oxide Synthase (iNOS), and improved expression levels of CD206, IL-4, and tissue growth factor-beta (TGF-β) in both LPS-treated microglia and SCI rats’ spinal cords (p < 0.05). Inhibition of NF-κB also effectively suppressed mitochondrial fission, evidenced by the reduced phosphorylation of dynamin-related protein 1 (DRP1) at Ser616 (p < 0.001). Conclusion: We show that inhibition of the NF-κB/DRP1 axis prevents mitochondrial fission and suppresses pro-inflammatory microglia polarization, promoting neurological recovery in SCI. Targeting the NF-κB/DRP1 axis therefore represents a novel approach for SCI.
High Glycolytic Activity Signature Reveals CCNB2 as a Key Therapeutic Target in Triple-Negative Breast Cancer
Authors: Liang Jing , Ma Haodi , Zhang Shunshun , Dong Yirui , Zheng Jiayu , Zeng Li , Xiong Xin , Huang Wenbin , Yin Qinan , Zheng Xuewei
Published: August 2024

Background: Aerobic glycolysis and the cell cycle are well-established tumor hallmarks. Understanding their relationship could help to unravel the pathogenic mechanisms of breast cancer (BC) and suggest potential new strategies for treatment. Methods: Glycolysis-related genes (GRGs) were downloaded from the Reactome database and screened using univariate Cox analysis. The consensus clustering method was employed to identify a glycolytic activity signature (GAS) using the Gene Expression Omnibus (GEO) dataset. A nomogram risk prediction model was constructed using coefficients from univariate Cox analysis. Immune cell infiltration was evaluated using single-sample gene set enrichment analysis (ssGSEA) and the ESTIMATE algorithm. Gene co-expression modules were created using weighted correlation network analysis (WGCNA) to identify hub genes. Gene expression in three BC cell lines was quantified using Quantitative Reverse Transcriptase Polymera (qRT-PCR). Single-cell RNA sequencing (scRNA-seq) data was used to examine the relationship between GAS and hub genes. The sensitivity of different groups to cell cycle-related clinical drugs was also examined. Results: BC with high GAS (HGAS) showed high tumor grade and recurrence rate. HGAS was a prognostic indicator of worse overall survival (OS) in BC patients. HGAS BC showed more abundant immune cells and significantly higher expression of immunomodulators compared to BC with low GAS (LGAS). HGAS BC also showed enhanced cell cycle pathway, with high mRNA and protein expression levels of Cyclin B2 (CCNB2), a key component of the cell cycle pathway. Importantly, scRNA-seq analysis revealed that elevated CCNB2 expression was positively correlated with HGAS in triple-negative BC (TNBC). This was validated in clinical samples from TNBC patients. High expression of CCNB2 was found in three BC cell lines, and was also an indicator of poor prognosis. HGAS BC showed high sensitivity to several cell cycle-related clinical drugs, with 9 of these also showing activity in BC with high CCNB2 expression. Conclusions: HGAS was associated with enhanced cell cycle pathway and immune activity in BC. These results suggest that CCNB2 is a potential key therapeutic target in BC patients.
Repair of Mechanical Cartilage Damage Using Exosomes Derived from Deer Antler Stem Cells
Authors: Zhou Jue , Zhao Jianwei , Wang Yimin , Jiang Yidi , Li Xunsheng , Wang Datao , Yue Zhigang , Lv Jinpeng , Sun Hongmei
Published: August 2024

Background: Articular cartilage has limited self-repair capacity, and current clinical treatment options for cartilage defects are inadequate. However, deer antler cartilage possesses unique regenerative properties, with the ability to rapidly repair itself. This rapid self-repair process is closely linked to the paracrine factors released by deer antler stem cells. These findings present potential for the development of cell-free therapies for cartilage defects in clinical settings. The aim of this study was to investigate a novel method for repairing cartilage. Methods: A rat model with articular cartilage defects was established through surgery. Hydrogels loaded with exosomes (Exos) derived from antler stem cells (ASC-Exos) were implanted into the rat cartilage defects. The extent of cartilage damage repair was assessed using histological methods. The effects of ASC-Exos on chondrocytes and rat bone marrow mesenchymal stem cells (BMSCs) were evaluated using cell viability assays, proliferation assays, and scratch assays. Additionally, the maintenance of the chondrocyte phenotype by ASC-Exos was assessed using real-time fluorescence quantitative PCR (qPCR) and western blot analysis. The protein components contained of the Exos were identified using data-independent acquisition (DIA) mass spectrometry. Results: ASC-Exos significantly promoted the repair of cartilage tissue damage. The level of cartilage repair in the experimental group (ASC-Exos) was higher than that in the positive control (human adipose-derived stem cells, hADSC-Exos) and negative control (dulbecco’s modified eagle medium) groups (p < 0.05). In vitro experiments demonstrated that ASC-Exos significantly enhanced the proliferation abilities of chondrocytes and the proliferation abilities and the migration abilities of BMSCs (p < 0.05). ASC-Exos up-regulated the expression levels of Aggrecan, Collagen II (COLII), and Sox9 mRNA and proteins in chondrocytes. Analysis of ASC-Exos protein components revealed the presence of active components such as Serotransferrin (TF), S100A4, and Insulin-like growth factor-binding protein 1 (IGF1). Conclusions: ASC-Exos have a significant effect on cartilage damage repair, which may be attributed to their promotion of chondrocyte and BMSCs proliferation and migration, as well as the maintenance of chondrocyte phenotype. This effect may be mediated by the presence of TF, S100A4, and IGF1.
Diagnostic Accuracy of the Persyst Automated Seizure Detector in the Neonatal Population
Authors: Duckworth Eleanor , Motan Daniyal , Howse Kitty , Boyd Stewart , Pressler Ronit , Chalia Maria
Published: August 2024

Background: Neonatal seizures are diagnostically challenging and predominantly electrographic-only. Multichannel video continuous electroencephalography (cEEG) is the gold standard investigation, however, out-of-hours access to neurophysiology support can be limited. Automated seizure detection algorithms (SDAs) are designed to detect changes in EEG data, translated into user-friendly seizure probability trends. The aim of this study was to evaluate the diagnostic accuracy of the Persyst neonatal SDA in an intensive care setting. Methods: Single-centre retrospective service evaluation study in neonates undergoing cEEG during intensive care admission to Great Ormond Street Hospital (GOSH) between May 2019 and December 2022. Neonates with <44 weeks corrected gestational age, who had a cEEG recording duration >60 minutes, whilst inpatient in intensive care, were included in the study. One-hour cEEG clips were created for all cases (seizures detected) and controls (seizure-free) and analysed by the Persyst neonatal SDA. Expert neurophysiology reports of the cEEG recordings were used as the gold standard for diagnostic comparison. A receiver operating characteristic (ROC) curve was created using the highest seizure probability in each recording. Optimal seizure probability thresholds for sensitivity and specificity were identified. Results: Eligibility screening produced 49 cases, and 49 seizure-free controls. Seizure prevalence within those patients eligible for the study, was approximately 19% with 35% mortality. The most common case seizure aetiology was hypoxic ischaemic injury (35%) followed by inborn errors of metabolism (18%). The ROC area under the curve was 0.94 with optimal probability thresholds 0.4 and 0.6. Applying a threshold of 0.6, produced 80% sensitivity and 98% specificity. Conclusions: The Persyst neonatal SDA demonstrates high diagnostic accuracy in identifying neonatal seizures; comparable to the accuracy of the standard Persyst SDA in adult populations, other neonatal SDAs, and amplitude integrated EEG (aEEG). Overdiagnosis of seizures is a risk, particularly from cEEG recording artefact. To fully examine its clinical utility, further investigation of the Persyst neonatal SDA’s accuracy is required, as well as confirming the optimal seizure probability thresholds in a larger patient cohort.
Resting-State Brain Function Alteration in Colorectal Cancer Patients
Authors: Xu Yanan , Ma Zihan , Chen Jieyu , Zhang Huiyan , Shen Guo , Huang Gang , Zhang Wenwen , Zhao Lianping
Published: August 2024

Background and Purpose: To investigate the abnormal pattern of altered functional activity in the brain and the neuroimaging mechanisms underlying the cognitive impairment of patients with colorectal cancer (CRC) via resting-state functional magnetic resonance imaging (rs-fMRI). Materials and Methods: CRC patients (n = 56) and healthy controls (HCs) (n = 50) were studied. The participants underwent rs-fMRI scans and the Montreal Cognitive Assessment (MoCA). The amplitude of low-frequency fluctuations (ALFF), degree centrality (DC), regional homogeneity (ReHo), and MoCA scores, were calculated for participants. Results: The scores of executives, visuospatial, memory, language and attention were lower in CRC patients. ReHo and ALFF values in the left postcentral gyrus, ReHo values in the right postcentral gyrus, ALFF and DC values in the left middle occipital gyrus, ReHo and DC values in the right lingual gyrus, DC values in the right angular gyrus and precuneus, and ALFF values in the left middle temporal gyrus decreased conspicuously in the CRC patients. Conclusion: CRC patients have abnormal resting state function, mainly in the brain areas involved in cognitive function. The overlapping brain regions with abnormal functional indicators are in the middle occipital gyrus, postcentral gyrus, and lingual gyrus. This study reveals the potential biological pathways involved in brain impairment and neurocognitive decline in patients with CRC.
Diffusion- and Perfusion-Weighted Imaging to Detect Neurological Deficits in Acute Focal Cerebral Ischemia in Rabbits
Authors: Zhang Yu , Deng Xuefei , Chu Jiangdong , Zhang Qian , Luo Xiangwei , Wang Xingxing
Published: August 2024

Purpose: To investigate the relationship of diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI) parameters with dysfunction in acute focal cerebral ischemia (ACI) rabbits. Methods: The model of ACI in the middle cerebral artery was made using 30 adult male New Zealand rabbits. The dysfunction severities of the ACI rabbits were assessed using Purdy’s score. A paired-sample rank sum test was adopted to compare the abnormal signal zone (ASZ) volumes from T2 weighted imaging (T2WI), dynamic susceptibility contrast-enhanced (DSC) imaging, and DWI with a relative cerebral blood flow (rCBF) map; correlations were analyzed between the volume of each ASZ and Purdy’s score by Spearman’s rank correlation coefficient. The degree of necrotic and apoptotic cells was evaluated in the ASZ from DWI and DSC PWI-DWI mismatch (PDM) zone. Correlations were analyzed between the index of cellular damage and Purdy’s score, the volume of ASZs by Spearman’s rank correlation coefficient. Results: The ASZ volumes from DSC-PWI and the rCBF maps were larger than those from DWI (p < 0.001 and p < 0.001, respectively); those from the rCBF map (Z = 0.959, p < 0.001) and DSC-PWI (Z = 0.970, p < 0.001) were positively correlated with DWI; a positive correlation was found between Purdy’s score and the ASZ volumes from DSC-PWI (Z = 0.889, p < 0.001), DWI (Z = 0.921, p < 0.001), and rCBF (Z = 0.891, p < 0.001). A significant difference was observed between the ASZ from DWI and the PDM zone in terms of the degree of necrotic (p < 0.001) and apoptotic cells (p < 0.001). The degree of cellular damage in the ASZ of DWI and PDM zone had no relationship with Purdy’s score and the volumes of ASZs. Conclusion: The ASZ volumes from DSC-PWI, rCBF, and particularly DWI reflected the level of dysfunction in rabbits with ACI.
Immediate Effects of Preconditioning Intermittent Theta Burst Stimulation on Lower Extremity Motor Cortex Excitability in Healthy Participants
Authors: Zhang Li , Chen Yating , Huang Guilan , Qian Yao , Yao Yu , Song Lianxin , Shao Yi , Jiang Nan , Liang Chengpan , Wang Hewei , Su Bin
Published: August 2024

Background: Previous studies have found that inhibitory priming with continuous theta burst stimulation (cTBS) can enhance the effect of subsequent excitatory conditioning stimuli with intermittent theta burst stimulation (iTBS) in the upper limbs. However, whether this combined stimulation approach elicits a comparable compensatory response in the lower extremities remains unclear. This study aimed to investigate how cTBS preconditioning modulated the effect of iTBS on motor cortex excitability related to the lower limb in healthy individuals. Methods: Using a randomised cross-over design, a total of 25 healthy participants (19 females, mean age = 24.80 yr) were recruited to undergo three different TBS protocols (cTBS + iTBS, sham cTBS + iTBS, sham cTBS + sham iTBS) in a random order. Each TBS intervention was administered with one-week intervals. cTBS and iTBS were administered at an intensity of 80% active motor threshold (AMT) delivering a total of 600 pulses. Before intervention (T0), immediately following intervention (T1), and 20 min after intervention (T2), the corticomotor excitability was measured for the tibialis anterior muscle of participants’ non-dominant leg using a Magneuro100 stimulator and matched double-cone coil. The average amplitude of the motor-evoked potential (MEP) induced by applying 20 consecutive monopulse stimuli at an intensity of 130% resting motor threshold (RMT) was collected and analysed. Results: Compare with T0 time, the MEP amplitude (raw and normalised) at T1 and T2 showed a statistically significant increase following the cTBS + iTBS protocol (p < 0.01), but no significant differences were observed in amplitude changes following other protocols (sham cTBS + iTBS and sham cTBS + sham iTBS) (p > 0.05). Furthermore, no statistically significant difference was found among the three protocols at any given time point (p > 0.05). Conclusions: Preconditioning the lower extremity motor cortex with cTBS prior to iTBS intervention can promptly enhance its excitability in healthy participants. This effect persists for a minimum duration of 20 min. Clinical Trial Registration: No: ChiCTR2300069315. Registered 13 March, 2023, https://www.chictr.org.cn.
Using Dual-Target rTMS, Single-Target rTMS, or Sham rTMS on Post-Stroke Cognitive Impairment
Authors: Xu Bingshan , Lin Chunrong , Wang Yiwen , Wang Hong , Liu Yao , Wang Xiaojun
Published: August 2024

Background: The clinical application of 10 Hz repetitive transcranil magnetic stimulation (rTMS) remains limited despite its demonstrated effectiveness in enhancing cortical excitability and improving cognitive function. The present study used a novel stimulus target [left dorsolateral prefrontal cortex + primary motor cortex] to facilitate the enhancement of cognitive function through the bidirectional promotion of cognitive and motor functions; Methods: Post-stroke cognitive impairment patients (n = 48) were randomly assigned to receive either dual-target, single-target, or sham rTMS for 4 weeks. Before and after 4 weeks of treatment, participants were asked to complete the Montreal Cognitive Assessment (MoCA) test, the Modified Barthel Index (MBI), the Trail-making Test (TMT), and the Digital Span Test (DST). In addition, the levels of brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) in serum were also measured. Results: After adjusting for pre-intervention (baseline) MoCA scores, the post-intervention MoCA scores varied significantly. After post-hoc analysis, differences existed between the post-treatment scores of the dual-target rTMS group and the sham rTMS group (the experimental group scores were significantly higher), and between those of the dual-target rTMS group and the single-target rTMS group (the dual-target rTMS scores were significantly higher). The serum VEGF levels of the dual-target rTMS group were significantly higher those that of the sham rTMS group. Conclusions: The present study presented data showing that a dual-target rTMS therapy is effective for Post-stroke cognitive impairment (PSCI). The stimulation exhibited remarkable efficacy, suggesting that dual-target stimulation (left dorsolateral prefrontal cortex+motor cortex (L-DLPFC+M1)) holds promise as a potential target for TMS therapy in individuals with cognitive impairment after stroke. Clinical Trial Registration: No: ChiCTR220066184. Registered 26 November, 2022, https://www.chictr.org.cn.
Causal Relationships between Lipid-Lowering Drug Target and Aortic Disease and Calcific Aortic Valve Stenosis: A Two-Sample Mendelian Randomization
Authors: Yang Liang , Xu Mingyuan , Gao Xixi , Liu Jingwen , Zhang Dingkai , Zhang Zhaohua , Ye Zhidong , Wen Jianyan , Liu Peng
Published: August 2024

Background: Proprotein convertase subtilisin/kexin type 9 (PCSK9), 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR), cholesteryl ester transfer protein (CETP) and apolipoprotein C3 (APOC3) are pivotal regulators of lipid metabolism, with licensed drugs targeting these genes. The use of lipid-lowering therapy via the inhibition of these genes has demonstrated a reduction in the risk of cardiovascular disease. However, concerns persist regarding their potential long-term impact on aortic diseases and calcific aortic valve disease (CAVS). This study aims to investigate causal relationships between genetic variants resembling these genes and aortic disease, as well as calcific aortic valve disease using Mendelian randomization (MR). Methods: We conducted drug-target Mendelian randomization employing summary-level statistics of low-density lipoprotein cholesterol (LDL-C) to proxy the loss-of-function of PCSK9, HMGCR, CETP and APOC3. Subsequently, we investigated the association between drug-target genetic variants and calcific aortic valve stenosis and aortic diseases, including thoracic aortic aneurysm (TAA), abdominal aortic aneurysm (AAA), and aortic dissection (AD). Results: The genetically constructed variants mimicking lower LDL-C levels were associated with a decreased risk of coronary artery disease, validating their reliability. Notably, HMGCR inhibition exhibited a robust protective effect against TAA (odds ratio (OR): 0.556, 95% CI: 0.372–0.831, p = 0.004), AAA (OR: 0.202, 95% CI: 0.107–0.315, p = 4.84 × 10-15), and AD (OR: 0.217, 95% CI: 0.098–0.480, p = 0.0002). Similarly, PCSK9, CETP and APOC3 inhibition proxies reduced the risk of AAA (OR: 0.595, 95% CI: 0.485–0.730, p = 6.75 × 10-7, OR: 0.127, 95% CI: 0.066–0.243, p = 4.42 × 10-10, and OR: 0.387, 95% CI: 0.182–0.824, p = 0.014, respectively) while showing a neutral impact on TAA and AD. Inhibition of HMGCR, PCSK9, and APOC3 showed promising potential in preventing CAVS with odds ratios of 0.554 (OR: 0.554, 95% CI: 0.433–0.707, p = 2.27 × 10-6), 0.717 (95% CI: 0.635–0.810, p = 9.28 × 10-8), and 0.540 (95% CI: 0.351–0.829, p = 0.005), respectively. However, CETP inhibition did not demonstrate any significant benefits in preventing CAVS (95% CI: 0.704–1.544, p = 0.836). The consistency of these findings across various Mendelian randomization methods, accounting for different assumptions concerning genetic pleiotropy, enhances the causal inference. Conclusions: Our MR analysis reveals that genetic variants resembling statin administration are associated with a reduced risk of AAA, TAA, AD and CAVS. HMGCR, PCSK9 and APOC3 inhibitors but not CETP inhibitors have positive benefits of reduced CAVS. Notably, PCSK9, CETP and APOC3 inhibitors exhibit a protective impact, primarily against AAA, with no discernible benefits extending to TAA or AD.
The Role of Natural Low Molecular Weight Dicarbonyls in Atherogenesis and Diabetogenesis
Authors: Lankin Vadim Z. , Tikhaze Alla K. , Sharapov Mars G. , Konovalova Galina G.
Published: August 2024

This review summarises the data from long-term experimental studies and literature data on the role of oxidatively modified low-density lipoproteins (LDL) in atherogenesis and diabetogenesis. It was shown that not “oxidized” (lipoperoxide-containing) LDL, but dicarbonyl-modified LDL are atherogenic (actively captured by cultured macrophages with the help of scavenger receptors), and also cause expression of lectin like oxidized low density lipoprotein receptor 1 (LOX-1) and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 1 (NOX-1) genes in endotheliocytes, which stimulate apoptosis and endothelial dysfunction. The obtained data allowed us to justify new approaches to pharmacotherapy of atherosclerosis and diabetes mellitus.
Effects of Nicotinamide Adenine Dinucleotide on Older Patients with Heart Failure
Authors: Pei Zuowei , Dong Min , Meng Xuyang , Yao Wei , Guo Ying , Wang Fang
Published: August 2024

Background: Heart failure (HF) is the main cause of death in middle-aged and older people and is characterized by high morbidity, high mortality, a high rehospitalization rate, and many high-risk groups. Nicotinamide adenine dinucleotide (NAD+) is widely present in the mitochondria of cardiomyocytes and maintains the redox balance in the body, which can effectively treat HF. We sought to evaluate whether NAD+ therapy has some clinical efficacy in patients with HF. Methods: Based on using conventional drugs to treat HF, patients (n = 60) were randomized 1:1 to saline and 50 mg NAD+ with 50 mL of normal saline for 7 days. The baseline characteristics of patients before and after treatment and cardiac function (N-terminal pro B-type natriuretic peptide (NT-proBNP) level and left ventricular ejection fraction (LVEF) value) were analyzed. Serological analysis (sirtuin-1 (SIRT1), sirtuin-3 (SIRT3), sirtuin-6 (SIRT6), reactive oxygen species (ROS), and endothelin) was also performed. Results: Among the 60 patients with HF who were treated with NAD+ for 7 days, the improvement rate in NT-proBNP levels and LVEF values was better than in the saline group, although not statistically significant. These patients were more likely to benefit from NAD+ because of higher levels of anti-oxidative stress (SIRT1, SIRT3, SIRT6, and ROS) and anti-endothelial injury (endothelin) than those in the saline control group. Conclusions: According to the results of this study, it is believed that 7 days of NAD+ injections has a positive effect on improving cardiac function, oxidative stress, and endothelial injury in patients with HF compared with the saline control. Clinical Trial Registration: Chinese Clinical Trial Registry (http://www.chictr.org.cn/) ChiCTR2300074326; retrospectively registered on 3 August 2023.
Navigating Complications in Cardiac Pacemakers: A Comprehensive Review and Management Strategies
Authors: Sriramoju Anil , Iyengar Shruti Krishna , Srivathsan Komandoor
Published: August 2024

The landscape of cardiac pacemaker technology has undergone significant evolution over the last two decades, transitioning from simple single-chamber devices to sophisticated multi-chamber rate-responsive systems and cardioverter defibrillators. This progression has introduced a complex array of complications inherent to device implantation and operation, encompassing both mechanical and clinical challenges. These complications notably include lead dislodgment, device migration, venous thrombosis, and hemothorax, which not only affect patient outcomes but also impose substantial economic burdens. This review meticulously analyzes these complications, elucidating their mechanisms, clinical implications, and the economic consequences associated with their management. It also outlines current and emerging strategies aimed at mitigating these complications, emphasizing the need for continual updates in clinical practices and protocols. Through this discourse, the review seeks to equip clinicians with a comprehensive understanding of these complications, thereby enhancing the safety and efficacy of cardiac pacing interventions.
Jailed Balloon Technique Versus Jailed Wire Technique for Side Branch Ostium Protection in Bifurcation Lesions: Evidence from Three-dimensional Optical Coherence Tomography Analysis
Authors: Cui JianGuo , Wu Xun , Jin QinHua , Chen YunDai
Published: August 2024

Background: There is controversy regarding the effectiveness the of jailed wire technique (JWT) and jailed balloon technique (JBT) in preserving the side branch (SB) during treatment. This study compares the protective effect of JBT versus JWT on the SB ostium area in coronary bifurcation lesions using three-dimensional optical coherence tomography (3D-OCT). Methods: We obtained data from coronary heart disease patients who received OCT-guided percutaneous coronary intervention (PCI) for bifurcation lesions. The SB protection strategies were divided into JWT and JBT, with the latter further subdivided into active JBT (A-JBT) and conventional JBT (C-JBT). The primary endpoint was the SB ostium area difference measured by 3D-OCT before and after PCI. Partial correlation analysis and propensity score matching (PSM) was used to mitigate confounding biases. Results: A total of 207 bifurcation lesions from 191 patients were analyzed, including 136 lesions treated with JWT and 71 lesions treated with JBT. The SB ostium area was significantly greater in the JBT group compared to the JWT group (0.41 ± 1.22 mm2 vs. –0.25 ± 1.40 mm2, p = 0.001). Following 1:1 PSM to adjust for 60 pairs, the difference between groups was not statistically significant (0.28 ± 1.06 mm2 vs. –0.02 ± 1.29 mm2, p = 0.165). Subgroup analysis revealed that A-JBT provided superior protection in both true (0.47 ± 1.22 mm2 vs. –0.10 ± 1.10 mm2, p = 0.011) and non-true bifurcation lesions (0.56 ± 1.43 mm2 vs. –0.38 ± 1.62 mm2, p = 0.030) over JWT, while C-JBT provided protection similar to JWT. A positive partial correlation was observed between the diameter of the jailed balloon and the increase in SB ostium area (r = 0.296, p = 0.013). Conclusions: Overall, A-JBT, but not C-JBT, provided better protection in bifurcation lesions compared to JWT. The larger diameter of the jailed balloon, rather than the application of higher pressure, enhanced the SB protection.