bluuebunny/crossref_metadata_2025 huggingface dataset:
DEVELOPMENT OF TAJWID MATERIAL LEARNING VIDEO BASED ON CAPCUT APPLICATION FOR ELEMENTARY SCHOOL STUDENTS
Authors: Silvia Faizatun Nuris , Fahyuni Eni Fariyatul , Nadlif Ainun
Published: January 2025

This study aimed to analyze video needs, design videos, analyze video development and analyze the implementation of tajwid material learning videos in the Reading and Writing Qur'an (BTQ) subject. This type of research used research and development methods or is called R&D (Reseach and development) with the ADDIE development model which consists of five stages, namely Analysis, Planning, Development, Implementation and Evaluation. Data collection in this study was based on the validation of media experts and material experts as well as questionnaires from the results of limited trials. The results of this study indicated that based on an analysis of the needs of students, materials and media, as well as adjustments to media design based on the characteristics of students, it has resulted in learning video products that have obtained a media expert eligibility percentage of 86% with a very valid category and material experts of 96% with very valid category. In terms of product practicality, it has known that the tajwid learning videos developed are very interesting and make it easier for students to understand recitation material. This was obtained based on the percentage results by 20 students of 96.2% in the very practical category. Thus, the learning video for tajwid material that has been developed with the CapCut application is considered to have met the eligibility and practical requirements so that it can be used in the learning process.
APPLICATION OF THE PEER TUTOR METHOD TO IMPROVE FIQIH LEARNING OUTCOMES
Authors: Karwadi Karwadi
Published: January 2025

The purpose of this study was to improve students' activities and learning outcomes in fiqh subjects by applying the peer tutor method. This research is a class action research consisting of two cycles. The subjects of this study were third grade students of MI Matla'ul Atfal, totaling 27 students. Data collection techniques are done by giving tests and observations. Based on the results of the study, it shows that students are more active in learning activities in the classroom. Student learning outcomes also increased from each cycle. This can be proven by the completeness of student learning in cycle I as many as 17 students who are complete and 24 students who are complete in cycle II with a total of 27 students. Therefore, the application of peer tutors can improve student learning outcomes in fiqh learning.
Molyneux’s question today: Introduction to the special issue
Authors: Ferretti Gabriele , Glenney Brian
Published: January 2025

Few topics in the philosophy of perception have received more attention than Molyneux’s question: would a person with congenital blindness, able to identify cubes and spheres by touch, immediately or even eventually identify these shapes by sight alone, if made to see? This special issue focuses on the new developments concerning the answers to this question, as well as on the new questions in the light of the results of the results from the sciences of the mind.
The Global Shift from Promising Pluralism to an Exclusionary Nationalism: Ideas, Policies and Power Relations at the Global Level
Authors: Khan Sagheer Ahmad
Published: January 2025

Victory of liberal USA over Communist USSR, following the end of the Cold War, fostered a plurality of human identities and associations. That seemed to herald the realization of a promising new age of rational-democratic pluralism, either within the framework of the nation-state or transcending it. However, the march of pluralism not only stalled but also reversed into exclusionary right-wing nationalism. This shift is attributed to global structural changes that drive ideational trends. The post-Cold War global order crowned liberal pluralism; however, 9/11 and the discourse of the 'War on Terror' reinvigorated existing undercurrents of religious-civilizational discourse. The global financial crisis of 2008, coupled with relative changes in global economic relations, enhanced the perceived civilizational appeal of emerging economies at the expense of liberalism. Finally, the relative decline and disengagement of the USA disrupted the institutionalized liberal structure, paving the way for exclusionary right-wing nationalism.
Pelatihan Alat Evaluasi Berbasis Teknologi Menggunakan Classpoint Bagi Guru SMK di Kabupaten Tulungagung
Authors: Pratiwi Vivi , Wahjudi Eko , Rohayati Suci
Published: January 2025

Saat ini pelaksanaan kegiatan evaluasi pembelajaran di Sekolah Menengah Kejuruan (SMK) masih banyak yang bersifat konvensional menggunakan tes berbasis kertas padahal kurikulum menuntut pemanfaatan teknologi dalam pembelajaran. Ada banyak pilihan aplikasi yang dapat memudahkan guru dalam melakukan proses evaluasi, salah satunya adalah aplikasi Classpoint. Tujuan pelaksanaan pengabdian kepada masyarakat ini adalah untuk memberikan solusi dan inovasi bagi guru-guru SMK, khususnya guru yang tergabung dalam Musyawarah Guru Mata Pelajaran (MGMP) Akuntansi Kabupaten Tulungagung dalam pelaksanaan evaluasi pembelajaran berbasis teknologi menggunakan aplikasi Classpoint. Aplikasi ini menyediakan banyak pilihan pembuatan bentuk soal dan fitur koreksi otomatis yang dapat mempersingkat waktu pengkoreksian bagi guru. Metode yang digunakan dalam pelatihan ini adalah metode ceramah interaktif, diskusi, demonstrasi dan pelatihan. Hasil pengabidan menunjukkan bahwa kegiatan pelatihan ini mampu meningkatkan pengetahuan dan keterampilan guru-guru peserta dalam pembuatan alat evaluasi berbasis teknologi menggunakan Classpoint. Hal ini menunjukkan peningkataan kompetensi guru dalam pemanfaatan teknologi untuk pencapaian tujuan pembelajaran yang lebih efektif dan efisien menggunakan alat evaluasi pembelajaran yang tepat.
PELATIHAN MODEL PEMBELAJARAN E-LEARNING BAGI GURU AL-FIRQOH AN NAJIAH YAYASAN MUJAHIDIN KABUPATEN MALANG
Authors: Maskan Mohammad , Suyono Achmad , Utomo Heru , Akmalia Masitha Nisa , Kusumasasti Ika
Published: January 2025

Current technological developments require human resources to keep up with the use of technology. One technological development that is widely used is information systems. An information system is a system within an organization that meets the needs of an electronic approach. Learning that originally used a manual approach changed to using electronics. Apart from that, the learning time is very flexible and the learning location does not have to be at school. junior high school and senior high school  Al Firqoh An Najiah's learning process is still classical. Electronic processes need to be used to optimize the learning process. With the existence of e-learning, learning will be more varied and will improve learning outcomes. The service aims to make it easier for teachers in the electronic learning process and enhance learning services for students to increase the achievement of learning outcomes using the RAD (Rapid Application Development) method, lecture methods, and training methods.
PELATIHAN USAHA KAWASAN PARIWISATA DI DESA TULUS BESAR, KECAMATAN TUMPANG, KABUPATEN MALANG
Authors: Cahyani Hilda , Hanayeen Nadia , Nouval Alvin , Hoesny Mariana Ulfah , Hariyanto Sugeng
Published: January 2025

This community service is aimed at accommodating the needs of the Tulus Besar village community, Tumpang District in improving the ability to manage natural tourist attractions and the potential of tourist villages in the Tulus Besar tourist village area by involving tourism business actors (travel agents) to increase tourist visits, both local and foreign. Participants in this training are tourism business actors in Tulus Besar village. Through this activity, it is hoped that there will be an increase in the economic value of tourism and arts potential as well as the quality of human resources for the managers of the tourist village through increasing the ability to manage tourist attractions and tourist villages owned by the Tulus Besar village community. This activity was carried out in five stages, namely planning (to find out the number of participants who are involved and the materials needed for the training), coordination to do a survey, survey with village officials and travel agents (to ensure the plans made are by needs), Focus Group Discussion, monitoring and evaluation (giving questionnaires to training participants regarding training implementation and materials).
Whole blood transcriptome profile identifies motor neurone disease RNA biomarker signatures
Authors: Kõks Sulev , Rallmann Karin , Muldmaa Mari , Price Jack , Pfaff Abigail L. , Taba Pille
Published: January 2025

Blood-based biomarkers for motor neuron disease are needed for better diagnosis, progression prediction, and clinical trial monitoring. We used whole blood-derived total RNA and performed whole transcriptome analysis to compare the gene expression profiles in (motor neurone disease) MND patients to the control subjects. We compared 42 MND patients to 42 aged and sex-matched healthy controls and described the whole transcriptome profile characteristic for MND. In addition to the formal differential analysis, we performed functional annotation of the genomics data and identified the molecular pathways that are differentially regulated in MND patients. We identified 12,972 genes differentially expressed in the blood of MND patients compared to age and sex-matched controls. Functional genomic annotation identified activation of the pathways related to neurodegeneration, RNA transcription, RNA splicing and extracellular matrix reorganisation. Blood-based whole transcriptomic analysis can reliably differentiate MND patients from controls and can provide useful information for the clinical management of the disease and clinical trials.
Organoids and spheroids: advanced in vitro models for liver cancer research
Authors: Pastore Mirella , Giachi Alessia , Spínola-Lasso Elena , Marra Fabio , Raggi Chiara
Published: January 2025

Liver cancer is a leading cause of cancer-related deaths worldwide, highlighting the need for innovative approaches to understand its complex biology and develop effective treatments. While traditional in vivo animal models have played a vital role in liver cancer research, ethical concerns and the demand for more human-relevant systems have driven the development of advanced in vitro models. Spheroids and organoids have emerged as powerful tools due to their ability to replicate tumor microenvironment and facilitate preclinical drug development. Spheroids are simpler 3D culture models that partially recreate tumor structure and cell interactions. They can be used for drug penetration studies and high-throughput screening. Organoids derived from stem cells or patient tissues that accurately emulate the complexity and functionality of liver tissue. They can be generated from pluripotent and adult stem cells, as well as from liver tumor specimens, providing personalized models for studying tumor behavior and drug responses. Liver organoids retain the genetic variability of the original tumor and offer a robust platform for high-throughput drug screening and personalized treatment strategies. However, both organoids and spheroids have limitations, such as the absence of functional vasculature and immune components, which are essential for tumor growth and therapeutic responses. The field of preclinical modeling is evolving, with ongoing efforts to develop more predictive and personalized models that reflect the complexities of human liver cancer. By integrating these advanced in vitro tools, researchers can gain deeper insights into liver cancer biology and accelerate the development of novel treatments.
Exploring the microbiome-gut-testis axis in testicular germ cell tumors
Authors: Ciernikova Sona , Sevcikova Aneta , Mego Michal
Published: January 2025

The microbiome-gut-testis axis has emerged as a significant area of interest in understanding testicular cancer, particularly testicular germ cell tumors (TGCTs), which represent the most common malignancy in young men. The interplay between the gut and testicular microbiomes is hypothesized to influence tumorigenesis and reproductive health, underscoring the complex role of microbial ecosystems in disease pathology. The microbiome-gut-testis axis encompasses complex interactions between the gut microbiome, systemic immune modulation, and the local microenvironment of the testis. Dysbiosis in the gut or testicular microbiomes may contribute to altered immune responses, inflammation, and hormonal imbalances, potentially playing a role in the pathogenesis of TGCTs. Concurrently, seminal microbiomes have been linked to variations in sperm quality, fertility potential, and possibly cancer susceptibility, underscoring the need for further evaluation. This review explores the emerging role of the microbiome-gut-testis axis in the context of testicular cancer, highlighting its implications for disease onset, progression, treatment efficacy, and toxicity. Identifying potential microbial biomarkers, followed by microbiota modulation to restore a balanced microbial community, might offer a novel supportive strategy for improving treatment efficacy in refractory TGCT patients while reducing chemotherapy-induced toxicity. We suggest a better understanding of the association between dysregulated microbial environments and TGCTs emphasizes potential pathways by which the gut microbiome might influence testicular cancer.
The effect of thermoelectric craniocerebral cooling device on protecting brain functions in post-cardiac arrest syndrome
Authors: Nadir Aydın , Kara Deniz , Turkoz Ayda
Published: January 2025

Aim

This study aimed to protect brain functions in patients who experienced in-hospital cardiac arrest through the application of local cerebral hypothermia. By utilizing a specialized thermal hypothermia device, this approach sought to mitigate ischemic brain injury associated with post-cardiac arrest syndrome, enhance survival rates, and improve neurological outcomes as measured by standardized scales.

Methods

A prospective, single-center cohort study was conducted involving patients aged ≥18 years who experienced in-hospital cardiac arrest and achieved return of spontaneous circulation (ROSC). Patients were cooled using a hypothermia helmet to achieve a target temperature of 32°C–34°C, maintained for 36–72 h, followed by controlled rewarming and normothermia for 72 h. Neurological recovery was assessed using the Cerebral Performance Category (CPC) scale, where CPC 1–2 denotes good recovery and CPC 3–5 indicates poor outcomes. Body temperature, hemodynamic parameters, biochemical changes, and survival data were meticulously recorded and analyzed. Statistical analysis included paired t-tests to compare pre- and post-treatment data.

Results

Of 116 cardiac arrest cases, 30 (25.86%) were in-hospital, and 16 (53.33%) of these achieved ROSC. Among the patients, 62.5% underwent emergency coronary angiography due to ST-elevation myocardial infarction (STEMI). The mean time to hypothermia initiation was 32.9 ± 13.5 min, with hypothermia maintained for 58 ± 6.4 h. Neurological outcomes were favorable, with 62.5% of patients achieving CPC scores of 1 or 2, indicating functional recovery and independence. In contrast, CPC scores of 3 or higher were observed in 37.5% of patients, reflecting varying degrees of disability. Biochemical analysis revealed significant decreases in sodium, potassium, calcium, and magnesium levels, alongside increased urea and creatinine concentrations. Hemodynamic improvements included elevated systolic blood pressure and heart rate, while left ventricular ejection fraction remained stable. Overall survival was 75%, and the majority (62.5%) of survivors were discharged without significant neurological deficits.

Conclusion

The findings suggest that early and targeted application of craniocerebral thermal hypothermia has the potential to improve survival and preserve neurological function in post-cardiac arrest syndrome. The high rates of favorable outcomes, as reflected by CPC scores, underscore the neuroprotective effects of localized hypothermia. Further large-scale, multicenter trials are recommended to validate these promising results and refine protocols for optimal clinical application.
Spatial allocation and sustainable development: a study of production-living-ecological spaces in the Yangtze River Delta
Authors: Li Shangbo , Chen Yong , Huang Qinshi
Published: January 2025

The overlap and irrational distribution of Production-Living-Ecological Spaces (PLES) has disrupted traditional urban-rural development patterns and impeded regional integration. This study, focusing on the Yangtze River Delta region, introduces a PLES framework and constructs a classification system based on multitemporal land use data. The CA-Markov model was employed to simulate land use changes for the years 2030 and 2040. By quantifying and analyzing the number, distribution, and transitions of PLES categories, the study identifies spatial and temporal patterns and evaluates the coupling coordination of the various PLES components. The key findings are as follows: (1) The proportion of Production-Living Space (PLS) increased from 9% in 2000 to 14% in 2020, with projections indicating further growth to 15% by both 2030 and 2040, while Ecological Space (ES) remained relatively stable; (2) The coupling coordination between the stages of PLES evolved from mild disharmony to weak coordination, reflecting a shift from localized improvements to broader, more integrated spatial development; (3) The spatial distribution of PLES coupling exhibited significant heterogeneity, characterized by higher values in the eastern region, lower values in the western region, and a pattern of concentration in the north and dispersion southward. These findings contribute to a deeper understanding of the spatial dynamics of PLES and provide strategic recommendations for optimizing the spatial layout of the Yangtze River Delta urban agglomeration, thereby promoting sustainable urban development.
Circle-seq reveals that eccDNA may be a key blood biomarker for HBV-associated liver cancer
Authors: Ran Xiao K. , Zhao Xiao F. , Wei Zhen W. , Pang Hua Z. , Tang Yan F. , Liu Rong , Wu Tie X. , Liu Xu D.
Published: January 2025

Introduction

Extrachromosomal circular DNA (eccDNA) regulates tumor occurrence and development. Relevant eccDNA profiles have been established for various types of cancer; however, the eccDNA expression profiles in the blood of patients with hepatocellular carcinoma (HCC) and liver cirrhosis (LC) remain unknown. The present study aimed to investigate the eccDNA expression profiles in the blood of patients with HCC and LC.

Methods

Circle-seq was used to detect eccDNAs in the blood samples. Full transcript sequencing was used to analyze the RNA in the samples. Geno Ontology enrichment and Kyoto Encyclopedia of Genes and Genome pathway analyses were performed on differentially expressed eccDNA-related genes. The identified eccDNA is combined with mRNA to screen target genes using bioinformatics analysis. EccDNAs were confirmed through polymerase chain reaction and Sanger sequencing.

Results

Overall, 103,235 eccDNAs were identified in HCC, whereas 67,110 eccDNAs were detected in LC. In total, 7,095 upregulated eccDNAs and 1,284 downregulated eccDNAs were identified. Following analysis of differential genes using bioinformatics, six candidate genes were screened out based on gene expression and cancer relevance. Experiments have verified that LAMA4[circle112550019-112550510] and KANK1[circle674459-674907] are real and expressed target genes, and their source genes are closely related to the survival time of patients with liver cancer.

Conclusion

Our research results revealed the main characteristics of eccDNAs in the blood of patients with HBV-related HCC and LC. It was found that eccDNAs were mainly less than 1,000 bp in length. Difference analysis showed that some eccDNAs had consistent and overlapping expressions with mRNAs. We found that LAMA4[circle112550019-112550510] and KANK1[circle674459-674907] are target genes related to HCC, and both of them may become potential biomarkers for the diagnosis and prognosis of HCC.
Impact of dysregulated microbiota-derived C18 polyunsaturated fatty acid metabolites on arthritis severity in mice with collagen-induced arthritis
Authors: Yoneda Katsuhiko , Sendo Sho , Okano Takaichi , Shimizu Hidenori , Yamada Hirotaka , Nishimura Keisuke , Ueda Yo , Saegusa Jun
Published: January 2025

Objective

We aimed to evaluate microbiome and microbiota-derived C18 dietary polyunsaturated fatty acids (PUFAs), such as conjugated linoleic acid (CLA), and to investigate their differences that correlate with arthritis severity in collagen-induced arthritis (CIA) mice.

Methods

On day 84 after induction, during the chronic phase of arthritis, cecal samples were analyzed using 16S rRNA sequencing, and plasma and cecal digesta were evaluated using liquid chromatography–tandem mass spectrometry. Differences in microbial composition between 10 control (Ctrl) and 29 CIA mice or between the mild and severe subgroups based on arthritis scores were identified. The cecal metabolite profile and its correlation with the microbiome were evaluated with respect to arthritis severity.

Results

The hydroxy and oxo metabolite levels were higher in CIA mice than in Ctrl mice, some of which, including 10-hydroxy-cis-6-18:1, were positively correlated with arthritis scores. The 9-trans,11-trans CLA levels in CIA mice had a negative linear correlation with arthritis scores. Microbial diversity was lower in severe CIA mice than in mild CIA or Ctrl mice. The abundance of Lactobacillus relatively increased in the severe subgroup of CIA mice compared with that in the mild subgroup and was positively correlated with arthritis severity.

Conclusion

Alterations in gut microbiota and microbiota-derived C18 PUFA metabolites are associated in CIA mice and correlated with arthritis scores, indicating that plasma or fecal C18 PUFA metabolites can be potential biomarkers for arthritis severity and dysbiosis.
The role of ferroptosis in colorectal cancer and its potential synergy with immunotherapy
Authors: Xia Wenhua , Lv Yuanhao , Zou Yan , Kang Zhanting , Li Zhaoyi , Tian Jiaqi , Zhou Hongyan , Su Wei , Zhong Jiateng
Published: January 2025

Colorectal cancer (CRC) is one of the most prevalent and deadly malignancies worldwide. Recently, ferroptosis, a novel form of regulated cell death characterized by iron dependency and lipid peroxidation, has garnered significant attention from researchers. The mechanisms underlying ferroptosis, including intracellular iron levels, lipid peroxidation, and antioxidant system regulation, offer new insights into cancer treatment strategies. This study aims to explore the emerging role of ferroptosis in the context of immunotherapy for CRC, highlighting its potential mechanisms and clinical applications. We employed a comprehensive review of current literature to elucidate the biological mechanisms of ferroptosis, its relationship with CRC, and the interplay between ferroptosis and immunotherapy. Ferroptosis reshapes the tumor microenvironment (TME) by regulating intracellular iron levels, lipid metabolism, and antioxidant systems, significantly enhancing the efficacy of immune checkpoint inhibitors (ICIs). Meanwhile, traditional Chinese medicine therapies promote antitumor immunity by modulating the TME and inducing ferroptosis. Additionally, advances in nanotechnology have facilitated precise therapy by enabling targeted delivery of ferroptosis inducers or immunomodulators, transforming “cold” tumors into “hot” tumors and further boosting ICI efficacy. This study comprehensively reviews the latest developments in ferroptosis, immunotherapy, traditional Chinese medicine, and nanotechnology in CRC, highlighting the importance of ferroptosis-related biomarkers and novel inducers for personalized treatment. In summary, ferroptosis offers a promising strategy to overcome CRC therapy resistance and enhance immunotherapy efficacy, warranting further investigation and translational application.
Changes in hematoma volume following aneurysmal subarachnoid hemorrhage and its impact on patient prognosis
Authors: Huang Zhenshan , Qian Feng , Ma Kui , Jiang Guowei , Zhang Lianfu , Zhang Yongming
Published: January 2025

Objective

This study aims to investigate the effects of preoperative intracerebral hematoma volume (HVpre), hematoma volume 6–8 days post-surgery (HVpost), and the rate of hematoma volume change (HVpre−HVpost)/HVpre on the prognosis of patients with aneurysmal subarachnoid hemorrhage (aSAH).

Materials and methods

CT imaging data from 62 aSAH patients admitted to our hospital’s Neurosurgery Department between January 2022 and December 2023 were obtained, both preoperatively and 6–8 days postoperatively. The hematoma volumes were measured using 3D-Slicer. Patients’ recovery at 3 months post-discharge was assessed using the Modified Rankin Scale (mRS), categorizing the patients into a good prognosis group (mRS score 1–2) and a poor prognosis group (mRS score 3–5). Multivariate logistic regression analysis was conducted to identify independent risk factors for poor prognosis. Statistical methods were employed to compare preoperative and postoperative hematoma volumes with commonly used clinical scores. The predictive value of HVpre and HVpost for poor prognosis was evaluated using ROC curves. The rate of volume change was stratified by interquartile ranges, and the impact of different change rates on prognosis was compared.

Results

Significant differences were found between good and poor prognosis groups in age, GCS score, Hunt-Hess grade, mFisher grade, BVpre, BVpost, and (HVpre−HVpost)/HVpre (p < 0.05). Logistic regression identified gender, age, BVpre, BVpost, and volume change rate as independent risk factors (p < 0.01). Increased GCS scores and higher Hunt-Hess and mFisher grades correlated with increased HVpre and HVpost. Higher hemorrhage reduction rates were linked to better outcomes. ROC curves showed HVpre and HVpost AUC values (0.831 and 0.857, respectively) were significantly higher than clinical scales. An HVpre volume over 22.25 mL and HVpost over 15.67 mL indicated a higher risk of poor prognosis, with sensitivities of 79.3 and 80.7%, and specificities of 67.1 and 69.3%.

Conclusion

HVpre, HVpost, and (HVpre−HVpost)/HVpre can serve as neuroimaging biomarkers for assessing patients after aSAH and can effectively predict clinical prognosis.
Safety of tenecteplase vs. alteplase in telestroke: a large multistate experience (STAT)
Authors: Figurelle Morgan , Corti Sandro , Collins Oleg , Gao Lan , Avila Amanda , Delfino Kristie , Mayer Laurie , Sevilis Theresa
Published: January 2025

Introduction

Prompt treatment with IV thrombolytics (IVT) in acute ischemic stroke (AIS) patients is critical for improved recovery and survival. Recently, hospital systems have switched to the IVT tenecteplase (TNK) instead of the FDA-approved alteplase (tPA) for treatment. Multiple studies and meta-analyses evaluating the efficacy and safety of TNK demonstrate similar or superior outcomes when compared to tPA. TNK is not FDA-approved for treatment, which has led to hesitation in its use and increased attention on its complication profile, including the risk of intracranial hemorrhage (ICH).

Methods

Data from AIS consults conducted in the emergency departments of 220 facilities across 26 states, between 1 January 2022 and 31 May 2023, were extracted from the TeleCare by TeleSpecialists™ database. The encounters were reviewed for IVT candidates, door-to-needle (DTN) time, type of IVT administered, use of advanced imaging, presence of LVO, occurrence and type of complications, complication type, symptomatic ICH, and the ECASS II ICH score.

Results

A total of 2,305 TNK patients and 3,337 tPA patients were extracted. DTN times were faster (37 min vs. 42 min, p < 0.0001), and more total complications were observed in the TNK group (87 vs. 80, p = 0.0035). In non-LVO IVT patients, the TNK group had more complications (57 vs. 47, p = 0.0078), specifically ICH (48 vs. 35, p = 0.0036). No statistically significant difference in the incidence of ICH was observed between the TNK group and the tPA group (21 vs. 18, p = 0.07). In IVT patients not accepted for NIR, the TNK group had more complications (77 vs. 69, p = 0.005), specifically ICH (63 vs. 51, p = 0.0026). In IVT patients accepted for NIR, no significant differences were observed. There were no statistically significant differences in symptomatic ICH between the groups.

Conclusion

The TNK group was found to have significantly more complications, including ICH, than the tPA group driven by non-LVO patients. A closer analysis of the potential for increased risk to non-LVO patients is warranted based on this large, multistate, and multi-hospital system study.
Unlocking the potential for optic nerve regeneration over long distances: a multi-therapeutic intervention
Authors: Liu Zhen-Gang , Zhou Lai-Yang , Sun Yong-Quan , Ma Yi-Hang , Liu Chang-Mei , Zhang Bo-Yin
Published: January 2025

Retinal ganglion cells (RGCs) generally fail to regenerate axons, resulting in irreversible vision loss after optic nerve injury. While many studies have shown that modulating specific genes can enhance RGCs survival and promote optic nerve regeneration, inducing long-distance axon regeneration in vivo through single-gene manipulation remains challenging. Nevertheless, combined multi-gene therapies have proven effective in significantly enhancing axonal regeneration. At present, research on promoting optic nerve regeneration remains slow, with most studies unable to achieve axonal growth beyond the optic chiasm or reestablish connections with the brain. Future research priorities include directing axonal growth along correct pathways, facilitating synapse formation and myelination, and modifying the inhibitory microenvironment. These strategies are crucial not only for optic nerve regeneration but also for broader applications in central nervous system repair. In this review, we discuss multifactors therapeutic strategies for optic nerve regeneration, offering insights into advancing nerve regeneration research.
Effects of exercise training on nigrostriatal neuroprotection in Parkinson’s disease: a systematic review
Authors: Ishaq Shahid , Shah Iqbal Ali , Lee Shin-Da , Wu Bor-Tsang
Published: January 2025

Introduction

Parkinson’s disease (PD) is characterized by progressive neurodegeneration within the nigrostriatum, leading to motor dysfunction. This systematic review aimed to summarize the effects of various exercise training regimens on protein or gene expression within the nigrostriatum and their role in neuroprotection and motor function improvement in animal models of Parkinson’s disease (PD).

Methods

PubMed, EMBASE, and Web of Science were searched up to June 2024 and included sixteen studies that adhere to PRISMA guidelines and CAMARADES checklist scores ranging from 4 to 6 out of 10. Various exercise training regimens, administered 5 days per week for 6.5 weeks, were applied to MPTP, 6-OHDA, and PFF-α-synuclein-induced PD animal models.

Results

Exercise training was found to downregulate the inflammatory pathway by attenuating α-synuclein aggregation, inhibiting the TLR/MyD88/IκBα signaling cascade and NF-κB phosphorylation, and decreasing pro-inflammatory cytokines IL-1β and TNF-α while increasing anti-inflammatory cytokines IL-10 and TGF-β within the nigrostriatum. It also inhibited the ASC and NLRP3 inflammasome complex and reduced the BAX/ Bcl-2 ratio and caspase-1/3 proteins, thereby decreasing neuronal apoptosis in the nigrostriatum. Exercise training elevated the expression of Pro-BDNF, BDNF, GDNF, TrkB, and Erk1/2, providing neurotrophic support to dopaminergic neurons. Furthermore, it upregulated the dopaminergic signaling pathway by increasing the expression of TH, DAT, PSD-95, and synaptophysin in the nigrostriatum.

Discussion

The findings suggested that exercise training downregulated inflammatory and apoptotic pathways while upregulated BDNF/GDNF pathways and dopaminergic signaling within the nigrostriatum. These molecular changes contributed to neuroprotection, reduced dopaminergic neuron loss, and improved motor function in PD animal models.

Systematic review registration

CRD42024484537 https://www.crd.york.ac.uk/prospero/#recordDetails.
Nanoparticles in gynecologic cancers: a bibliometric and visualization analysis
Authors: Zhou Yunzhe , Chen Lizhang , Wang Tingting
Published: January 2025

Background

Gynecological cancers are characterized by uncontrolled cell proliferation within the female reproductive organs. These cancers pose a significant threat to women’s health, impacting life expectancy, quality of life, and fertility. Nanoparticles, with their small size, large surface area, and high permeability, have become a key focus in targeted cancer therapy. The aim of this study is to review recent advancements in nanoparticles applied to gynecologic cancers, providing valuable insights for future research.

Methods

We retrieved all literature on nanoparticles in gynecologic cancers from the Web of Science Core Collection (WOSCC) database between January 1, 2004, and June 4, 2024. Data analysis and visualization were conducted using R software (version 4.4.0), VOSviewer (version 1.6.19.0), and CiteSpace (version 6.1).

Results

A total of 2,843 publications from January 1, 2004, to June 4, 2024 were searched. Over the past 20 years, there has been a significant increase in publications. The leading countries and institutions in terms of productivity are China and the Chinese Academy of Sciences. The most prolific author and the most co-cited author are Sood, A K and Siegel, Rl. The top journals are the International Journal of Nanomedicine (n=97), followed by ACS Applied Materials & Interfaces (n=72) and Journal of Materials Chemistry B (n=53). Keyword analysis shows current research focuses on two main areas: the application of nanoparticles for drug delivery and their broader applications in gynecologic cancers. Future research will likely focus on “silver nanoparticles,” “gold nanoparticles,” and “green synthesis.”

Conclusions

Over the past two decades, nanoparticles have rapidly advanced in the field of gynecologic cancers. Research has primarily focused on the applications of nanoparticles in drug delivery and applications. Future trends point toward optimizing synthesis techniques and advancing preclinical studies to clinical applications, particularly for silver and gold nanoparticles. These findings provide valuable scientific insights for researchers.
Rational strategies for designing next-generation oncolytic viruses based on transcriptome analysis of tumor cells infected with oncolytic herpes simplex virus-1
Authors: Javid Naeme , Abdoli Shahriyar , Shahbazi Majid
Published: January 2025

Introduction

Oncolytic herpes simplex viruses (oHSVs) are a type of biotherapeutic utilized in cancer therapy due to their ability to selectively infect and destroy tumor cells without harming healthy cells. We sought to investigate the functional genomic response and altered metabolic pathways of human cancer cells to oHSV-1 infection and to elucidate the influence of these responses on the relationship between the virus and the cancer cells.

Methods

Two datasets containing gene expression profiles of tumor cells infected with oHSV-1 (G207) and non-infected cells from the Gene Expression Omnibus (GEO) database were processed and normalized using the R software. Common differentially expressed genes between datasets were selected to identify hub genes and were further analyzed. Subsequently, the expression of hub genes was verified by real-time polymerase chain reaction (qRT-PCR) in MDA-MB-231 (a breast cancer cell line) infected with oHSV-1 and non-infected cells.

Results

The results of our data analysis indicated notable disparities in the genes associated with the proteasome pathway between infected and non-infected cells. Our ontology analysis revealed that the proteasome-mediated ubiquitin-dependent protein catabolic process was a significant biological process, with a p-value of 5.8E−21. Additionally, extracellular exosomes and protein binding were identified as significant cellular components and molecular functions, respectively. Common hub genes with degree and maximum neighborhood component (MNC) methods, including PSMD2, PSMD4, PSMA2, PSMD14, PSMD11, PSMC3, PSMC2, PSMD8, and PSMA4, were also identified. Analysis of gene expression by qRT-PCR and differential gene expression revealed that GADD45g genes can be effective genes in the proliferation of oncolytic HSV-1 virus.

Conclusion

The transcriptome changes in tumor cells infected by oHSV-1 may be utilized to predict oncolytic efficacy and provide rational strategies for designing next-generation oncolytic viruses.
CT-based radiomics predicts HRD score and HRD status in patients with ovarian cancer
Authors: Wu Yujiao , Zhang Qianhui , Jiang Wenyan , Gao Yuhua , Qu Bin , Wang Xingling
Published: January 2025

Introduction

This study predicted HRD score and status based on intra- and peritumoral radiomics in patients with ovarian cancer (OC) for better guiding the use of PARPi in clinical.

Methods

A total of 106 and 95 patients with OC were included between January 2022 and November 2023 for predicting HRD score and status, respectively. Radiomics features were extracted and quantitatively analyzed from intra- and peri-tumor regions in the CT image. Radiomics signatures (RSs) were built based on features from intra- and peri-tumor regions for predicting HRD score and status alone or in combination. Subject working characteristics (ROC) area under the curve (AUC), sensitivity (SEN), and specificity (SPE) were calculated as comparative metrics.

Results

For predicting HRD score, 4 and 2 features were selected as the most important predictors from the intra- and peritumoral regions, respectively. For predicting HRD status, 4 features from the intratumoral region and 2 from the peritumoral region were identified as the most important predictors. Radiomics nomograms created by combining RSs and important clinical factors showed good predictive results with AUCs of 0.852 (95% confidence interval [CI]: 0.765-0.938, SEN = 0.907, SPE = 0.655) and 0.781 (95% CI: 0.621-0.941, SEN = 0.688, SPE = 0.833) in the training and validation cohort for predicting HRD score, respectively; with AUCs of 0.874 (95% CI: 0.790-0.957, SEN = 0.765, SPE = 0.867) and 0.824 (95% CI: 0.663-0.985, SEN = 0.762, SPE = 0.800) in the training and validation cohort for predicting HRD status, respectively.

Discussion

Calibration curves and decision curve analysis (DCA) confirmed potential clinical usefulness of our nomograms. Our findings suggest that radiomics features derived from the CT image of OC have the potential to predict HRD score and status, and the developed nomograms can enrich the range of applicable population of PARPi, prolong progression-free survival and provide personalized treatment for OC patients.
Autophagic flux modulates tumor heterogeneity and lineage plasticity in SCLC
Authors: Hao Yujie , Li Mingchen , Liu Wenxu , Ma Zhenyi , Liu Zhe
Published: January 2025

Introduction

Small cell lung cancer (SCLC) is characterized by significant heterogeneity and plasticity, contributing to its aggressive progression and therapy resistance. Autophagy, a conserved cellular process, is implicated in many cancers, but its role in SCLC remains unclear.

Methods

Using a genetically engineered mouse model (Rb1fl/fl; Trp53fl/fl; GFP-LC3-RFP-LC3△G), we tracked autophagic flux in vivo to investigate its effects on SCLC biology. Additional in vitro experiments were conducted to modulate autophagic flux in NE and non-NE SCLC cell lines.

Results

Tumor subpopulations with high autophagic flux displayed increased proliferation, enhanced metastatic potential, and neuroendocrine (NE) characteristics. Conversely, low-autophagic flux subpopulations exhibited immune-related signals and non-NE traits. In vitro, increasing autophagy induced NE features in non-NE cell lines, while autophagy inhibition in NE cell lines promoted non-NE characteristics.

Discussion

This study provides a novel model for investigating autophagy in vivo and underscores its critical role in driving SCLC heterogeneity and plasticity, offering potential therapeutic insights.
Case report: Accidental aconitine poisoning caused by the inappropriate use of a type of Chinese patent medicine
Authors: Shang Ruikai , Liu Hongyu , Tian Qiaoxin , Liu Yuru , Jian Xiangdong , Li Qilu
Published: January 2025

Background

Compound schizonepeta fumigation lotion is a type of Chinese patent medicine for external use. It has the effect of dispelling wind, eliminating dampness, reducing swelling, and relieving pain. Clinically, it is used for anal fumigation and treatment of external hemorrhoids, anal fissures, and other diseases. Aconitum species are widely used in the field of traditional Chinese medicine. However, improper use and overdose can easily cause acute poisoning, leading to malignant arrhythmias, cardiogenic shock, and even death.

Methods

This study retrospectively analyzed the clinical data of eight patients who were treated in our hospital from June 2023 to February 2024 after taking compound schizonepeta fumigation lotion by mistake.

Case presentation

We report 8 cases of patients who took compound schizonepeta fumigation lotion by mistake. Most patients were illiterate and older, and poisoning was attributed to the misuse of an external drug. The affected patients exhibited different degrees of arrhythmia, with 2 receiving tracheal intubation, assisted ventilation, and hemoperfusion. Finally, all patients were clinically cured and subsequently discharged.

Conclusion

A considerable number of accidental aconitine poisoning cases were reported over a short period, alerting clinicians to their growing incidence. Meanwhile, when prescribing medications, clinicians must provide clear instructions on proper usage and ensure that patients strictly adhere to the dosage and administration guidelines outlined in the drug instructions. Additionally, patients should be informed that any errors in medication administration require urgent medical attention. Health professionals should aim to improve public understanding of safe medication practices, promote health literacy.
Consistent RNA expression and RNA modification patterns in cardiotoxicity induced by Matrine and Evodiamine
Authors: Fang Guanhua , Shen Yanming , Gao Xinyue , Yang Lele , Zhu An , Liao Dongshan
Published: January 2025

Recent research has demonstrated the efficacy of traditional Chinese medicine (TCM) and its active compounds in combating cancer, leading to an increasing utilization of TCM as adjunctive therapy in clinical oncology. However, the optimal dosage of TCM remains unclear, and excessive use may result in cardiotoxicity, which poses a significant health concern for patients undergoing systemic treatment. Therefore, elucidating the underlying mechanisms of cytotoxicity induced by TCM can provide valuable insights for clinical management. In this study, we employed a comprehensive bioinformatics analysis to present sequencing data obtained from AC16 myocardial cells treated with two bioactive derived from botanical drugs: Matrine and Evodiamine. We aim to investigate the dysregulated signaling pathways associated with cardiotoxicity induced by these compounds. Based on our sequencing results, we observed consistent patterns of gene expression and epitranscriptome regulation (m6A and A-to-I modifications) across various drugs-treated AC16 cells when analyzed using KEGG pathway enrichment and gene ontology analyses. Furthermore, m6A writers VIRMA and A-to-I writers ADARB1 is consistent target of Evodiamine and Matrine. In general, our findings suggest that different Chinese botanical drugs induced cardiotoxicity may share common therapeutic strategies.
Gut microbiota derived metabolite trimethylamine N-oxide influences prostate cancer progression via the p38/HMOX1 pathway
Authors: Zhou Yuhua , Lv Jing , Jin Shengkai , Fu Chaowei , Liu Bo , Shen Yang , Li Menglu , Zhang Yuwei , Feng Ninghan
Published: January 2025

Background

Prostate cancer was the fourth most diagnosed cancer worldwide in 2022. Radical treatments and androgen deprivation therapy benefit newly diagnosed patients but impact quality of life, often leading to castration-resistant prostate cancer. Short-term dietary changes significantly affect the gut microbiota, which differs markedly between prostate cancer patients and healthy individuals, impacting both cancer progression and treatment response. A high-choline diet increases the risk of fatal prostate cancer, potentially mediated by the conversion of choline to the trimethylamine N-oxide (TMAO) by the gut microbiota.

Methods

The CCK8 assay was employed to investigate whether TMAO affects the proliferation ability of prostate cancer cells and to determine the appropriate drug concentration. Subsequently, CCK8 time gradients, colony formation assays, and EdU assays measured TMAO’s influence on cell proliferation. Wound healing and transwell migration assays evaluated TMAO’s effect on cell migration. RNA-seq analysis was performed to explore the mechanisms by which TMAO influences the proliferation and migration of prostate cancer cells. qPCR and Western blotting were utilized to validate the expression of related mRNA or proteins. Finally, we performed in vivo experiments to evaluate the effect of a high choline diet on the growth of subcutaneous tumors and lung metastases in mice.

Results

Our study found that TMAO enhances the proliferation and migration of prostate cancer cells by upregulating HMOX1 via activation of the MAPK signaling pathway, specifically p38 MAPK. In mouse subcutaneous tumor and lung metastatic tumor experiments, the high-choline diet increased prostate cancer cell proliferation and migration, resulting in significantly greater tumor volume and number of metastases than controls.

Conclusion

This study is the first to demonstrate the role of the gut microbiota-derived metabolite TMAO in prostate cancer. TMAO promotes the proliferation and migration of prostate cancer cells by activating the p38 pathway and increasing HMOX1 expression. Reducing choline intake through dietary intervention may delay the onset and progression of prostate cancer, presenting significant clinical application value.