bluuebunny/crossref_metadata_2025 huggingface dataset:
Penerapan Pemberian Terapi Massage Payudara Dengan Metode SPEOS untuk Kelancaran ASI Terhadap Pasien Post Sectio Caesaria: Studi Kasus
Authors: Zubaidah Siti , Prasetyorini Heny
Published: February 2025

Ibu menyusui yang menjalani persalinan sectio caesaria memiliki risiko yang lebih tinggi untuk mengalami kesulitan menyusui dibandingkan dengan ibu yang melahirkan secara normal. Hal ini disebabkan oleh beberapa faktor, antara lain trauma fisik yang dialami ibu akibat tindakan operasi sesar yang dapat menyebabkan nyeri dan ketidaknyamanan pada payudara, sehingga ibu menjadi enggan untuk menyusui. Kurang stimulasi pada payudara akibat posisi bayi yang sulit untuk menyusui dapat menyebabkan produksi ASI menurun. Pengaruh hormonal akibat tindakan operasi sesar dapat mengganggu produksi ASI. Mengetahui penerapan pemberian terapi massage payudara dengan metode SPEOS (stimuasi pijat endorpin, oksitosin dan sugestif) untuk kelancaran ASI terhadap pasien post sectio caesaria di RS Permata Medika. Metode: Studi kasus adalah jenis metode penelitian yang menggunakan desain penelitian pre eksperimental yang disebut desain pre-post test dalam satu kelompok untuk menjelaskan kejadian secara metodis dan obyektif serta menarik kesimpulan. Pasien dalam penelitian ini sebanyak 4 Pasien post SC yang mengalami ketidakefektifan menyusui (kurangnya produksi ASI, ketidakmampuan bayi untuk menghisap, teknik menyusui yang tidak benar). Didapatkan dari keempat ibu mengalami sedikit ASI yang keluar sebelum dilakukan metode SPEOS (stimuasi pijat endorpin, oksitosin dan sugestif), setelah dilakukan metode SPEOS (stimuasi pijat endorpin, oksitosin dan sugestif) ASI keluar banyak. Ada pengaruh kelancaran ASI terhadap pasien post sectio caesaria sebelum dan sesudah dilakukan penerapan pemberian terapi massage payudara dengan metode SPEOS (stimuasi pijat endorpin, oksitosin dan sugestif)
Body Image dan Self Confidence Pada Remaja Putri: Studi Korelasional
Authors: Apriliana Dwika , Kurniati Fitri Dian
Published: February 2025

Masa remaja merupakan masa peralihan, sehingga proses pertumbuhan fisik, mental dan emosional terjadi secara cepat. Body image merupakan persepsi atau penilaian puas dan tidak puas seseorang terhadap dirinya secara fisik, yang dapat menciptakan evaluasi positif ataupun negative terhadap diri sendiri. Self-confidence merupakan sikap positif individu yang memampukan dirinya untuk mengembangkan penilaian positif terhadap dirinya maupun terhadap lingkungan. Tujuan penelitian ini adalah untuk mengetahui hubungan body image dengan self-confidence pada remaja putri. Jenis penelitian yang digunakan adalah non-eskperimen dengan menggunakan pendekatan cross sectional. Sampel penelitian ini adalah remaja putri kelas 10 SMA Negeri 2 Banguntapan Yogyakarta berjumlah 66 responden. Teknik sampling menggunakan purvosive sampling. Instrument penelitian yang digunakan yaitu kuesioner body image dan kuesioner self confidence dengan menggunakan analisis uji kendall tau. Hasil penelitian ini menunjukan bahwa sebagian besar responden memiliki body image tinggi yaitu sebanyak 38 responden (57.6%) dan sebagian besar responden juga memiliki self confidence kategori tinggi sebanyak 48 responden (72.7%). Hasil uji statistik kendall tau didapatkan nilai korelasi = 0,483 dengan nilai signifikan 0.000 (p<0,05). Kesimpulan penelitian ini menunjukkan adanya hubungan body image dengan self confidence pada remaja putri di SMA Negeri 2 Banguntapan Yogyakarta.
Hubungan Perilaku Caring Perawat dengan Tingkat Kecemasan dan Kepuasan Pasien Pre Operasi
Authors: Yunalia Endang Mei , Samudera Wahyu Sukma , Suharto Idola Perdana Sulistyoning , Astuti Widi
Published: February 2025

Pembedahan adalah tindakan pengobatan menggunakan cara invasive yang dapat menimbulkan respon kecemasan pada pasien yang mengalami tindakan pembedahan. Perilaku caring perawat dapat meminimalisir kecemasan yang dirasakan pasien. Penelitian ini bertujuan untuk mengetahui hubungan perilaku caring perawat dengan tingkat kecemasan dan kepuasan pasien di Kamar Operasi IBS RSUD Kabupaten Mimika. Desain yang digunakan dalam penelitian ini adalah korelasi dilakukan secara cross sectional. Populasi dalam penelitian ini adalah seluruh pasien di kamar operasi IBS RSUD Kabupaten Mimika pada bulan Oktober 2024 dan jumlah sampel penelitian sebanyak 50 responden, yang ditentukan dengan menggunakan teknik accidental sampling. Pengambilan data menggunakan instrument berupa kuesioner. Hasil penelitian yang didapatkan yaitu hampir setengah responden yang mendapatkan perilaku caring kategori sedang memiliki tingkat kecemasan ringan. Uji statistic dalam penelitian ini menggunakan uji Spearman Rank. Hasil penelitian menunjukkan adanya hubungan perilaku caring perawat dengan tingkat kecemasan pasien di kamar operasi IBS RSUD Kabupaten Mimika dengan tingkat hubungan yang cukup kuat. Sebagian besar responden yang mendapatkan perilaku caring sedang dari perawat, puas terhadap pelayanan yang diberikan. Hasil penelitian menggunakan uji Spearman Rank menunjukkan adanya hubungan perilaku caring perawat dengan tingkat kepuasan pasien di kamar operasi IBS RSUD Kabupaten Mimika dengan tingkat hubungan yang cukup kuat. Kesimpulan yang didapatkan dari penelitian ini adalah ada hubungan perilaku caring perawat dengan tingkat kecemasan dan kepuasan pasien di Kamar Operasi IBS RSUD Kabupaten Mimika.
Book Review: Laboratories of Learning: Social Movements, Education, and Knowledge-Making in the Global South by Mario Novelli, Birgül Kutan, Patrick Kane, Adnan Çelik, Tejendra Pherali, and Saranel Benjamin
Authors: Souto-Maior João
Published: February 2025

In his review of Laboratories of Learning: Social Movements, Education, and Knowledge-Making in the Global South by Mario Novelli, Birgül Kutan, Patrick Kane, Adnan Celik, Tejendra Pherali, and Saranel Benjamin, João Souto-Maior highlights the authors' in-depth qualitative analysis of how social movements create spaces for learning, knowledge creation, and social transformation. Souto-Maior points out the unique contribution this book makes to the education in emergencies field through its discussion of the microlevel processes that shape social movements. Based on the authors' participatory action research, this book is a meaningful methodological addition to the education in emergencies field for scholars and practitioners who are interested in forging meaningful relationships with individuals and organizations directly engaged in social change.
Responsible AI in biotechnology: balancing discovery, innovation and biosecurity risks
Authors: Wheeler Nicole E.
Published: February 2025

The integration of artificial intelligence (AI) in protein design presents unparalleled opportunities for innovation in bioengineering and biotechnology. However, it also raises significant biosecurity concerns. This review examines the changing landscape of bioweapon risks, the dual-use potential of AI-driven bioengineering tools, and the necessary safeguards to prevent misuse while fostering innovation. It highlights emerging policy frameworks, technical safeguards, and community responses aimed at mitigating risks and enabling responsible development and application of AI in protein design.
Analysis and mitigation of fire and explosion hazards in hospital environments from a biomedical engineering perspective
Authors: Ibáñez-Cruz Augusto Jorge Antonio , Espinoza-Morriberon Dante , Vergara-Florián Alejandra Micaela Elena , Algoner William C.
Published: February 2025

Background

Hospitals are complex and dynamic facilities that house vulnerable people, medical equipment, and hazardous materials, making them susceptible to fires and explosions with potentially catastrophic effects. This study aims to understand and address fire and explosion risks in hospital environments using biomedical engineering, safety, and fire prevention concepts to develop effective mitigation strategies.

Materials and Methods

The study employed a mixed-methods approach, integrating quantitative and qualitative techniques. Data from an insurance and reinsurance company in Peru were analyzed, and surveys, data analysis, and interviews were conducted. The preferred reporting items for systematic review and meta-analysis (PRISMA) methodology was also applied to conduct a thorough literature review.

Results

The results revealed the most frequent risk factors in hospital settings and identified the most effective mitigation strategies. Implementing these strategies resulted in a considerable decrease in the incidences of fires and explosions.

Discussion

The research provides a comprehensive explanation of hospital fire and explosion risks and proposes evidence-based strategies to improve the safety. These results underscore the relevance of biomedical engineering in managing risks within hospital settings. Despite certain limitations, the study lays a firm foundation for future research aimed at improving hospital safety.
Exploring precision therapeutics: computational design of antisense oligonucleotides targeting AXL gene transcripts in multiple sclerosis treatment management
Authors: Shreevatsa Bhargav , Nagaraj Abhigna , Dharmashekar Chandan , Jain Anisha , Harendra Bhavana , Siddalingegowda Siddesh V. , Al-Mazroua Haneen A. , Ahmad Sheikh F. , Prasad Shashanka K. , Srinivasa Chandrashekar , Shivamallu Chandan , Kollur Shiva Prasad
Published: February 2025

Multiple sclerosis (MS) is a chronic autoimmune illness characterized by demyelination, neurodegeneration, and inflammation in the central nervous system. The AXL gene, which codes for a receptor tyrosine kinase, has emerged as a promising therapeutic target due to its involvement in neuroinflammation and oligodendrocyte dysfunction. In the current study, we employed in silico techniques to design Antisense Oligonucleotides (ASOs) that selectively target AXL gene transcripts to modulate AXL expression and mitigate MS pathology. Three ASOs, A1, A2, and A3, were designed to specifically target the 5′ untranslated region (5′UTR) and coding region of the AXL gene transcripts. The ASOs were optimized with a focus on stability, binding affinity, and specificity towards AXL mRNA while minimizing off-target effects. To investigate ASO-mRNA interactions and gauge their ability to alter AXL expression, Molecular Docking was performed. Our analyses showed that A1, A2, and A3 had substantial interactions with AXL mRNA, with binding affinities of −9.5 kcal/mol, −10.8 kcal/mol, and −10.6 kcal/mol, respectively. The targeting of AXL gene transcripts through ASOs shows promise in reducing MS symptoms. Precision ASO-based therapies could effectively manage MS by targeting the essential pathways involved in the disease. ASOs provide a highly targeted approach for treating MS and offer a precise therapeutic strategy for this debilitating condition. The study lays the groundwork for future in vitro and in vivo studies to confirm the therapeutic potential of these ASOs for the treatment of MS.
Gut microbiota interacting with vitamin D but not anandamide might contribute to the pathogenesis of preeclampsia: a preliminary study
Authors: Han Xiao-Qiang , Jiang Hui-Hui , Chen Meng-Ling , Han De-Yang , Zhou Su-Fen , Wang Jin-Wen , Ji Shu-Shen , Wang Ling-Yun , Lou Jing-Wei , Li Ming-Qun
Published: February 2025

Introduction

Preeclampsia (PE) is a pregnancy-specific multisystem disorder and a leading cause of maternal and perinatal mortality globally. Despite numerous studies highlighting the potential roles of gut microbiota, anandamide (AEA), and Vitamin D (VitD) in PE, none have established them as reliable biomarkers for predicting disease onset. Moreover, their interactions in late-stage pregnancy women remain poorly understood.

Methods

Thirty-four preeclamptic patients (called PE group) and thirty-nine matched healthy late-pregnant women (called LP group) were involved in this case-control study. Fecal samples, which were used to acquire the diversity and composition of gut microbiota, were analyzed by 16S rRNA gene sequencing. Plasma AEA concentrations and serum VitD levels were determined by high-performance liquid chromatography-mass spectrometry (HPLC-MS) and liquid chromatography-tandem mass spectrometry (LC-MS/MS), respectively.

Results

In this study, β diversity but not α diversity significantly differed between the LP and PE groups. Compared with the LP group, the relative abundances of Prevotella, Erysipelotrichaceae_UCG-003, and Dorea were increased dramatically in the PE group, whereas the relative abundances of Subdoligranulum, Parabacteroides, Bacteroides were significantly decreased in the PE group. Furthermore, women with PE had a substantially lower plasma level of AEA and a marked decrease in serum VitD compared to normal late-pregnant women. Lastly, although the serum level of AEA was not significantly correlated with VitD or any of the top 6 marker genera, VitD was significantly negatively correlated with the relative abundance of Dorea, a novel finding in this context.

Discussion

The gut microbiota profile of the PE group was significantly different from that of the LP group. Although no significant correlations were identified between the plasma AEA levels and serum VitD levels or any of the top 6 identified marker genera, a significant negative correlation was observed between VitD and Dorea, indicating VitD and gut microbiota have the potential to be combined targets for early diagnosis and management of PE.
Machine learning cluster analysis identifies increased 12-month mortality risk in transcatheter aortic valve replacement recipients
Authors: Meredith Thomas , Mohammed Farhan , Pomeroy Amy , Barbieri Sebastiano , Meijering Erik , Jorm Louisa , Roy David , Kovacic Jason , Feneley Michael , Hayward Christopher , Muller David , Namasivayam Mayooran
Published: February 2025

Background

Long-term mortality risk is seldom re-assessed in contemporary clinical practice following successful transcatheter aortic valve implantation (TAVR). Unsupervised machine learning permits pattern discovery within complex multidimensional patient data and may facilitate recognition of groups requiring closer post-TAVR surveillance.

Methods

We analysed and differentiated routinely collected demographic, biochemical, and cardiac imaging data into distinct clusters using unsupervised machine learning. k-means clustering was performed on data from 200 patients who underwent TAVR for severe aortic stenosis (AS). Input features were ranked according to their influence on cluster assignment. Survival analyses were performed with Kaplan–Meier and Cox proportional hazards models. Nested cox models were used to identify any incremental prognostic benefit cluster assignment achieved beyond conventional risk scores.

Results

Analysis identified two distinct clusters. Compared to Cluster 1, Cluster 2 demonstrated significantly worse all-cause mortality at 12 months (HR 6.3, p < 0.01), and was characterised by more advanced cardiac remodelling with worse indices of multi-chamber cardiac function, as quantified by strain imaging. Cluster assignment demonstrated greater predictive power for 12-month mortality as compared with conventional risk and frailty calculators.

Conclusion

k-means clustering identified two prognostically distinct phenogroups of patients who had undergone TAVR with better discriminatory power than conventional risk and frailty calculators. Our results highlight the utility of machine learning applications for clinical risk prediction and scope to improve patient surveillance.
Transcriptomic signatures of subcutaneous adipose tissue in patients with diabetes and coronary artery disease: a pilot study
Authors: Doulamis Ilias P. , Pan Bernard , Tzani Aspasia , Plutzky Jorge , Wong G. William , Kilic Ahmet , Wolf Risa M.
Published: February 2025

The exact role of subcutaneous adipose tissue in the interplay between type 2 diabetes (T2D) and coronary artery disease (CAD) is yet to be determined. A prospective cohort study of adult patients with and without T2D undergoing CABG was performed. Subcutaneous adipose tissue was collected during the procedure and RNA seq analysis was performed. A total of 741 differentially expressed genes (DEGs) were identified (332 up- and 409 down-regulated in the T2D group). Our results demonstrated that pathways related to apoptosis and immune response were significantly dysregulated in the adipose tissue of T2D subjects. The main molecular pathways involved were CXCR, NOTCH, STAT, NFKB1 and FGFR pathways, which have a well-documented role in diabetes and CAD. SPI1 and MTF1 were two novel upstream transcription factors identified which have been suggested to be involved in the inflammatory cascade and insulin regulation in diabetes. Three miRNAs were differentially expressed between the two groups (miR-27a, miR-335 and miR-146). These preliminary results provide fertile ground for further research of potential targets for patients with diabetes and coronary artery disease.
Adaptive learning in bionics: transforming science education
Authors: Honke Nadine , Becker-Genschow Sebastian
Published: February 2025

Introduction

Adaptive learning platforms offer innovative teaching approaches by tailoring educational content to individual learner’s needs, abilities, and paces.

Methods

This study investigates the effects of an adaptive digital learning platform on user experience, motivation, and learning outcomes among 56 sixth-grade students from two German grammar schools. Students completed three bionics-focused modules— “polar bear”, “heat transfer”, and “temperature and heat”—integrated into science lessons. Data from questionnaires and performance tests assessed prior knowledge, learning success, cognitive activation, and situational interest.

Results

The findings indicate that 98% of students found digital media motivating, with 81% favoring a hybrid mix of traditional and digital teaching methods. Positive emotional responses were reported by 62% of participants, though 38% experienced uncertainty. The “polar bear” module achieved the highest learning gain (+41%), followed by “heat transfer” (+23%) and “temperature and heat” (+13%) module.

Discussion

These results suggest that adaptive digital learning platforms can enhance learning outcomes and cognitive engagement, particularly when the content aligns with student interests and needs.
Measuring coordination between land ecological security and high-quality economic development: a case of the Beijing-Tianjin-Hebei region
Authors: Zhong Xiaoyong , Guo Dongyan , Tang Yandong , Chuai Yafei
Published: February 2025

The interplay between land ecological security (LES) and high-quality economic development (HED) is intricately linked to the sustainable development of regions, with their combined influence at the county level being pivotal for the harmonious growth of urban agglomerations. In this study, we employ the entropy-weighted technique for order preference by similarity to ideal solution (EW-TOPSIS), coupling coordination degree (CCD), deviation coordination degree, and relative development degree methodologies to assess the developmental status of LES and HED, as well as the coupling coordination between these two systems, and introduce a novel approach for delineating functional regions. Our findings reveal a pronounced polarization of LES and HED within the Beijing-Tianjin-Hebei (BTH) region, with the majority of areas exhibiting a high degree of coupling but moderate imbalance. Spatial analysis highlights distinct characteristics, allowing for the segmentation of the region into seven distinct development functional zones. Recommendations include the establishment of a collaborative framework for the BTH region, enhancing the innovation, openness, and coordination within HED, and focusing on the advancement of HED in leading, key, and stable development areas. Furthermore, it is essential to elevate the visibility and responsiveness of LES, and strategically implement land ecological engineering in key and stable development areas. These strategic initiatives aim to improve the developmental standards of LES and HED, thereby enhancing the coordination and synergy between these two key systems.
Training of female health workers (FHWs) to enhance the advocacy and communication skills on COVID-19 vaccine and routine Immunization in District Peshawar Khyber Pakhtunkhwa (KP) Pakistan in 2023—a report from the field
Authors: Al-Gunaid Magid , Hussain Zakir , Daoud Leen , Akram Khurram
Published: February 2025

Introduction

In 2021, a comprehensive evaluation was conducted across five countries, including Pakistan, to explore the factors influencing the demand for COVID-19 vaccines among priority groups. The study uncovered significant challenges, including low vaccination rates among females, limited trust in the COVID-19 vaccine, accessibility issues, and a notable gap in dose administration.

Methods

To address these challenges, a targeted pilot intervention was proposed in Peshawar, Pakistan. This intervention aimed to enhance vaccine demand among young women (aged 18–24), including pregnant and lactating women (PLWs), by equipping approximately 300 female health workers (FHWs) with improved advocacy and communication skills. These skills were designed to combat vaccine hesitancy and increase vaccine acceptance among women. Moreover, efforts were made to strengthen social support from community leaders. The pilot initiative encompassed baseline and endline evaluations to assess its impact. The baseline evaluation involved analyzing existing vaccination data, disaggregated by age and gender. Key informant interviews (KIIs) were conducted to capture qualitative insights into the perceptions of vaccines within the target population.

Findings

Data from the Department of Health KP and Expanded Program on Immunization Management Information System (EPIMIS) highlighted improvements in both COVID-19 and routine Expanded Program on Immunization (EPI) vaccinations across 25 union councils (UCs) in district Peshawar. KIIs with stakeholders, including health workers and community influencers, revealed enhanced knowledge and willingness to vaccinate, particularly among PLWs and females aged 18–24. The evaluation also observed increased confidence and reduced vaccine hesitancy due to advocacy sessions. Additionally, training of FHWs significantly improved their knowledge and attitudes towards COVID-19 vaccination and routine EPI, contributing to the overall success of the intervention. Monitoring visits further validated the effective conduct of advocacy sessions by trained health workers, leading to increased vaccination uptake in the community.

Conclusion

The comprehensive approach undertaken in this pilot intervention aimed not only to improve vaccine uptake but also to bolster confidence in the COVID-19 vaccine within the community. The findings and outcomes of this initiative provided valuable insights for future public health strategies, particularly in addressing vaccine hesitancy and increasing vaccine acceptance among priority groups.
Interactions between NAD+ metabolism and immune cell infiltration in ulcerative colitis: subtype identification and development of novel diagnostic models
Authors: Tian Linglin , Gao Huiyang , Yao Tian , Chen Yuhao , Gao Linna , Han Jingxiang , Zhu Lanqi , Huang He
Published: February 2025

Background

Ulcerative colitis (UC) is a chronic inflammatory disease of the colonic mucosa with increasing incidence worldwide. Growing evidence highlights the pivotal role of nicotinamide adenine dinucleotide (NAD+) metabolism in UC pathogenesis, prompting our investigation into the subtype-specific molecular underpinnings and diagnostic potential of NAD+ metabolism-related genes (NMRGs).

Methods

Transcriptome data from UC patients and healthy controls were downloaded from the GEO database, specifically GSE75214 and GSE87466. We performed unsupervised clustering based on differentially expressed NAD+ metabolism-related genes (DE-NMRGs) to classify UC cases into distinct subtypes. GSEA and GSVA identified potential biological pathways active within these subtypes, while the CIBERSORT algorithm assessed differential immune cell infiltration. Weighted gene co-expression network analysis (WGCNA) combined with differential gene expression analysis was used to pinpoint specific NMRGs in UC. Robust gene features for subtyping and diagnosis were selected using two machine learning algorithms. Nomograms were constructed and their effectiveness was evaluated using receiver operating characteristic (ROC) curves. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) was conducted to verify gene expression in cell lines.

Results

In our study, UC patients were classified into two subtypes based on DE-NMRGs expression levels, with Cluster A exhibiting enhanced self-repair capabilities during inflammatory responses and Cluster B showing greater inflammation and tissue damage. Through comprehensive bioinformatics analyses, we identified four key biomarkers (AOX1, NAMPT, NNMT, PTGS2) for UC subtyping, and two (NNMT, PARP9) for its diagnosis. These biomarkers are closely linked to various immune cells within the UC microenvironment, particularly NAMPT and PTGS2, which were strongly associated with neutrophil infiltration. Nomograms developed for subtyping and diagnosis demonstrated high predictive accuracy, achieving area under curve (AUC) values up to 0.989 and 0.997 in the training set and up to 0.998 and 0.988 in validation sets. RT-qPCR validation showed a significant upregulation of NNMT and PARP9 in inflamed versus normal colonic epithelia, underscoring their diagnostic relevance.

Conclusion

Our study reveals two NAD+ subtypes in UC, identifying four biomarkers for subtyping and two for diagnosis. These findings could suggest potential therapeutic targets and contribute to advancing personalized treatment strategies for UC, potentially improving patient outcomes.
Dynamics of blood microsatellite instability (bMSI) burden predicts outcome of a patient treated with immune checkpoint inhibitors: a case report of hyperprogressive disease
Authors: Kravchuk Daria , Lebedeva Alexandra , Kuznetsova Olesya , Kavun Alexandra , Taraskina Anastasiia , Belova Ekaterina , Grigoreva Tatiana , Veselovsky Egor , Mileyko Vladislav , Nikulin Vladislav , Nekrasova Lidia , Tryakin Alexey , Fedyanin Mikhail , Ivanov Maxim
Published: February 2025

Microsatellite instability (MSI) is a widely studied molecular signature, which is associated with long-term benefit in patients treated with immune checkpoint inhibitor therapy. This approach has been proven to be effective in the treatment of patients with MSI-positive colorectal cancer (CRC). Analysis of serial liquid biopsy samples allows to detect changes in the tumor in response to therapy. Typically, somatic mutations are used for tracing the dynamics of the tumor, and the assessment of DNA signatures such as MSI is not currently used for these purposes. Here, we describe a case of a MSI-positive CRC, who received nivolumab monotherapy. Sequential sampling of the patient’s plasma demonstrated an increase in MSI burden (bMSI), which was found to correlate with the increase of driver mutation burden one month after starting nivolumab, and hyperprogressive disease. Thus, analysis of bMSI in liquid biopsy via NGS may be a promising method for timely assessment of the treatment effectiveness received by patients with MSI-positive CRC.
Exosomes secreted by ATF3/Nrf2-mediated ferroptotic renal tubular epithelial cells promote M1/M2 ratio imbalance inducing renal interstitial fibrosis following ischemia and reperfusion injury
Authors: Tang Qiao , Xie Jiatao , Wang Yifei , Dong Chong , Sun Qian
Published: February 2025

Background

Severe renal ischemia and reperfusion injury (IRI) progresses to renal interstitial fibrosis (RIF) with limited therapeutic strategies. Although ferrptosis and macrophage polarization both play important roles in this model, their specific pathogenesis and interactions have not been elucidated. Therefore, we aimed to explore the mechanisms by which ferrotosis occurs in renal tubular epithelial cells (RTECs) and ferroptotic cell-derived exosomes induce macrophage polarization in IRI-related RIF model.

Methods

In vivo, C57BL/6J mice were randomly divided into four groups: sham group, ischemia and reperfusion (IR) group, IR + Ferrostatin-1 (Fer-1) group, and IR +ATF3 knockdown (ATFKD) group. In vitro, RTECs were divided into control (CON) group, hypoxia/reoxygenation (HR) group, HR +Fer-1 group, HR + siRNA-ATF3 (siATF3) group.

Result

Compared with the sham group, the IR group showed more severe kidney injury in HE staining, more collagen fibers in Masson staining, and higher α-SMA expression levels in immunohistochemistry. Total iron and MDA content increased while GSH content decreased. The IR group had more significant mitochondrial damage and higher PTGS2 and TFRC mRNA levels than those in the sham group. Compared with the IR group, the above indexes were all alleviated in the IR+Fer-1 or IR+ATF3KD groups. In addition, the protein expressions of ATF3, Nrf2 and HO-1 in the IR group were increased than those in sham group. Compared with the IR group, ATF3 expressions in the IR+Fer-1 or IR+ATF3KD groups were decreased, and the protein contents of Nrf2 and HO-1 were further increased. Moreover, there were higher levels of M2 markers (Arg1, TGF-β and IL-10 mRNA) in the IR group than those in the sham group, and lower levels in the IR+Fer-1 group or in the IR+ATF3KD group compared with the IR group. The results of in vitro experiment are consistent with those of in vivo experiment. Mechanistically, the release of exosomes carrying miR-1306-5p by the HR group promoted more M2 macrophage.

Conclusion

ATF3 might accelerate the ferroptosis by inhibiting Nrf2/ARE pathway, and exosomes from ferroptotic cells reduced the M1/M2 macrophage ratio, promoting fibrosis.
Epigenetic modifications in bladder cancer: crosstalk between DNA methylation and miRNAs
Authors: Li Wei , Luo Peiyue , Chen Qi , Cheng Le , Gan Lifeng , Zhang Fangtao , Zhong Haidong , Zheng Liying , Qian Biao
Published: February 2025

Bladder cancer (BC) is a malignant tumor characterized by a high incidence of urinary system diseases. The complex pathogenesis of BC has long been a focal point in medical research. With the robust development of epigenetics, the crucial role of epigenetic modifications in the occurrence and progression of BC has been elucidated. These modifications not only affect gene expression but also impact critical biological behaviors of tumor cells, including proliferation, differentiation, apoptosis, invasion, and metastasis. Notably, DNA methylation, an important epigenetic regulatory mechanism, often manifests as global hypomethylation or hypermethylation of specific gene promoter regions in BC. Alterations in this methylation pattern can lead to increased genomic instability, which profoundly influences the expression of proto-oncogenes and tumor suppressor genes. MiRNAs, as noncoding small RNAs, participate in various biological processes of BC by regulating target genes. Consequently, this work aims to explore the interaction mechanisms between DNA methylation and miRNAs in the occurrence and development of BC. Research has demonstrated that DNA methylation not only directly influences the expression of miRNA genes but also indirectly affects the maturation and functionality of miRNAs by modulating the methylation status of miRNA promoter regions. Simultaneously, miRNAs can regulate DNA methylation levels by targeting key enzymes such as DNA methyltransferases (DNMTs), thereby establishing a complex feedback regulatory network. A deeper understanding of the crosstalk mechanisms between DNA methylation and miRNAs in BC will contribute to elucidating the complexity and dynamics of epigenetic modifications in this disease, and may provide new molecular targets and strategies for the early diagnosis, treatment, and prognostic evaluation of BC.
Iron and ferroptosis in kidney disease: molecular and metabolic mechanisms
Authors: Wang Wenjie , Chen Jingdi , Zhan Liying , Zou Handong , Wang Lu , Guo Mengmeng , Gao Hang , Xu Jing , Wu Wei
Published: February 2025

Maintaining iron homeostasis is necessary for kidney functioning. There is more and more research indicating that kidney disease is often caused by iron imbalance. Over the past decade, ferroptosis’ role in mediating the development and progression of renal disorders, such as acute kidney injury (renal ischemia-reperfusion injury, drug-induced acute kidney injury, severe acute pancreatitis induced acute kidney injury and sepsis-associated acute kidney injury), chronic kidney disease (diabetic nephropathy, renal fibrosis, autosomal dominant polycystic kidney disease) and renal cell carcinoma, has come into focus. Thus, knowing kidney iron metabolism and ferroptosis regulation may enhance disease therapy. In this review, we discuss the metabolic and molecular mechanisms of iron signaling and ferroptosis in kidney disease. We also explore the possible targets of ferroptosis in the therapy of renal illness, as well as their existing limitations and future strategies.
Transcriptome analysis reveals hypoxic response key genes and modules as well as adaptive mechanism of crucian carp (Carassius auratus) gill under hypoxic stress
Authors: Xing Mengchao , Rong Zhen , Zhao Xin , Gao Xiaowei , Hou Zhiguang , Zhang Lihan , Khor Waiho , Xu Yihuan , Chen Li , Wu Chengbin
Published: February 2025

Fish gill tissue is a primary organ responsive to acute oxygen deprivation or dissolved oxygen (DO) fluctuations in aquatic environments. However, the adaptive mechanism of crucian carp to hypoxic stress remains largely unknown. Here, we investigated gill physiological and transcriptomic changes of crucian carp exposed to hypoxic conditions (dissolved oxygen concentration of 0.6 ± 0.3 mg/L) for different durations (0 d, 1 d, 2d, 3d, 4 d, and 5d). Transcriptomic analysis revealed that the hypoxia group (0.6 ± 0.3 mg/L DO) exhibited a reduction in interlamellar cell mass (ILCM) on the gill filaments, compared with the control group (6.6 ± 0.3 mg/L DO). With prolonged hypoxia stress, the epithelial cells in the gill lamellae became sparse at 3 d to 5 d, and gill vacuoles were increased. A total of 3,502 differentially expressed genes (DEGs) were identified, and 3 hypoxia-specific modules were screened through differential expression analysis, weighted gene co-expression network analysis (WGCNA), and Bayesian network analysis. The apoptosis, necroptosis, efferocytosis and FoxO signaling pathways were significantly enriched based on the KEGG enrichment pathway analysis. The VEGF pathway genes are significantly expressed, enhancing the generation of microvessels in the gill filaments, and improving the capacity to carry oxygen, thus enabling the crucian carp to adapt to hypoxia stress. Hypoxia activated glycolysis, enhanced anaerobic metabolism, promoted β-oxidation of fatty acids, providing energy and maintaining normal physiological metabolism, eventually improving antioxidant and immune capabilities in crucian carp. In summary, this study reveals the molecular mechanism by which crucian carp adapt to hypoxic stress. Our findings provide valuable references for promoting the healthy aquaculture of hypoxic-sensitive fish and breeding hypoxia-tolerant fish varieties.
Effect of symbiont-targeted control of Halyomorpha halys on the co-occurring pentatomid community
Authors: Prieto Sofia V. , Orrù Bianca , Gonella Elena , Alma Alberto
Published: February 2025

Several native species in the family Pentatomidae are recorded in north-western Italy, associated with different crops. The arrival of Halyomorpha halys led to a reorganization of the role of other pentatomids, some of them becoming secondary pests. Symbiont-targeted control strategies, which disrupt beneficial interactions in stink bugs, have so far been applied to H. halys. However, this approach could also be useful for controlling other pentatomid pests. Additionally, the effects of this strategy on non-target stink bug species need further investigation to assess its potential impact on agroecosystems. Here the effect of symbiont disruption was assessed for stink bugs that share host crops (e.g., hazelnut, wheat, soybean) or the environment (especially wild areas adjacent to crops) with H. halys in north-western Italy (Carpocoris purpureipennis, Dolycoris baccarum, Graphosoma italicum, Palomena prasina and Rhaphigaster nebulosa). Their symbionts were identified as allied to the genus Pantoea through 16S rRNA gene sequencing and also other bacteria were detected in the V4 ventricle of the midgut. Strikingly, variable symbiont infection was found across species. Laboratory tests were conducted assessing the consequences of symbiont deprivation during the first nymphal instar. Egg masses treatment with an anti-symbiont formulation affected hatching rates in D. baccarum and G. italicum, while the mortality rates during the first instar increased in C. purpureipennis and G. italicum. A correspondence between mortality induction and the alteration of symbiont infection rates was observed, with species showing the highest infection drop being the most affected by treatments. These results provide new insights into pentatomid symbionts and reveal significant variability in the response to symbiosis disruption, likely due to species-specific intensity of symbiotic interactions. The consequences of this variability are discussed.
Effects of hypoxia on the heart of the juvenile four-finger threadfin (Eleutheronema tetradactylum) based on physiological indicators and transcriptome analysis
Authors: Lu Yi , Amenyogbe Eric , Yang Ye- , Wang Zhong-liang , Jin Jing-hui , Xie Rui-tao , Droepenu Eric Kwabena , Huang Jian-sheng
Published: February 2025

This study evaluated the effects of hypoxia on the heart of juvenile four-finger threadfin (Eleutheronema tetradactylum) through physiological and transcriptome analysis. Juveniles with an average weight of 122.82 g and length of 24.60 cm were used. Hypoxia significantly increased serum myocardial enzyme activities, including creatine kinase (CK), creatine kinase-MB isoenzyme, lactate dehydrogenase (LDH), and α-hydroxybutyrate dehydrogenase (HDBH). These indicators initially rose and then declined, reflecting cardiac stress and suggesting their potential as early hypoxia biomarkers for real-time aquaculture monitoring. Histological analysis revealed structural damage in myocardial fibers under hypoxia, with increasing severity over time. This underscores the need to minimize oxygen fluctuations to prevent cardiac tissue degeneration. Transcriptome analysis identified upregulated genes involved in cell communication, immune responses, and intracellular signaling, offering potential targets for breeding hypoxia-tolerant species. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis highlighted key pathways such as mitogen-activated protein kinase (MAPK), hypoxia-inducible factor-1 (HIF-1), endocytosis, and phagosome formation. The MAPK pathway plays a critical role in cellular stress responses, including survival, proliferation, and apoptosis. Hypoxia-induced activation of MAPKs like ERK, JNK, and p38 regulates stress-responsive genes. HIF-1 signaling regulates oxygen homeostasis, with HIF-1α stabilizing hypoxia-responsive genes such as VEGFA, which promotes vascular remodeling and enhances oxygen delivery. These findings collectively offer practical applications for enhancing aquaculture management, such as monitoring biochemical markers, adopting hypoxia-tolerant breeding, and adjusting environmental conditions to mitigate stress, ensuring better productivity and sustainability. This research provides a foundation for further studies on the molecular mechanisms of hypoxia stress in aquaculture species.
Dupilumab for treatment of primary cutaneous amyloidosis in adults: two case reports and literature review
Authors: Guo Feiying , Zhong Huajie , Wu Yuan , Xu Xue , Tan Jiarong , Zhou Qiang , Tang Shunli
Published: February 2025

Lichenoid amyloidosis (LA), a subtype of primary cutaneous amyloidosis (PCA), is featured by intensely pruritic, hyperkeratotic papules which lacks standardized treatment. Dupilumab, a human monoclonal antibody targeting for interleukin (IL)-4/13 receptor α chain, is widely applied in type 2 inflammation diseases treatment. This article reported two cases of refractory LA successfully treated with dupilumab and reviewed publications reporting dupilumab treatment for PCA.
Impact of religious fasting on ocular dryness: objective and subjective assessment
Authors: Alomari Amal F. , Issa Sara , Musleh Asma , Abusamak Mohammad , Bdair Omar , AlRyalat Saif Aldeen , Al-Wakfi Alanoud , Jaber Mohammed , Alloubani Ahmad , Sahawneh Haitham , El-Faouri Muhannd , Abdul Aziz Ayman , Al Bdour Muawyah
Published: February 2025

Background

Certain religions require long hours of fasting, abstaining from fluid intake for durations extending up to 16 h. Lack of fluid intake may alter multiple physiological parameters, which can influence the ocular system. In this prospective study, we evaluated the effect of prolonged fasting on dry eye disease using both objective and subjective measures.

Methods

We included patients who fasted for at least 12 h a day for at least 2 weeks, including the testing day, and retested them at least 1 week after the fasting period had ended with no fasting on the testing day. At each visit, Non-Invasive Keratograph Break up time (NIKBUT) and Tear meniscus height (TM) were measured using the Oculus Keratograph 5 M. Ocular Surface Disease Index (OSDI) was evaluated at each timepoint to assess dryness symptoms subjectively.

Results

This study included a total of 40 patients. NIKBUT values during the fasting times were higher than during the non-fasting times; however, the difference was statistically non-significant. There were no significant differences in TM and OSDI measurements between non-fasting and fasting periods (p > 0.05). Lubricating eyedrop use was significantly lower in fasting patients.

Conclusion

Our study showed that prolonged fasting, including complete abstinence from fluid intake, did not lead to significant dryness, neither subjectively nor objectively. During fasting, patients used significantly fewer lubricating drops compared to non-fasting periods.
Predictive value of neutrophil to lymphocyte ratio for the clinical outcomes of acquired immune deficiency syndrome: a systematic review and meta-analysis
Authors: Guo Fuyu , Chen Jiamei , Zhang Hengkai
Published: February 2025

Objective

This study aimed to explore the predictive value of the neutrophil-to-lymphocyte ratio (NLR) for outcomes in Acquired Immune Deficiency Syndrome (AIDS) patients.

Methods

PubMed, Embase, Cochrane, and Web of Science were conducted to search literature up to May 2024 and cohort and case–control studies were included. The primary outcomes were mortality and progression-free survival (PFS). Pooled odds ratios (ORs) or hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using a random-effects model. We conducted sensitivity analyses to assess result stability, reliability, and subgroup analyses to identify sources of heterogeneity using Review Manager 5.4.1. Egger’s tests were performed with Stata 15.1, and funnel plots were generated using Review Manager 5.4.1. Microsoft Excel was used for the initial data summarization.

Results

Fourteen studies involving 30,752 AIDS patients were included. The pooled data showed higher NLR significantly associated with increased mortality (OR: 1.85, 95% CI: 1.43–2.41, p < 0.00001) and shorter progression-free survival (PFS) (HR: 2.46, 95% CI: 1.32–4.59, p = 0.005). Subgroup analyses revealed that NLR’s predictive value was greater in studies with post-ART measurements. Sensitivity analyses show stable and reliable results. Egger’s test and funnel plot analysis revealed no significant publication bias.

Conclusion

NLR is a key prognostic biomarker for predicting mortality and progression-free survival (PFS) in AIDS patients. Incorporating NLR into predictive models may improve prognostic assessments and guide clinical decision-making.

Systematic Review Registration

PROSPERO (CRD42024532918: https://www.crd.york.ac.uk/PROSPERO).
Effects of multidrug-resistant bacteria and multi-antibiotic combination on intestinal microbiota in mice
Authors: Ma Jing , Gong Zheng , Kang Meiling , Tian Zhongjing , You Liping , Ding Chengshi
Published: February 2025

Multidrug-resistant bacteria are a clinical and an epidemiological challenge. However, the effects of multidrug-resistant bacteria and multi-antibiotic combination on gut microbiota are unclear. In this study, the effects of multidrug-resistant bacteria and multi-antibiotic combination on intestinal microbiota in mice have been observed by high-throughput sequencing. Resistant Escherichia coli (RP4) and 0.5, 1, and 2 mg/L antibiotics (Amp, Km, and Tet multi-antibiotic combination) could decrease the number of specific operational taxonomic units from 223 in the normal saline control group to 178 in the antibiotic-resistant bacteria group and 34 in the antibiotic group, and antibiotics are the biggest influencing factor. Multidrug-resistant bacteria and multi-antibiotic combination could affect the function of intestinal microbiota, and the effect of multidrug-resistant bacteria was similar to that of multi-antibiotic combination. Small intestine is the main colonization site of antibiotic-resistant bacteria, and Proteobacteria and Bacteroidetes are the major antibiotic-resistance acquired bacteria as determined by transmission electron microscopy and agarose plate screening culture.
Effects of nitrogen fertilizer basal-to-top-dressing ratios on maize straw decomposition, soil carbon and nitrogen, and bacterial community structure in different soil textures on the north china plain
Authors: Li Jingyu , Yang Xiaonan , Hou Rui , Ma Yujie , Wang Yanqun , Ma Yang , Zhen Wenchao , Huang Yuanyuan , Fu Xin , Peng Zhengping , Men Mingxin
Published: February 2025

Straw return is a recognized agricultural practice that improves soil quality, reduces reliance on chemical fertilizers, and supports sustainable agriculture. Its effectiveness is influenced by microbial changes under varying soil properties and fertilization practices. In a wheat–maize rotation system, field experiments were conducted over 2 years in loam and clay loam soils with five fertilizer (N) application treatments (i.e., no N fertilizer (N0) and N fertilizer basal-to-top-dressing ratios of 3:7 (N3:7), 4:6 (N4:6), 5:5 (N5:5), and 6:4 (N6:4)) to investigate the dynamics of maize straw decomposition, changes in soil organic carbon (SOC) and total nitrogen (TN) concentrations, soil bacterial diversity and abundance, and their interactions. Our results showed that the optimization of N fertilizer basal-to-top-dressing ratios enhanced SOC and TN by accelerating maize straw decomposition and nutrient release, as well as increasing plant carbon and nitrogen inputs. At the wheat maturity stage, the decomposition rate of maize straw reached 69.48–75.04%. The N4:6 and N5:5 ratios exhibited higher decomposition rates and C and N release rates in both soil textures. Compared to N0, N application treatments increased SOC and TN concentrations by 7.90–14.17% and 7.94–33.60%, respectively. The effects were most pronounced with the N4:6 ratio in loam and the N5:5 ratio in clay loam. Both soil textures had the same dominant bacterial phyla, but species abundance differed significantly. Loam had a significantly higher relative abundance of Proteobacteria and lower relative abundances of Gemmatimonadetes, Actinobacteria, and Chloroflexi than clay loam. N application significantly influenced bacterial diversity, with higher diversity observed with the N4:6 ratio in loam and the N5:5 ratio in clay loam. Structural equation modeling indicated that different N application treatments in loam influenced maize straw decomposition by altering the soil C/N ratio and bacterial community diversity, while in clay loam, N application treatments influenced maize straw decomposition mainly by altering the soil C/N ratio. Overall, the N4:6 treatment in loam and the N5:5 treatment in clay loam accelerated the decomposition and nutrient release of maize straw, enhanced SOC, TN, and bacterial community abundance, and provided a scientific basis for efficient straw utilization and sustainable agricultural development in the North China Plain region.