bluuebunny/crossref_metadata_2025 huggingface dataset:
PENTINGNYA ALAT KESELAMATAN OPERATOR KAPAL IKAN KABUPATEN BANYUASIN DI PROVINSI SUMATERA SELATAN
Authors: Setiawan Bambang , Surnata Surnata , Latuheru Paulina
Published: March 2024

Alat keselamatan Â operator kapal ikan adalah sebagai bentuk upaya untuk mencegah atau meminimalisir resiko kecelakan bagi nelayan dan sebagai wujud nyata dari kegiatan Pengabdian Kepada Masyarakat. Kesadaran yang rendah dan didukung dengan harga peralatan keselamatan yang dirasa cukup mahal membuat para penguna pelayaran kurang memenuhi kebutuhan keselamatanÂ  di Kabupaten Banyuasin Provinsi Sumatera Selatan, kurang peduli terhadap pentingnya alat keselamatan di dalam pelayaran. Kegiatan Pengabdian Kepada Masyarakat ini bertujuan untuk memberikan pengetahuan tentang keselamatan berlayar bagi para pengguna kapal ikan di kabupaten Banyuasin. Pemberian pengetahuan serta bantuan peralatan keselamatan bagi para peserta penyuluhan ini bermaksud agar terjadi peningkatan kemampuan, sikap dan kesadaran para pelayananÂ  diperairan sungai. tentang pentingnya keselamatan serta mengenal teknik penyelamatan diri saat terjadi kecelakaan pada saat berlayar. Kegiatan ini dilaksanakan dengan metode pelatihan dengan ceramah dan diskusi antara narasumber dan peserta dengan materi fokus pada keselamatan pelayaran. Hasil kegiatan ini, diharapkan mampu menunjukkan adanya peningkatan kesadaran peserta akan pentingnya keselamatan pelayaran dan pemahaman teknik penyelamatan diri saat terjadi kecelakaan.
IMPROVING SKI LEARNING OUTCOMES BASED ON CLASS MANAGEMENT USING A WHOLE GROUP DISCUSSION APPROACH
Authors: Hunaidah Hunaidah
Published: March 2024

Teacher competence in implementing classroom management functions based on student activity, as well as student interest and active participation in the learning process, is one of the factors that can influence the achievement of learning objectives and improve student learning outcomes, so innovative learning management is needed. The purpose of this study is to examine how classroom management using the whole group discussion technique and increasing the History of Islam (SKI) learning achievement of class V students of Madrasah Ibtidaiyah (MI) Attaqwa 19 Bogor sero Bekasi. This research used an experimental method with a classroom action research (PTK) approach applied to 80 students in class V MI 19 Bogor Sero Bekasi, who were divided into two classes, through the use of Simple Random Sampling Techniques. Shows that there is an increase in SKI learning results after conducting experiments using a classroom management approach based on the use of whole group discussion techniques, and the results of rxy and t calculations show t-count is 4.352 while t-table is 1.685954; this shows t-count is greater than t-table, meaning there is a significant influence So, classroom management using the Whole Group Discussion Technique has a significant influence on student learning outcomes in SKI subjects with a Gain Score of 63.6, meaning there is a significant increase between the experimental class and the control class. This research can be used as a reference for teachers to improve student learning outcomes.
Implementation of the Concept of I'tibar Al Ma'alat in Sharia Banks Toward Customer Late Fines for Delaying Payment Obligations
Authors: Aminuddin Aminuddin , Puspa Devi Chindya Pratisti
Published: March 2024

The concept of I'tibar Al Ma'alat is a legal consideration that is carried out based on the participation or understanding of a guideline study and sees its relationship with the consequences that occur, be it good or bad consequences. This study aims to determine the principle of I'tibar Al Ma'alat, the rules and regulations of Islamic banks related to fines on customers who are late in paying obligations to be in line with the concept of I'tibar Al Ma'alat and the impact of the implementation of the concept of I'tibar Al Ma'alat in terms of fines on customers and Islamic banks. This research uses a qualitative method with a normative juridical approach by extrapolating the legal texts set to consider the results with data collection through library research by reading and analysing in the form of fatwa books of DSN-MUI scholars, laws. The findings in this study indicate that the concept of I'tibar Al Ma'alat in the form of the bank continues to impose fines in the bank's internal system with the opportunity for customers to appeal the imposition of fines accompanied by evidence of force majeure faced with a certain period of time. The principle of I'tibar Al Ma'alat provides a solution that is more valuable, just and beneficial in accordance with the objectives of Maqashid Sharia.
Does Chitosan Introduce Protection Against Methotrexate-Induced Hepatorenal Injury in Rats?
Authors: Şehirli Ahmet Özer , Sayıner Serkan , Bilginaylar Kani , Özkayalar Hanife , Aykaç Aslı
Published: March 2024

Objective: Chitosan possesses antioxidant properties and exhibits anti-inflammatory characteristics. The objective of the investigation was to assess the effectiveness of chitosan in protecting against hepatorenal injury induced by methotrexate (MTX), a medication utilized for immunosuppression and chemotherapy.

Methods: Wistar albino rats were allocated into 3 different groups, each consisting of six animals (n=6). The control group received saline for 5 days (i.p.), the MTX group was administrated a single dose MTX (60 mg/kg, i.p.) along with saline for four days (i.p.), while MTX+Chitosan group received a single dose of MTX (60 mg/kg, i.p.) followed by Chitosan administration (200 mg/kg, i.p.) for four days. On the sixth day, the animals were decapitated, and blood and tissue samples were collected. BUN, creatinine and tissue inhibitors of metalloproteinase-1 (TIMP-1) levels and activities of AST, ALT, ALP, LDH, matrix metalloproteinases (MMP-3, MMP-8, MMP-9) activities were quantified in the blood. The liver and kidney were evaluated for caspase-3 and-9 through western blotting, while structural damage was examined using light microscopy.

Results: In the MTX administered group, blood and tissues values except for all TIMP-1 statistically increased when compared to the control group, while activity of TIMP-1 decreased significantly. The Chitosan-treated MTX group had comparable values to the control group.

Conclusion: Based on its influence on metalloproteinases and caspases, our findings lead to the conclusion that Chitosan offers a protective effect against liver and kidney damage induced by MTX.
The Relationship Between Intensive Care Experience and State Anxiety in Patients Treated in Coronary Intensive Care Units
Authors: Türker Esra , Yazgan Eda Özge
Published: March 2024

Objective: This study aimed to determine the correlation between the intensive care experience and the state anxiety of patients hospitalized in the coronary intensive care unit.

Methods: This descriptive cross-sectional study included 192 patients from the coronary intensive care unit of a university hospital. Data were collected using a Patient Information Form, the Intensive Care Experience Scale (ICE), and the Spielberger State Anxiety Inventory (STAI-I). The analysis was conducted using SPSS software version 25.0. Descriptive statistics were reported as counts, percentages, means, and standard deviations. A p-value of less than 0.05 was considered to indicate statistical significance.

Results: Among the participants, 38% were aged 65 and older, 76.6% were male, 93.2% were married, 63% were admitted to the intensive care unit from the emergency room, and 88.5% had prior experience in an intensive care unit. The total and sub-dimension scores of the ICE and STAI-I were moderate. We found a weak positive correlation between the STAI-I total score and the ICE total score (r= 0.320). There was a very strong positive correlation between pessimistic experiences in the intensive care unit and the STAI-I total score (r=0.907). Additionally, there was a moderate negative correlation between satisfaction with care received in the intensive care unit and the sub-dimensions of memory of experiences (Awareness of Surroundings, Satisfaction with the Care, Recollection of Experiences) (r=0.252, r=-0.489, r=-0.496).

Conclusion: The study found that pessimistic experiences in the intensive care unit can significantly impact patients' state anxiety.
The Relationship of Mental Health and Cognitive-Emotional States with Family Planning Attitudes in Young Women with Chronic Diseases
Authors: Çankaya Seyhan , Buran Gonca , Güler Lütfiye
Published: March 2024

Objective: The aim of this study was to determine the relationship of mental health and cognitive emotional states with family planning attitudes in young women with chronic diseases.

Methods: This cross-sectional and descriptive study was conducted between 12 January 2022 and 01 April 2022. The study included a total of 410 young women with chronic diseases who were hospitalized in the internal medicine clinics of a university hospital or presented to the internal medicine clinics for examination. Data were collected using a Personal Information Form, the Mental Health Continuum–Short Form (MHC–SF), the Cognitive Emotion Regulation Questionnaire (CERQ), and the Family Planning Attitude Scale (FPAS).

Results: It was found that 20.2% (n=83) of the young women with chronic diseases had scores below the FPAS (135.5±22.1) cut-off point (
Challenges of user data privacy in self-sovereign identity verifiable credentials for autonomous building access during the COVID-19 pandemic
Authors: Naicker Denver , Moodley Mackaylan
Published: March 2024

Self-sovereign identity is an emerging blockchain technology field. Its use cases primarily surround identity and credential management and advocate the privacy of user details during the verification process. Our endeavor was to test and implement the features promoted for self-sovereign identity through open- and closed-source frameworks utilizing a scenario of building access management to adhere to health risk and safety questionnaires during the COVID-19 pandemic. Our investigation identifies whether user data privacy could be ensured through verifiable credentials and whether business practices would need to evolve to mitigate storing personal data centrally.
Differential responses to avian pathogenic E. coli and the regulatory role of splenic miRNAs in APEC infection in Silkie chickens
Authors: Li Wenqing , Li Wanli , Wu Pinhui , Jin Wei , Yuan Lin , Wang Bingxun , Li Shengli , Kang Xiangtao
Published: March 2024

Avian pathogenic Escherichia coli (APEC) is a bacterial disease that harms the poultry industry worldwide, but its effect on Chinese Silkie has not been reported. Studies on whether there are differences in Silkie individual resistance to APEC and the regulatory role of spleen miRNAs lay the foundation for strategies against APEC. Therefore, 270 Silkie chickens were infected with the median lethal dose of an E. coli O1, O2, and O78 mixture. These chickens were divided into a susceptible group (Group S) and a recovery group (Group R) according to whether they survived 15 days postinfection (dpi). Moreover, 90 uninfected APEC Silkie served as controls (Group C). The splenic miRNA expression profile was examined to evaluate the role of miRNAs in the APEC infection response. Of the 270 Silkies infected with APEC, 144 were alive at 15 dpi. Cluster analysis and principal component analysis (PCA) of splenic miRNAs revealed that the four Group R replicates were clustered with the three Group C replicates and were far from the three Group S replicates. Differentially expressed (DE) miRNAs, especially gga-miR-146b-5p, play essential roles in immune and inflammatory responses to APEC. Functional enrichment analyses of DEmiRNAs suggested that suppression of immune system processes (biological processes) might contribute to susceptibility to APEC and that FoxO signaling pathways might be closely associated with the APEC infection response and postinfection repair. This study paves the way for screening anti-APEC Silkies and provides novel insights into the regulatory role of miRNAs in APEC infection.
Case Report: Neurological adverse events in subject with myasthenia gravis after PCSK9 inhibitor administration
Authors: Adámková Věra , Vitásková Martina , Hubáček Jaroslav A.
Published: March 2024

Background

Myasthenia gravis is a rare chronic autoimmune neuromuscular disorder mainly caused by autoantibodies to the nicotinic acetylcholine receptor. Cholesterol is an essential molecule that affects the distribution and proper functioning of this receptor. Several reports have described the potential worsening of myasthenia gravis in patients treated with statins.

Case presentation

The patient was an obese 72 years old man, past smoker, diagnosed with ischaemic heart disease, type 2 diabetes mellitus and lipid metabolism disorder. Statin treatment was not implemented because of chronic myasthenia gravis and PCSK9i monotherapy [Repatha (evolucamab), 140 mg] was implemented to treat dyslipidaemia. Within 24 h after the first dose of PCSK9i the patient developed severe muscle weakness, joint pain, fever, and general discomfort, lasting for several days. Despite strong advice against the second dose administration, this was self-administered approximately 2 weeks later, leading to report significant worsening of the muscle problems, leading to the patient admittion to the neurology department where he was being treated for myasthenia gravis attack.

Conclusion

Based on the neurologist's conclusion, it can be assumed that in this case, treatment with PCSK9i resulted in significant worsening of the patient's chronic disease.
Topic mining for theses and job ads in ICT sector: can higher education institutes respond to job market demands?
Authors: Kauttonen Janne , Khan Umair Ali , Aunimo Lili , Nyqvist Antti , Klemetti Aarne
Published: March 2024

Introduction

This study aims to tackle the challenge of ensuring higher education students are equipped with high-demand skills for today’s job market. The focus is on aligning the knowledge acquired during their studies, as represented by final-year thesis projects, with the skills and topics specified in actual job advertisements.

Methods

We developed a computational framework that uses automated subject indexing to extract representative skills and topics from two major datasets: thesis abstracts from Information and Communication Technology (ICT) programmes of Finnish Universities of Applied Sciences, and ICT-related job ads from a top Finnish job portal. Our dataset spans 12 years, comprising 18,254 theses and 107,335 ads. The framework includes a subject indexing model for keyword extraction, dimension reduction techniques for data simplification, clustering algorithms to group similar items, and correlation analysis to compare similarities and differences between the two datasets.

Results

The analysis uncovered both similarities and differences between thesis topics and trends in job ads. It highlighted areas where education aligns with industry demands but also pointed out existing gaps.

Discussion

Our framework not only helps to align the education provided with industry demands but also ensures that higher education institutes can stay up-to-date with the latest skills and knowledge in the field, thereby better equipping students for success in their careers. While the framework was applied to the ICT sector in this instance, its design allows expansion into other fields offering a data-informed approach for continuous development of teaching curricula and methodologies.
Developmental potential of non- and mono-pronuclear zygotes and associated clinical outcomes in IVF cycles
Authors: Zhu Mengyi , Dong Qiyin , Zhu Yurong , Le Yun , Wang Tengfei , Zhou Yuanping , Yang Sheng
Published: March 2024

Purpose

This study aims to evaluate the developmental potential of 0PN, 1PN, and 2PN zygotes in IVF cycles and compare their clinical outcomes.

Methods

We conducted a retrospective cohort study involving IVF patients. Blastocyst formation rates were assessed with 0PN, 1PN, and 2PN zygotes. Subsequently, we collected clinical outcome data following the transfer of these zygotes.

Results

The overall blastulation rate was similar between 0PN (29.6%) and 2PN (32.1%) zygotes, but 1PN zygotes exhibited a significantly lower blastulation rate (17.0%) compared to both 0PN and 2PN zygotes. Similarly, the overall rate of good-quality blastulation was comparable between 0PN (15.3%) and 2PN (17.5%) zygotes, while 1PN zygotes showed a significantly lower rate (7.0%) compared to both 0PN and 2PN. Clinical pregnancy, ectopic pregnancy, implantation, and live birth rates were similar among single blastocyst frozen embryo transfers (FET) of 0PN, 1PN, and 2PN. Additionally, no significant differences were observed between single- and double-blastocyst FET of 0PN and 2PN.

Conclusions

Our findings suggest that 0PN and 2PN zygotes have comparable developmental potential, while 1PN embryos exhibit lower developmental potential. Blastocyst FET outcomes appear similar among 0PN, 1PN, and 2PN zygotes.
Landsat series images for evaluating ecological restoration effect from multi-time scale based on an ideal reference
Authors: Wang Zhenkun , An Zhihong
Published: March 2024

Multi-time scale assessment of ecological restoration effects based on objective and scientific approaches can provide crucial information for implementing environmental protection policies and ensuring sustainable regional development. This study evaluated the effect of ecological restoration based on a natural evolution as a reference frame, using yearly Landsat time series. Southern Ningxia in China was selected as the study area. The remote sensing ecological index (RSEI) was calculated. The features of natural evolution were derived from the time series of the RSEI in the natural reserve areas (NRAs). LandTrendr was employed to characterize the disturbance–recovery processes. Furthermore, we adopted the dynamic time-warping method for the entire study period, along with the relative variation ratio (during the disturbance–recovery cycle) to capture the long-term and short-term ecological restoration effects, respectively. The following conclusions were drawn: First, a time-series RSEI based on LandTrendr was used to successfully monitor disturbance–recovery processes. Second, the majority of RSEI disturbances (i.e., >60%) occurred between 2000 and 2005. It is characterized by fewer disturbance times and obvious spatial heterogeneity in disturbance duration. Notably, from 2000 to 2022, the RSEI improved. Additionally, approximately 40% of the study area portrayed a strong similarity to the RSEI of the NRAs. We conclude that quantifying the ecological restoration effect at multi-time scales is a practical operational approach for policymakers and environmental protection. Our study presents novel insights for assessing regional ecological quality, by capturing the processes of natural evolution features in NRAs.
Engineered therapeutic antibodies with mannose 6-phosphate analogues as a tool to degrade extracellular proteins
Authors: Daurat Morgane , Gauthier Corentin , El Cheikh Khaled , Ali Lamiaa M. A. , Morère Elodie , Bettache Nadir , Gary-Bobo Magali , Morère Alain , Garcia Marcel , Maynadier Marie , Basile Ilaria
Published: March 2024

Inducing the degradation of pathological soluble antigens could be the key to greatly enhancing the efficacy of therapeutic monoclonal antibodies (mAbs), extensively used in the treatment of autoimmune and inflammatory disorders or cancer. Lysosomal targeting has gained increasing interest in recent years due to its pharmaceutical applications far beyond the treatment of lysosomal diseases, as a way to address proteins to the lysosome for eventual degradation. Mannose 6-phosphonate derivatives (M6Pn), called AMFA, are unique glycovectors that can significantly enhance the cellular internalization of the proteins conjugated to AMFA via the cation-independent mannose 6-phosphate receptor (M6PR) pathway. AMFA engineering of mAbs results in the generation of a bifunctional antibody that is designed to bind both the antigen and the M6PR. The improvement of the therapeutic potential by AMFA engineering was investigated using two antibodies directed against soluble antigens: infliximab (IFX), directed against tumor necrosis factor α (TNF-α), and bevacizumab (BVZ), directed against the vascular endothelial growth factor (VEGF). AMFA conjugations to the antibodies were performed either on the oligosaccharidic chains of the antibodies or on the lysine residues. Both conjugations were controlled and reproducible and provided a novel affinity for the M6PR without altering the affinity for the antigen. The grafting of AMFA to mAb increased their cellular uptake through an M6PR-dependent mechanism. The antigens were also 2.6 to 5.7 times more internalized by mAb-AMFA and rapidly degraded in the cells. Additional cell culture studies also proved the significantly higher efficacy of IFX-AMFA and BVZ-AMFA compared to their unconjugated counterparts in inhibiting TNF-α and VEGF activities. Finally, studies in a zebrafish embryo model of angiogenesis and in xenografted chick embryos showed that BVZ-AMFA was more effective than BVZ in reducing angiogenesis. These results demonstrate that AMFA grafting induces the degradation of soluble antigens and a significant increase in the therapeutic efficacy. Engineering with mannose 6-phosphate analogues has the potential to develop a new class of antibodies for autoimmune and inflammatory diseases.
Single-cell transcriptome sequencing provides insight into multiple chemotherapy resistance in a patient with refractory DLBCL: a case report
Authors: Zhao Kewei , Li Qiuhui , Li Pengye , Liu Tao , Liu Xinxiu , Zhu Fang , Zhang Liling
Published: March 2024

Relapsed and refractory diffuse large B-cell lymphoma (DLBCL) is associated with poor prognosis. As such, a comprehensive analysis of intratumoral components, intratumoral heterogeneity, and the immune microenvironment is essential to elucidate the mechanisms driving the progression of DLBCL and to develop new therapeutics. Here, we used single-cell transcriptome sequencing and conventional bulk next-generation sequencing (NGS) to understand the composite tumor landscape of a single patient who had experienced multiple tumor recurrences following several chemotherapy treatments. NGS revealed several key somatic mutations that are known to contribute to drug resistance. Based on gene expression profiles at the single-cell level, we identified four clusters of malignant B cells with distinct transcriptional signatures, showing high intra-tumoral heterogeneity. Among them, heterogeneity was reflected in activating several key pathways, human leukocyte antigen (HLA)-related molecules’ expression, and key oncogenes, which may lead to multi-drug resistance. In addition, FOXP3+ regulatory CD4+ T cells and exhausted cytotoxic CD8+ T cells were identified, accounted for a significant proportion, and showed highly immunosuppressive properties. Finally, cell communication analysis indicated complex interactions between malignant B cells and T cells. In conclusion, this case report demonstrates the value of single-cell RNA sequencing for visualizing the tumor microenvironment and identifying potential therapeutic targets in a patient with treatment-refractory DLBCL. The combination of NGS and single-cell RNA sequencing may facilitate clinical decision-making and drug selection in challenging DLBCL cases.
Imidazole propionate ameliorates atopic dermatitis-like skin lesions by inhibiting mitochondrial ROS and mTORC2
Authors: Kim Ha Eun , Lee Jong Yeong , Yoo Dong-Hoon , Park Hyo-Hyun , Choi Eun-Ju , Nam Kyung-Hwa , Park Jin , Choi Jin Kyeong
Published: March 2024

Background

Imidazole propionate (IMP) is a histidine metabolite produced by some gut microorganisms in the human colon. Increased levels of IMP are associated with intestinal inflammation and the development and progression of cardiovascular disease and diabetes. However, the anti-inflammatory activity of IMP has not been investigated. This study aimed to elucidate the role of IMP in treating atopic dermatitis (AD).

Methods

To understand how IMP mediates immunosuppression in AD, IMP was intraperitoneally injected into a Dermatophagoides farinae extract (DFE)/1-chloro-2,4 dinitrochlorobenzene (DNCB)-induced AD-like skin lesions mouse model. We also characterized the anti-inflammatory mechanism of IMP by inducing an AD response in keratinocytes through TNF-α/IFN-γ or IL-4 stimulation.

Results

Contrary to the prevailing view that IMP is an unhealthy microbial metabolite, we found that IMP-treated AD-like skin lesions mice showed significant improvement in their clinical symptoms, including ear thickness, epidermal and dermal thickness, and IgE levels. Furthermore, IMP antagonized the expansion of myeloid (neutrophils, macrophages, eosinophils, and mast cells) and Th cells (Th1, Th2, and Th17) in mouse skin and prevented mitochondrial reactive oxygen species production by inhibiting mitochondrial energy production. Interestingly, we found that IMP inhibited AD by reducing glucose uptake in cells to suppress proinflammatory cytokines and chemokines in an AD-like in vitro model, sequentially downregulating the PI3K and mTORC2 signaling pathways centered on Akt, and upregulating DDIT4 and AMPK.

Discussion

Our results suggest that IMP exerts anti-inflammatory effects through the metabolic reprogramming of skin inflammation, making it a promising therapeutic candidate for AD and related skin diseases.
Disease-associated immune cell endotypes in anti-MDA5-positive dermatomyositis using unbiased hierarchical clustering
Authors: Guo Ruru , Yang Yang , Gu Liyang , Li Xinyu , Ma Yiyangzi , Liu Xuesong , Lu Liangjing
Published: March 2024

Objective

Clinical and prognostic features of Anti-MDA5-Positive Dermatomyositis (MDA5+ DM) are diverse. This study aimed to examine the peripheral immune cell profiles of patients with MDA5+ DM, identify disease endotypes related to the heterogeneous manifestations and prognosis, and guide individualized therapy regimen.

Methods

This inpatient cohort included 123 patients with MDA5+ DM. Unsupervised hierarchical clustering analysis was used to derive disease endotypes from the circulating immune cell profiles on admission. Clinical symptoms, laboratory test results, inpatient treatments, and disease outcomes were then analyzed among the identified endotypes.

Results

Three disease endotypes in MDA5+ DM were identified from peripheral immune cell profiles. Endotype1 had the highest percentages of CD4+ T cells and monocytes, and the lowest percentage of neutrophils; Endotype2 had the highest percentage of B cells; Endotype3 had the highest percentage of CD8+ T cells and NK cells. Clinical and prognostic heterogeneity of the endotypes were revealed. Endotype1 had the lowest 3-month mortality with the high incidence of periungual capillary changes. Endotype2 and Endotype3 had higher prevalence of rapidly progressive interstitial lung disease (RPILD) and mortality at 3 months than Endotype1. Meanwhile, Endotype3 had higher pneumocystis jiroveci and CMV viremia cases with significantly elevated of activated CD8+ T cells and multiple cytokines than Endotype1.

Conclusion

Clustering analysis of peripheral immune cell profiles identified three different endotypes in MDA5+ dermatomyositis. Endotpye2 and 3 showed higher RPILD, 3-month mortality, pneumocystis jiroveci and CMV viremia.
5,6-dimethylxanthenone-4-acetic acid (DMXAA), a partial STING agonist, competes for human STING activation
Authors: Temizoz Burcu , Shibahara Takayuki , Hioki Kou , Hayashi Tomoya , Kobiyama Kouji , Lee Michelle Sue Jann , Surucu Naz , Sag Erdal , Kumanogoh Atsushi , Yamamoto Masahiro , Gursel Mayda , Ozen Seza , Kuroda Etsushi , Coban Cevayir , Ishii Ken J.
Published: March 2024

5,6-dimethylxanthenone-4-acetic acid (DMXAA) is a mouse-selective stimulator of interferon gene (STING) agonist exerting STING-dependent anti-tumor activity. Although DMXAA cannot fully activate human STING, DMXAA reached phase III in lung cancer clinical trials. How DMXAA is effective against human lung cancer is completely unknown. Here, we show that DMXAA is a partial STING agonist interfering with agonistic STING activation, which may explain its partial anti-tumor effect observed in humans, as STING was reported to be pro-tumorigenic for lung cancer cells with low antigenicity. Furthermore, we developed a DMXAA derivative—3-hydroxy-5-(4-hydroxybenzyl)-4-methyl-9H-xanthen-9-one (HHMX)—that can potently antagonize STING-mediated immune responses both in humans and mice. Notably, HHMX suppressed aberrant responses induced by STING gain-of-function mutations causing STING-associated vasculopathy with onset in infancy (SAVI) in in vitro experiments. Furthermore, HHMX treatment suppressed aberrant STING pathway activity in peripheral blood mononuclear cells from SAVI patients. Lastly, HHMX showed a potent therapeutic effect in SAVI mouse model by mitigating disease progression. Thus, HHMX offers therapeutic potential for STING-associated autoinflammatory diseases.
A review of mechanistic learning in mathematical oncology
Authors: Metzcar John , Jutzeler Catherine R. , Macklin Paul , Köhn-Luque Alvaro , Brüningk Sarah C.
Published: March 2024

Mechanistic learning refers to the synergistic combination of mechanistic mathematical modeling and data-driven machine or deep learning. This emerging field finds increasing applications in (mathematical) oncology. This review aims to capture the current state of the field and provides a perspective on how mechanistic learning may progress in the oncology domain. We highlight the synergistic potential of mechanistic learning and point out similarities and differences between purely data-driven and mechanistic approaches concerning model complexity, data requirements, outputs generated, and interpretability of the algorithms and their results. Four categories of mechanistic learning (sequential, parallel, extrinsic, intrinsic) of mechanistic learning are presented with specific examples. We discuss a range of techniques including physics-informed neural networks, surrogate model learning, and digital twins. Example applications address complex problems predominantly from the domain of oncology research such as longitudinal tumor response predictions or time-to-event modeling. As the field of mechanistic learning advances, we aim for this review and proposed categorization framework to foster additional collaboration between the data- and knowledge-driven modeling fields. Further collaboration will help address difficult issues in oncology such as limited data availability, requirements of model transparency, and complex input data which are embraced in a mechanistic learning framework
Yarrowia lipolytica as a promising protein source for Pacific white shrimp (Litopenaeus vannamei) diet: impact on growth performance, metabolism, antioxidant capacity, and apparent digestibility
Authors: Zhang Lei , Zhang Pian , Tan Peng , Xu Dongdong , Wang Ligai , Ding Zhili , Shao Qingjun
Published: March 2024

Exploring alternatives to fishmeal (FM) in aquaculture nutrition remains a hot topic in this area. Yarrowia lipolytica (YL), a promising single-cell protein source, has yet to be evaluated for its use on the Pacific white shrimp (Litopenaeus vannamei) diet. This investigation assessed the effects of YL on growth performance, metabolism, antioxidant capacity, and nutrient digestibility in shrimp. Seven diets with equal protein and lipid contents were prepared, incorporating gradient YL (dry matter basis): 0% (control), 1.50%, 3.00%, 4.50%, 6.00%, 9.00%, and 12.00%. During a 56-day feeding trial involving shrimp, with an initial average weight of 0.32 ± 0.02 g, each kind of diet was randomly assigned to six tanks. It was observed that the growth performance improved initially but then exhibited a declining trend as the dietary inclusion of YL increased. Regression analysis indicated 2.68% as the optimal YL percentage for a specific growth rate (SGR), accounting for 10.54% of the dietary FM content. A higher YL (over 6.00%), which is equivalent to replacing over 23.6% of the FM, led to increased feed intake and conversion ratios, possibly correlating with decreased YL digestibility. However, YL inclusion across the studied range had no detrimental impact on intestinal or hepatopancreatic morphology. Notably, higher YL levels significantly enhanced hepatopancreatic trypsin activity and reduced serum triglyceride and cholesterol levels. The inclusion of YL notably augmented antioxidant defense mechanisms in shrimp, as evidenced by increased total antioxidant capacity and catalase activities, as well as reduced malondialdehyde levels in the hepatopancreas, possibly due to the presence of β-glucan and mannan oligosaccharides in YL. These findings support YL being viable as a protein source in shrimp feeds.
Adrenal insufficiency following cerebellar intracranial hemorrhage: a case report
Authors: Lu Yu-Yang , Lin Chien-Ming , Chiang Shang-Lin
Published: March 2024

This report presents a case of a previously healthy 58 years-old man who had suffered from persistent weakness and dizziness after a cerebellar intracranial hemorrhage (ICH). Endocrine function tests revealed low levels of plasma cortisol (3.05 μg/dL; normal range: 5–25 μg/dL) and adrenocorticotropic hormone (ACTH) (6.0 pg/mL; normal range: 10–60 pg/mL). The subsequent ACTH stimulation test suggested partial or recent hypopituitarism, resulting in adrenal gland atrophy and a subnormal cortisol response. Ultimately, the dizziness was found to be caused by undiagnosed adrenal insufficiency, which was detected when a hypotensive fainting incident occurred during rehabilitation. The symptoms improved significantly with oral prednisone supplementation. Notably, the duration of impaired hypothalamic-pituitary-adrenal axis may last as long as a year. This case highlights that adrenal insufficiency can easily be overlooked since its symptoms are similar to those commonly seen with cerebellar stroke alone. Physicians must be aware of the symptoms of adrenal insufficiency in patients with brain insults and conduct the appropriate endocrine tests to clarify the underlying comorbidity.
Effects of online tDCS and hf-tRNS on reading performance in children and adolescents with developmental dyslexia: a study protocol for a cross sectional, within-subject, randomized, double-blind, and sham-controlled trial
Authors: Battisti Andrea , Lazzaro Giulia , Varuzza Cristiana , Vicari Stefano , Menghini Deny
Published: March 2024

Background

Developmental Dyslexia (DD) is a brain-based developmental disorder causing severe reading difficulties. The extensive data on the neurobiology of DD have increased interest in brain-directed approaches, such as transcranial direct current stimulation (tDCS), which have been proposed for DD. While positive outcomes have been observed, results remain heterogeneous. Various methodological approaches have been employed to address this issue. However, no studies have compared the effects of different transcranial electrical stimulation techniques (e.g., tDCS and transcranial random noise stimulation, tRNS), on reading in children and adolescents with DD.

Methods

The present within-subject, double-blind, and sham-controlled trial aims to investigate the effects of tDCS and hf-tRNS on reading in children and adolescents with DD. Participants will undergo three conditions with a one-week interval session: (A) single active tDCS session; (B) single active hf-tRNS session; and (C) single sham session (tDCS/hf-tRNS). Left anodal/right cathodal tDCS and bilateral tRNS will be applied over the temporo-parietal regions for 20 min each. Reading measures will be collected before and during each session. Safety and blinding parameters will be recordered.

Discussion

We hypothesize that tRNS will demonstrate comparable effectiveness to tDCS in improving reading compared to sham conditions. Additionally, we anticipate that hf-tRNS will exhibit a similar safety profile to tDCS. This study will contribute novel insights into the effectiveness of hf-tRNS, expediting the validation of brain-based treatments for DD.
Berberine-based self-assembly agents with enhanced synergistic antitumor efficacy
Authors: Wang Yun , Li Zhongrui , Zhang Haili , Wu Peiye , Zhao Yu , Li Renshi , Han Chao , Wang Lei
Published: March 2024

Tumors are still a major threat to people worldwide. Nanodrug delivery and targeting systems can significantly improve the therapeutic efficacy of chemotherapeutic drugs for antitumor purposes. However, many nanocarriers are likely to exhibit drawbacks such as a complex preparation process, limited drug-loading capacity, untargeted drug release, and toxicity associated with nanocarriers. Therefore, new therapeutic alternatives are urgently needed to develop antitumor drugs. Natural products with abundant scaffold diversity and structural complexity, which are derived from medicinal plants, are important sources of new antitumor drugs. Here, two carrier-free berberine (BBR)-based nanoparticles (NPs) were established to increase the synergistic efficacy of tumor treatment. BBR can interact with glycyrrhetinic acid (GA) and artesunate (ART) to self-assemble BBR-GA and BBR-ART NPs without any nanocarriers, respectively, the formation of which is dominated by electrostatic and hydrophobic interactions. Moreover, BBR-GA NPs could lead to mitochondria-mediated cell apoptosis by regulating mitochondrial fission and dysfunction, while BBR-ART NPs induced ferroptosis in tumor cells. BBR-based NPs have been demonstrated to possess significant tumor targeting and enhanced antitumor properties compared with those of simple monomer mixes both in vitro and in vivo. These carrier-free self-assemblies based on natural products provide a strategy for synergistic drug delivery and thus offer broad prospects for developing enhanced antitumor drugs.
A real-world disproportionality analysis of Everolimus: data mining of the public version of FDA adverse event reporting system
Authors: Zhao Bin , Fu Yumei , Cui Shichao , Chen Xiangning , Liu Shu , Luo Lan
Published: March 2024

Background: Everolimus is an inhibitor of the mammalian target of rapamycin and is used to treat various tumors. The presented study aimed to evaluate the Everolimus-associated adverse events (AEs) through data mining of the US Food and Drug Administration Adverse Event Reporting System (FAERS).

Methods: The AE records were selected by searching the FDA Adverse Event Reporting System database from the first quarter of 2009 to the first quarter of 2022. Potential adverse event signals were mined using the disproportionality analysis, including reporting odds ratio the proportional reporting ratio the Bayesian confidence propagation neural network and the empirical Bayes geometric mean and MedDRA was used to systematically classify the results.

Results: A total of 24,575 AE reports of Everolimus were obtained using data from the FAERS database, and Everolimus-induced AEs occurrence targeted 24 system organ classes after conforming to the four algorithms simultaneously. The common significant SOCs were identified, included benign, malignant and unspecified neoplasms, reproductive system and breast disorders, etc. The significant AEs were then mapped to preferred terms such as stomatitis, pneumonitis and impaired insulin secretion, which have emerged in the study usually reported in patients with Everolimus. Of note, unexpected significant AEs, including biliary ischaemia, angiofibroma, and tuberous sclerosis complex were uncovered in the label.

Conclusion: This study provided novel insights into the monitoring, surveillance, and management of adverse drug reaction associated with Everolimus. The outcome of serious adverse events and the corresponding detection signals, as well as the unexpected significant adverse events signals are worthy of attention in order to improving clinical medication safety during treatment of Everolimus.
A theory of the neural mechanisms underlying negative cognitive bias in major depression
Authors: Jiang Yuyue
Published: March 2024

The widely acknowledged cognitive theory of depression, developed by Aaron Beck, focused on biased information processing that emphasizes the negative aspects of affective and conceptual information. Current attempts to discover the neurological mechanism underlying such cognitive and affective bias have successfully identified various brain regions associated with severally biased functions such as emotion, attention, rumination, and inhibition control. However, the neurobiological mechanisms of how individuals in depression develop this selective processing toward negative is still under question. This paper introduces a neurological framework centered around the frontal-limbic circuit, specifically analyzing and synthesizing the activity and functional connectivity within the amygdala, hippocampus, and medial prefrontal cortex. Firstly, a possible explanation of how the positive feedback loop contributes to the persistent hyperactivity of the amygdala in depression at an automatic level is established. Building upon this, two hypotheses are presented: hypothesis 1 revolves around the bidirectional amygdalohippocampal projection facilitating the amplification of negative emotions and memories while concurrently contributing to the impediment of the retrieval of opposing information in the hippocampus attractor network. Hypothesis 2 highlights the involvement of the ventromedial prefrontal cortex in the establishment of a negative cognitive framework through the generalization of conceptual and emotional information in conjunction with the amygdala and hippocampus. The primary objective of this study is to improve and complement existing pathological models of depression, pushing the frontiers of current understanding in neuroscience of affective disorders, and eventually contributing to successful recovery from the debilitating affective disorders.
A survey on autonomous environmental monitoring approaches: towards unifying active sensing and reinforcement learning
Authors: Mansfield David , Montazeri Allahyar
Published: March 2024

The environmental pollution caused by various sources has escalated the climate crisis making the need to establish reliable, intelligent, and persistent environmental monitoring solutions more crucial than ever. Mobile sensing systems are a popular platform due to their cost-effectiveness and adaptability. However, in practice, operation environments demand highly intelligent and robust systems that can cope with an environment’s changing dynamics. To achieve this reinforcement learning has become a popular tool as it facilitates the training of intelligent and robust sensing agents that can handle unknown and extreme conditions. In this paper, a framework that formulates active sensing as a reinforcement learning problem is proposed. This framework allows unification with multiple essential environmental monitoring tasks and algorithms such as coverage, patrolling, source seeking, exploration and search and rescue. The unified framework represents a step towards bridging the divide between theoretical advancements in reinforcement learning and real-world applications in environmental monitoring. A critical review of the literature in this field is carried out and it is found that despite the potential of reinforcement learning for environmental active sensing applications there is still a lack of practical implementation and most work remains in the simulation phase. It is also noted that despite the consensus that, multi-agent systems are crucial to fully realize the potential of active sensing there is a lack of research in this area.
Sexual experiences among multicultural adolescents in Korea: evidence from the Korean Youth’s Risk Behavior Survey
Authors: Kim Keuntae , Jo Se Hee
Published: March 2024

Several studies have examined adolescent sexual behaviors by family immigration status, but most of these failed to account for heterogeneity within youths’ multicultural backgrounds. To fill this gap in the literature, this paper draws data from the 2011 to 2022 rounds of the Korean Youth’s Risk Behavior Survey (N = 769,160) and compares the likelihood of sexual intercourse across four groups of adolescents. Results from logistic regression indicate that the odds of having sexual contact increased 2.8 times for youths with a non-Korean father and Korean mother, compared with those from families with two Korean parents. When both father and mother are foreign-born, the odds of being sexually active increased 4.7 times. In both cases, the discrepancies might be primarily associated with the foreign fathers’ lack of socioeconomic resources. Therefore, the father’s role deserves more examination, and sex education in schools should be tailored to reflect multicultural adolescents’ needs.
Preliminary Nose Landing Gear Digital Twin for Damage Detection
Authors: Pinello Lucio , Hassan Omar , Giglio Marco , Sbarufatti Claudio
Published: March 2024

An increase in aircraft availability and readiness is one of the most desired characteristics of aircraft fleets. Unforeseen failures cause additional expenses and are particularly critical when thinking about combat jets and Unmanned Aerial Vehicles (UAVs). For instance, these systems are used under extreme conditions, and there can be situations where standard maintenance procedures are impractical or unfeasible. Thus, it is important to develop a Health and Usage Monitoring System (HUMS) that relies on diagnostic and prognostic algorithms to minimise maintenance downtime, improve safety and availability, and reduce maintenance costs. In particular, within the realm of aircraft structures, landing gear emerges as one of the most intricate systems, comprising several elements, such as actuators, shock absorbers, and structural components. Therefore, this work aims to develop a preliminary digital twin of a nose landing gear and implement diagnostic algorithms within the framework of the Health and Usage Monitoring System (HUMS). In this context, a digital twin can be used to build a database of signals acquired under healthy and faulty conditions on which damage detection algorithms can be implemented and tested. In particular, two algorithms have been implemented: the first is based on the Root-Mean-Square Error (RMSE), while the second relies on the Mahalanobis distance (MD). The algorithms were tested for three nose landing gear subsystems, namely, the steering system, the retraction/extraction system, and the oleo-pneumatic shock absorber. A comparison is made between the two algorithms using the ROC curve and accuracy, assuming equal weight for missed detections and false alarms. The algorithm that uses the Mahalanobis distance demonstrated superior performance, with a lower false alarm rate and higher accuracy compared to the other algorithm.
Proposal of a Service Model for Blockchain-Based Security Tokens
Authors: Park Keundug , Youm Heung-Youl
Published: March 2024

The volume of the asset investment and trading market can be expanded through the issuance and management of blockchain-based security tokens that logically divide the value of assets and guarantee ownership. This paper proposes a service model to solve a problem with the existing investment service model, identifies security threats to the service model, and specifies security requirements countering the identified security threats for privacy protection and anti-money laundering (AML) involving security tokens. The identified security threats and specified security requirements should be taken into consideration when implementing the proposed service model. The proposed service model allows users to invest in tokenized tangible and intangible assets and trade in blockchain-based security tokens. This paper discusses considerations to prevent excessive regulation and market monopoly in the issuance of and trading in security tokens when implementing the proposed service model and concludes with future works.