bluuebunny/crossref_metadata_2025 huggingface dataset:
Machine Learning Decision Support Model Construction for Craniotomy Approach of Pineal Region Tumors Based on MRI Images
Authors: Chen Ziyan , Chen Yinhua , Su Yandong , Jiang Nian , Wanggou Siyi , Li Xuejun
Published: January 2025

Background: Pineal region tumors (PRTs) are but deep-seated brain tumors, and complete surgical resection is crucial for effective tumor treatment. The choice of surgical approach is often challenging due to the low incidence and deep location. This study aims to combine machine learning and deep learning algorithms with pre-operative MRI images to build a model for PRTs surgical approaches recommendation, striving to model clinical experience for practical reference and education.
Methods: This study is a retrospective study which enrolled a total of 173 patients diagnosed with PRTs radiologically from our hospital. Three traditional surgical approaches of were recorded for prediction label. Clinical and VASARI related radiological information were selected for machine learning prediction model construction. And MRI images from axial, sagittal and coronal views of orientation were also used for deep learning craniotomy approach prediction model establishment and evaluation.
Results: 5 machine learning methods were applied to construct the predictive classifiers with the clinical and VASARI features and all methods could achieve area under the ROC (Receiver operating characteristic) curve (AUC) values over than 0.7. And also, 3 deep learning algorithms (ResNet-50, EfficientNetV2-m and ViT) were applied based on MRI images from different orientations. EfficientNetV2-m achieved the highest AUC value of 0.89, demonstrating a significant high performance of prediction. And class activation mapping was used to reveal that the tumor itself and its surrounding relations are crucial areas for model decision-making.
Conclusion: In our study, we used machine learning and deep learning to construct surgical approach recommendation models. Deep learning could achieve high performance of prediction and provide efficient and personalized decision support tools for PRTs surgical approach.
Clinical trial number: not applicable
Proton Pump Inhibitor Use, CYP2C19 genotypes, and Subsequent Incidence of Chronic Kidney Disease
Authors: Wang Xu , Shan Ying , Wei Yanling , He Yujian , wang Pengpeng , Yang Guang , Huang Xiaoyan , Xiong Zibo
Published: January 2025

Background
The widespread use of proton pump inhibitors (PPIs) has generated concerns about side effects Numerous studies have suggested that PPIs use may increase the risk of kidney disease. In particular, it is unclear whether genotype of the CYP2C19 enzyme system, the main metabolic pathway of PPIs, modifies the association between PPIs and the development of chronic kidney disease (CKD) or end-stage kidney disease (ESKD).
Methods
This was a prospective cohort study of white European participants from the UK Biobank. CKD and ESKD were determined by ICD-10 coding. Self-reported PPI use was recorded using an electronic questionnaire and confirmed by trained staff. The CYP2C19 genotype is defined by two of the most common CYP2C19 functional polymorphisms (rs4244285 and rs12248560). Multivariable Cox proportional hazards regression models were used to assess the associations of PPIs with incident CKD or ESKD.
Results
A total of 419670 participants were included in the study, of which 39,493 participants were PPIs users. Compared with non-user, PPI users had a significantly higher risk of developing CKD (HR 1.408, CI 1.352–1.467) and ESKD (HR 1.288, CI 1.03–1.609). This association persisted in sensitivity analyses. However, there was no significant difference in the risk of developing CKD among participants taking PPIs between the different CYP2C19 genotypes.
Conclusion
The use of PPIs was associated with the risks of developing CKD and ESKD. There was no evidence supporting the CYP2C19 genotype as a moderator on the relationship between PPIs and kidney diseases.
Predicting Clinically Significant Brain Injuries following Mild TBI: A Comparative Study of Canadian CT Head Rule and New Orleans Criteria at a National Trauma Centre.
Authors: Kpuduwei Selekeowei Peter Kespi , Yusuf Ayodeji Salman , Ismail Nasir Jinjiri , Adebiyi Jamiu Ayodele
Published: January 2025

Background
Mild traumatic brain injury (mTBI) is one of the most common injuries treated at any trauma centre. Whereas the general use of CT for all patients with mTBI is inefficient and wasteful, the omission of a clinically important brain injury is not desirable. Several guidelines have been developed to assist physicians in determining who actually needs a head CT. For this reason, the Canadian CT Head Rule (CCHR) and the New Orleans Criteria (NOC) were compared in this study on their efficacy in predicting surgically significant brain injuries and need for neurosurgical intervention.
Materials and Methods
The research was a prospective cross-sectional study at a level 1 trauma centre that received ethical approval from the Hospital. Consenting adult patients who presented with mild TBI within 24 hours were recruited. They were assessed with the NOC and CCHR, which decisions were compared between them and with CT head findings.
Results
A total of 103 patients were successfully enrolled, males were 91 and females were 12 with mean age of 32.48 ± 12.27 years old. The sensitivity, specificity, positive predictive value and negative predictive value of clinically significant brain injury under the NOC guideline compared with that of CCHR guideline were not significantly statistically different with P-value of 0.39. Similarly, there was no statistically significant difference between the two guidelines for need for neurosurgical intervention as P-value was 0.48.
Conclusion
Following the findings this study either NOC or CCHR is safe to be used for ordering head CT for patients with mild TBI.
Patients with Prior Cerebral Venous Sinus Thrombosis Presenting to the Emergency Department with Neurological Symptoms- The Yield of Neuroimaging
Authors: Grishin Evgeny , Budnik Ivan , Efros Orly , Cohen Omri , Kenet Gili , Levy-Mendelovich Sarina , Barg Assaf Arie
Published: January 2025

Background
Cerebral venous sinus thrombosis (CVST) is a relatively rare condition that may be associated with significant morbidity and may potentially be life-threatening. This study aimed to evaluate the yield of neuroimaging and to assess risk factors for CVST progression among patients presenting to the emergency department (ED) after a prior CVST diagnosis.
Methods
We collected data from the hospital’s electronic medical records on patients diagnosed with CVST at our tertiary care center between January 2002 and April 2023. For patients who had subsequent ED visits related to their initial CVST diagnosis, data regarding demographics, clinical presentation, imaging outcomes and alterations in therapeutic management was retrieved.
Results
Our initial cohort included 251 patients diagnosed with CVST. Of these, 107 patients (42.6%) returned to the ED with symptoms potentially related to CVST. Headache was the most common presenting symptom (59%), and imaging was performed in 71% of relevant ED visits. Thrombus progression was observed in only 6% of cases. No significant associations were found between demographic factors, clinical presentation, anticoagulation status, and neuroimaging findings. Among patients whose initial CVST diagnosis occurred more than two years prior to ED evaluation, only those with thrombophilia experienced thrombus progression.
Conclusions
Thrombus progression is a rare finding among patients with a history of CVST presenting to the ED with neurological complaints. Pediatric patients showed low rates of thrombotic worsening, suggesting a more judicious use of neuroimaging in this population. Treatment with anticoagulation at the time of ED visit could not predict neuroimaging results.
Eco-Friendly Drilling of AA 5052-H32 Alloy: Influence of Jasmine-Based Cutting Fluid on Surface Quality and Burr Formation
Authors: Yasir Muhammad , Khawaja Amar ul Hassan , Gulzar Mubashir , Khan Muhammad Saad , Ali Imtiaz , Iqbal Shahid , Sarikaya Murat
Published: January 2025

The aerospace and automotive sectors are increasingly emphasizing sustainable production, requiring environmentally benign methods for machining activities. This study examines a biodegradable cutting fluid composed of 85% jasmine oil and 15% organic petroleum-based additives as an eco-friendly substitute for traditional lubricants in the drilling of AA 5052-H32 aluminum alloy, a material widely utilized in structural applications. Response Surface Methodology (RSM) was employed to examine the impacts of cutting speed and feed rate on surface quality, burr development, and temperature, based on 27 experimental observations across three lubrication conditions: dry, 90 − 10% water-to-oil, and 80 − 20% water-to-oil mixes. Findings indicate that increased cutting speeds and appropriate feed rates markedly improve surface quality, attaining a minimal surface roughness of 7.3 µm at 6370 rpm and 2867 mm/min under the 80 − 20% coolant condition. This lubrication regime exhibited the least burr height of 0.07 mm and the most efficient cooling, with a lowest temperature of 33.8°C. In comparison, dry drilling demonstrated subpar performance, characterized by heightened burr height and surface roughness resulting from raised tool temperatures and material deformation. Also, jasmine-based cutting fluid enhances machining performance by improving temperature and lubricating characteristics, minimizing environmental impact, and promoting sustainability in precision drilling operations. This research emphasizes the significance of parameter optimization for attaining enhanced hole quality while advocating for a shift towards ecologically sustainable production processes. Future research is advised to investigate the prolonged impacts of biodegradable lubricants on tool longevity and their compatibility with various machining processes and materials.
The effect of lung-protective ventilation on Pa-etCO 2 in elderly surgical patients
Authors: Li Mingye , Ren Shihuai , Chen Tongle , Dong Chun-shan
Published: January 2025

Objective: This study aimed to determine whether the lung-protective strategy of reducing driving pressure can optimize the Pa-etCO2 gradient in elderly patients and improve patient prognosis.
Methods: Under anaesthesia, patients in the PV group were compared with those in the CV group via an individualized method of increasing positive end expiratory pressure (PEEP) to reduce driving pressure (PEEP starting from 9 cmH2O, reducing tidal volume from 8 ml/kg–6 ml/kg estimated body weight (PWB) to lower the plateau pressure (Pplat)<20 cmH2O, and lowering the PEEP if the target plateau pressure was not achieved).
Result: There was no significant difference in the changes in Pa-etCO2 between the PV group five minutes after anaesthesia (T0) and the suture group (Tend) (p>0.05), whereas the Pa-etCO2 in the CV Tend group increased compared with that in the CV T0 group (p<0.01). The Tend to respiratory recovery time (p<0.05), extubation time (p<0.05), and conscious time (p<0.05) in the PV group were shorter than those in the CV group.
Conclusion: Individual ventilation strategies that reduce driving pressure can optimize the Pa-etCO2 gradient in elderly prone spine surgery patients, shorten the recovery time, and improve patient prognosis.
Quantitative Real-Time PCR Detection of Porphyromonas gingivalis and Filifactor alocis in Peri- Implantitis
Authors: Fragkioudakis Ioannis , Konstantopoulos Georgios , Kottaridi Christine , Batas Leonidas , Sakellari Dimitra
Published: January 2025

Aim: To assess the prevalence and levels of P. gingivalis and F. alocis in peri-implantitis and healthy peri-implant sites using quantitative real-time PCR (qPCR).Materials and Methods: This cross-sectional study included 110 participants, 52 with peri-implantitis and 58 with healthy peri-implant sites. Clinical parameters were recorded, including probing depth, clinical attachment level, and bleeding on probing. Microbiological samples were analyzed using qPCR, and significance was tested using the Mann-Whitney U test and Spearman’s rank correlation.Results: P. gingivalis and F. alocis levels were significantly higher in peri-implantitis sites, with P. gingivalis at 4.80 × 10⁶ ± 4.78 × 10⁶ copies/µL and F. alocis at 4.58 × 10⁵ ± 3.40 × 10⁵ copies/µL, compared to healthy sites, with P. gingivalis at 2.09 × 10³ ± 1.26 × 10³ copies/µL and F. alocis at 2.45 × 10³ ± 1.64 × 10³ copies/µL, with p < 0.001. P. gingivalis strongly correlated with clinical parameters, such as probing depth, clinical attachment level, and bleeding on probing. F. alocis showed moderate correlations with probing depth and clinical attachment level but not bleeding on probing.Conclusion: The findings suggest a potential synergistic role of P. gingivalis and F. alocis in peri-implantitis, emphasizing the importance of therapies targeting these pathogens. Clinicians might explore antimicrobial strategies disrupting biofilm formation and microbial synergy to improve outcomes. Further research is needed to refine treatment approaches and understand these bacteria's contributions to disease progression.
Increased survival rate by the pediatric acute lymphoblastic leukemia therapy intensification based on minimal residual disease levels along with protocol-based risk classification by early response.
Authors: Kim Hyery , Yoon Su Hyun , Kang Sunghan , Koh Kyung-Nam , Im Ho Joon , Chu Daehyun , Kim Mi Young , Cho Young-Uk , Hwang Sang-Hyun , Jang Seongsoo
Published: January 2025

Purpose
Minimal residual disease (MRD)-guided therapy is a global standard for pediatric acute lymphoblastic leukemia (ALL). We assessed the impact of MRD-driven intensification alongside protocol-defined risk groups.
Methods
This retrospective analysis included 209 patients with ALL (January 2013–June 2023). MRD was assessed using 6- to 8-color flow cytometry at the end of each phase before the maintenance phase. Post-induction treatment was determined by early response, National Cancer Institute risk, and cytogenetics. High-risk (HR) patients followed the Korean HR or CCG-1882 protocols; standard-risk (SR) patients followed a modified COG-AALL0331 protocol. Treatment was intensified if flow-MRD ≥ 0.1% was identified.
Results
Overall, 103 and 106 patients were classified as SR and HR, respectively. The 5-year overall survival (OS) and event-free survival (EFS) were 92.5% and 84.3% in all patients, respectively. Thirty SR and 18 HR patients received intensified chemotherapy. Treatment intensification significantly improved EFS in patients with high MRD (94.2% vs 75.5%, p = 0.04), particularly marked in post-induction MRD-high patients (90.0% vs 19.0%, p = 0.035). The survival difference between RER and SER groups was eliminated after MRD-based intensification. The implementation rates of treatment intensification varied over time (9.1% before 2015, 28.6% in 2016–2019, 13.9% in 2020–2023), reflecting improved risk stratification and therapy selection.
Conclusion
MRD-guided therapy intensification markedly improved survival outcomes in pediatric ALL when combined with risk-based protocols, highlighting the importance of MRD monitoring for optimizing risk-adapted treatment strategies.
The Effect of Interpersonal Psychotherapy-Based Group Psychological Counseling on the Psychological Resilience Levels of University Students
Authors: BATMAZ HASAN , ÇELİK EYÜP
Published: January 2025

This study aimed to examine the effect of interpersonal psychotherapy-based group counseling on the psychological resilience levels of university students. The study was planned and conducted online as Application 2 and Application 2. In the experimentally designed study, the dependent variable was Psychological Resilience scores, and the independent variable was interpersonal psychotherapy-based group counseling. Data were collected using the 'Brief Psychological Resilience Scale (BRS)'. The study was based on a pretest-posttest control group design. The experimental groups received 8 sessions of counseling, while the control groups received no intervention. The BRS was administered before and after the intervention, and follow-up tests were conducted three months later. The results showed that there was a significant difference between the follow-up and pre-test scores in Applications 1 and 2.
Integrative Analysis of tRNA-Derived Fragments in Plant Adaptation to Biotic Stress: A Comparative Study and Database
Authors: Swain Supriya P. , Bisht Niyati , Kumar Shailesh
Published: January 2025

Plants face significant challenges from biotic stresses, that adversely impact their growth and development. Amongst the various regulatory molecules, transfer RNA-derived fragments (tRFs) play crucial roles in modulating adaptive defense mechanisms. Although the role of tRFs in response to biotic stresses is still emerging, it is evident that different biotic stressors elicit distinct regulatory pathways. This study investigates the involvement of tRFs in stress response and resistance across three plant species: Arabidopsis thaliana, Oryza sativa, and Solanum lycopersicum. Our findings reveal a complex regulatory network where tRFs interact with mRNA targets, miRNAs, and transposable elements, underscoring their significance in adaptive biotic stress responses. This research advances the understanding of tRF regulatory mechanisms and lays the foundation for new strategies to enhance resilience against biotic stress. The database supporting this study is freely accessible at http://www.nipgr.ac.in/PbtRFdb, providing a valuable resource for further research on the tRFs in plant biotic stress responses.
Unspecified Pain, Chronic Pain and High-Impact Chronic Pain in Lesotho, Southern Africa: a Population-based Cross-sectional study
Authors: Firima Emmanuel , Gonzalez Lucia , Manthabiseng Molulela , Sematle Mamoronts’ane P. , Bane Matumaole , Khomolishoele Makhebe , Lee Tristan , Chammartin Frédérique , Gupta Ravi , McCrosky Stephen , Weisser Maja , Amstutz Alain , Labhardt Niklaus Daniel
Published: January 2025

Background. Pain and its associated disorders are among the most common causes of disability and contributors to healthcare costs globally. Pain is understudied in Africa and there are no data on high-impact chronic pain from this region. In a population-based survey in Lesotho, Southern Africa, we assessed the prevalence of unspecified pain, chronic pain and high-impact chronic pain, and their determinants.
Method. We conducted a household-based, cross-sectional survey among adults ≥18 years old in 120 randomly sampled villages across Butha Buthe and Mokhotlong districts in Lesotho. Unspecified pain, chronic pain, and high-impact chronic pain were defined as current or recurrent pain regardless of duration; pain on most days of the week lasting for 3 or more months; and chronic pain with restriction of routine activities, respectively.
Result. Among the 6039 adults included, the median age was 39 years (interquartile range: 27-58), 3153/6039 (52.2%) were female. Overall, 1194 (19.8%) had unspecified pain (95% confidence interval [CI]: 18.8 – 20.8); 909 (15.1%) had chronic pain (95% CI: 14.2 – 16.0); and 428 (7.1%) had high-impact chronic pain (95% CI: 6.5 – 7.8) corresponding to 47.1% among the participants with chronic pain. Higher age groups were associated with increasing odds of unspecified pain, chronic pain and high-impact chronic pain. Male participants were less likely to have unspecified pain (adjusted odds ratio [aOR], 0.68; 95% CI: 0.56 – 0.82; p < 0.001). There was no association between sex and chronic pain or high-impact chronic pain. Participants living in less wealthy households had higher odds of high-impact chronic pain. Furthermore, high-impact chronic pain was associated with hypertension (aOR, 1.47; 95% CI: 1.14 – 1.90; p = 0.003), diabetes mellitus (aOR, 1.86; 95% CI: 1.27 – 2.74; p = 0.002), moderate to high risk of depression (aOR, 4.93; 95% CI: 2.75 – 8.86; p < 0.001), and moderate to high risk of generalized anxiety disorder (aOR, 2.85; 95% CI: 1.18 – 6.92; p = 0.023).
Conclusion. Prevalence of chronic pain, including high impact chronic pain was high in this population-based survey in Lesotho. Its association with further non-communicable chronic conditions, such as hypertension and diabetes, supports the need for health systems to provide integrated chronic care, including the management of chronic pain.
Performance Enhancement of Trimetallic Nanoparticles in Photocatalysis through Chemical Etching
Authors: Cheng Yu-Chun , Dou Yun-Qi , Deng Tian-Song
Published: January 2025

Trimetallic nanoparticles have shown significant potential as multifunctional nanomaterials due to their superior photocatalytic performance, making them highly promising in materials science and nanotechnology. In this study, we designed and synthesized a trimetallic nanostructure consisting of a gold nanorod (Au NR) core, a silver (Ag) intermediate shell, and a silver-platinum (AgPt) alloy outer layer. The Au@Ag core-shell structure was first prepared by depositing silver onto the Au NR surface through a reduction reaction. Subsequently, an AgPt alloy was deposited via a reduction and replacement process, followed by oxidative etching to remove excess silver, resulting in the etched trimetallic nanostructure (Au@AgPt-E). Using methylene blue (MB) as the model system, the photocatalytic activity of Au@AgPt-E under visible and near-infrared light irradiation was significantly enhanced, achieving a rate 4.19 times higher than Au@Ag@AgPt and 7.67 times higher than single-metal Au NRs. The performance enhancement is primarily attributed to the surface plasmon resonance (SPR) effect of the Au NR core, which efficiently absorbs light energy and converts it into heat, facilitating the generation and separation of charge carriers. Additionally, the etching process increases the catalytic active sites on the AgPt surface. This study provides a novel approach for developing efficient plasmon-mediated photocatalysts and demonstrates broad application prospects in photocatalytic reduction processes.
Establishing 3D Organoid Models from Patient-Derived Conditionally Reprogrammed Cells to Bridge Preclinical and Clinical Insights in Pancreatic Cancer
Authors: Kim Jin Su , Park Chan Hee , Lee Jinyoung , Kim Jeehoon , Kam Eun Hee , Nam Sanghee , Lee Hee Seung , Park Jeong Youp , Leem Galam , Bang Seungmin
Published: January 2025

Background
Pancreatic cancer is a highly lethal malignancy with limited treatment response. Despite advancements in treatment, systemic chemotherapy remains the primary therapeutic approach for over 80% of patients, with no established biomarkers to guide drug selection. Traditional two-dimensional (2D) culture models fail to replicate the tumor microenvironment, necessitating the development of more advanced models, such as three-dimensional (3D) organoid models.
Methods
We established 3D organoid cultures using patient-derived conditionally reprogrammed cell (CRC) lines, originally cultured under 2D conditions. These CRC organoids were developed using a Matrigel-based platform without organoid-specific medium components to preserve the intrinsic molecular subtypes of the cells. Morphological, molecular, and drug sensitivity analyses were performed to compare the clinical responses of 3D CRC organoids with those of their 2D counterparts and clinical responses.
Results
The 3D CRC organoids retained the molecular characteristics and mutational profiles of the original CRCs and displayed distinct morphologies corresponding to cancer stages and differentiation. Drug response profiling of gemcitabine plus nab-paclitaxel (Abraxane) and FOLFIRINOX demonstrated that the 3D organoids more accurately mirrored patient clinical responses than the 2D cultures. Notably, the IC50 values for the 3D organoids were higher, reflecting the structural complexity and drug penetration barriers observed in vivo.
Conclusion
Matrigel-based 3D organoid culture models provide a robust platform for pre-clinical drug evaluation, overcoming the limitations of 2D models. Although time- and resource-intensive, integrating both 2D and 3D platforms enables efficient initial screening and validation. This approach holds promise for identifying predictive biomarkers and advancing precision medicine in pancreatic cancer treatment.
Plane based optimization method: A method for better global minimum cost function localization.
Authors: Bermudez Dalton H
Published: January 2025

Background As a popular optimization algorithm, gradient descent is more prone to converge at a local minimum rather than a global one since it is highly dependent on how initial values are instantiated and an iterative process of updates, reducing its efficiency for non-convex cost functions. This limitation is of utmost importance in domains such as medical physics, where there exist many treatment parameters that need to be optimized.Purpose We introduce the flat plane with maximum perpendicular distance method, a new optimization algorithm which identifies global minima robustly and efficiently in convex cost functions. This facilitates an initialization-free, non-iterative update method that serves as a complementary approach to classic methods.Methods 1D and 2D convex cost functions, with both global and relative minima, were tested using the flat plane method. Further, the approach was employed to determine optimal locations for radiation beams in a medical physics problem. Results were compared to existing gradient descent methods for effectiveness assessment.Results The flat plane algorithm found the global minimum in all the scenarios considered while the use of gradient descent would have failed to do so in many cases due to initialization issues. However, due to a less direct but highly parallelizable strategy (i.e. flat plane method), these techniques are certainly scalable for high-dimensional problems with potentially higher expense (e.g. dimensionality reduction, sampling, parallel computing).Conclusion In low-dimensional problems, the flat plane method provides a strong alternative to gradient descent for the global optimization problem. We are yet to adapt the method for high-dimensional applications but will work in that direction to increase its applicability over more complex optimization problems.
Novel mutations in the RECQL4 gene affect its helicase functions, interactions with the BLM helicase and chemotherapeutics-induced cell death
Authors: Kaminska Bozena , Kaczmarczyk Agnieszka , Sokolowski Mikolaj , Wojnicki Kamil , Pabiś Marta , Wojtas Bartosz , Poleszak Katarzyna , Gielniewski Bartlomiej , Król Sylwia , Guille Matthew , Glatt Sebastian
Published: January 2025

RecQ family of DNA helicases play pivotal roles in DNA replication, repair and responses to DNA damage or replication stress. Several human RecQ helicases are defective in diseases associated with chromosomal instability, premature aging and cancer. We recently discovered novel mutations in the RECQL4 gene in glioblastoma (GBM), the most malignant brain tumour in adults. Transcriptomic profiles of GBMs with REQCL4 mutations resembled those in REQCL4 KO glioma cells. We employ structural modelling and biochemical approaches to elucidate impacts of novel mutations on RECQL4 helicase activities. We modelled the impact of mutations on the DNA helicase domain. Using recombinant RECQL4P532S and RECQL4R766Q proteins we demonstrate that P532S substitution reduces the RECQL4 ability to unwind DNA and disrupts DNA-coupled ATP-hydrolysis activity. WT and mutated RECQL4 were overexpressed in RECQL4 KO glioma cells to study interactions with BLM helicases, cell viability and specific responses to UVC- and chemotherapy-induced DNA damage/repair. Overexpression of RECQL4P532S or RECQL4R766Q variants affected DNA repair and responses to chemotherapeutics in glioma cells, and RECQL4R766Q disturbed interactions with the BLM helicase. Our results reveal deleterious consequences of novel RECQL4 mutations in GBMs. The newly identified RECQL4 mutations affect RECQL4 helicases and their interactions with BLM contributing to glioma progression.
Differentiable MadNIS-Lite
Authors: Heimel Theo , Mattelaer Olivier , Plehn Tilman , Winterhalder Ramon
Published: January 2025

Differentiable programming opens exciting new avenues in particle physics, also affecting future event generators. These new techniques boost the performance of current and planned MadGraph implementations. Combining phase-space mappings with a set of very small learnable flow elements, MADNIS-Lite, can improve the sampling efficiency while being physically interpretable. This defines a third sampling strategy, complementing VEGAS and the full MADNIS.
Mitochondrial DNA Mutations as a Factor in the Heritability of Atherosclerosis and Other Diseases
Authors: Orekhov Alexander N. , Orekhov Nikolay A. , Sukhorukov Vasily N. , Khotina Victoria A. , Kovianova Tatiana I. , Sobenin Igor A.
Published: January 2025

This review discusses the possibility of inheritance of some diseases through
mutations in mitochondrial DNA. These are examples of many mitochondrial diseases
that can be caused by mutations in mitochondrial DNA. Symptoms and severity can
vary widely depending on the specific mutation and affected tissues. An association between
certain mutations in the mitochondrial genome and cancer was reported. In other
studies of 2-4 generations in each family, we found that mitochondrial mutations associated
with atherosclerosis are inherited. This may at least partially explain the inheritance
of predisposition to atherosclerotic disease by maternal line. Furthermore, to prove the
important role of mitochondrial mutations in the development of atherosclerotic manifestations
at the cellular level, we developed a technique for editing the mitochondrial
genome. A recent article described how one of the pro-atherogenic mutations, namely
m.15059G>A, was eliminated from such monocyte-derived cells using the technique we
developed. Elimination of this mutation resulted in the restoration to normal levels of initially
defective mitophagy and impaired inflammatory response. These data strongly
suggest that mitochondrial mutations are closely associated with the development of
atherosclerotic lesions. Considering that they are inherited, it can be assumed that, at
least partly, the genetic predisposition to atherosclerotic diseases is transmitted from
mother to offspring. Thus, despite the small size of mitochondrial DNA, its mutations
may play a role in the pathogenesis of diseases. Further study of their role will make it
possible to consider mitochondrial mutations as promising diagnostic markers and disorders
caused by mutations as pharmacological targets.
Experimental Research Progress of mPGES-1 Inhibitor 2,5-Dimethylcelecoxib in Various Diseases
Authors: Chen Zhanfei , Chen Rong , Wang Laiping , Yu Zihao , Chen Weitong , Lin Hua , Yu Liumin , Li Jinqiu , Chen Zhonghui , Shen Jianlin , Tang Nanhong
Published: January 2025

Prostaglandin E2 (PGE2) plays a crucial role in inflammation. Non-steroidal
anti-inflammatory medications are commonly utilized to alleviate pain and address inflammation
by blocking the production of PGE2 and cyclooxygenase (COX). However,
selective inhibition of COX can easily lead to a series of risks for cardiovascular diseases.
Hence, it is imperative to discover safer and more efficient targets for reducing inflammation.
Research has demonstrated that mPGES-1 serves as the final enzyme that
controls the rate of prostaglandin E2 synthesis. Moreover, it is only triggered by inflammation
and could serve as a possible treatment target instead of COX in cases of inflammation.
2,5-dimethylcelecoxib (DMC) can effectively inhibit mPGES-1 expression,
maintain the overall balance of prostaglandins, reduce the secretion of PGE2, and, most
importantly, avoid the side effects of COX inhibitors. DMC has the ability to address illnesses
through the stimulation of autophagy and apoptosis, as well as the regulation of
the immune microenvironment and intestinal flora. This study provides a comprehensive
overview of the advancements in DMC within experimental research and offers suggestions
for potential avenues of future investigation.
Cordycepin and Its Structural Derivatives Effectively Suppress the High Expression of Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase in Breast Carcinomas: A Computational Drug Development Approach
Authors: Bibi Shabana , Biswas Partha , Tareq Md. Mohaimenul Islam , Imtiaz Md. , Shovon Md. Hasan Jafre , Hossain Md Ridoy , Ahmed Nasim , Albekairi Norah A. , Alshammari Abdulrahman , Hasan Md. Nazmul
Published: January 2025

Background:

Breast cancer is a frequently diagnosed malignant disease and the primary
cause of mortality among women with cancer worldwide. The therapy options are influenced by the
molecular subtype due to the intricate nature of the condition, which consists of various subtypes.
By focusing on the activation of receptors, Epidermal Growth Factor Receptor (EGFR) tyrosine kinase
can be utilized as an effective drug target for therapeutic purposes of breast cancer.

Objectives:

The objective of this study is to compare the underlying pharmacological properties of
several modified agents to the parental Cordycepin to target and inhibit the EGFR tyrosine kinase
high expression, and to discover the inhibitor with the highest affinity for this drug target to treat the
breast cancer patients.

Methods:

The Maestro Application of Schrödinger Suite Paid Software was initially employed for
conducting extra precision (XP) structure-based virtual screening to evaluate the binding affinity of
the Cordycepin and its 500 structural derivatives with the EGFR tyrosine kinase protein structure. In
addition, the anti-breast cancer activity of the chosen compounds was assessed by looking at their
drug-likeness and ADMET characteristics using Lipinski's rule of five along with Quantitative structure-
activity relationship (QSAR) validation, the prediction of cell line anti-cancer, as well as anti-
breast cancer activity of top docked scored compounds. Subsequently, the Desmond paid software-
based molecular dynamics simulations (MDS) were conducted for a duration of 100 nanoseconds
on the promising candidates followed by the binding free energy estimation was performed
utilizing MM-GBSA analysis. To determine the stability of the protein-ligand complex, root-meansquare
deviation (RMSD), root-mean-square fluctuation (RMSF), protein-ligand interactions, and
other necessary parameters were evaluated from the 100 ns MDS Trajectory.

Results:

Based on the overall analysis of our study, N (6)-octylamine adenosine (CID-194932) reported
the optimum inhibitory potential against the EGFR tyrosine kinase protein, followed by
Adenosine 5-monophosphate (CID-83862) and Cordycepin (CID-6303), which compared favorably
to the control drug Vandetanib (CID-3081361).

Conclusion:

Consequently, these derivative compounds Cordycepin have the potential
to be utilized as lead molecules in the development of highly effective and potent EGFR
tyrosine kinase inhibitors for the treatment of breast cancer patients.
Theoretical Modeling of the Interactions of CoFe2O4-BaTiO3 Magnetoelectric Nanoparticles with Cancer and Healthy Cells
Authors: Sevim Gençay , Değer Gizem , Büyükköroğlu Gülay
Published: January 2025

Introduction:

The effectiveness of pharmaceutical treatment methods is vital
in cancer treatment. In this context, various targeted drug delivery systems are being developed
to minimize or eliminate existing deficiencies and harms. This study aimed to
model the interaction of MEN-based drug-targeting systems with cancer cells and determine
the properties of interacting MENs.

Methods:

Magnetoelectric Nanostructures (MENs) have both targeting and nano-electroporation
effects due to their ferroic properties. Among these structures, the most used
nanoparticles as targeting mechanisms are CoFe2O4-BaTiO3 structures. For this purpose,
the electrical field produced by MENs was modeled using MATLAB R2023b, and a theoretical
data pool of appropriate physical properties was created. Testing and applying
other magnetoelectric materials defined in the literature may be costly and time-consuming.

Results:

The problems with MENs can be eliminated by performing theoretical simulations
of each material before proceeding with laboratory tests.

Conclusion:

By simulating the interaction of CoFe2O4-BaTiO3 MENs with cancer cells,
physical properties affecting drug targeting were theoretically identified and a data pool
of MENs with these properties was created.
Cinacalcet Improves Erythropoietin Resistance in Patients with Secondary Hyperparathyroidism Receiving Dialysis Treatment
Authors: Weng Wenjuan , Li Yingjuan , Lin Yongda , Wang Jiali , Chen Xiutian , Zhou Tianbiao
Published: January 2025

Introduction:

Chronic Kidney Disease (CKD) is recognized as a major global public health problem.
Dialysis is the mainstay of treatment for patients with end-stage renal disease and can prolong survival in
patients with CKD. As patient survival increases, the treatment of complications becomes more important.
CKD-mineral and bone disorders (CKD-MBD) and renal anemia are common complications in patients
with CKD. Cinacalcet is a calcimimetic for the treatment of Secondary Hyperparathyroidism (SHPT) in adult
dialysis patients, which regulates the synthesis and secretion of parathyroid hormone by increasing the sensitivity
of calcium-sensitive receptors. This retrospective study evaluated the efficacy of cinacalcet in dialysis
patients.

Method:

Forty-seven patients on dialysis with elevated parathyroid hormone were included. The selected patients
have regular follow-up visits in our outpatient clinic and regular use of cinacalcet for no less than 6
months.

Result:

During the 6-month efficacy evaluation phase, cinacalcet not only reduced the levels of the intact parathyroid
hormone (iPTH, P ≤ 0.05), serum calcium (P ≤ 0.01), and Ca×P (P ≤ 0.05) but also reduced weekly
erythropoietin dosage (P ≤ 0.01) and erythropoietin resistance index (ERI, P ≤ 0.05).

Conclusion:

While controlling SHPT in patients with CKD, cinacalcet reduced EPO resistance and improved
renal anemia. In conclusion, cinacalcet not only decreased the levels of the iPTH, serum calcium, and Ca×P
but also reduced weekly EPO dosage and ERI levels. Controlling SHPT in patients with CKD, cinacalcet also
reduced ERI and improved renal anemia.
Recent Advances on the α-Functionalization and Ring Transformations of Cycloheptane-based β-ketoesters
Authors: Sanad Sherif M. H.
Published: January 2025

This review investigates the reactivity of cycloheptane-based β-ketoesters in producing α-
functionalized derivatives. Cyclic β-ketoesters are a versatile chemical reagent that can react with suitable electrophiles
to produce a variety of α-functionalized derivatives with excellent synthetic potential and promising
biological properties. This review covers all reports on α-functionalization of cycloheptane-based β-ketoesters,
including those demonstrating enantioselective synthesis using appropriate asymmetric catalysts. The review is
divided into sections based on the α-center reaction. We reviewed also all available papers on the ring transformation
of cycloheptane-based β-ketoesters, including their ring-opening and ring-expansion reactions. The
mechanistic postulates of some complex procedures are highlighted.
Betanin Mitigates Inflammation and Ankle Joint Damage by Subduing the MAPK/NF-κB Pathway in Arthritis Triggered by Type II Collagen in Rats
Authors: He Yongxiang , Hussain Shaik Althaf , Dai Wenjie
Published: January 2025

Background:

Rheumatoid Arthritis (RA), a chronic inflammatory autoimmune illness,
is characterized by synovitis, progressive joint damage, and bone erosion. Even though the
potent drugs available contain biologics, several patients fail to react to them or cause hostile effects.

Objectives:

Betanin (BTN), the betacyanin present in the red beetroot, has antioxidant, antiinflammatory,
and apoptotic properties. In this study, we assessed the anti-inflammatory and
apoptotic effect of BTN on collagen-induced arthritis (CIA).

Materials and Methods:

The rats were arbitrarily separated into four sets: Normal, CIA,
CIA+BTN (25 mg/kg bw), and CIA+BTN (50 mg/kg bw). The hematological, biochemical
markers, cytokines, inflammatory enzymes, histopathology of the ankle joint, and protein expression
of inflammatory and apoptotic proteins were studied.

Results:

Inflammatory enzymes, histopathological variations, cytokines generation, and joint inflammation
were strongly alleviated, and apoptosis was augmented by BTN in a concentrationdependent
manner. Bcl-2 and MAPK/NF-κB proteins were reduced, while the caspase-3, caspase-
9, and Bax were intensified. The anti-rheumatic action of BTN was correlated to the attenuation
of the MAPK/NF-κB pathway, which suppresses cytokine production, inflammation, and
reduced cartilage impairments.

Conclusion:

These outcomes recommend that BTN can be employed as a strong healing alternative
for RA management.
Neutrophil Elastase as A Potential Target in Ischemia-Reperfusion Injury
Authors: Tan Yiqing , Zuo Wei
Published: January 2025

Neutrophil elastase (NE), a major protease in neutrophils, is important in promoting inflammation
and multiple pathological processes. While NE is released abundantly in ischemiareperfusion
(I/R) injury, the intricate relationship between NE and I/R injury remains unclear. We
examine several aspects of how NE is involved in I/R injury. We also discuss the possibility of NE
inhibitors used for abbreviating various types of I/R injury, such as myocardial infarction, based on
preclinical research and clinical trials. Furthermore, we highlight the key question, the balance of NE
and NE inhibitors, and propose new research directions. This review is useful for understanding the
intrinsic interplay between NE and I/R injury-related diseases and expects to facilitate the development
of effective NE inhibitors applied for I/R injury.
Recent Advances in Diversity-Oriented Synthesis of N-containing Organic Molecules Through Carbodiimide-based Reactions
Authors: Abedinifar Fahimeh , Fakhrioliaei Azadeh , Nazarian Ahmad , Larijani Bagher , Mahdavi Mohammad
Published: January 2025

Carbodiimides (R-N=C=N-R) are well-known intermediates for the preparation of a variety of N-containing compounds, including heterocycles and amide linkages. Be-cause of their high reactivity and easy availability, carbodiimides have been broadly used as building blocks in the synthesis of structurally complex and diverse heterocyclic com-pounds in multi-component reactions (MCRs). Recent advances in diversity-oriented syn-thesis with carbodiimide-based MCRs are discussed in this minireview and are classified into different sections based on the key transformation involved in the reactions, such as heteroannulation and nucleophilic addition reactions which containing metal-catalyzed re-actions, multi-component reactions, and catalyst-free reactions subsections.
Effects of Inulin and Fructooligosaccharide on the Survival of Microencapsulated Probiotic Pediococcus pentosaceus GS4 in Alginate Beads Coated
with Chitosan in Simulated Gastrointestinal Fluid and at Different Storage Conditions
Authors: George Jeneesha , Ghosh Asit Ranjan
Published: January 2025

Background:

Microencapsulated Pediococcus pentosaceus GS4 (MTCC 12683) with
prebiotics and chitosan coating can be used in food functional products, enhancing shelf life and
restoring probiotic properties.

Objective:

This study aimed to analyze the effects of inulin (I) fructooligosaccharide (FOS) and
chitosan coating in microencapsulation of probiotic strain P. pentosaceus GS4 survivability in simulated
gastrointestinal (GI) conditions and at different storage conditions.

objective:

To analyse the effects of inulin (I) and fructooligosaccharide (FOS) and chitosan coating in microencapsulation of probiotic strain P. pentosaceus GS4 survivability in simulated gastrointestinal (GI) conditions and at different storage conditions.

Methods:

To enhance the stable viability of probiotic P. pentosaceus, GS4, inulin, and FOS were
separately combined into alginate (Alg) following chitosan (C) coating during the process of microencapsulation.
Encapsulation efficiency, morphological characterization, and cell survival of
different microbeads were evaluated before and after exposure to simulated GI conditions at different
storage conditions.

Results:

Alginate-inulin-FOS combined chitosan coated (Alg/I/FOS/C) microbeads showed higher
viability than other groups. Chitosan-coated beads had increased diameter (2.52- 2.71 mm) in
comparison to uncoated beads (1.98- 2.42 mm). On successive challenges through simulated GI
conditions, microencapsulated probiotics demonstrated higher viable cells than control cells
(P<0.05). At different storage conditions, stable cell viability occurred at -20°C> 4°C> room temperature.

Conclusion:

In conclusion, Alg/I/FOS/C beads stored at -20°C maintained stable probiotic viability
and are found to be suitable for food technological applications.
The Impact of Non-pharmacologic Traditional Chinese Medicine on Health-Related Quality of Life and Symptom Management in Breast Cancer Patients: A Systematic Review and Meta-Analysis
Authors: Fei Wang , Zaremohzzabieh Zeinab , Abdullah Haslinda
Published: January 2025

Background:

Breast cancer remains a prevalent malignancy among women globally.
Survivors often experience diminished quality of life, pain, and sleep disturbances after treatment
and suffer feelings of isolation. Non-pharmacological traditional Chinese medicine (NP-TCM) interventions
have been increasingly applied in clinical practice, yet their efficacy requires further
clarification.

Objective:

This meta-analysis aimed to evaluate the impact of NP-TCM interventions (e.g. Qigong,
Tai Chi, Baduanjin) on the health-related quality of life (HRQOL) in breast cancer patients.

Methods:

Randomized controlled trials published between 1999 and 2024 were retrieved from various
databases. Studies comparing NP-TCM and control groups in quality of life and other outcomes
were included. Meta-analysis was performed using RevMan 5.4 software. 14 RCTs with 688
patients were included.

Results:

NP-TCM interventions significantly improved overall quality of life (SMD=0.13, 95%CI
0.24~0.51, P<0.001). Specifically, Baduanjin demonstrated substantial benefits (SMD=0.82,
P<0.001). NP-TCM also enhanced sleep (SMD=1.16, P=0.04) and alleviated anxiety (SMD=-0.46,
P<0.05).

Conclusion:

NP-TCM interventions effectively improved the HRQOL and certain symptoms for
breast cancer patients, providing practical adjunctive therapies. However, study qualities require optimization.