bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploring Molecular Drivers of PARPi Resistance in BRCA1-Deficient Ovarian Cancer: The Role of LY6E and Immunomodulation
Authors: Petta Tirzah Braz , Carlson Joseph
Published: September 2024

Approximately 50% of patients diagnosed with ovarian cancer harbor tumors with mutations in BRCA1, BRCA2, or other genes involved in homologous recombination repair (HR). The presence of homologous recombination deficiency (HRD) is an approved biomarker for poly-ADP-ribose polymerase inhibitors (PARPis) as a maintenance treatment following a positive response to initial platinum-based chemotherapy. Despite this treatment option, the development of resistance to PARPis is common among recurrent disease patients, leading to a poor prognosis. In this study, we conducted a comprehensive analysis using publicly available datasets to elucidate the molecular mechanisms driving PARPi resistance in BRCA1-deficient ovarian cancer. Our findings reveal a central role for the interferon (IFN) pathway in mediating resistance in the context of BRCA1 deficiency. Through integrative bioinformatics approaches, we identified LY6E, an interferon-stimulated gene, as a key mediator of PARPi resistance, with its expression linked to an immunosuppressive tumor microenvironment (TME) encouraging tumor progression and invasion. LY6E amplification correlates with poor prognosis and increased expression of immune-related gene signatures, which is predictive of immunotherapy response. Interestingly, LY6E expression upon PARPi treatment resistance was found to be dependent on BRCA1 status. Gene expression analysis in the Orien/cBioPortal database revealed an association between LY6E and genes involved in DNA repair, such as Rad21 and PUF60, emphasizing the interplay between DNA repair pathways and immune modulation. Moreover, PUF60, Rad21, and LY6E are located on chromosome 8q24, a locus often amplified and associated with the progression of ovarian cancer. Overall, our study provides novel insights into the molecular determinants of PARPi resistance and highlights LY6E as a promising prognostic biomarker in the management of HRD ovarian cancer. Future studies are needed to fully elucidate the molecular mechanisms underlying the role of LY6E in PARPi resistance.
Mitochondrial Genome Characteristics and Phylogenetic Analysis of Fulmekiola serrata (Kobus) (Thysanoptera: Thripidae)
Authors: Yin Jiong , Luo Zhi-Ming , Li Yin-Hu , Wang Chang-Mi , Li Jie , Zhang Rong-Yue , Shan Hong-Li , Wang Xiao-Yan , Chen You-Qing
Published: September 2024

Sugarcane thrips, Fulmekiola serrata (Kobus) (Thysanoptera: Thripidae), is a common foliar pest that infests sugarcane and is found throughout tropical and subtropical countries. In this study, we obtained and analyzed the complete mitochondrial genome of F. serrata for the first time and explored the phylogenetic relationships of the higher-order elements of Thysanoptera members at the mitochondrial level. The complete mitochondrial genome of F. serrata is 16,596 bp in length and includes 13 protein-coding genes (PCGs), 22 transfer RNA (tRNA) genes, 2 ribosomal RNA (rRNA) genes, and 1 noncoding control region. A+T accounted for 75% of the total bases in the mitochondrial genome of F. serrata, revealing an obvious AT bias. Among the 13 PCGs, except for nad5, which had a start codon of TTG, the remaining genes had ATNs typical of insects (ATA, ATT, ATC, and ATG); nad1, nad2, nad3, and atp8 had incomplete termination codons of TA or T. The remaining nine PCGs were complete with the termination codon TAA. Of the 22 tRNA secondary structures, all were typical cloverleaf secondary structures except for trnS1, which was missing the DHU arm. Compared with the hypothetical ancestral gene arrangement of arthropods, F. serrata presented extensive gene rearrangement, with 23 translocated genes, 8 inverted genes, and 5 shuffled genes. Both maximum likelihood (ML) and Bayesian inference (BI) phylogenetic trees resulted in similar topologies: ((Thripidae + (Stenurothripidae + Aeolothripidae)) + Phlaeothripidae), with Thripidae, Aeolothripidae and Phlaeothripidae being monophyletic groups, whereas F. serrata is closely related to Thrips palmi, and the two are sister groups.
SHH Signaling as a Key Player in Endometrial Cancer: Unveiling the Correlation with Good Prognosis, Low Proliferation, and Anti-Tumor Immune Milieu
Authors: Snijesh V. P. , Krishnamurthy Shivakumar , Bhardwaj Vipul , Punya K. M. , Niranjana Murthy Ashitha S. , Almutadares Mahmoud , Habhab Wisam Tahir , Nasser Khalidah Khalid , Banaganapalli Babajan , Shaik Noor Ahmad , Albaqami Walaa F.
Published: September 2024

Endometrial Cancer (EC) is one of the most common gynecological malignancies. Despite its prevalence, molecular pathways, such as the Sonic Hedgehog (SHH) pathway, have not been extensively studied in the context of EC. This study aims to explore the clinical implications of SHH expression in EC, potentially uncovering new insights into the disease’s pathogenesis and offering valuable insights for therapeutic strategies in EC. We utilized data from The Cancer Genome Atlas (TCGA) to divide the dataset into ‘High SHH’ and ‘Low SHH’ groups based on a gene signature score derived from SHH pathway-related genes. We explored the clinical and tumor characteristics of these groups, focusing on key cancer hallmarks, including stemness, proliferation, cytolytic activity, tumor micro-environment, and genomic instability. ‘High SHH’ tumors emerged as a distinct category with favorable clinical and molecular features. These tumors exhibited lower proliferation rates, reduced angiogenesis, and diminished genomic instability, indicating a controlled and less aggressive tumor growth pattern. Moreover, ‘High SHH’ tumors displayed lower stemness, highlighting a less invasive phenotype. The immune micro-environment in ‘High SHH’ tumors was enriched with immune cell types, such as macrophage M0, monocytes, B cells, CD8 T cells, CD4 T cells, follicular helper T cells, and natural killer cells. This immune enrichment, coupled with higher cytolytic activity, suggested an improved anti-tumor immune response. Our study sheds light on the clinical significance of Sonic signaling in EC. ‘High SHH’ tumors exhibit a unique molecular and clinical profile associated with favorable cancer hallmarks, lower grades, and better survival. These findings underscore the potential utility of SHH expression as a robust prognostic biomarker, offering valuable insights for tailored therapeutic strategies in EC. Understanding the SHH pathway’s role in EC contributes to our growing knowledge of this cancer and may pave the way for more effective treatment strategies in the future.
c-Jun N-terminal Kinase Supports Autophagy in Testicular Ischemia but Triggers Apoptosis in Ischemia-Reperfusion Injury
Authors: Alotaibi Sarah R. , Renno Waleed M. , Al-Maghrebi May
Published: September 2024

Oxidative stress triggered by testicular torsion and detorsion in young males could negatively impact future fertility. Using a rat animal model for testicular IRI (tIRI), we aim to study the induction of autophagy (ATG) during testicular ischemia and tIRI and the role of oxidative-stress-induced c-Jun N-terminal Kinase (JNK) as a cytoprotective mechanism. Sixty male Sprague-Dawley rats were divided into five groups: sham, ischemia only, ischemia+SP600125 (a JNK inhibitor), tIRI only, and tIRI+SP600125. The tIRI rats underwent an ischemic injury for 1 h followed by 4 h of reperfusion, while ischemic rats were subjected to 1 h of ischemia only without reperfusion. Testicular-ischemia-induced Beclin 1 and LC3B expression was associated with decreased p62/SQSTM1 expression, increased ATP and alkaline phosphatase (AP) activity, and slightly impaired spermatogenesis. SP600125 treatment improved p62 expression and reduced the levels of Beclin 1 and LC3B but did not affect ATP or AP levels. The tIRI-induced apoptosis lowered the expression of the three ATG proteins and AP activity, activated caspase 3, and caused spermatogenic arrest. SP600125-inhibited JNK during tIRI restored sham levels to all investigated parameters. This study emphasizes the regulatory role of JNK in balancing autophagy and apoptosis during testicular oxidative injuries.
Examination of Joint Effusion Magnetic Resonance Imaging of Patients with Temporomandibular Disorders with Disc Displacement
Authors: Mizuhashi Fumi , Ogura Ichiro , Mizuhashi Ryo , Watarai Yuko , Oohashi Makoto , Suzuki Tatsuhiro , Kawana Momoka , Nagata Kotono
Published: September 2024

In this study, we investigated joint effusion in patients with temporomandibular disorders (TMDs) with disc displacement. The magnetic resonance (MR) images of 97 temporomandibular joints (TMJs) were evaluated, and the appearance of joint effusion was investigated. Myofascial pain and TMJ pain were considered in addition to the duration from manifestation. Disc displacement with and without reduction, as well as the region and the area of joint effusion, were investigated using the MR images. Fisher’s test was used for the analyses. Joint effusion was recognized in 70 TMJs, including 55 in the superior articular cavity, 1 in the inferior articular cavity, and 14 in both the superior and inferior articular cavities. The appearance of joint effusion did not differ with the existence of myofascial pain or TMJ pain. The region of joint effusion did not differ between disc displacement with and without reduction. A larger area of joint effusion was recognized in disc displacement without reduction (p < 0.05). The results showed that the amount of synovial fluid in the joint effusion did not change with the existence of myofascial pain or TMJ pain. Joint effusion commonly appeared in disc displacement without reduction.
The Combination of Morphological and Phylogenetic Evidence Reveals Four New Gymnopus Species and New Distribution
Authors: Hu Jia-Jun , Tuo Yong-Lan , Qi Zheng-Xiang , Li Xue-Fei , Jiang Dong-Hua , Zhang Bo , Li Yu
Published: September 2024

The genus Gymnopus plays a significant role in ecological systems, with certain species holding potential as food or medicinal resources. However, the species diversity of Gymnopus in China remains unclear. In recent years, more than one thousand Gymnopus specimens have been collected across China. Thus, through the integration of ecological evidence, detailed morphological studies, and phylogenetic analysis using a multiloci dataset of ITS + nLSU + tef1-ɑ, four new species—Gymnopus longistipes, Gymnopus striatipileatus, Gymnopus viridiscus, and Gymnopus spadiceus—have been differentiated from known species. Gymnopus similis has been newly documented from Jiangxi Province, China. Detailed descriptions and vivid illustrations have been provided based on the newly collected specimens, along with comparisons to closely related species. Additionally, a key to the reported species of Gymnopus s.l. from East China has been included.
Predicting Fungemia in the ICU: Unveiling the Value of Weekly Fungal Surveillance and Yeast Colonisation Monitoring
Authors: Suárez-Urquiza Pedro , Pemán Javier , Gordon Monica , Favier Patricio , Muñoz-Brell Paula , López-Hontangas Jose Luis , Ruiz-Gaitán Alba
Published: September 2024

Fungemia remains a major threat in intensive care units (ICUs), with high mortality rates despite advances in diagnostics and treatment. Colonisation by yeasts is an independent risk factor for fungemia; however, its predictive utility requires further research. In this 8-year study, we analysed 38,017 samples from 3206 patients and 171 fungemia episodes as part of a weekly fungal surveillance programme. We evaluated species-specific colonisation patterns, the predictive value of the Colonisation Index (CI) and Corrected Colonisation Index (CCI), and candidemia risks associated with different yeast species and anatomical site colonisation. Our results showed that C. auris, N. glabratus, and C. parapsilosis colonisation increased with longer hospital stays (0.8% to 11.55%, 8.13% to 16.8%, and 1.93% to 5.14%, respectively). The CI and CCI had low discriminatory power (AUROC 67% and 66%). Colonisation by any yeast genera demonstrated high sensitivity (98.32%) and negative predictive value (NPV) (95.90%) but low specificity and positive predictive value (PPV) (23.90% and 6.64%). Tracheal and urine cultures had the highest PPV (15.64% and 12.91%), while inguinal cultures had the highest NPV (98.60%). C. auris (12.32%) and C. parapsilosis (5.5%) were associated with a higher fungemia risk (log-rank < 0.001). These findings support the use of weekly surveillance to better stratify the fungemia risk and optimise antifungal use in ICUs.
Promoting Inclusive Contexts and Journalism: Testing the Effectiveness of a Training Program
Authors: Santilli Sara , Sbalchiero Stefano , Ginevra Maria Cristina , Andolfatto Monica , Reale Roberto , Giulietti Giuseppe , Ferri Enrico , Nota Laura
Published: September 2024

Struggles for social inclusion necessitate efforts to enhance democratic communication. Communication practices and institutions are deeply intertwined with movements advocating for and against social justice, particularly in contemporary contexts of developing inclusion. We designed and evaluated the “Telling the Truth: How to Inform While Promoting an Inclusive Society” program. This program aimed to enhance knowledge and increase positive attitudes toward inclusion among 61 journalism students through quantitative and qualitative methods. The results indicate that participants demonstrated higher positive attitudes in the post-test, showing increased support for a more inclusive socio-economic vision and a greater inclination toward activism. Overall, these findings underscore the significance of journalism training in advancing a socially inclusive context.
The Impact of Perceived Timeliness of Information Release on Subjective Well-Being: A Heterogeneity Perspective
Authors: Ma Yiyun , Zhou Shiwei
Published: September 2024

The perceived timeliness of information release (PTIR) refers to the public’s overall assessment of the interval between the generation of information and its dissemination. Scholars are increasingly concerned with understanding how PTIR influences subjective well-being (SWB), which encompasses individuals’ self-evaluation of their life satisfaction, emotional experiences, and overall quality of life. This study proposes a research framework to investigate the relationship between PTIR and SWB among social media users, focusing on the mediating roles of social comparison, social security, and information stock. Utilizing data collected from 708 respondents via the Questionnaire Star app, we employed structural equation modeling to analyze the data. The results indicate that PTIR has a significant positive impact on SWB, primarily through the mediating effects of social security and information stock, while social comparison does not show a significant mediating effect. Additionally, it highlights the varying impact of these mediators based on individuals’ social media usage patterns, with frequent users experiencing a diminished influence of social security and information stock on their SWB. These findings provide valuable insights into the pathways through which PTIR and social media dynamics influence SWB, offering important implications for the theory and practice in enhancing individual well-being in the digital age.
Reconstructing Childhood via Reimagined Memories: Life Writing in Children’s Literature
Authors: Silva Emma-Louise
Published: September 2024

For authors who revisit their experiences of childhood to write stories for young readers, imaginatively drawing on memories plays a prominent role in the creative process. Whereas connections between memories and narratives have featured in literary studies and children’s literature studies, the unfolding of negotiations between memory and imagination as authors create narratives of life writing is underexplored. This article examines how negotiations of memory and imagination unfold on paper during the writing processes for Roald Dahl’s Boy (1984), David Almond’s Counting Stars (2000), and Jacqueline Woodson’s Brown Girl Dreaming (2014). While positioning itself in the field of cognitive literary studies and the archival study of creative writing processes, this article aims to generate insights on the reconstructive approach to memory, which considers episodic remembering as imagining the past. By transposing the study of the dynamics of writing processes, or genetic criticism, to children’s literature, I explore notes, mindmaps, manuscripts, and typescripts held at the archives of Dahl, Almond, and Woodson to chart how they imaginatively incorporate memories of their youth into their life writing. As such, this research informs understandings of the narrative genesis of the authors’ works, while drawing on the manifestations of their literary creativity in an attempt to broaden knowledge regarding memory and imagination.
Microstructural Characterization of Friction Stir Welds of Aluminum 6082 Produced with Bobbin Tool
Authors: Kopyściański Mateusz , Dymek Stanisław , Hamilton Carter , Węglowska Aleksandra , Kalemba-Rec Izabela
Published: September 2024

This study utilized a bobbin tool to friction stir weld aluminum 6082 workpieces under two sets of process parameters: a tool rotation speed of 280 rev/min with a weld velocity of 280 mm/min (280/280) and a tool rotation speed of 450 rev/min with a weld velocity of 450 mm/min (450/450). The weld microstructures were characterized through optical microscopy utilizing polarized light and through transmission electron microscopy (TEM) and scanning electron microscopy (SEM) coupled with chemical analysis by energy dispersive spectroscopy and electron back scatter diffraction. The microstructural studies were supplemented by hardness measurements (Vickers) performed on the same sections as the metallographic examinations. The produced weldments were free from cracks and any discontinuities. Fine, equiaxed grains that were several microns in size characterized the stir zones (SZs), and the advancing (AS) and retreating (RS) sides revealed distinct microstructural features. On the AS, the transition from the thermo-mechanically affected zone to the SZ was well defined and sharp, but on the RS, the transition appeared as a continuous, gradual change in microstructure. The lower weld energy (280/280) produced lower hardness in the stir zone than the higher energy weld (450/450), ~95 HV1 versus ~115 HV1; however, the 280/280 welds showed higher tensile strengths than the 450/450 welds, ~238 MPa as opposed to ~172 MPa. These behaviors in mechanical performance correlated with the temperature histories produced by each set of weld parameters in relation to the precipitation behavior of the alloy. The fracture characteristics of the weldments were notably different with the 450/450 sample fracturing in a quasi-brittle manner with slight plastic deformation and the 280/280 sample fracturing ductilely. A numerical simulation supported the investigation by elucidating the temperature and material flow behavior during the joining process.
Improvement of the Stability of Quantum-Dot Light Emitting Diodes Using Inorganic HfOx Hole Transport Layer
Authors: Yun Jung Min , Park Min Ho , Kim Yu Bin , Choi Min Jung , Kim Seunghwan , Yi Yeonjin , Park Soohyung , Kang Seong Jun
Published: September 2024

One of the major challenges in QLED research is improving the stability of the devices. In this study, we fabricated all inorganic quantum-dot light emitting diodes (QLEDs) using hafnium oxide (HfOx) as the hole transport layer (HTL), a material commonly used for insulator. Oxygen vacancies in HfOx create defect states below the Fermi level, providing a pathway for hole injection. The concentration of these oxygen vacancies can be controlled by the annealing temperature. We optimized the all-inorganic QLEDs with HfOx as the HTL by changing the annealing temperature. The optimized QLEDs with HfOx as the HTL showed a maximum luminance and current efficiency of 66,258 cd/m2 and 9.7 cd/A, respectively. The fabricated all-inorganic QLEDs exhibited remarkable stability, particularly when compared to devices using organic materials for the HTL. Under extended storage in ambient conditions, the all-inorganic device demonstrated a significantly enhanced operating lifetime (T50) of 5.5 h, which is 11 times longer than that of QLEDs using an organic HTL. These results indicate that the all-inorganic QLEDs structure, with ITO/MoO3/HfOx/QDs/ZnMgO/Al, exhibits superior stability compared to organic-inorganic hybrid QLEDs.
Toward Stabilizing the Keyhole in Laser Spot Welding of Aluminum: Numerical Analysis
Authors: SaediArdahaei Saeid , Pham Xuan-Tan
Published: September 2024

The inherent instability of laser welding, particularly keyhole instability, poses significant challenges in industrial applications, leading to defects such as porosities that compromise weld quality. Various forces act on the keyhole and molten pool during laser welding, influencing process stability. These forces are categorized into those promoting keyhole opening and penetration (e.g., recoil pressure) and those promoting keyhole collapse (e.g., surface tension, Darcy’s damping forces), increasing instability and defect likelihood. This paper provides a comprehensive instability analysis to uncover key factors affecting keyhole and process instability, presenting future avenues for improving laser welding stability. Using a novel numerical method for simulating laser spot welding on aluminum with COMSOL Multiphysics 5.6, we investigated the effect of laser pulse shaping on keyhole and process instability. Our analysis focused on keyhole morphology, fluid flow behaviour, and force analysis. The results indicated that the curvature effect, Marangoni effect, and Darcy’s damping force are primary contributors to instability, with the curvature effect and Darcy’s damping force being the most dominant. Additionally, erratic and high-velocity magnitudes induce intense fluid flow behaviour, exacerbating keyhole instability. Moreover, single/quadruple peak triangular and variant rectangular ramp-down pulse shapes produced the least instability, while multi-pulse rectangular shapes exhibited intense instability. It was found that combining triangular/rectangular pulse shapes can reduce force and keyhole instability by smoothing spontaneous force spikes, resulting in a more stabilized welding process. Controlling fluid flow and abrupt force changes with appropriate pulse shaping is key to defect-free welded products.
An Improved Mampel Model of the Non-Isothermal Crystallization Kinetics of Fiber-Reinforced Thermoplastic Composites
Authors: Song Zengrui , Ning Huiming , Liu Feng , Hu Ning , Gong Youkun
Published: September 2024

Fiber-reinforced thermoplastic composites (FRTPs) are gaining increasing attention and widespread use in engineering applications due to their high specific strength and stiffness, excellent toughness, and recyclability. The mechanical properties of these composites are closely tied to their crystallization process, making it crucial to accurately describe this phenomenon. Existing theoretical models for analyzing the non-isothermal crystallization of thermoplastic composites often face challenges relating to the complexity of obtaining multiple parameters and the difficulty of achieving a final relative crystallinity of 1. To address these issues, this paper introduces a novel functional form of the crystallization rate parameter K(T), tailored for engineering applications, and proposes an improved Mampel model. This model assumes K(T) to be zero before the onset of crystallization and also to be linearly dependent on temperature thereafter, ensuring that the final relative crystallinity reaches 1. The model requires only two easily accessible parameters: the initial crystallization temperature (Ts) and the linear slope (k). The simplicity of the model makes it particularly well suited to engineering applications. This provides a straightforward and effective tool for describing the non-isothermal crystallization kinetics of fiber-reinforced thermoplastic composites.
Fractional-Order Modeling of Heat and Moisture Transfer in Anisotropic Materials Using a Physics-Informed Neural Network
Authors: Sokolovskyy Yaroslav , Drozd Kazimierz , Samotii Tetiana , Boretska Iryna
Published: September 2024

Mathematical models of heat and moisture transfer for anisotropic materials, based on the use of the fractional calculus of integro-differentiation, are considered because such two-factor fractal models have not been proposed in the literature so far. The numerical implementation of mathematical models for determining changes in heat exchange and moisture exchange is based on the adaptation of the fractal neural network method, grounded in the physics of processes. A fractal physics-informed neural network architecture with a decoupled structure is proposed, based on loss functions informed by the physical process under study. Fractional differential formulas are applied to the expressions of non-integer operators, and finite difference schemes are developed for all components of the loss functions. A step-by-step method for network training is proposed. An algorithm for the implementation of the fractal physics-informed neural network is developed. The efficiency of the new method is substantiated by comparing the obtained numerical results with numerical approximation by finite differences and experimental data for particular cases.
Al(SO4)(OH)·5H2O Stemming from Complexation of Aluminum Sulfate with Water-Soluble Ternary Copolymer and further Stabilized by Silica Gel as Effective Admixtures for Enhanced Mortar Cementing
Authors: Song Zhiyuan , Bibi Zainab , Chaudhary Sidra , Jia Qinxiang , Li Xiaoyong , Sun Yang
Published: September 2024

A water-soluble ternary copolymer bearing carboxyl, sulfonic, and amide functional groups was synthesized using ammonium persulfate-catalyzed free radical polymerization in water, resulting in high monomer conversion. This copolymer was then complexed with aluminum sulfate, forming an admixture containing Al(SO4)(OH)·5H2O, which was subsequently combined with silica gel. Characterization revealed that the synthesized copolymer formed a large, thin membrane that covered both the aluminum compounds and the silica gel blocks. The introduction of this complex admixture, combining the copolymer and aluminum sulfate, not only reduced the setting times of the cement paste but also enhanced the mechanical strengths of the mortar compared to using aluminum sulfate alone. The complex admixture led to the formation of katoite, metajennite, and C3A (tricalcium aluminate) in the mortar, demonstrating significant linking effects, whereas pure aluminum sulfate could not completely transform C3S within 24 h. Further addition of silica gel to the complex admixture further shortened the setting times of the paste, slightly reduced compressive strength, but improved flexural strength compared to the initial complex admixture. The silicon components appeared to fill the micropores and mesopores of the mortar, accelerating cement setting and enhancing flexural strength, while slightly decreasing compressive strength. This study contributed to the development of new cementing accelerators with improved hardening properties.
Right Ventricular Longitudinal Strain-Related Indices in Acute Pulmonary Embolism
Authors: Tzourtzos Ioannis , Lakkas Lampros , Katsouras Christos S.
Published: September 2024

Pulmonary embolism (PE) is correlated with serious morbidity and mortality. Efforts have been made to establish and validate mortality predictive scores based mainly on clinical parameters. Patients with PE and traditional indices of echocardiographic right ventricular (RV) dysfunction or pressure overload have a higher probability of a worse outcome. During the last two decades, studies regarding the use of two-dimensional speckle-tracking echocardiography (2DSTE) and its derived indices in the setting of acute PE have been conducted. In this comprehensive review of the literature, we aimed to summarize these studies. Safe conclusions and comparisons among the reviewed studies are prone to statistical errors, mainly because the studies published were heterogenous in design, different 2DSTE-derived parameters were tested, and different clinical outcomes were used as endpoints. Nonetheless, RV strain indices and, more commonly, regional longitudinal strain of the RV free wall have shown a promising correlation with mortality, assisting in the differential diagnosis between PE and other acute or chronic disorders.
The Impact of Preoperative and Postoperative Nutritional Interventions on Treatment Outcomes and Quality of Life in Colorectal Cancer Patients—A Comprehensive Review
Authors: Piekarska Barbara , Prusisz Mateusz , Włodarczyk Marcin , Włodarczyk Jakub , Porc Mateusz , Bilińska Inez , Maryńczak Kasper , Dziki Łukasz
Published: September 2024

Colorectal cancer (CRC) is one of the most prevalent cancers worldwide, with high morbidity and mortality rates. Nutritional status has emerged as a significant factor influencing the prognosis and survival of CRC patients. This comprehensive literature review examines the role of nutritional support in improving treatment outcomes, including the efficacy of interventions, patient quality of life (QoL), and the modulation of inflammatory responses. The findings suggest that tailored nutritional interventions improve clinical outcomes, enhance QoL, and reduce treatment-related complications, particularly by attenuating inflammation. Furthermore, the review highlights the cost-effectiveness of nutritional strategies and identifies key methods to enhance patient compliance with dietary recommendations. In conclusion, integrating nutritional support into CRC treatment plans is crucial for optimizing clinical management and improving patient well-being.
Precision of Cup Positioning Using a Novel Computed Tomography Based Navigation System in Total Hip Arthroplasty
Authors: Nemati Hassan M. , Christensson Albin , Pettersson Andreas , Németh Gunnar , Flivik Gunnar
Published: September 2024

Background and Objectives: Navigation systems are designed to enhance surgical precision, improving patient outcomes and reducing the risk of implant misplacement. In this study, we have evaluated a novel orthopedic surgical platform that utilizes CT imaging with AI-based algorithms to automate several critical aspects of total hip arthroplasty. It contains three modules—preoperative planning, navigation during surgery, and follow-up analysis. The primary objective of the current study was to evaluate the precision of the navigation tool in cup placement, i.e., whether the information displayed for navigation correctly reflected the actual position of the implant. Materials and Methods: Surgery outcomes of 15 inter-rater measurements on human cadavers and 18 surgeries on patients who underwent total hip replacement using the navigation tool were analyzed. Results: In the inter-rater assessment, the mean errors were −0.31 ± 1.42° for anteversion, 1.06 ± 1.73° for inclination, and −0.94 ± 1.76 mm for cup position depth. In patients’ surgeries, the mean errors were −0.07 ± 2.72° for anteversion, −0.2 ± 0.86° for inclination, and 0.28 ± 0.78 mm for cup depth. Conclusions: The navigation tool offers intra-operative guidance on notable precision in cup placement, thereby effectively mitigating the risk of cup malpositioning outside the patient-specific safe zone.
Methicillin-Resistant Staphylococcus aureus among Students: Nasal Carriage Rate, Contributing Factors, and Antimicrobial Susceptibility
Authors: Taqveem Ahsen , Rasool Muhammad Hidayat , Aslam Bilal , Mujahid Fatima , Ibrar Azalfah , Ejaz Hasan , Abdalla Abualgasim Elgaili , Alruwaili Yasir , Alruwaili Muharib , Abosalif Khalid , Nawaz Zeeshan , Khurshid Mohsin
Published: September 2024

Background and Objectives: Staphylococcus aureus is a prominent component of the human flora; however, it can cause various pathological conditions. The emergence of methicillin-resistant S. aureus (MR-SA) has been significantly influenced by the overuse and inappropriate administration of antibiotics. The frequency of MR-SA nasal colonization among healthcare workers (HCWs) is increasing, and MR-SA is not restricted to hospital settings, with a notable rise in infections among individuals unrelated to HCWs. This study aimed to assess the prevalence of S. aureus nasal carriage among students at Government College University Faisalabad (GCUF), University of Agriculture Faisalabad (UAF), a Government School (GS), and a Private School (PS) to characterize the phenotypic traits of isolates and evaluate antimicrobial resistance profiles. Materials and Methods: A total of 1200 nasal swabs were inoculated on blood and mannitol salt agar, followed by phenotypic identification of S. aureus and MR-SA using biochemical tests. Antimicrobial susceptibility testing was conducted via the Kirby–Bauer disk diffusion method, and minimum inhibitory concentration (MIC) determination was performed using the broth dilution method. Additionally, nuc and mecA gene amplification through PCR aided in isolate identification. Results: The results revealed that 14% (168) of students harbored S. aureus in their nasal cavities, with 8.5% (102) carrying methicillin-sensitive S. aureus (MSSA) and 5.5% (66) carrying MR-SA. Male students exhibited higher S. aureus (57.7%) and MR-SA (21.4%) prevalence compared to females (42.3% and 17.9%, respectively). Urban students showed a higher S. aureus prevalence (54.2%), while rural students exhibited a higher MR-SA rate (22%). Overall, 80.3% of S. aureus isolates displayed resistance to erythromycin followed by fluoroquinolones (47.6%) and clindamycin (42.2%). All the S. aureus isolates, including MR-SA, remained susceptible to vancomycin and linezolid. PCR results revealed that 95.5% (63) of MR-SA isolates carried the mecA gene. Conclusions: The high prevalence of multi-drug-resistant (MDR) S. aureus raises significant public health concerns, with educational institutions potentially serving as reservoirs for bacterial transmission. The improper use of antibiotics contributes to bacterial resistance and increased infection rates. It is crucial to implement measures to prevent antibiotic misuse and develop comprehensive strategies within educational settings to effectively combat S. aureus and MR-SA prevalence.
Hyperglycosylation as an Indicator of Aging in the Bone Metabolome of Oryzias latipes
Authors: Labeille Remi O. , Elliott Justin , Abdulla Hussain , Seemann Frauke
Published: September 2024

Chronological aging of bone tissues is a multi-faceted process that involves a complex interplay of cellular, biochemical, and molecular mechanisms. Metabolites play a crucial role for bone homeostasis, and a changed metabolome is indicative for bone aging, although bone metabolomics are currently understudied. The vertebral bone metabolome of the model fish Japanese medaka (Oryzias latipes) was employed to identify sex-specific markers of bone aging. 265 and 213 metabolites were differently expressed in 8-month-old vs. 3-month-old female and male fish, respectively. The untargeted metabolomics pathway enrichment analysis indicated a sex-independent increased hyperglycosylation in 8-month-old individuals. The upregulated glycosylation pathways included glycosphingolipids, glycosylphosphatidylinositol anchors, O-glycans, and N-glycans. UDP-sugars and sialic acid were found to be major drivers in regulating glycosylation pathways and metabolic flux. The data indicate a disruption of protein processing at the endoplasmic reticulum and changes in O-glycan biosynthesis. Dysregulation of glycosylation, particularly through the hexosamine biosynthetic pathway, may contribute to bone aging and age-related bone loss. The results warrant further investigation into the functional involvement of increased glycosylation in bone aging. The potential of glycan-based biomarkers as early warning systems for bone aging should be explored and would aid in an advanced understanding of the progression of bone diseases such as osteoporosis.
Euler Force-Driven Siphon Valve Control for Precise Sequential Release in Centrifugal Microfluidic Chips
Authors: Lu Yu , Shen Hao , Chen Guangyao , Yang Kaichao , Zhang Jing , Xue Liwei , Ou Jianzhen , Chen Liguo
Published: September 2024

Controlling the fluids in centrifugal microfluidic chips for precise sequential release is critical for multi-step reactions and immunoassays. Currently, the traditional methods of liquid sequential release mainly rely on various types of microvalves, which face the problems of complex operation and high costs. Here, this work presents a method for driving liquid release using the Euler force. Under continuous acceleration and deceleration, the centrifugal and Euler forces can transfer the liquid from the sample chamber to the collection chamber. The liquid sequential release mechanism based on the Euler force was analyzed, which showed that the angular acceleration is key to the liquid release. Then, the geometrical parameters affecting the angular acceleration of complete release were investigated and simulated. Finally, based on the relationship between the geometrical parameters of the connecting channels and the angular acceleration of complete release, a simple and precise sequential release structure was designed, which allowed for a sequential and stable transfer of the liquid into the reaction chamber. The results showed that the proposed method is capable of transferring liquid, and its simple structure, low manufacturing cost, and ease of operation enable precise sequential liquid release in centrifugal microfluidic platforms.
Application of UHPLC-QqQ-MS/MS Method for Quantification of Beta-Adrenergic Blocking Agents (β-Blockers) in Human Postmortem Specimens
Authors: Szpot Paweł , Tusiewicz Kaja , Wachełko Olga , Zawadzki Marcin
Published: September 2024

Betablockers are one of the most frequently used medications in cardiology. They can lead to fatal drops in blood pressure and heart rhythm disturbances. Death is functional, and poisoning with this group of drugs can be difficult to detect. The liquid–liquid extraction (LLE) method developed using ethyl acetate at pH 9 successfully identified 18 β-blockers in human blood. The method’s limit of quantification (LOQ) was in the range of 0.1 to 0.5 ng/mL. No carryover of substances between samples was detected, and no interfering ion current signals were observed in the biological samples at the retention times of the compounds or internal standards. All compounds had a coefficient of determination (R2) above 0.995. Intraday and interday precision (RSD%) and accuracy (RE%) for low and high QC levels were within 1.7–12.3% and −14.4 to 14.1%, respectively. Very good recovery (80.0–119.6%) and matrix effect (±20.0%) values were achieved for all compounds. In addition, fragmentation spectra were collected for all the examined substances, and high-resolution spectra were presented for landiolol and metipranolol, because they are not available in commercial HRMS spectra databases. The developed method was applied in authentic postmortem samples.
1-Acetyl-β-Carboline from a Jeju Gotjawal Strain Lentzea sp. JNUCC 0626 and Its Melanogenic Stimulating Activity in B16F10 Melanoma Cells
Authors: Hyun Kyung-A , Xu Yang , Boo Kyung-Hwan , Hyun Chang-Gu
Published: September 2024

The genus Lentzea is a prolific source of bioactive and structurally diverse secondary metabolites. We isolated a novel strain, Lentzea sp. JNUCC 0626, from Hwasun Gotjawal on Jeju Island, Korea. Based on 16S rRNA partial gene sequence analysis, strain JNUCC 0626 is closely related to Lentzea isolaginshaensis NX62 (99.41% similarity), Lentzea pudingi DHS C021 (99.31%), and Lentzea cavernae SYSU K10001 (99.26%). From the fermentation broth of JNUCC 0626, we isolated 1-acetyl-β-carboline, whose structure was established using IR, HR-ESI-MS, and 1D- and 2D-NMR techniques. 1-acetyl-β-carboline was found to activate melanogenesis in mouse B16F10 cells without cytotoxicity at concentrations up to 50 μM. At this concentration, the compound increased melanin content by 27.44% and tyrosinase activity by 240.64% compared to the control, by upregulating key melanogenic enzymes, including tyrosinase, TRP-1, TRP-2, and microphthalmia-associated transcription factor (MITF), a central regulator of melanogenesis. In addition, 1-acetyl-β-carboline significantly inhibited ERK phosphorylation, reducing it by 20.79% at a concentration of 12.5 μM and by 25.63% at 25 μM. This inhibition supports the hypothesis that 1-acetyl-β-carboline enhances melanin synthesis by upregulating MITF and melanogenic enzymes via the ERK signaling pathway. This study aimed to isolate and identify 1-acetyl-β-carboline from a novel strain of Lentzea sp. JNUCC 0626, discovered in Gotjawal, Jeju Island, and to evaluate its effect on melanin production in B16F10 melanoma cells. Skin irritation tests on 32 subjects confirmed its safety for topical use, and the findings suggest that 1-acetyl-β-carboline, which enhances melanogenesis without cytotoxicity, holds promise as a therapeutic agent for hypopigmentation-related conditions or as a cosmetic ingredient.
Pushing at the Boundaries of Pterin Chemistry
Authors: Correia Jevy V. , Bandaru Siva S. M. , Schulzke Carola
Published: September 2024

Pterins are molecules of substantial interest as they occur in nature in a number of forms with quite distinct and often indispensable roles. Chemically, the synthesis of the principle pterin scaffold is comparably simple, while the insolubility of the pterin building block renders synthetic derivatization extremely difficult. When aiming at modeling naturally occurring pterins of extended chemical structure, this is a considerable problem. A notable set of strategies was developed in the course of the present study, which are able to overcome the lack of reactivity of the pterin backbone. These include a strategic choice regarding protection groups, uncommon chemical transformation, ball milling and combinations thereof. Some novel pterins with quite distinct substitution motifs were successfully synthesized and characterized by spectroscopic and spectrometric analyses as well as single-crystal structural analyses for three of them.
Advancing Bioanalytical Method Validation: A Comprehensive ICH M10 Approach for Validating LC–MS/MS to Quantify Fluoxetine in Human Plasma and Its Application in Pharmacokinetic Studies
Authors: El Orche Aimen , Cheikh Amine , El Khabbaz Choukri , Bouchafra Houda , Faouzi My El Abbes , Cherrah Yahya , Ansari Siddique Akber , Alkahtani Hamad M. , Ansari Shoeb Anwar , Bouatia Mustapha
Published: September 2024

A fast and sample cleanup approach for fluoxetine in human plasma was developed using protein precipitation coupled with LC–MS-MS. Samples were treated with methanol prior to LC–MS-MS analysis. Chromatographic separation was performed on a reverse phase column with an isocratic mobile phase of methanol and 10 mM ammonium formate pH acidified with formic acid (80:20, v/v) at a flow rate of 0.2 mL/min. The run time was 4 min. Mass parameters were optimized to monitor transitions at m/z [M + H]+ 310 > > 148 for fluoxetine and m/z [M + H]+ 315.1 > > 153 for fluoxetine-d5 as an internal standard. The lower limit of quantification and the dynamic range were 0.25 and 0.25–50 ng/mL, respectively. Linearity was good for intra-day and inter-day validations (R2 = 0.999). The matrix effect was acceptable with CV% < 15 and accuracy% < 15. The hemolytic effect was negligible. Fluoxetine was stable in human plasma for 48 h at room temperature (25 °C), for 12 months frozen at −25 °C, for 48 h in an auto-sampler at 6 °C, and for three freeze/thaw cycles. The validated method was applied in a pharmacokinetic study to determine the concentration of fluoxetine in plasma samples. The study provides a fast and simple bioanalytical method for routine analysis and may be particularly useful for bioequivalence studies. The method was successfully applied to a pharmacokinetic study of fixed-dose fluoxetine in nine healthy volunteers.
The Effect of Different Surfactants and Polyelectrolytes on Nano-Vesiculation of Artificial and Cellular Membranes
Authors: Zagorc Urška , Božič Darja , Arrigler Vesna , Medoš Žiga , Hočevar Matej , Romolo Anna , Kralj-Iglič Veronika , Kogej Ksenija
Published: September 2024

Nano- and micro-sized vesicular and colloidal structures mediate cell–cell communication. They are important players in the physiology of plants, animals, and humans, and are a subject of increasing interest. We investigated the effect of three surfactants, N-cetylpyridinium chloride (CPC), sodium dodecyl sulfate (SDS), and Triton X-100 (TX100), and two anionic polyelectrolytes, sodium polystyrene sulfonate (NaPSS) and sodium polymethacrylate (NaPMA), on nanoliposomes. In addition, the effect of SDS and TX100 on selected biological membranes (erythrocytes and microalgae) was investigated. The liposomes were produced by extrusion and evaluated by microcalorimetry and light scattering, based on the total intensity of the scattered light (Itot), hydrodynamic radius (Rh), radius of gyration (Rg), shape parameter p (=Rh/Rg,0), and polydispersity index. The EPs shed from erythrocytes and microalgae Dunaliella tertiolecta and Phaeodactylum tricornutum were visualized by scanning electron microscopy (SEM) and analyzed by flow cytometry (FCM). The Rh and Itot values in POPC liposome suspensions with added CPC, SDS, and TX100 were roughly constant up to the respective critical micelle concentrations (CMCs) of the surfactants. At higher compound concentrations, Itot dropped towards zero, whereas Rh increased to values higher than in pure POPC suspensions (Rh ≈ 60–70 nm), indicating the disintegration of liposomes and formation of larger particles, i.e., various POPC–S aggregates. Nanoliposomes were stable upon the addition of NaPSS and NaPMA, as indicated by the constant Rh and Itot values. The interaction of CPC, SDS, or TX100 with liposomes was exothermic, while there were no measurable heat effects with NaPSS or NaPMA. The SDS and TX100 increased the number density of EPs several-fold in erythrocyte suspensions and up to 30-fold in the conditioned media of Dunaliella tertiolecta at the expense of the number density of cells, which decreased to less than 5% in erythrocytes and several-fold in Dunaliella tertiolecta. The SDS and TX100 did not affect the number density of the microalgae Phaeodactylum tricornutum, while the number density of EPs was lower in the conditioned media than in the control, but increased several-fold in a concentration-dependent manner. Our results indicate that amphiphilic molecules need to be organized in nanosized particles to match the local curvature of the membrane for facilitated uptake. To pursue this hypothesis, other surfactants and biological membranes should be studied in the future for more general conclusions.