bluuebunny/crossref_metadata_2025 huggingface dataset:
Cancer Stem Cells and the Renin–Angiotensin System in the Tumor Microenvironment of Melanoma: Implications on Current Therapies
Authors: Kilmister Ethan J. , Tan Swee T.
Published: February 2025

Multiple signaling pathways are dysregulated in melanoma, notably the Ras/RAF/MAPK/ERK and PI3K/AKT/mTOR pathways, which can be targeted therapeutically. The high immunogenicity of melanoma has been exploited using checkpoint inhibitors. Whilst targeted therapies and immune checkpoint inhibitors have improved the survival of patients with advanced melanoma, treatment resistance, their side effect profiles, and the prohibitive cost remain a challenge, and the survival outcomes remain suboptimal. Treatment resistance has been attributed to the presence of cancer stem cells (CSCs), a small subpopulation of pluripotent, highly tumorigenic cells proposed to drive cancer progression, recurrence, metastasis, and treatment resistance. CSCs reside within the tumor microenvironment (TME) regulated by the immune system, and the paracrine renin–angiotensin system, which is expressed in many cancer types, including melanoma. This narrative review discusses the role of CSCs and the paracrine renin–angiotensin system in the melanoma TME, and its implications on the current treatment of advanced melanoma with targeted therapy and immune checkpoint blockers. It also highlights the regulation of the Ras/RAF/MAPK/ERK and PI3K/AKT/mTOR pathways by the renin–angiotensin system via pro-renin receptors, and how this may relate to CSCs and treatment resistance, underscoring the potential for improving the efficacy of targeted therapy and immunotherapy by concurrently modulating the renin–angiotensin system.
Programmable LED Array for Evaluating Artificial Light Sources to Improve Insect Trapping
Authors: Paryavi Mohsen , Weiser Keith , Melzer Michael , Crook Damon , Ramadugu Chandrika , Jenkins Daniel M.
Published: February 2025

We developed a programmable LED array to evaluate different wavelength illumination (UV, blue, green, yellow, amber, and red) and modulation schemes to improve catch rates in insect traps. The device can communicate through Bluetooth® with a simple Android app to update the operational settings to facilitate field experiments, including which LEDs to operate, when to operate (always, night only, or predefined intervals after sunset and/or before sunrise), and to change the LED intensities/modulation during operation. We used the devices to evaluate different wavelengths to improve catches in traps for coconut rhinoceros beetle (CRB; Oryctes rhinoceros Linnaeus) in the field, as well as to evaluate lighting preferences of Asian citrus psyllid (ACP; Diaphorina citri Kuwayama). In both cases, insects were most strongly attracted to constant UV illumination. However, CRB avoided traps with any “visible” wavelength LEDs placed in panels of traps, while ACP was moderately attracted to blue, yellow, and amber. For CRB, UV illumination of cups at the bottom of panel traps reduced catch rates compared to UV illumination higher in the panels of traps, consistent with observations of dorsal orientation towards light observed by other researchers in nocturnal beetles and moths. Finally, we provide some hardware design recommendations to improve the energy efficiency of similar devices for more widespread deployment in insect traps and for controlling the LEDs to evaluate the effects of intensity and modulation with minimal pulsing, which our observations suggest may result in insects avoiding traps.
Assessment of Scalable Fractionation Methodologies to Produce Concentrated Lauric Acid from Black Soldier Fly (Hermetia illucens) Larvae Fat
Authors: Vázquez Luis , Reyero Carlota , Hurtado-Ribeira Raúl , Villanueva-Bermejo David , Belinchón Alejandro , Palomar José , Fornari Tiziana , Martín Diana
Published: February 2025

In the present study, different methodologies with potential scalability and environmental friendliness, such as winterization, supercritical fluid extraction, and multistage distillation, were evaluated for lauric acid concentration. In all cases, to facilitate fractionation, the transformation of triacylglycerols into free fatty acids or fatty acid ethyl esters was required as a previous step. For the winterization experimental assays, the amount and type of solvent was studied, resulting in a product containing ~65% lauric acid with a recovery of ~81% using a 1:10 oil-to-solvent ratio with hexane. On the other hand, the experimental extraction with supercritical carbon dioxide in a counter current packed column at 55 °C, 115 bar, and 70 g CO2/min, resulted in a product composed of ~80% lauric acid as ethyl ester with a recovery of ~85%. Finally, flash and multistage distillation were analysed using process simulation (Aspen Plus V14), demonstrating that this methodology can achieve 80% recovery with high purity (lauric acid: 96.7%; ethyl laurate: 97.4%), but a high vacuum is required to prevent thermal degradation of the product (lauric acid: 0.2 mbar; ethyl laurate: 1.1 mbar). Overall, the employed methodologies proved highly efficient in concentrating lauric acid, yielding a product of commercial interest and high added value.
Clinical Decision Support for Patient Cases with Asymptomatic Carotid Artery Stenosis Using AI Models and Electronic Medical Records
Authors: Madison Mackenzie , Luo Xiao , Silvey Jackson , Brenner Robert , Gannamaneni Kartik , Sawchuk Alan P.
Published: February 2025

An artificial intelligence (AI) analysis of electronic medical records (EMRs) was performed to analyze the differences between patients with carotid stenosis who developed symptomatic disease and those who remained asymptomatic. The EMRs of 872 patients who underwent a carotid endarterectomy between 2009 and 2022 were analyzed with AI. This included 408 patients who had carotid intervention for symptomatic carotid disease and 464 patients for asymptomatic, >70% stenosis. By analyzing the EMRs, the Support Vector Machine achieved the highest sensitivity at 0.626 for predicting which of these patients would go on to develop a stroke or TIA. Random Forest had the highest specificity at 0.906. The risk for stroke in patients with carotid stenosis was a balance between optimum medical treatment and the underlying disease processes. Risk factors for developing symptomatic carotid disease included elevated glucose, chronic kidney disease, hyperlipidemia, and current or recent smoking, while protective factors included cardiovascular agents, antihypertensives, and beta blockers. An AI review of EMRs can help determine which patients with carotid stenosis are more likely to develop a stroke to assist with decision making as to whether to proceed with intervention or to demonstrate and encourage reduced stroke risk with risk factor modification.
Urgent Endoscopic Biliary Procedures: “Run Like the Wind”?
Authors: Lodato Francesca , Landi Stefano , Bassi Marco , Ghersi Stefania , Cennamo Vincenzo
Published: February 2025

Emergency endoscopy is an activity that must be guaranteed 7 days a week and 24 h a day. The pathologies of endoscopic interest that require emergency intervention are mainly hemorrhages of the upper digestive tract, the removal of foreign bodies, and the ingestion of caustics. The emergency endoscopist must therefore be experienced in the management of these pathologies. Nowadays, however, we know that even some biliary tract pathologies must be managed within a variable period between 12 and 72 h, in particular acute cholangitis (Ach), acute biliary pancreatitis (ABP), biliary duct leaks (BDLs), and acute cholecystitis (AC). If, on one hand, there is little awareness among doctors about which pathologies of the biliary tract really deserve urgent treatment, on the other, the international guidelines, although not uniformly, have acquired the results of the studies and have clarified that only severe Ach should be treated within 12 h; in other cases, endoscopic treatment can be delayed up to 72 h according to the specific condition. This obviously has a significant organizational implication, as not all endoscopists have training in biliary tract endoscopy, and guaranteeing the availability of a biliary endoscopist 24/7 may be incompatible with respecting the working hours of individual professionals. This review aims to evaluate which pathologies of the biliary tract really require an endoscopic approach in emergency or urgency and the organizational consequences that this can determine. Based on the guidelines, we can conclude that a daytime availability for urgent biliary tract procedures 7 days a week should be provided for the management of severe ACh. Patients with ABP, AC unfit for surgery, and not responsive to medical therapy or BDLs can be treated over a longer period, allowing its scheduling on the first available day of the week.
Quality of Life in Patients with Inflammatory Bowel Diseases Is Associated with Affective Temperament Traits: A Cross-Sectional Survey of a Polish Clinical Sample
Authors: Mokrowiecka Anna , Kopczynska Magdalena , Borkowska Alina , Malecka-Wojciesko Ewa
Published: February 2025

Background: Affective temperaments can be considered the subclinical manifestations of affective and stress-related disorders, which could have a relationship with many chronic diseases. The purpose of this study was to explore the influence of affective temperament traits on disease-specific quality of life in patients with ulcerative colitis (UC) and Crohn’s disease (CD), two types of inflammatory bowel disease (IBD). Methods: The patients completed the Temperament Evaluation of the Memphis, Pisa, Paris, San Diego-Auto-questionnaire (TEMPS-A), which is the 110-item self-reported assessment for five dimensions of temperament: depressive, cyclothymic, hyperthymic, irritable, and anxious, already validated in Poland. For comprehensive assessment of the health-related quality of life (HRQoL), the Inflammatory Bowel Disease Questionnaire (IBDQ) was applied. Results: The study included 116 patients with IBD-61 with UC and 55 with CD, with mean age 43 years, in remission, without serious mental or medical co-morbidities. Mean HRQoL in patients with IBD was poor and mean IBDQ scores were 145, despite clinical remission. A significant negative correlation was found between HRQoL in all the IBDQ domains and TEMPS-A traits: D (p < 0.001), C (p < 0.01), I (p < 0.05), and A (p < 0.001). No significant correlation between hyperthymic temperament and IBDQ scores was found. Conclusions: Poor quality of life in IBD could be associated with affective temperament. Affective temperament traits should be taken into account when identifying patients at risk of worse IBD course and further introducing personalized therapy.
Analyzing Information Exchange in Parkinson’s Disease via Eigenvector Centrality: A Source-Level Magnetoencephalography Study
Authors: Ambrosanio Michele , Troisi Lopez Emahnuel , Autorino Maria Maddalena , Franceschini Stefano , De Micco Rosa , Tessitore Alessandro , Vettoliere Antonio , Granata Carmine , Sorrentino Giuseppe , Sorrentino Pierpaolo , Baselice Fabio
Published: February 2025

Background: Parkinson’s disease (PD) is a progressive neurodegenerative disorder that manifests through motor and non-motor symptoms. Understanding the alterations in brain connectivity associated with PD remains a challenge that is crucial for enhancing diagnosis and clinical management. Methods: This study utilized Magnetoencephalography (MEG) to investigate brain connectivity in PD patients compared to healthy controls (HCs) by applying eigenvector centrality (EC) measures across different frequency bands. Results: Our findings revealed significant differences in EC between PD patients and HCs in the alpha (8–12 Hz) and beta (13–30 Hz) frequency bands. To go into further detail, in the alpha frequency band, PD patients in the frontal lobe showed higher EC values compared to HCs. Additionally, we found statistically significant correlations between EC measures and clinical impairment scores (UPDRS-III). Conclusions: The proposed results suggest that MEG-derived EC measures can reveal important alterations in brain connectivity in PD, potentially serving as biomarkers for disease severity.
Analysis of Early Post-Radiation Surgical Management of Metastatic Spinal Tumors
Authors: Seok Sang Yun , Cho Jae Hwan , Lee Hyung Rae , Park Jae Woo , Park Jin Hoon , Lee Dong-Ho , Hwang Chang Ju , Park Sehan
Published: February 2025

Background/Objectives: Radiotherapy is one of the various treatment options for patients with metastatic spinal tumors (MST). However, it is difficult to say that this is definitely an optimal treatment for MST, and there are several patients who need surgical treatment because pain or neurologic deficits occur even after radiotherapy. Therefore, this study aimed to analyze which patients received early operative treatment after radiotherapy. Methods: We included 81 patients who underwent decompression and fusion surgery after radiotherapy for MST. Patients who underwent surgery within 6 months after radiotherapy were classified as the early operation group (group E, n = 47), while surgery cases after 6 months after radiotherapy were assigned to the late operation group (group L, n = 34). Risk factor analysis using multivariate regression analysis for early operative treatment after radiotherapy was performed. Also, we analyzed the period from radiotherapy to surgery according to the Bilsky grade. Results: In multivariate analysis, pathologic fractures and semirigid (thoracic) lesions were more frequent in group E than group L (adjusted odds ratio, 4.282, 10.524; p = 0.001, 0.039). In subgroup analysis, there was a difference in the period from radiotherapy to surgery in Bilsky grades above 2 than Bilsky grade 1 (grade 1, 13.6 ± 11.4 months, grade 2, 6.9 ± 6.8 months, grade 3, 6.6 ± 7.5 months; grade 1 vs. 2, p = 0.049, grade 1 vs. 3, p = 0.047). Conclusions: Although the information in this study may only be limited to patients who underwent surgery, early operative treatment after radiotherapy is highly likely for patients with MST accompanied by a Bilsky grade above 2, pathologic fracture and thoracic lesion. In these patients, surgical treatment could be considered as the primary treatment.
A Longitudinal Cohort Assessing the Carotid Intima-Media Thickness Progression and Cardiovascular Risk Factors in a Rural Black South African Community
Authors: Mashaba Given R. , Phoswa Wendy N. , Lebelo Sogolo L. , Choma Solomon S. R. , Maimela Eric , Mokgalaboni Kabelo
Published: February 2025

Background: Diabetes mellitus [DM) is a fast-increasing non-communicable disease in South Africa, with a prevalence of 11.3%. The present study aimed to longitudinally investigate the association of carotid intima-media thickness [CIMT) progression and cardiovascular risk factors in the T2DM and non-DM rural black population of South Africa. Methods: This population-based retrospective cohort study was conducted in the Dikgale Mamabolo Mothiba Surveillance area between 2014 and 2023 by the Africa Wits INDEPTH Partnership for Genomic Research (AWI-Gen). The IBM Statistical Package for the Social Sciences version 27 was used to analyze data. The paired T-test was used to determine the mean differences between baseline and follow-up. Longitudinal estimates of the association of CIMT with CVD risk factors in the T2DM and non-DM groups were analyzed using linear mixed models. Results: The baseline mean age was 51.64 years. There was a significant increase in CIMT (left and mean CIMT), low-density lipoprotein-cholesterol (LDL-C), systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse rate in the T2DM and non-DM groups. In the T2DM group, there was a strong significant association between age (2.20 mm), LDL-C (4.30 mm), SBP (4.57 mm), and waist/hip ratio (0.24 mm) with CIMT progression. The non-DM group revealed a significant association between LDL-C (0.001 mm), SBP (1.41 mm), and CIMT progression. Conclusion: CIMT was associated with other main CVD-related risk factors (age, LDL-C, LDL-C/HDL-C ratio, TC/HDL-C ratio, waist/hip ratio, and SBP). CIMT progression was more pronounced in the T2DM group than non-DM, suggesting a higher risk of atherosclerosis and cardiovascular complications in T2DM individuals.
Immune Checkpoint Inhibitor in Hepatocellular Carcinoma: Response Rates, Adverse Events, and Predictors of Response
Authors: Swaroop Shekhar , Biswas Sagnik , Mehta Shubham , Aggarwal Arnav , Arora Umang , Agarwal Samagra , Chavan Amitkumar , Nayak Baibaswata , Shalimar
Published: February 2025

Background/Objectives: Hepatocellular carcinoma (HCC) is the most common primary hepatic malignancy. Barcelona Clinic Liver Cancer (BCLC) guidelines recommend antiangiogenic agents with immune checkpoint inhibitors as first-line therapy for advanced HCC. We present our experience of treating HCC patients with Atezolizumab–Bevacizumab, their response rates, adverse events, survival, and response and survival predictors. Methods: This retrospective analysis included HCC patients diagnosed at All India Institute of Medical Sciences, New Delhi, India between July 2021 and April 2024 and receiving at least one dose of Atezolizumab–Bevacizumab. The primary outcome was overall response rate (ORR), comprising complete response (CR) and partial response (PR), as per mRECIST criteria. Secondary outcomes were overall survival (OS), progression-free survival (PFS), and predictors of response and survival. Results: Sixty-three patients were analyzed {mean age: 56.0 + 12.7 years; 82.5% males}. Forty-three (68.2%) patients had BCLC stage C HCC. Thirty-five (55.5%) patients belonged to Child–Pugh class A and 28 (44.5%) belonged to Child–Pugh class B. At 1 year, OS was 39% and PFS was 27%. Among 43 patients with data for radiological response, ORR was 48.8% (CR—9.3% and PR—39.5%) and DCR was 62.7% with stable disease (SD) in 13.9% of patients. PD occurred in 37.2% of patients. AFP response predicted radiological response, while Child–Pugh class and BCLC stage predicted survival. Adverse events were reported in 49.2% of patients. Conclusions: Our study shows slightly lower survival than previous studies with Child–Pugh class being the most important determinant of survival. AFP response predicts radiological response and not survival.
Comparative Analysis of the Alternative Energy: Case of Reducing GHG Emissions of Estonian Pilot Fleet
Authors: Otsason Riina , Laasma Andres , Gülmez Yiǧit , Kotta Jonne , Tapaninen Ulla
Published: February 2025

The FuelEU Maritime Regulation, part of the European Union’s (EU’s) Fit for 55 initiative, aims to achieve significant reductions in greenhouse gas (GHG) emissions within the maritime sector. This study assesses the feasibility of alternative fuels for the Estonian pilot fleet using a Well-to-Wake (WtW) life cycle assessment (LCA) methodology. Operational data from 18 vessels, sourced from the Estonian State Fleet’s records, were analyzed, including technical specifications, fuel consumption patterns, and operational scenarios. The study focused on marine diesel oil (MDO), biomethane, hydrogen, biodiesel, ammonia, and hydrotreated vegetable oil (HVO), each presenting distinct trade-offs. Biomethane achieved a 59% GHG emissions reduction but required a volumetric storage capacity up to 353% higher compared to MDO. Biodiesel reduced GHG emissions by 41.2%, offering moderate compatibility with existing systems while requiring up to 23% larger storage volumes. HVO demonstrated a 43.6% emissions reduction with seamless integration into existing marine engines. Ammonia showed strong potential for long-term decarbonization, but its adoption is hindered by low energy density and complex storage requirements. This research underscores the importance of a holistic evaluation of alternative fuels, taking into account technical, economic, and environmental factors specific to regional and operational contexts. The findings offer a quantitative basis for policymakers and maritime stakeholders to develop effective decarbonization strategies for the Baltic Sea region.
Phosphodegrons in Health and Disease: From Cellular Homeostasis to Therapeutic Potential
Authors: Nakagawa Tadashi , Nakagawa Makiko
Published: February 2025

Phosphodegrons are critical motifs that play a pivotal role in the regulation of protein stability and function via phosphorylation-dependent signaling pathways. These motifs serve as recognition elements for ubiquitin ligases, facilitating the targeted degradation of proteins. By modulating key cellular processes such as cell cycle progression, DNA repair, and apoptosis, phosphodegrons are essential for maintaining cellular homeostasis. Dysregulation of phosphodegrons has been implicated in a wide range of diseases, including cancer and neurodegenerative disorders, highlighting their potential as therapeutic targets. This review provides an overview of phosphodegron functions along with their biological significance in health and disease. Additionally, we discuss current methodologies for studying phosphodegrons and explore emerging trends in their identification and therapeutic targeting. By synthesizing recent advances in the field, this article aims to offer insights into the future directions and challenges in phosphodegron research, ultimately underscoring their importance in cellular regulation and disease pathology.
Influence of Nutrient Medium Components on In Vitro Tuberization of Solanum tuberosum L. and Subsequent Minituber Production in Aeroponic and Greenhouse Conditions
Authors: Melyan Gayane Hrant , Martirosyan Yuri Tsatur , Sahakyan Aghvan Jumshud , Sayadyan Hovik Yakshibek , Melikyan Andreas Shmavon , Barseghyan Andranik Hakob , Vardanyan Arayik Sajan , Martirosyan Hamlet Sargis , Harutyunyan Margarita Gurgen , Mkrtchyan Anzhela Liparit , Hakobjanyan Inna Lendrush , Dangyan Kima Seryozha , Terteryan Khachik Harut , Khazaryan Kamo Atam , Galstyan Meruzhan Haykaram
Published: February 2025

Potatoes, a vital global food crop, have shown remarkable adaptability, significantly contributing to food security. Technological advancements now enable their cultivation from soil-based systems to liquid synthetic nutrient media, even in artificial closed environments without natural light or fertile soil. This study examined the effects of Benzylaminopurine (BAP) and Kinetin (Kin) at concentrations ranging from 0 to 5 mg/L and sucrose concentrations ranging from 20 to 120 g/L on in vitro tuberization, focusing on microtuber size, weight, and tuberization rate. Nodal segments from virus-free ‘Red Scarlet’ in vitro potato plantlets were used as explants. These explants were cultured on Murashige and Skoog (MS) medium solidified with 0.5% agar. The study also compared minituber production efficiency under soil-based greenhouse and aeroponic conditions. The highest in vitro potato tuberization rate (90%) was achieved with 80 g/L sucrose and 3.0 mg/L BAP. After induction, virus-free microtubers were transferred to both greenhouse conditions and aeroponic systems for further assessment of minituber production and biochemical composition. These findings demonstrate the potential of aeroponics as a superior method for producing high-quality, pathogen-free minitubers. Aeroponics resulted in significantly higher minituber yields compared to soil-based greenhouse systems, offering a scalable and efficient solution for seed production.
Advances in Multitarget Therapeutic Approaches for Immune-Mediated Glomerular Diseases
Authors: Voroneanu Luminita , Covic Andreea , Tesar Vladimir , Kanbay Mehmet , Covic Adrian
Published: February 2025

Glomerulonephritis (GN) encompasses a diverse group of immune-mediated diseases that damage the glomerular component of the nephron. While kidney biopsy remains the gold standard for diagnosis, it often fails to provide adequate insight into the underlying etiology of GN. Current classification systems have limited our understanding of the disease’s pathophysiology and hinder the development of targeted therapies. Immunosuppressive treatments, such as glucocorticoids, calcineurin inhibitors, cyclophosphamide, and rituximab, remain the mainstay of therapy, though many patients fail to achieve remission or experience significant adverse effects. Moreover, the complex and multifactorial nature of GN pathogenesis calls for more refined therapeutic approaches. In recent years, multitarget therapies—combining different immunosuppressive agents targeting distinct immune pathways—have emerged as promising alternatives. Evidence suggests that multitarget therapy may offer superior outcomes compared to standard treatments. Despite early success, further studies are needed to optimize these regimens, reduce toxicity, and extend benefits to a broader range of GN patients. The development of personalized, biomarker-driven treatments, potentially leveraging innovative drug delivery systems and targeted biologics, holds promise for transforming GN care in the future.
Exploring Multidisciplinary Approaches to Comorbid Psychiatric and Medical Disorders: A Scoping Review
Authors: Țenea-Cojan Ștefăniță-Tiberiu , Dinescu Venera-Cristina , Gheorman Veronica , Dragne Ioana-Gabriela , Gheorman Victor , Forțofoiu Mircea-Cătălin , Fortofoiu Maria , Dobrinescu Adrian Gabriel
Published: February 2025

Psychiatric disorders often coexist with internal medical conditions, posing significant challenges to diagnosis, treatment, and overall patient outcomes. This study examines the bidirectional relationship between these conditions, emphasizing their impact on morbidity, treatment adherence, and quality of life. Through a comprehensive review of the peer-reviewed literature, we explore the physiological, neuroinflammatory, and psychosocial mechanisms that underpin these interactions. Key psychiatric disorders, including depression, anxiety, cognitive impairments, and psychosis, are identified as critical contributors to diagnostic complexity and therapeutic hurdles. Our findings underscore the importance of integrated, multidisciplinary care models, advocating for early detection, routine mental health screening, and personalized treatment strategies. Challenges such as overlapping symptoms, diagnostic ambiguities, and potential drug interactions are critically analyzed, with practical, evidence-based recommendations proposed for clinical practice. Despite advancements, significant research gaps persist, particularly the lack of longitudinal studies and the limited application of precision medicine tailored to this population. Future directions focus on enhancing diagnostic tools, developing innovative therapeutic approaches, and integrating mental health services into routine care. This study highlights the critical need for holistic, patient-centered approaches to manage comorbid psychiatric and internal medical conditions, offering actionable insights to improve outcomes and bridge existing gaps in research and practice.
Evolution of Focal Conic Domains in SmA-N Phase Transition
Authors: Plée Vincent , Lacam Jordan , Pascoli Gianni , Meyer Claire
Published: February 2025

Focal conics are nice geometric structures of liquid crystal phases which present periodicity such as smectic phase, cholesteric phase, etc. Here, we focus on focal conic domains (FCD) in smectic A liquid crystal. During a phase transition from smectic A to nematic, these FCDs evolve as the eccentricity increases until they completely disappear. Here, we present experimental observations of this phenomenon, along with a modeling approach that allows for an interestingly precise description of the phenomenon, revealing, in particular, a coefficient that seems to exhibit the behavior of a critical exponent.
Effect of Initial Rolling Temperature on the Microstructure Evolution of Liquified Nature Gas Low-Temperature-Resistant Steel Bars
Authors: Ma Zhenghong , Cao Jun , Zhang Zhibo , Zhang Huanhuan , Yin Shubiao , Liu Bingguo , Zhang Xiaosong
Published: February 2025

In order to gain insight into the changes of the organization and hardness of 500 MPa steel-grade low-temperature-resistant steel bars (HRB500DW) for liquefied nature gas (LNG) storage tanks during the continuous cooling phase transformation process, the effects of different rolling temperatures and cooling speeds on the organization of the phase change law, microstructure and hardness were studied. The results show that the critical phase transformation points AC1 and AC3 of the test steel were 702 and 880 °C, respectively. The organization of the test steel was polygonal ferrite and pearlite when the cooling rate was 1–2 °C/s. At a cooling speed of 5 °C/s, a small amount of bainite started to be produced in the region of a large deformation of rolling, and at 15 °C/s, some slate martensite started to be produced. At a cooling speed of 10 to 25 °C/s, the organization was mainly bainite. At a cooling rate of 40 °C/s, continuous pre-eutectic reticulated ferrite was formed at the austenite grain boundaries, reducing material properties. As the cooling speed increased, the hardness of the matrix organization of the test bars increased. The lower initial rolling temperature led to the expansion of the martensitic transformation zone. For rebar producers, the initial rolling temperature of 1050 °C was better than the initial rolling temperature of 1000 °C.
Protein Cage-like Vesicles Fabricated via Polymerization-Induced Microphase Separation of Amphiphilic Diblock Copolymers
Authors: Yoshida Eri
Published: February 2025

Highly symmetric protein cages represent one of the most artistic architectures formed by biomolecules. However, the underlying reasons for the formation of some of these architectures remain unknown. The present study aims to investigate the significance behind their morphological formation by fabricating protein cage-like vesicles using a synthetic polymer. The vesicles were synthesized by combining polymerization-induced self-assembly (PISA) with polymerization-induced microphase separation (PIMS), employing an amphiphilic poly(methacrylic acid)-block-poly(n-butyl methacrylate-random-cyclohexyl methacrylate-random-methacrylic acid) diblock copolymer, PMAA-b-P(BMA-r-CMA-r-MAA). The copolymer, with a 60 mol% molar ratio of CMA to the BMA units, produced clathrin-like vesicles with angular windows in their shell, resulting from the segregation of the hard CMA units from the soft BMA matrix in the hydrophobic phase of the vesicle. These vesicles were highly stable against rising temperatures. In contrast, the vesicles with a 30 mol% CMA ratio dissociated upon heating to 50 °C into triskelion-like segments due to intramolecular microphase separation. These findings indicate that designing synthetic polymers can mimic living organ morphologies, aiding in elucidating their morphological significance and inspiring the development of new materials utilizing these morphologies.
Apexification of an Endodontically Failed Permanent Tooth with an Open Apex: A Case Report with Histologic Findings
Authors: Bukhary Sundus
Published: February 2025

The management of an endodontic failure in a traumatized tooth with an open apex presents a major dilemma. The arrest of root growth after traumatic injury is a substantial consequence of pulpal necrosis. Conventional endodontic treatment procedures will be challenging by the resulting thin, fragile dentinal walls, which will impede the appropriate debridement and optimal apical sealing. Apexification is a well-established procedure that is designed to treat or preserve a tooth with an incomplete root apex and necrotic pulpal tissue by promoting the formation of a calcified apical barrier through the application of a bioactive substance at the root apex. The present case report demonstrates a successful apexification procedure for an endodontically failed permanent central incisor with an open apex with a two-year follow-up time. The clinical and radiographical results revealed the absence of signs and symptoms and the formation of hard tissue at the root apex. The tooth was extracted for prosthodontic reasons and processed for histologic examination. The histologic evaluation revealed dentin-like and cementum-like tissues formed at the apical barrier.
Acute Hepatic Porphyria Should Be Included in the Diagnostic Work-Up of Patients with Resistant Hypertension or Suspected Secondary Hypertension
Authors: de Lima Serrano Paulo , de Mattos Lombardi Badia Bruno , Barile João Paulo , Mendes Patrícia Marques , Cavalheiro Renan Brandão Rambaldi , Peixoto Kaliny Oliveira , Farias Igor Braga , Machado Roberta Ismael Lacerda , Seneor Daniel Delgado , de Rezende Pinto Wladimir Bocca Vieira , Oliveira Acary Souza Bulle , Sgobbi Paulo
Published: February 2025

Secondary hypertension and resistant hypertension may result from potentially treatable acquired or hereditary diseases. Inherited Metabolic Disorders are not routinely included in the differential diagnosis of these contexts associated with hypertension, despite the key importance of diagnosis for several of them which enable the early treatment of them. We aim to discuss the current evidence that indicates that a significant portion of cases of unknown resistant hypertension or suspected secondary hypertension may result from unrecognized Acute Hepatic Porphyria (AHP). Diagnostic work-up for AHP is not routinely performed during the evaluation of patients with resistant or refractory hypertension nor in the investigation of secondary hypertension. AHP may present both with neurological and systemic involvement, and hypertension may be observed as part of acute dysautonomia during acute neurovisceral attacks and as a chronic complication during disease course. As AHP represent a potentially treatable group of metabolic disorders, clinicians should consider the inclusion of this group in the diagnostic evaluation of patients with secondary or resistant hypertension.
Microbial Diversity Drives Decomposition More than Advantage of Home Environment—Evidence from a Manipulation Experiment with Leaf Litter
Authors: Ardestani Masoud M. , Kukla Jaroslav , Cajthaml Tomáš , Baldrian Petr , Frouz Jan
Published: February 2025

Microbial diversity plays a crucial role in litter decomposition. However, the relationships between microbial diversity and substrate successional stage are the drivers of this decomposition. In this study, we experimentally manipulated microbial diversity and succession in post-mining soil. We used leaf litter samples from two forests of a post-mining site near Sokolov, Czech Republic: one alder plantation and one mixed forest with birch aspen and willow. Litter from each site was decomposed in the field for 3 and 12 months. The litter was X-ray sterilized and part of the litter was kept unsterilized to produce inoculum. Leaf litter samples of two different ages (3 and 12 months) from each site were each inoculated with litter of two different ages (3 and 12 months), using less and more diluted inoculum, producing two levels of microbial diversity. In each of these eight treatments, the bacterial community was then characterized by amplicon sequencing of the 16S rRNA gene and microbial respiration was used to assess the rate of decomposition. A significantly higher respiration (p < 0.05) was found for the litter inoculated with the higher level of microbial diversity. Higher respiration was also found for the younger litter compared to the older litter and both litter origins. This shows a reduction in microbial respiration with substrate age and inoculation diversity, suggesting that microbial diversity supports the decomposition of soil organic matter.
Synergistic Effect of Anionic-Tuning and Architecture Engineering in BiPO4@C Anode for Durable and Fast Potassium Storage
Authors: Chu Heying , Li Yong , Liu Yuanjie , Chai Xueping , Zhang Hongzhou , Zhang Jingchuan
Published: February 2025

Bismuth-based materials that adhere to the alloy/dealloy reaction mechanism are regarded as highly promising anode materials for potassium-ion batteries due to their high volume-specific capacity and moderate reaction potentials. However, their commercial viability has been limited by the effects of structural collapse due to volume distortion and impeded electron conduction, resulting in rapid capacity decline. In this work, a carbon-coated nanosized BiPO4 rod (BiPO4@C) was designed and fabricated to overcome the aforementioned challenges through the architecture engineering and anionic-tuning strategy. In particular, the nanosized nanorods significantly reduce the volume expansion; the incorporation of the bulk and open-skeleton anion PO43− serves to mitigate the considerable volume distortion and generates the high ionic conductivity product (K3PO4) to ameliorate the poor ionic transport due to the structural deformation. The elaborated BiPO4 rods exhibit high specific capacity (310.3 mAh g−1, at 500 mA g−1), excellent cycling stability (over 700 cycles at 500 mA g−1) and superior rate performance (137.8 mAh g−1, at 1000 mA g−1). Systematic ex-situ XRD and TEM, as well as kinetic tests, have revealed the “conversion-multistep alloying” reaction process and the “battery-capacitance dual-mode” potassium storage mechanism. Moreover, the thick electrodes showed excellent specific capacity and rate performance, demonstrating their significant application potential in the next generation of SIBs.
Oleanolic Acid Slows Down Aging Through IGF-1 Affecting the PI3K/AKT/mTOR Signaling Pathway
Authors: Xu Yan , Wei Jianlei , Wang Wang , Mao Zebin , Wang Didi , Zhang Tao , Zhang Pengxia
Published: February 2025

Objective: A pentacyclic triterpene, oleanolic acid (OA), has anti-inflammatory activity. The role of oleanolic acid in aging is poorly understood, and the regulatory mechanism of IGF-1 signaling in aging is still not fully understood. Thus, we hypothesized that OA could delay aging by regulating the PI3K/AKT/mTOR pathway via insulin-like growth factor-1 (IGF-1). Method: This study initially established a replicative aging model and a bleomycin-induced aging model in human dermal fibroblast (HDF) and mouse embryonic fibroblast (MEF) cell lines. On this basis, IGF-1 inhibitors or IGF-1 recombinant proteins were then combined with OA (at a concentration of 20 μM) and treated for 72 h. The project plans to detect the expression of aging-related proteins such as CDKN2A (p16) using Western blot technology, detect the expression of aging-related factors such as Interleukin-1 beta (IL-1β), Interleukin-6 (IL-6), and Interleukin-8 (IL-8) using Real-Time Quantitative Polymerase Chain Reaction (RT-qPCR), Enzyme-Linked Immunosorbent Assay (ELISA), and other technologies, and combine Senescence-Associated β-Galactosidase (SA-β-gal) staining to detect changes in aging. Results: The expression of IGF-1, PI3K/AKT/mTOR, aging-related proteins P16, and aging-related secretory factors (SASP) IL-1β, IL-6, and IL-8 was increased in senescent cells. After treatment with jujuboside, the expression of IGF-1, PI3K/AKT/mTOR, aging-related protein P16, and aging-related secretory factors IL-1β, IL-6, and IL-8 were decreased. Conclusion: The findings suggested that OA slowed down aging by inhibiting the PI3K/AKT/mTOR expression through IGF-1. These findings suggest OA as a potential new drug and its mechanisms for anti-aging.
Vitamin D Deficiency Meets Hill’s Criteria for Causation in SARS-CoV-2 Susceptibility, Complications, and Mortality: A Systematic Review
Authors: Wimalawansa Sunil J.
Published: February 2025

Clinical trials consistently demonstrate an inverse correlation between serum 25-hydroxyvitamin D [25(OH)D; calcifediol] levels and the risk of symptomatic SARS-CoV-2 disease, complications, and mortality. This systematic review (SR), guided by Bradford Hill’s causality criteria, analyzed 294 peer-reviewed manuscripts published between December 2019 and November 2024, focusing on plausibility, consistency, and biological gradient. Evidence confirms that cholecalciferol (D3) and calcifediol significantly reduce symptomatic disease, complications, hospitalizations, and mortality, with optimal effects above 50 ng/mL. While vitamin D requires 3–4 days to act, calcifediol shows effects within 24 h. Among 329 trials, only 11 (3%) showed no benefit due to flawed designs. At USD 2/patient, D3 supplementation is far cheaper than hospitalization costs and more effective than standard interventions. This SR establishes a strong inverse relationship between 25(OH)D levels and SARS-CoV-2 vulnerability, meeting Hill’s criteria. Vitamin D3 and calcifediol reduce infections, complications, hospitalizations, and deaths by ~50%, outperforming all patented, FDA-approved COVID-19 therapies. With over 300 trials confirming these findings, waiting for further studies is unnecessary before incorporating them into clinical protocols. Health agencies and scientific societies must recognize the significance of these results and incorporate D3 and calcifediol for prophylaxis and early treatment protocols of SARS-CoV-2 and similar viral infections. Promoting safe sun exposure and adequate vitamin D3 supplementation within communities to maintain 25(OH)D levels above 40 ng/mL (therapeutic range: 40–80 ng/mL) strengthens immune systems, reduces hospitalizations and deaths, and significantly lowers healthcare costs. When serum 25(OH)D levels exceed 70 ng/mL, taking vitamin K2 (100 µg/day or 800 µg/week) alongside vitamin D helps direct any excess calcium to bones. The recommended vitamin D dosage (approximately 70 IU/kg of body weight for a non-obese adult) to maintain 25(OH)D levels between 50–100 ng/mL is safe and cost-effective for disease prevention, ensuring optimal health outcomes.
Changes in Workplace Choice Reasons and Individual Influencing Factors for Nurses Across Job Changes: Cross-Sectional Observational Study
Authors: Hara Yukari , Sato Kasumi , Hirayama Hideyuki , Ito Satomi , Omori Junko
Published: February 2025

Background/Objectives: The global nursing shortage encompasses issues such as the uneven nurse distribution in low- and middle-income countries, nurse outflow to other countries, and nurse retirement in developed countries, necessitating effective retention strategies. Our objective was to clarify the changes in facility selection reasons among Japanese nurses after changing jobs and the personal attributes influencing facility selection. Methods: In January 2023, an online survey was conducted among licensed practical nurses, registered nurses, midwives, and public health nurses in Japan. The survey items included personal attributes (age and sex), information on ≤five employment facilities, and facility selection reasons. The variations in facility selection reasons by facility number were analyzed using a generalized linear model with a binomial distribution. A logistic regression analysis was conducted with personal attributes and reasons for workplace selection as the independent and dependent variables, respectively. Results: In total, 721 participants were included; 90.8% selected hospitals as their first place of employment. As nurses changed jobs, they increasingly selected non-hospital facilities, including nursing homes, nursery schools, and government agencies. With multiple job changes, the facility selection reasons included “good location for commuting”, “good salary”, and “convenient working style”. Among personal attributes, “age”, “sex”, “age at employment at the facility”, “educational background”, “number of children”, and “living alone” influenced workplace choice reasons. Conclusions: Considering the study results, country-specific demographic trends, medical policy changes, and nursing-shortage-related causes, medical facility managers and policymakers should devise appropriate employment conditions and develop recruitment strategies, especially for situations with severe nursing shortages. Nurses can learn from the career choices of others to manage their own careers.
A Novel LC-MS/MS Method for the Measurement of Elexacaftor, Tezacaftor and Ivacaftor in Plasma, Dried Plasma Spot (DPS) and Whole Blood in Volumetric Absorptive Microsampling (VAMS) Devices
Authors: Pigliasco Federica , Cafaro Alessia , Barco Sebastiano , Cresta Federico , Casciaro Rosaria , Pedemonte Nicoletta , Mattioli Francesca , Castellani Carlo , Cangemi Giuliana
Published: February 2025

Background: The combination of ivacaftor, tezacaftor and elexacaftor (ETI) is approved for patients with cystic fibrosis (CF) aged two years and older and at least one F508del mutation in the CFTR gene. Variability in ETI treatment response has been repeatedly reported, and its reasons are unclear and understudied. Objectives: We present a novel liquid chromatography–tandem mass spectrometry (LC–MS/MS) method for the rapid and simultaneous quantification of ETI in plasma, dried plasma spots (DPS), and whole blood volumetric absorptive microsampling (VAMS). Methods: The method utilizes a rapid extraction protocol with 200 μL methanol after the addition of deuterated internal standards. Chromatographic separation was achieved using a reversed-phase Hypersil Gold aQ column (Thermo Fisher Scientific). The method was validated according to ICH (International Council on Harmonisation) guidelines M10 for bioanalytical method validation, demonstrating linearity in the concentration range 0.020–12.000 µg/mL. It was also proved accurate and reproducible with no matrix effect. This method was applied to anonymized samples from patients undergoing ETI treatment: eight plasma and DPS and five VAMS samples were analyzed. Results: ETI concentrations measured in plasma and DPS were interchangeable, whereas ETI concentrations in VAMS were lower than in plasma, as expected for molecules with high plasma protein binding (99%). A correction factor based on the hematocrit value was used to calculate the equivalent plasma concentration from VAMS concentrations. Conclusions: This method is suitable for pharmacokinetic (PK) studies and could facilitate the centralization of samples to specialized laboratories, supporting multicenter studies.
Sustained Delivery of Liraglutide Using Multivesicular Liposome Based on Mixed Phospholipids
Authors: Zhang Runpeng , Yao Xinyu , Gao Siqi , Xu Tingting , Wang Da , Sha Luping , Yang Li
Published: February 2025

Background: Although peptides are widely used in the clinical treatment of various diseases due to their strong biological activity, they usually require frequent injections owing to their poor in vivo half-life. Therefore, there is a strong clinical need for sustained peptide formulations. Methods: In this study, liraglutide (Lir) and biocompatible multivesicular liposomes (MVLs) were utilized as the model drug and sustained-release carriers, respectively. The drug release rate of Lir-MVLs was controlled by changing the ratio of SPC and DEPC with different phase transition temperatures (PTT, PTTSPC = −20 °C, PTTDEPC = 13 °C). Results: As the SPC ratio increased, Lir-MVLs had more flexible lipid membranes, poorer structural stabilization, and fewer internal vesicles with larger particle sizes, contributing to faster release of Lir. After subcutaneous injection of Lir-MVLs, the blood glucose concentration (BGC) of db/db mice decreased to different levels. When the SPC-DEPC ratio was greater than 85:15, the drug release rate was too fast; the BGC remained below 16 mM for only 2–4 days, while when the drug release rate was too slow, was the case when the SPC-DEPC ratio was less than 50:50, the BGC also remained below 16 mM for only 2–3 days. However, when the SPC-DEPC ratio was 75:25, the BGC could be maintained below 16 mM for 8 days, indicating that the release properties of this ratio best met the pharmacological requirements of Lir. Conclusions: This study investigated the effects of phospholipids with different PTT on the release characteristics of Lir-MVLs, and provided ideas for the design of sustained-release peptide preparations.