bluuebunny/crossref_metadata_2025 huggingface dataset:
The Impact of COVID-19 and Racial Injustices on Resilience of Incoming Medical Students
Authors: Matari Yanal , Starkman Rebecca , Briskin Camille , Alper David P. , Petersen Kellen K. , Yang Rebecca , Petersen Kristina H.
Published: March 2024

Medical students (MS) are at higher risk for depression than their peers. Incoming U.S. MS completed a survey that included the validated RS-14, which measures resilience and its two subcomponents: self-assuredness and drive. Surveys were administered before classes started in 2019 (pre-pandemic-cohort; n = 178) and 2020 (pandemic-cohort; n = 181). Resiliency, self-assuredness, and drive were not different between cohorts. Demographic subgroup analyses revealed that underrepresented in medicine (URiM) MS in the pre-pandemic-cohort scored higher on drive (p = 0.007) than non-URiM MS (6.07 ± 1.00 vs. 5.59 ± 0.97); however, this difference was not significant in the pandemic-cohort. Additionally, students in the pandemic-cohort were more likely to agree that peer discussions about emotional challenges would be beneficial (p = 0.014). Qualitative analysis revealed that 45.9% of pandemic-cohort respondents felt more motivated to pursue medicine. This is the first study to report differences in drive between URiM MS cohorts matriculating before and during a pandemic, a positive correlation between multiple-mini-interview (MMI) scores and drive, and a negative correlation between MCAT scores and drive. Collectively, these results suggest that the circumstances of 2020 may have negatively influenced the drive of URiM students, positively impacted the receptivity of MS to peer discussions, and motivated students to pursue medicine.
Reducing the Power Consumption of Edge Devices Supporting Ambient Intelligence Applications
Authors: Fanariotis Anastasios , Orphanoudakis Theofanis , Fotopoulos Vassilis
Published: March 2024

Having as a main objective the exploration of power efficiency of microcontrollers running machine learning models, this manuscript contrasts the performance of two types of state-of-the-art microcontrollers, namely ESP32 with an LX6 core and ESP32-S3 with an LX7 core, focusing on the impact of process acceleration technologies like cache memory and vectoring. The research employs experimental methods, where identical machine learning models are run on both microcontrollers under varying conditions, with particular attention to cache optimization and vector instruction utilization. Results indicate a notable difference in power efficiency between the two microcontrollers, directly linked to their respective process acceleration capabilities. The study concludes that while both microcontrollers show efficacy in running machine learning models, ESP32-S3 with an LX7 core demonstrates superior power efficiency, attributable to its advanced vector instruction set and optimized cache memory usage. These findings provide valuable insights for the design of power-efficient embedded systems supporting machine learning for a variety of applications, including IoT and wearable devices, ambient intelligence, and edge computing and pave the way for future research in optimizing machine learning models for low-power, embedded environments.
A Wearable Internet of Things Device for Noninvasive Remote Monitoring of Vital Signs Related to Heart Failure
Authors: Iqbal Sheikh Muhammad Asher , Leavitt Mary Ann , Mahgoub Imadeldin , Asghar Waseem
Published: March 2024

Cardiovascular disease is one of the leading causes of death in the world. Heart failure is a cardiovascular disease in which the heart is unable to pump sufficient blood to fulfill the body’s requirements and can lead to fluid overload. Traditional solutions are not adequate to address the progression of heart failure. Herein, we report a body-mounted wearable sensor to monitor the parameters related to heart failure. These include heart rate, blood oxygen saturation, thoracic impedance, and activity status. The device is compact and wearable and measures the parameters continuously in real time. The device is an Internet of Things (IoT) device connected with a cloud-based database enabling the parameters to be visualized on a mobile application.
Meckel’s Diverticulum Injuries after Blunt Trauma
Authors: Arkuszewski Piotr T. , Kłosiński Karol K. , Kawa Oliwia J. , Czyżewski Bartosz M. , Pasieka Zbigniew W.
Published: March 2024

Background: The complications associated with Meckel’s diverticulum (MD) are well-known. However, blunt injuries regarding MD have not been widely described in the literature. This was the reason for undertaking research on MD lesions. Materials and Methods: The materials consisted of 28 cases of damage to MD after blunt trauma published during the years 1921–2022. The collected data were subjected to statistical analysis. Results: The following MD injuries have been identified, starting with the most common isolated perforation of MD, bleeding from the area of MD, perforation of MD with concomitant tearing of the mesentery intestines and bleeding, intussusception of MD, and intramural hematoma of MD with adjacent mesenteric hematoma. Most injuries were caused by a traffic accident, followed by sports, accidents at work, and then violence. Almost all the cases (27) involved men. Several possible mechanisms may contribute to post-traumatic damage to MD. First of all, they are associated with abdominal compression and a secondary increase in intra-abdominal pressure as well as with the action of shearing forces during deceleration. Conclusions: Traumatic MD injuries are differentiated and very rare. They can coexist with other serious injuries to the abdominal organs.
Echocardiography and Cardiac Magnetic Resonance in the Assessment of Left-Ventricle Remodeling: Differences Implying Clinical Decision
Authors: Haberka Maciej , Starzak Monika , Smolka Grzegorz , Wojakowski Wojciech , Gąsior Zbigniew
Published: March 2024

Introduction: Transthoracic echocardiography (TTE) and cardiovascular magnetic resonance (CMR) are the most important modalities used in clinical practice to assess cardiac chambers. However, different imaging techniques may affect their results and conclusions. The aim of our study was to compare left-ventricle (LV) remodeling assessed using TTE and CMR in the context of various cardiovascular diseases. Methods: A total of 202 consecutive patients sent for an elective cardiovascular diagnosis were scheduled for a 2D TTE and CMR, performed within 2 weeks. The study group was divided and analyzed based on the clinical indications for CMR, including coronary artery disease, heart failure, native aortic valve regurgitation or paravalvular leak after aortic valve replacement, or cardiomyopathies. Results: The mean LV mass index (LVMi) values calculated using TTE were significantly larger (127.1 ± 44.5 g/m²) compared to the LVMi assessed using CMR (77.1 ± 26.2 g/m²; p < 0.001). The LV end-diastolic volumes assessed using TTE were underestimated for all the study patients (78.6 ± 43 mL vs. 100.5 ± 39 mL; p < 0.0001) and subgroups, but a statistical trend was observed in patients with cardiomyopathy. Those differences in single parameters led to differences in LV remodeling and the final treatment decision. CMR and TTE provided similar conclusions on LV systolic dysfunction in 68% of the patients. Conclusions: Our results showed that the greater the degree of LV remodeling and dysfunction, the greater the difference between the modalities. Therefore, CMR should be introduced into routine clinical practice, especially for patients undergoing LV remodeling, which may change clinical decisions in a considerable number of cases.
The Depressiveness, Quality of Life and NEO-FFI Scale in Patients with Selected Genodermatoses
Authors: Wawrzycki Bartlomiej , Fryze Magdalena , Mlak Radosław , Pelc Alicja , Wertheim-Tysarowska Katarzyna , Bygum Anette , Kulbaka Aleksandra Wiktoria , Matosiuk Dariusz , Pietrzak Aldona
Published: March 2024

Background: Dermatological conditions extend beyond physical symptoms, profoundly impacting the psychological well-being of patients. This study explores the intricate relationship between depressive symptoms, quality of life (QoL), and personality traits in individuals diagnosed with specific genodermatoses. Methods: The study cohort comprised 30 patients with genodermatoses treated at the dermatology clinic, and a healthy control group. Standardized survey questionnaires: The Dermatology Life Quality Index (DLQI), Beck’s Depression Inventory (BDI), and NEO Five-Factor Inventory (NEO-FFI) were employed for assessments. Results: The findings indicate a significantly elevated risk of severely or very severely reduced QoL in the study group compared to matched controls (OR = 22.2, 95% CI: 2.7–184.8). Specifically, individuals with ichthyosis exhibited a staggering 131-fold higher risk of diminished QoL compared to the control group. Furthermore, the prevalence of depression was higher in the study group than in the control group (36.7% vs. 10%; p = 0.0086). A detailed analysis revealed that patients with low or average agreeableness exhibited a notably higher incidence of depression compared to those with high agreeableness (100% or 75% vs. 28.6%; p = 0.0400). Similarly, individuals with high levels of neuroticism had a significantly higher incidence of depression compared to those with average or low levels of neuroticism (rates: 66.7% vs. 9.1% or 0%, respectively; p = 0.0067). Conclusions: The study underscores a substantial correlation between genodermatoses and the mental health of affected individuals, underscoring the imperative consideration of psychological factors in the management of hereditary skin disorders. Our study’s primary limitation is the small sample size, stemming from difficulties in recruiting participants due to the rare nature of the studied conditions.
Texture Features of 18F-Fluorodeoxyglucose Positron Emission Tomography for Predicting Programmed Death-Ligand-1 Levels in Non-Small Cell Lung Cancer
Authors: Norikane Takashi , Ishimura Mariko , Mitamura Katsuya , Yamamoto Yuka , Arai-Okuda Hanae , Manabe Yuri , Murao Mitsumasa , Morita Riku , Obata Takafumi , Tanaka Kenichi , Murota Makiko , Kanaji Nobuhiro , Nishiyama Yoshihiro
Published: March 2024

Background: Identifying programmed death-ligand-1 (PD-L1) expression is crucial for optimizing treatment strategies involving immune checkpoint inhibitors. However, the role of intratumoral metabolic heterogeneity specifically derived from 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) images in predicting PD-L1 expression in patients with newly diagnosed non-small cell lung cancer (NSCLC) remains unexplored. Here, we investigated the association between FDG PET texture features and PD-L1 expression by retrospectively analyzing the data of patients newly diagnosed with NSCLC who underwent FDG PET/CT scans and PD-L1 immunohistochemical staining before treatment. Methods: Patients were categorized based on their tumor proportion scores (TPSs) into negative-, low-, and high-PD-L1 expression groups. We computed the maximum standardized uptake value and 31 texture features for the primary tumor from PET images and compared differences in parameters among the groups. Results: Of the 83 patients, 12, 45, and 26 were assigned to the negative-, low-, and high-PD-L1 expression groups, respectively. Six specific texture features (low gray-level run emphasis, short-run low gray-level emphasis, long-run high gray-level emphasis, low gray-level zone emphasis, high gray-level zone emphasis, and short-zone low gray-level emphasis) helped distinguish among all possible combinations. Conclusions: Our findings revealed that FDG PET texture features are potential imaging biomarkers for predicting PD-L1 expression in patients newly diagnosed with NSCLC.
Personalized Approach in Transcatheter Palliation of Congenital Heart Disease with Duct-Dependent Pulmonary Circulation: Right Ventricular Outflow Tract Stenting vs. Arterial Duct Stenting
Authors: Scalera Silvia Teresa , Pizzuto Alessandra , Marchese Pietro , Cantinotti Massimiliano , Franchi Eliana , Marrone Chiara , Assanta Nadia , Santoro Giuseppe
Published: March 2024

Despite significant improvements in techniques, the treatment of neonates and infants with congenital heart disease resulting in duct-dependent pulmonary circulation is still significantly challenging. Despite current trends toward early primary surgical repair, temporary palliation is still necessary in those patients who are at high surgical risk for complete correction due to unfavorable clinical or anatomic characteristics. Recent advances in interventional cardiology have led to the emergence of right ventricular outflow tract and arterial duct stenting as cost-effective alternatives to surgical palliation in high-risk surgical candidates or whenever short-term pulmonary blood flow support is anticipated. This review aims to explore the evolving landscape of these transcatheter approaches, highlighting their role, efficacy and potential complications in the context of duct-dependent pulmonary circulation anatomies.
Plant Biotic and Abiotic Stresses
Authors: Manghwar Hakim , Zaman Wajid
Published: March 2024

In the complex field of plant science, knowledge of the many difficulties that plants encounter from both living and non-living stresses is essential for maintaining biodiversity and managing natural resources in a sustainable manner, in addition to guaranteeing global food security [...]
1-(3,4-Dimethoxyphenyl)-3-(4-methoxyphenyl)-3-(1H-1,2,4-triazol-1-yl)propan-1-one
Authors: Nacher-Luis Anna , Pastor Isidro M.
Published: March 2024

The study of new catalytic protocols for the synthesis of organic compounds with a more sustainable perspective is of interest. The use of ionic organic solids, such as 1,3-bis(carboxymethyl)imidazolium chloride as a catalyst has allowed the Michael addition of N-heterocycles to chalcones. This methodology has been applied to the unique preparation of the potential bioactive compound 1-(3,4-dimethoxyphenyl)-3-(4-methoxyphenyl)-3-(1H-1,2,4-triazol-1-yl)propan-1-one with moderate yield, due to the retro-Michael reaction. Both synthetic reactions (i.e., preparation of chalcone and triazole Michael-addition to chalcone) have good green metrics.
Diagnostic Challenges in Inflammatory Choroidal Neovascularization
Authors: Karska-Basta Izabella , Pociej-Marciak Weronika , Żuber-Łaskawiec Katarzyna , Markiewicz Anna , Chrząszcz Michał , Romanowska-Dixon Bożena , Kubicka-Trząska Agnieszka
Published: March 2024

Inflammation plays a key role in the induction of choroidal neovascularization (CNV). Inflammatory choroidal neovascularization (iCNV) is a severe but uncommon complication of both infectious and non-infectious uveitides. It is hypothesized that its pathogenesis is similar to that of wet age-related macular degeneration (AMD), and involves hypoxia as well as the release of vascular endothelial growth factor, stromal cell-derived factor 1-alpha, and other mediators. Inflammatory CNV develops when inflammation or infection directly involves the retinal pigment epithelium (RPE)–Bruch’s membrane complex. Inflammation itself can compromise perfusion, generating a gradient of retinal–choroidal hypoxia that additionally promotes the formation of choroidal neovascularization in the course of uveitis. The development of choroidal neovascularization may be a complication, especially in conditions such as punctate inner choroidopathy, multifocal choroiditis, serpiginous choroiditis, and presumed ocular histoplasmosis syndrome. Although the majority of iCNV cases are well defined and appear as the “classic” type (type 2 lesion) on fluorescein angiography, the diagnosis of iCNV is challenging due to difficulties in differentiating between inflammatory choroiditis lesions and choroidal neovascularization. Modern multimodal imaging, particularly the recently introduced technology of optical coherence tomography (OCT) and OCT angiography (noninvasive and rapid imaging modalities), can reveal additional features that aid the diagnosis of iCNV. However, more studies are needed to establish their role in the diagnosis and evaluation of iCNV activity.
Metaphedrone (3-Methylmethcathinone): Pharmacological, Clinical, and Toxicological Profile
Authors: Kelečević Igor , Vejnović Ana-Marija , Javorac Jovan , Gvozdenović Nemanja , Janjić Nataša , Mijatović Jovin Vesna
Published: March 2024

Introduction: Synthetic cathinones are a group of novel psychoactive substances used as an alternative to classical recreational drugs. As a result of legal prohibitions on older generations of these compounds, new formulations appeared on the drug market. One of them is metaphedrone (3-methylmethcathinone, 3-MMC), a structural isomer of 4-methylmethcathinone and a psychostimulant drug. Metaphedrone became popular in a large number of countries in a short period of time. The aim: The collection, analysis, and review of relevant research on the subject of metaphedrone in order to present information about the pharmacological, clinical, and toxicological profile of this compound. An assessment of the significance and role of metaphedrone in consumption patterns of novel psychoactive substances among recreational drug users. Methodology: By using search engines like Google Scholar and PubMed, the relevant literature on metaphedrone was looked for and analyzed. The search was not limited to a specific period of time. All information regarding the compound of interest was analyzed and presented. Key results and discussion: All novel psychoactive substances are abused due to their pronounced stimulatory, hallucinogenic, dissociative, and euphoric and/or relaxing characteristics. Users of 3-methylmethcathinone usually opt for this substance for recreational purposes and/or sexual stimulation. Metaphedrone has the potential to cause a psychological dependence to the users. It was determined in relevant studies that most users are from 17 to 50 years of age. Older users usually administer metaphedrone intravenously, while younger ones usually choose snorting and oral ingestion of the drug. In Serbia, metaphedrone is a legally controlled substance. The pharmacodynamic properties make metaphedrone similar to classical recreational drugs. The method of administration, mainly repeated administration in a single session, could be explained using the pharmacokinetic profile of the drug. The most reported symptoms of intoxication were those of a sympathomimetic nature, such as tachycardia, chest pain, hypertension, diaphoresis, and agitation. Most intoxications and fatal outcomes occurred to users who combined several psychoactive substances. The correlation between measured blood concentrations of the drug and outcomes of intoxication was not found. The mechanisms of metaphedrone’s toxicity are not fully understood. Conclusions: There is an increasing trend of abuse of metaphedrone among recreational drugs users. Future studies should focus on pharmacological and toxicological effects of metaphedrone on animals and humans.
Evaluating Knowledge, Self-Reported Confidence Levels, and Prescription Patterns among Dental Practitioners Regarding Analgesics in Dentistry: A Cross-Sectional Study
Authors: Badrov Marija , Tadin Antonija
Published: March 2024

Background and Objectives: Dental pain is a common problem that often leads to unscheduled dental visits and requires a comprehensive understanding of analgesics, including their indications and contraindications. The aim of this study was to investigate dentists’ knowledge, self-reported confidence levels, and prescribing patterns of analgesics in dentistry. Materials and Methods: A nationwide cross-sectional online survey was conducted, resulting in 379 responses. Of these, 68.6% were general dentists, and 31.4% were specialists. The collected data included sociodemographic information, levels of knowledge, and prescription patterns. The survey questionnaire explored self-perceived practices, patient information during prescription, and guiding factors. Descriptive statistics and a generalized linear model for regression were used for data analysis. Results: Higher levels of knowledge were observed in specific contexts such as secondary/tertiary healthcare (p = 0.022), specialization in endodontics (p = 0.003), and a higher number of working hours with patients (p = 0.038). Conversely, increased self-confidence was observed among endodontists (p = 0.008), oral surgeons (p = 0.011), and dentists with more than 6 h of patient interaction (p ≤ 0.001). Orthodontists and prosthodontists demonstrated lower knowledge levels, while specialists in family dentistry exhibited lower self-confidence. Self-confidence and knowledge displayed a significant positive correlation (r = 0.039, p < 0.001). The most frequently prescribed medication was ibuprofen (97.9%), primarily for surgical (83.9%) and endodontic procedures (60.9%), with the main indications being pulpal (85.8%), periradicular (57.3%), and postoperative pain (40.1%). Conclusions: This study reveals significant knowledge and confidence gaps among dentists, including limited awareness of the efficacy of nonsteroidal anti-inflammatory drugs for odontogenic pain, a lack of time for effective counseling, and perceived deficits in pharmacology education. To address these issues, targeted educational interventions are recommended to improve analgesic prescribing practice, close knowledge gaps, and increase dentists’ confidence in more effective pain management.
Efficient Recovery of Feldspar, Quartz, and Kaolin from Weathered Granite
Authors: Huang Hongjun , Li Shihan , Gou Haoran , Zhang Ning , Liu Liming
Published: March 2024

Weathered granite contains a high concentration of feldspar, quartz, and kaolin. However, while it becomes rich in clay due to strong physical weathering, the granite minerals that are not fully weathered are still very hard, which makes the grinding process more difficult and limits its use. This study proposes a multi-step process involving grinding, desliming, and flotation to address this issue. The study determines the appropriate grinding time and power index for the original ore, as well as the optimal desliming method using a hydrocyclone. To remove iron-containing impurities like mica, a combination of NaOL/BHA/A CO collectors is used for the reverse rough flotation of quartz. Additionally, a combination of DDA/SDS collectors is employed to separate quartz and feldspar through flotation, resulting in a quartz product with a silicon dioxide content of 99.51%. The objective of efficiently recycling feldspar, quartz, and kaolin from weathered granite is accomplished. Additionally, the inclusion of intermediate mineral components as by-products of feldspar and raw materials for aerated bricks is introduced, resulting in the complete utilization of all components. This innovative approach ensures a clean and environmentally friendly process, eliminating the need for solid waste disposal.
A Cell-Penetrating Peptide Improves Anti-HER2 Single-Chain Variable Fragment Internalization and Antitumor Activity against HER2-Positive Breast Cancer In Vitro and In Vivo
Authors: Li Junmin , Zhou Yanting , Su Zhuowei , Li Xue , Zhang Lei , Li Shan
Published: March 2024

Cell-penetrating peptides (CPPs) are invaluable tools for delivering various substances into cells by crossing biological membranes. However, the effects of cell-penetrating peptide fusion proteins on the biological activity of antibodies remain to be fully understood. Here, we engineered a recombinant protein, LP-scFv, which combines the single-chain variable region of anti-human epidermal growth factor receptor-2 with a novel and non-oxic cell-penetrating peptide as a leader peptide. The introduction of this leader peptide led to a more than twofold increase in the internalization efficiency of the single-chain antibody, as confirmed using microscopic analysis and flow cytometry. The effects of the single-chain antibodies and LP-scFv on cell viability were evaluated using the MTT assay. Both the single-chain antibodies and LP-scFv reduced the viability of BT474 and NCI-N87 cells in a dose-dependent manner while exhibiting minimal toxicity towards MCF-7 and MCF-10A cells. Further investigation into LP-scFv’s mechanism revealed that the induced leader peptide does not alter the MAPK-ERK1/2 and PI3K/AKT pathways of single-chain antibodies. An enhanced antitumor activity was also confirmed in an NCI-N87 tumor xenograft model in mice with a reduction of 45.2% in tumor growth inhibition (vs. 23.1% for scFv) with a 50 mg/kg dose after orthotopic injection administration, which was equivalent to that of trastuzumab (vs. 55.7% for trastuzumab). Overall, these results indicate that LP-scFv exhibits significant permeation activity in HER2-positive cells to enhance the intracellular dose effect on antitumor activity in vitro and in vivo. This research lays the foundation for designing novel antibody-based therapies for cancer.
Approximated Uncertainty Propagation of Correlated Independent Variables Using the Ordinary Least Squares Estimator
Authors: Lim Jeong Sik , Kim Yong Doo , Woo Jin-Chun
Published: March 2024

For chemical measurements, calibration is typically conducted by regression analysis. In many cases, generalized approaches are required to account for a complex-structured variance–covariance matrix of (in)dependent variables. However, in the particular case of highly correlated independent variables, the ordinary least squares (OLS) method can play a rational role with an approximated propagation of uncertainties of the correlated independent variables into that of a calibrated value for a particular case in which standard deviation of fit residuals are close to the uncertainties along the ordinate of calibration data. This proposed method aids in bypassing an iterative solver for the minimization of the implicit form of the squared residuals. This further allows us to derive the explicit expression of budgeted uncertainties corresponding to a regression uncertainty, the measurement uncertainty of the calibration target, and correlated independent variables. Explicit analytical expressions for the calibrated value and associated uncertainties are given for straight-line and second-order polynomial fit models for the highly correlated independent variables.
Insulin Conformation Changes in Hybrid Alginate–Gelatin Hydrogel Particles
Authors: Yerlan Gulzhan Ye. , Shen Michael , Tyussyupova Bakyt B. , Tazhibayeva Sagdat M. , Musabekov Kuanyshbek , Takhistov Paul
Published: March 2024

There is a strong need to develop an insulin delivery system suitable for oral administration and preserving natural (α-helix) insulin conformation. In this work, we fabricated alginate–gelatin hydrogel beads for insulin encapsulation. Altering matrix composition and crosslinking agents has resulted in various surface morphologies and internal spatial organization. The structures of the insulin-loaded matrices were studied using optical and field emission electronic microscopy. We use FTIR spectroscopy to identify insulin conformation changes as affected by the hydrogel matrices. It was found that blended alginate–gelatin matrices demonstrate better encapsulation efficiency and stronger swelling resistance to a simulated gastric environment than sodium alginate beads crosslinked with the CaCl2. FTIR measurements reveal conformation changes in insulin. It is also confirmed that in the presence of gelatin, the process of insulin fibrinogenesis ceases due to intermolecular interaction with the gelatin. Performed molecular modeling shows that dipole–dipole interactions are the dominating mechanism that determines insulin behavior within the fabricated matrix.
High-Pressure Processing of Fruit Smoothies Enriched with Dietary Fiber from Carrot Discards: Effects on the Contents and Bioaccessibilities of Carotenoids and Vitamin E
Authors: Donda Zbinden Melisa , Schmidt Mario , Vignatti Charito Ivana , Pirovani María Élida , Böhm Volker
Published: March 2024

The effects of high-pressure processing (HPP) (450 MPa/600 MPa/3 min) on the carotenoid and vitamin E contents of smoothies made from strawberry, orange juice, banana and apple, and the same smoothies enriched with dietary fiber from discarded carrots were compared. The contents and bioaccessibilities of these compounds were also evaluated over the course of 28 days at 4 °C. The application of HPP in the formulations significantly increased the contents of β-cryptoxanthin, α-carotene and β-carotene and retained the contents of lutein, zeaxanthin and vitamin E compared to untreated samples. A decreasing trend in the content of each compound was observed with an increase in storage time. The application of HPP initially led to reductions in the bioaccessibility of individual compounds. However, overall, during storage, there was an increase in bioaccessibility. This suggests that HPP influences cell structure, favoring compound release and micelle formation. HPP is a sustainable method that preserves or enhances carotenoid extractability in ready-to-drink fruit beverages. Furthermore, the incorporation of dietary fiber from carrot processing discards supports circular economy practices and enhances the health potential of the product.
Deep Eutectic Solvents as Agents for Improving the Solubility of Edaravone: Experimental and Theoretical Considerations
Authors: Jeliński Tomasz , Przybyłek Maciej , Mianowana Magdalena , Misiak Kinga , Cysewski Piotr
Published: March 2024

In this study, both practical and theoretical aspects of the solubility of edaravone (EDA) in Deep Eutectic Solvents (DESs) were considered. The solubility of edaravone in some media, including water, can be limited, which creates the need for new efficient and environmentally safe solvents. The solubility of EDA was measured spectrophotometrically and the complex intermolecular interactions within the systems were studied with the COSMO-RS framework. Of the four studied DES systems, three outperformed the most efficient classical organic solvent, namely dichloromethane, with the DES comprising choline chloride and triethylene glycol, acting as hydrogen bond donor (HBD), in a 1:2 molar proportion yielding the highest solubility of EDA. Interestingly, the addition of a specific amount of water further increased EDA solubility. Theoretical analysis revealed that in pure water or solutions with high water content, EDA stacking is responsible for self-aggregation and lower solubility. On the other hand, the presence of HBDs leads to the formation of intermolecular clusters with EDA, reducing self-aggregation. However, in the presence of a stoichiometric amount of water, a three-molecular EDA–HBD–water complex is formed, which explains why water can also act as a co-solvent. The high probability of formation of this type of complexes is related to the high affinity of the components, which exceeds all other possible complexes.
High-Performance Memristive Synapse Composed of Ferroelectric ZnVO-Based Schottky Junction
Authors: Lee Youngmin , Hong Chulwoong , Sekar Sankar , Lee Sejoon
Published: March 2024

In pursuit of realizing neuromorphic computing devices, we demonstrated the high-performance synaptic functions on the top-to-bottom Au/ZnVO/Pt two-terminal ferroelectric Schottky junction (FSJ) device architecture. The active layer of ZnVO exhibited the ferroelectric characteristics because of the broken lattice-translational symmetry, arising from the incorporation of smaller V5+ ions into smaller Zn2+ host lattice sites. The fabricated FSJ devices displayed an asymmetric hysteresis behavior attributed to the ferroelectric polarization-dependent Schottky field-emission rate difference in between positive and negative bias voltage regions. Additionally, it was observed that the magnitude of the on-state current could be systematically controlled by changing either the amplitude or the width of the applied voltage pulses. Owing to these voltage pulse-tunable multi-state memory characteristics, the device revealed diverse synaptic functions such as short-term memory, dynamic range-tunable long-term memory, and versatile rules in spike time-dependent synaptic plasticity. For the pattern-recognition simulation, furthermore, more than 95% accuracy was recorded when using the optimized experimental device parameters. These findings suggest the ZnVO-based FSJ device holds significant promise for application in next-generation brain-inspired neuromorphic computing systems.
Effect of a Multicomponent Food Pantry Intervention in Client Subgroups
Authors: Jia Jenny , Gombi-Vaca Maria F. , Bliss Barsness Christina , Peterson Hikaru , Pratt Rebekah , Wolfson Julian , Caspi Caitlin E.
Published: March 2024

Nutrition promotion programs may have varying effects and influence health disparities. SuperShelf promotes healthy choices in food pantries through inventory changes and nudge implementation (e.g., choice architecture). This secondary analysis of the SuperShelf cluster-randomized trial assessed whether the effect of SuperShelf on client diet quality differed by equity characteristics. English-, Spanish-, or Somali-speaking adult clients from 11 food pantries in Minnesota were included (N = 193). We measured change in diet quality by the Healthy Eating Index 2015 (HEI-2015; maximum score 100) using up to two 24 h dietary recalls from pre-intervention and post-intervention periods. We used linear mixed-effects models to determine whether the effect of SuperShelf on diet quality varied by self-reported gender, race/ethnicity, education, and employment status. In separate adjusted models, the interactions of SuperShelf and gender, education, or employment status were not significant. The interaction of SuperShelf and race/ethnicity was significant (p-interaction = 0.008), but pairwise comparisons in diet quality were non-significant in all racial/ethnic subgroups. SuperShelf did not have differential effects on diet quality by gender, race/ethnicity, education, or employment status, suggesting it does not worsen dietary disparities among food pantry clients, though more subgroup analyses are needed to explore potential racial/ethnic disparities in this context.
Myostatin and Activin A as Biomarkers of Sarcopenia in Inflammatory Bowel Disease Patients
Authors: Godala Małgorzata , Gaszyńska Ewelina , Walczak Konrad , Małecka-Wojciesko Ewa
Published: March 2024

The prevalence of sarcopenia in inflammatory bowel disease patients has received increasing attention. The aim of this study is to assess the usefulness of determining levels of myostatin (MSTN) and activin A (Act A) as potential markers of disease activity and occurrence of sarcopenia in Crohn’s disease and ulcerative colitis patients. The case-control study included 82 patients with Inflammatory Bowel Disease. The control group consisted of 25 healthy volunteers. The serum levels of myostatin and activin A were determined by the quantitative sandwich enzyme-linked immunosorbent assay. Sarcopenia was diagnosed based on the EWGSOP2 criteria. The study found lower levels of myostatin and activin A in the IBD patients. There were significantly lower levels of myostatin (80.6 pg/mL vs. 186.2 pg/mL; p = 0.0364) as well as activin A (32.1 pg/mL vs. 35.2 pg/mL; p = 0.0132) in the IBD patients with sarcopenia compared to those without sarcopenia. Positive correlations were found between MSTN levels and Muscle Mass Index (rho = 0.31; p < 0.005) and hand grip strength (rho = 0.34, p < 0.05) in the IBD patients. The determination of serum levels of MSTN and Act A may be useful in the early diagnosis of sarcopenia in IBD patients.
Indoor Inactivation of SARS-CoV-2 Virus by Liquid Hyperoxygen
Authors: Barco Giovanni , Khalid Zumama , Pulliero Alessandra , Angelinetta Claudio , Prati Ubaldo , Izzotti Alberto
Published: March 2024

The possible future emergence of new SARS-CoV-2 virus variants pushes the development of new chemoprophylaxis protocols complementary to the unspecific and specific immune-prophylaxis measures currently used. The SARS-CoV-2 virus is particularly sensitive to oxidation, due to the relevant positive electrical charge of its spike protein used as a ligand for target cells. The present study evaluated the safety and efficacy of a new oxidant preparation, liquid hyperoxygen (IOL), to neutralize the SARS-CoV-2 virus. IOL was incubated with throat swabs containing a human-type virus. The samples were then incubated with cells expressing the ACE2 receptor and, therefore, very sensitive to SARS-CoV-2 infection. The ability to neutralize SARS-CoV-2 was determined by assessing the amount of viral nucleic acid inside cells by PCR. The results obtained indicate that IOL, even at considerable dilutions, is capable, after incubation times of less than 30 min and even equal to 5 min, of completely inhibiting SARS-CoV-2 infection. This inhibitory effect has been shown to be due to the oxidizing capacity of the IOL. This oxidizing capacity is exerted towards the virus but does not damage eukaryotic cells either in the in vitro or in vivo skin models. Obtained results indicate that the use of IOL, a hydrophilic liquid mixture saturated with highly reactive oxygen and nitrogen species, is a new powerful, safe, and effective tool for preventing possible future outbreaks of the COVID-19 disease.
A Monocarbonyl Curcuminoid Derivative Inhibits the Activity of Human Glutathione Transferase A4-4 and Chemosensitizes Glioblastoma Cells to Temozolomide
Authors: Tsouri Steliana , Tselo Evanthia , Premetis Georgios E. , Furlan Veronika , Pantiora Panagiota D. , Mavroidi Barbara , Matiadis Dimitris , Pelecanou Maria , Papageorgiou Anastassios C. , Bren Urban , Sagnou Marina , Labrou Nikolaos E.
Published: March 2024

Human glutathione transferase A4-4 (hGSTA4-4) displays high catalytic efficiency towards 4-hydroxyalkenals and other cytotoxic and mutagenic products of radical reactions and lipid peroxidation. Its role as a target for the chemosensitization of cancer cells has not been investigated so far. In this study, the inhibitory potency of twelve selected natural products and ten monocarbonyl curcumin derivatives against hGSTA4-4 was studied. Among natural products, ellagic acid turned out to be the strongest inhibitor with an IC50 value of 0.44 ± 0.01 μM. Kinetic analysis using glutathione (GSH) and 1-chloro-2,4-dinitrobenzene (CDNB) as variable substrates showed that ellagic acid behaved as a competitive inhibitor towards both GSH and CDNB, with Ki values of 0.39 ± 0.02 and 0.63 ± 0.03 μM, respectively. Among the curcumin derivatives studied, three proved to be the most potent inhibitors, in the order DM151 > DM101 > DM100, with IC50 values of 2.4 ± 0.1 μM, 12.7 ± 1.1 μΜ and 16.9 ± 0.4 μΜ, respectively. Further kinetic inhibition analysis of the most active derivative, DM151, demonstrated that this compound is a mixed inhibitor towards CDNB with inhibition constants of Ki = 4.1 ± 0.5 μM and Ki’ = 0.536 ± 0.034 μM, while it is a competitive inhibitor towards GSH with a Ki = 0.98 ± 0.11 μM. Molecular docking studies were performed to interpret the differences in binding of ellagic acid and curcumin derivatives to hGSTA4-4. The in silico measured docking scores were consistent with the obtained experimental data. Hydrogen bonds appear to be the main contributors to the specific binding of monocarbonyl curcumin derivatives, while π-π stacking interactions play a key role in the enzyme–ellagic acid interaction. In vitro cytotoxicity assessment of the worst (DM148) and the best (DM151) inhibitors was performed against glioblastoma cell lines U-251 MG and U-87 MG. The results revealed that DM151 displays considerably higher cytotoxicity against both glioblastoma cell lines, while the glioblastoma cytotoxicity of DM148 was very limited. Furthermore, low and non-toxic doses of DM151 sensitized U-251 MG cells to the first-line glioblastoma chemotherapeutic temozolomide (TMZ), allowing us to propose for the first time that hGSTA4-4 inhibitors may be attractive therapeutic partners for TMZ to optimize its clinical effect in glioblastoma chemotherapy.
Affordability of Paediatric Oral Anti-Infective Medicines in a Selected District, Sri Lanka
Authors: Kumarasinghe Malith , Weerasinghe Manuj C.
Published: March 2024

In this cross-sectional descriptive study conducted in the Ratnapura district, Sri Lanka, we assessed the affordability of oral pediatric anti-infective medicines (OPAIMs). Using a modified WHO/HAI medicinal price methodology, we examined the availability, median price ratios (MPRs), mean percentage difference, and affordability of the standard treatment of the originator brand (OB) and lowest-priced generic (LPG) OPAIMs in 30 private and 2 state-owned pharmacies. The study revealed disparities in availability, with only 50% of private pharmacies offering all 11 medicinal drugs in their generic form. The MPRs of OPAIMs for OB and LPG varied, with three drugs exceeding the financially acceptable MPR of 2 (albendazole, amoxicillin, and erythromycin). The standard treatment with LPGs costs between 0.17 and 0.85 and between 0.06 and 0.28 days’ wages for the lowest daily salary of the private sector and unskilled public employees, respectively. We identified erythromycin and albendazole as having less than 50% availability in their generic form in private pharmacies. To address these findings, we recommend frequent pricing revisions based on exchange rates and associated costs, coupled with the establishment of a transparent scientific criterion to subsidize essential medicines deemed “unaffordable.” Failure to implement such measures amidst economic crises may adversely impact financial access to essential medications.
In Vitro Profile of Hydrocortisone Release from Three-Dimensionally Printed Paediatric Mini-Tablets
Authors: Protopapa Chrystalla , Siamidi Angeliki , Kolipaka Siva Satyanarayana , Junqueira Laura Andrade , Douroumis Dennis , Vlachou Marilena
Published: March 2024

Three-dimensional (3D) printing is quickly being adopted in pharmaceutics due to the many advantages it offers, including treatment, adaptability, the reduction in waste and the accelerated development of new formulations. In this study, micro-extrusion printing was implemented for the production of modified-release hydrocortisone (HCT) mini-tablets for paediatric patients. For the developed formulations, Gelucire® 44/14 and Precirol® ATO 5 were used as the main inks at three different ratios: 70%/30%, 60%/40% and 50%/50%, respectively. The printing parameters (temperature and pressure) were altered accordingly for each ratio to achieve printability. The printed mini-tablets exhibited excellent printing quality, featuring consistent layer thicknesses and smooth surfaces. Dissolution tests were performed, and the results indicated a successful modified release of HCT from the mini-tablets. In summary, micro-extrusion exhibited favourable processing abilities for powder blends, facilitating quick printing and the fabrication of potential personalized dosages.
Tobramycin Reduces Pulmonary Toxicity of Polymyxin B via Inhibiting the Megalin-Mediated Drug Uptake in the Human Lung Epithelial Cells
Authors: Ahmed Maizbha Uddin , Li Jian , Zhou Qi (Tony)
Published: March 2024

Accumulation of polymyxins in the lung epithelial cells can lead to increased mitochondrial oxidative stress and pulmonary toxicity. Aminoglycosides and polymyxins are used, via intravenous and pulmonary delivery, against multidrug-resistant Gram-negative pathogens. Our recent in vitro and animal studies demonstrated that the co-administration of polymyxins with aminoglycosides decreases polymyxin-induced pulmonary toxicity. The aim of this study was to investigate the in vitro transport and uptake of polymyxin B and tobramycin in human lung epithelial Calu-3 cells and the mechanism of reduced pulmonary toxicity resulting from this combination. Transport, intracellular localization, and accumulation of polymyxin B and tobramycin were investigated using doses of 30 mg/L polymyxin B, 70 mg/L tobramycin, and the combination of both. Adding tobramycin significantly (p < 0.05) decreased the polymyxin B-induced cytotoxicity in Calu-3 cells. The combination treatment significantly reduced the transport and uptake of polymyxin B and tobramycin in Calu-3 cells, compared to each drug alone, which supported the reduced pulmonary toxicity. We hypothesized that cellular uptake of polymyxin B and tobramycin shared a common transporter, megalin. We further investigated the megalin expression of Calu-3 cells using confocal microscopy and evaluated megalin activity using a megalin substrate, FITC-BSA, and a megalin inhibitor, sodium maleate. Both polymyxin B and tobramycin significantly inhibited FITC-BSA uptake by Calu-3 cells in a concentration-dependent manner. Sodium maleate substantially inhibited polymyxin B and tobramycin transport and cellular accumulation in the Calu-3 cell monolayer. Our study demonstrated that the significantly reduced uptake of polymyxin B and tobramycin in Calu-3 cells is attributed to the mechanism of action that determines that polymyxin B and tobramycin share a common transporter, megalin.
Casimir Forces with Periodic Structures: Abrikosov Flux Lattices
Authors: Castillo-López Shunashi Guadalupe , Esquivel-Sirvent Raúl , Pirruccio Giuseppe , Villarreal Carlos
Published: March 2024

We investigate the influence of the Abrikosov vortex lattice on the Casimir force in a setup constituted by high-temperature superconductors subject to an external magnetic field. The Abrikosov lattice is a property of type II superconductors in which normal and superconducting carriers coexist and the latter define a periodic pattern with square symmetry. We find that the optical properties determined by spatial redistribution of the superconducting order parameter induce Casimir forces with a periodic structure whose minimal strengths coincide with the vortex cores.
Environmental Controls on Evapotranspiration and Its Components in a Qinghai Spruce Forest in the Qilian Mountains
Authors: Gao Guanlong , Guo Xiaoyun , Feng Qi , Xu Erwen , Hao Yulian , Wang Rongxin , Jing Wenmao , Ren Xiaofeng , Liu Simin , Shi Junxi , Wu Bo , Wang Yin , Wen Yujing
Published: March 2024

Qinghai spruce forests, found in the Qilian mountains, are a typical type of water conservation forest and play an important role in regulating the regional water balance and quantifying the changes and controlling factors for evapotranspiration (ET) and its components, namely, transpiration (T), evaporation (Es) and canopy interceptions (Ei), of the Qinghai spruce, which may provide rich information for improving water resource management. In this study, we partitioned ET based on the assumption that total ET equals the sum of T, Es and Ei, and then we analyzed the environmental controls on ET, T and Es. The results show that, during the main growing seasons of the Qinghai spruce (from May to September) in the Qilian mountains, the total ET values were 353.7 and 325.1 mm in 2019 and 2020, respectively. The monthly dynamics in the daily variations in T/ET and Es/ET showed that T/ET increased until July and gradually decreased afterwards, while Es/ET showed opposite trends and was mainly controlled by the amount of precipitation. Among all the ET components, T always occupied the largest part, while the contribution of Es to ET was minimal. Meanwhile, Ei must be considered when partitioning ET, as it accounts for a certain percentage (greater than one-third) of the total ET values. Combining Pearson’s correlation analysis and the boosted regression trees method, we concluded that net radiation (Rn), soil temperature (Ts) and soil water content (SWC) were the main controlling factors for ET. T was mainly determined by the radiation and soil hydrothermic factors (Rn, photosynthetic active radiation (PAR) and TS30), while Es was mostly controlled by the vapor pressure deficit (VPD), atmospheric precipitation (Pa), throughfall (Pt) and air temperature (Ta). Our study may provide further theoretical support to improve our understanding of the responses of ET and its components to surrounding environments.