bluuebunny/crossref_metadata_2025 huggingface dataset:
The Role of Ranolazine in the Treatment of Ventricular Tachycardia and Atrial Fibrillation: A Narrative Review of the Clinical Evidence
Authors: Murai Kyosuke , Vasigh Amir , Alexy Tamás , Tóth Kálmán , Czopf László
Published: July 2024

Cardiac arrhythmias are among the leading causes of morbidity and mortality worldwide. While antiarrhythmic drugs traditionally represent the first-line management strategy, their use is often limited by profound proarrhythmic effects. Several studies, including randomized control trials (RCTs), have demonstrated the antiarrhythmic efficacy of ranolazine, which is registered as an antianginal agent, while also establishing its safety profile. This review compiles clinical evidence investigating the antiarrhythmic properties of ranolazine, focusing primarily on ventricular tachycardia (VT) and atrial fibrillation (AF), as they are common rhythm abnormalities with serious complications. Data from RCTs indicate that ranolazine reduces VT incidence, although this effect is not universal. Therefore, we attempt to better describe the patient population that gains the most benefit from ranolazine due to VT suppression. Additionally, ranolazine is known to enhance the conversion rate of AF to sinus rhythm when combined with other antiarrhythmic drugs such as amiodarone, highlighting its synergistic effect in the atrium without provoking ventricular dysrhythmias. Despite the heterogeneity in the currently available data, ranolazine appears to be an effective and safe option for the management of various arrhythmias.
Post-Bariatric Hypoglycemia in Individuals with Obesity and Type 2 Diabetes after Laparoscopic Roux-en-Y Gastric Bypass: A Prospective Cohort Study
Authors: Kehagias Dimitrios , Lampropoulos Charalampos , Vamvakas Sotirios-Spyridon , Kehagia Eirini , Georgopoulos Neoklis , Kehagias Ioannis
Published: July 2024

Post-bariatric hypoglycemia (PBH) is an increasingly recognized complication after metabolic bariatric surgery (MBS). The aim of this study is to investigate potential factors associated with PBH. A cohort of 24 patients with type 2 diabetes mellitus (T2DM) and body mass index (BMI) ≥40 kg/m2 who underwent laparoscopic Roux-en-Y gastric bypass (LRYGBP) was retrospectively investigated for PBH at 12 months. PBH was defined as postprandial glucose at 120 min below 60 mg/dL. Questionnaires based on the Edinburgh hypoglycemia scale were filled out by the participants. Glycemic parameters and gastrointestinal (GI) hormones were also investigated. Based on the questionnaires, five patients presented more than four symptoms that were highly indicative of PBH at 12 months. According to glucose values at 120 min, one patient experienced PBH at 6 months and four patients experienced it at 12 months. Postprandial insulin values at 30 min and 6 months seem to be a strong predictor for PBH (p < 0.001). GLP-1 and glucagon values were not significantly associated with PBH. PBH can affect patients with T2DM after MBS, reaching the edge of hypoglycemia. Postprandial insulin levels at 30 min and 6 months might predict the occurrence of PBH at 12 months, but this requires further validation with a larger sample size.
Heterogeneous Patterns of Endothelial NF-κB p65 and MAPK c-Jun Activation, Adhesion Molecule Expression, and Leukocyte Recruitment in Lung Microvasculature of Mice with Sepsis
Authors: Wang Zhendong , Dayang Erna-Zulaikha , Zwiers Peter J. , Hernandez Garcia Martha L. , Luxen Matthijs , van Meurs Matijs , Moser Jill , Kamps Jan A. A. M. , Molema Grietje
Published: July 2024

Background: Sepsis is an uncontrolled systemic inflammatory response to an infection that can result in acute failure of the function of the lung called acute respiratory distress syndrome. Leukocyte recruitment is an important hallmark of acute lung failure in patients with sepsis. Endothelial cells (EC) participate in this process by facilitating tethering, rolling, adhesion, and transmigration of leukocytes via adhesion molecules on their cell surface. In in vivo studies, endothelial nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) p65 and mitogen-activated protein kinase (MAPK) c-Jun intracellular signal transduction pathways were reported to regulate the expression of adhesion molecules. Methods: Mice underwent cecal ligation and puncture (CLP) to induce polymicrobial sepsis and were sacrificed at different time points up to 72 h after sepsis onset. Immunohistochemistry and reverse transcription–quantitative polymerase chain reaction (RT-qPCR) analyses were used to determine the kinetics of nuclear localization of p65 and c-Jun in EC, expression and location of adhesion molecules E-selectin and vascular cell adhesion molecule 1 (VCAM-1). Furthermore, the extent and location of leukocyte recruitment were assessed based on Ly6G staining of neutrophils, cluster determinant (CD) 3 staining of T lymphocytes, and CD68 staining of macrophages. Results: In all pulmonary microvascular beds, we identified p65 and c-Jun nuclear accumulation in a subset of endothelial cells within the first 24 h after CLP-sepsis initiation. E-selectin protein was expressed in a subset of microvessels at 4 and 7 h after sepsis initiation, while VCAM-1 was expressed in a scattered pattern in alveolar tissue and microvessels, without discernible changes during sepsis development. CLP-induced sepsis predominantly promoted the accumulation of neutrophils and T lymphocytes 4 and 7 h after disease onset. Neutrophil accumulation occurred in all pulmonary microvascular beds, while T lymphocytes were present in alveolar tissue and postcapillary venules. Taken together, nuclear localization of p65 and c-Jun in EC and neutrophil recruitment could be associated with induced E-selectin expression in the pulmonary microvessels in CLP-septic mice at the early stage of the disease. In alveolar capillaries, on the other hand, activation of these molecular pathways and leukocyte accumulation occurred in the absence of E-selectin or VCAM-1. Conclusions: Endothelial activation and leukocyte recruitment in sepsis-induced lung injury are regulated by multiple, heterogeneously controlled mechanisms, which vary depending on the type of microvascular bed involved.
Mesenchymal Stem Cells in Myelodysplastic Syndromes and Leukaemia
Authors: Eroz Ilayda , Kakkar Prabneet Kaur , Lazar Renal Antoinette , El-Jawhari Jehan
Published: July 2024

Mesenchymal stem cells (MSCs) are one of the main residents in the bone marrow (BM) and have an essential role in the regulation of haematopoietic stem cell (HSC) differentiation and proliferation. Myelodysplastic syndromes (MDSs) are a group of myeloid disorders impacting haematopoietic stem and progenitor cells (HSCPs) that are characterised by BM failure, ineffective haematopoiesis, cytopenia, and a high risk of transformation through the expansion of MDS clones together with additional genetic defects. It has been indicated that MSCs play anti-tumorigenic roles such as in cell cycle arrest and pro-tumorigenic roles including the induction of metastasis in MDS and leukaemia. Growing evidence has shown that MSCs have impaired functions in MDS, such as decreased proliferation capacity, differentiation ability, haematopoiesis support, and immunomodulation function and increased inflammatory alterations within the BM through some intracellular pathways such as Notch and Wnt and extracellular modulators abnormally secreted by MSCs, including increased expression of inflammatory factors and decreased expression of haematopoietic factors, contributing to the development and progression of MDSs. Therefore, MSCs can be targeted for the treatment of MDSs and leukaemia. However, it remains unclear what drives MSCs to behave abnormally. In this review, dysregulations in MSCs and their contributions to myeloid haematological malignancies will be discussed.
A Narrative Review of Compassion Focused Therapy on Positive Mental Health Outcomes
Authors: Kotera Yasuhiro , Beaumont Julie , Edwards Ann-Marie , Cotterill Matthew , Kirkman Ann , Tofani Aiesha Carew , McPhilbin Merly , Takhi Simran , Barnes Kristian , Todowede Olamide , Ingall Benjamin-Rose , Asano Kenichi , Arimitsu Kohki
Published: July 2024

Background: Compassion-focused therapy (CFT) has been attracting attention in mental health practice and research. CFT is effective in reducing a variety of negative mental health symptoms. Positive mental health (PMH) focuses on an individual’s functioning, quality of life, and well-being, aiming to achieve fulfilment. A need for PMH has been increasingly recognised such as national policies incorporating recovery-oriented approaches. However, how effective CFT is for PMH outcomes remains to be investigated. This narrative review aimed to identify the literature that reports evidence on CFT used against PMH outcomes. Methods: Our research questions (RQs) were as follows: RQ1. What PMH outcomes are targeted in CFT intervention research? RQ2. Is CFT effective for PMH?” Medline, Embase, and PsycINFO were searched on the Ovid platform. All studies that mentioned “compassion focused therapy” and “compassion-focused therapy” were searched. Results: Sixteen RCTs were included published since 2012. Nine studies were from Europe, four from Asia, two from Northern America, and one from Australia and New Zealand. CFT was used for diverse PMH outcomes, and the effects were overall positive. Self-compassion and compassion were the most frequently evaluated outcomes. Conclusions: The mechanism of action for CFT on PMH needs to be evaluated. CFT can be used as part of personal recovery in mental health. More evidence from non-WEIRD countries including LMICs is needed.
Horizontal Hysteretic Behavior of Circular Concrete-Filled Steel Tubular Columns with Ultra-Large Diameter-to-Thickness Ratios
Authors: Wei Jun , Hu Bo , Wang Zhenshan , Meng Hao
Published: July 2024

Thin-walled concrete-filled steel tubes are efficient and economical with promising applications in civil and light industrial buildings. However, their local buckling resistance and deformation capacity are low, which adversely affects the seismic safety of structures. There are relatively few studies on thin-walled concrete-filled steel tubular columns with ultra-large diameter-to-thickness ratios, and there is also a lack of relevant experimental research on them. In this study, horizontal hysteresis tests were conducted on concrete columns with a large diameter-to-thickness ratio. The seismic performances of regular and straight-ribbed specimens were analyzed and compared, including the analyses of load-displacement hysteresis curves, strain distribution, skeleton curves, ductility, and energy dissipation capacity. Using these results, a restoring force model for concrete columns with a large diameter-to-thickness ratio was established. The findings indicate that under horizontal loading, the ductility of concrete columns with a regular thin-walled steel tube is 3.9, with an equivalent viscous damping coefficient of 1.65. Meanwhile, the ultimate bearing capacity is 201 kN. After adding stiffening ribs, the ultimate bearing capacity reaches 266 kN and the ductility coefficient reaches 4.4, resulting in the stiffeners increasing the ultimate bearing capacity and ductility by >30% and 12.8%, respectively. However, they have a less pronounced effect on deformation and energy dissipation. Building on these research outcomes, we propose a dimensionless three-line skeleton curve model and a restoring force model. The calculation results from these models align well with the test results, offering valuable insights for the seismic safety analysis of real-world engineering structures.
Experimental and Analytical Investigations of Torsional Strength in Ultra-High-Performance Concrete Beams with Transverse Openings
Authors: Ali Lina H. , Hassan Rafea F. , Hussein Husam H.
Published: July 2024

This study investigates the torsional performance of reinforced concrete beams with transverse circular openings and examines methods to mitigate the detrimental effects of these openings using Ultra-High-Performance Concrete (UHPC) and diagonal reinforcement. The experimental component involved casting and evaluating eight beams with dimensions of 150 × 200 × 1200 mm under pure torsion. Among these, two beams were solid (without openings), one was made from normal-strength concrete (NSC), and the rest were cast with UHPC. The beams with openings were categorized into two groups based on the size of the openings—small and large. Each group comprised three beams: the first was cast from NSC and included diagonal reinforcement, the second from UHPC with diagonal reinforcement, and the third from UHPC but without diagonal reinforcement. Results indicated that all beams with openings cast from UHPC exhibited a substantial increase in ultimate torque compared to the control NSC solid beam. NSC beams with small openings showed a marginal decrease in ultimate load capacity by 1.47%, whereas those with large openings experienced a significant reduction of 17.65%. UHPC effectively compensated for the strength lost due to the absence of diagonal reinforcement in both small and large openings. Initial stiffness in NSC beams decreased by 19.4% and 70.1% for small and large openings, respectively. Conversely, UHPC beams demonstrated improved initial stiffness, with increases of approximately 64% for small and 34% for large openings. This study proposes ultimate torsional equations for UHPC beams with various opening sizes. These equations are validated by comparing them with results from previous experimental research, examining the performance of UHPC beams with and without openings.
Quantitative Analysis of Vernacular Residential Building Typologies and Bioclimatic Strategies in the Warm-Summer Mediterranean Climate: The Montesinho Natural Park as a Case Study
Authors: Khei Soon , Mateus Ricardo , Ortega Javier , Briones-Llorente Raúl
Published: July 2024

Vernacular architecture embodies a lasting connection between communities, climates, and topographic landscapes, providing basic shelter needs for centuries. Adopting Montesinho Natural Park as a case study, this paper explores the essence of vernacular architecture, highlighting its adaptation and dynamic relationships with local climates, geographical features, and scarce resources. This paper firstly provides a quantitative characterisation of residential vernacular building typologies in several villages of the park based on field-collected data, using photography and videography for data reliability. The building typologies were then categorised according to their prominent architectural features, prioritising the access to the upper floor and door’s relative location and their integration within the landscape’s topography. The collected data were analysed by averaging each typology percentage across the villages and calculating dependency probabilities between each typology and the villages, aiming to identify the most frequent typologies and their dependency relationships with villages. This paper’s outcome entails the Protruding Staircase typology as the most common typology in the selected villages. Despite modern interventions, traditional features endure, emphasising practicality and resource efficiency. Among them, several bioclimatic strategies were identified and analysed qualitatively based on their potential contribution to energy efficiency and savings, highlighting their relationships with the local context and the typologies presented. The findings are important in supporting decision-making related to vernacular heritage in Northeastern Portugal. The bioclimatic construction strategies identified may be used as preliminary references to incorporate into rehabilitation projects and sustainable architecture practices, enhancing inhabitants’ thermal comfort and living conditions.
Improvement of Latent Heat Thermal Energy Storage Rate for Domestic Solar Water Heater Systems Using Anisotropic Layers of Metal Foam
Authors: Younis Obai , Mozaffari Masoud , Ahmed Awadallah , Ghalambaz Mehdi
Published: July 2024

Latent Heat Transfer Thermal Energy Storage (LHTES) units are crucial in managing the variability of solar energy in solar thermal storage systems. This study explores the effectiveness of strategically placing layers of anisotropic and uniform metal foam (MF) within an LHTES to optimize the melting times of phase-change materials (PCMs) in three different setups. Using the enthalpy–porosity approach and finite element method simulations for fluid dynamics in MF, this research evaluates the impact of the metal foam’s anisotropy parameter (Kn) and orientation angle (ω) on thermal performance. The results indicate that the configuration placing the anisotropic MF layer to channel heat towards the lower right corner shortens the phase transition time by 2.72% compared to other setups. Conversely, the middle setup experiences extended melting periods, particularly when ω is at 90°—an increase in Kn from 0.1 to 0.2 cuts the melting time by 4.14%, although it remains the least efficient option. The findings highlight the critical influence of MF anisotropy and the pivotal role of ω = 45°. Angles greater than this significantly increase the liquefaction time, especially at higher Kn values, due to altered thermal conductivity directions. Furthermore, the tactical placement of the anisotropic MF layer significantly boosts thermal efficiency, as evidenced by a 13.12% reduction in the PCM liquefaction time, most notably in configurations with a lower angle orientation.
An Epilepsy-Associated CILK1 Variant Compromises KATNIP Regulation and Impairs Primary Cilia and Hedgehog Signaling
Authors: Limerick Ana , McCabe Ellie A. , Turner Jacob S. , Kuang Kevin W. , Brautigan David L. , Hao Yi , Chu Cheuk Ying , Fu Sean H. , Ahmadi Sean , Xu Wenhao , Fu Zheng
Published: July 2024

Mutations in human CILK1 (ciliogenesis associated kinase 1) are linked to ciliopathies and epilepsy. Homozygous point and nonsense mutations that extinguish kinase activity impair primary cilia function, whereas mutations outside the kinase domain are not well understood. Here, we produced a knock-in mouse equivalent to the human CILK1 A615T variant identified in juvenile myoclonic epilepsy (JME). This residue is in the intrinsically disordered C-terminal region of CILK1 separate from the kinase domain. Mouse embryo fibroblasts (MEFs) with either heterozygous or homozygous A612T mutant alleles exhibited a higher ciliation rate, shorter individual cilia, and upregulation of ciliary Hedgehog signaling. Thus, a single A612T mutant allele was sufficient to impair primary cilia and ciliary signaling in MEFs. Gene expression profiles of wild-type versus mutant MEFs revealed profound changes in cilia-related molecular functions and biological processes. The CILK1 A615T mutant protein was not increased to the same level as the wild-type protein when co-expressed with scaffold protein KATNIP (katanin-interacting protein). Our data show that KATNIP regulation of a JME-associated single-residue variant of CILK1 is compromised, and this impairs the maintenance of primary cilia and Hedgehog signaling.
Integration of Ion Exchange—AOP—Biological System for the Treatment of Real Textile Wastewater
Authors: Giraldo-Loaiza Camila , Salazar-Loaiza Aura M. , Sandoval-Barrera María A. , Macías-Quiroga Iván F. , Ocampo-Serna Diana M. , Sanabria-González Nancy R.
Published: July 2024

Real textile wastewater (RTWW) poses significant environmental challenges. RTWW typically contains high levels of organic compounds, such as dyes, as well as inorganic substances like salts. These contaminants can harm aquatic life when released into water bodies without appropriate treatment. RTWW was subjected to a series of sequential treatments: exchange resins for removing ions, advanced oxidation with bicarbonate-activated peroxide to degrade organic matter, and a biological treatment based on the Zahn–Wellens test to remove remaining chemical oxygen demand (COD) The advanced oxidation process based on the activation of H2O2 with NaHCO3 (catalyzed with cobalt impregnated on a pillared clay, Co/Al–PILC)) was optimized using central composite design (CCD) and response surface methodology (RSM). After the process integration, reductions in ion concentrations, chemical oxygen demand (COD), and total organic carbon content (TOC) were achieved. Reduced hardness (99.94%) and ions (SO42− and acid black 194 dye of 99.88 and 99.46%, respectively), COD (96.64%), and TOC (96.89%), guaranteeing complete treatment of RTWW, were achieved. Additionally, the biodegradability index of RTWW increased from 0.28 ± 0.01 to 0.90 ± 0.01, and phytotoxicity was reduced, going from a phytotoxic that inhibited the germination of lettuce seeds to a phytostimulant after biological treatment with activated sludge.
Orofacial Features, Oral Health-Related Quality of Life, and Exposure to Bullying in Osteogenesis Imperfecta: A Cross-Sectional Study
Authors: Broutin Alice , Salles Jean-Pierre , Porquet-Bordes Valérie , Edouard Thomas , Vaysse Frédéric , Noirrit-Esclassan Emmanuelle
Published: July 2024

Background/Objectives: Osteogenesis imperfecta (OI) is a rare genetic disease that is responsible for bone fragility, but also for dental malocclusions and dentinogenesis imperfecta (DI). The aim of this study was to assess whether the severity of dental malocclusion influenced the oral health-related quality of life (OHRQoL) and exposure to bullying in a paediatric OI population compared with a control group. Methods: Dental and occlusal characteristics were noted during oral and radiographic examination. The severity of malocclusion was assessed using the PAR index. P-CPQ, COHIP(34), and BCS-A questionnaires were used to evaluate, respectively, externally and self-perceived OHRQoL and bullying. Results: We included 39 patients with a mean age of 11.3 (±4.8 SD) in the OI group, and 45 patients with a mean age of 12.3 (±3.2 SD) in the control group. There were no significant differences between the two groups in terms of occlusal vertical and transverse dimensions. Patients with severe OI, presenting with bone fractures, bones deformities, and short stature, had significantly more anterior (p < 0.05) and posterior openbites (p < 0.05) and more DI (p < 0.05) compared to patients who had moderate or mild OI. Self-perceived OHRQoL was negatively impacted by the disease (p = 0.01), particularly in the domains of oral health (p < 0.05) and self-image (p < 0.001), but not by its severity. Exposure to bullying did not differ significantly between the two groups, although more patients with OI reported being teased (21.4% face to face and 7.1% online vs. 14.6% and 2.4% in the control group). Conclusion: Interventions for dental malocclusion and oral health in OI patients would help to improve their quality of life and self-image.
Understanding Knowledge Mobilisation between Community Champions and Parents: Evidence from a Community-Based Programme to Support Parents with Young Children
Authors: Wilkinson Kath , Berry Vashti , Lloyd Jenny , Marks Georgina , Lang Iain
Published: July 2024

Background: Community champions have been employed across various settings to disseminate evidence-based public health information. The Building Babies’ Brains programme trains champions to work with parents in communities, equipping them with child development knowledge and parental engagement strategies. We explored what makes community champions effective in distributing information to parents, including how the champion–parent relationship and champions’ personal characteristics affect information dissemination. Methods: Champions included both peers and professionals working with parents in target communities. We administered an online survey (n = 53) and follow-up interviews (n = 14) with champions, with representation from across all training cohorts. We conducted a realist-informed reflexive thematic analysis to generate themes in the data and highlight the contexts, mechanisms, and outcome patterns identified. Results: We observed 15 Context–Mechanism–Outcome configurations across five themes: information sharing opportunities, information relevance, the nature of the champion–parent relationship, interaction expectations, and champion confidence. Our programme theory for how the community champion approach works identified that peer champions focused more on building rapport, modelling behaviours, and being a trusted community resource than direct information transfer. Professional champions, in contrast, showed greater expertise and confidence in discussing parenting practices directly. For both groups, traits such as friendliness and the ability to establish a trusting relationship enhanced effectiveness. Conclusions: This research identifies the impacts of champion role, characteristics, and the champion–parent relationship on the effectiveness of knowledge mobilisation in this context, with implications for training and recruitment of champions. Those using a champion model in comparable settings should ensure that champions have the necessary knowledge, skills, and confidence to engage parents and share information effectively.
Decoding India’s Child Malnutrition Puzzle: A Multivariable Analysis Using a Composite Index
Authors: Shah Gulzar , Siddiqa Maryam , Shankar Padmini , Karibayeva Indira , Zubair Amber , Shah Bushra
Published: July 2024

Background: This study examines the levels and predictors of malnutrition in Indian children under 5 years of age. Methods: Composite Index of Anthropometric Failure was applied to data from the India National Family Health Survey 2019–2021. A multivariable logistic regression model was used to assess the predictors. Results: 52.59% of children experienced anthropometric failure. Child predictors of lower malnutrition risk included female gender (adjusted odds ratio (AOR) = 0.881) and average or large size at birth (AOR = 0.729 and 0.715, respectively, compared to small size). Higher birth order increased malnutrition odds (2nd-4th: AOR = 1.211; 5th or higher: AOR = 1.449) compared to firstborn. Maternal predictors of lower malnutrition risk included age 20–34 years (AOR = 0.806), age 35–49 years (AOR = 0.714) compared to 15–19 years, normal BMI (AOR = 0.752), overweight and obese BMI (AOR = 0.504) compared to underweight, and secondary or higher education vs. no education (AOR = 0.865). Maternal predictors of higher malnutrition risk included severe anemia vs. no anemia (AOR = 1.232). Protective socioeconomic factors included middle (AOR = 0.903) and rich wealth index (AOR = 0.717) compared to poor, and toilet access (AOR = 0.803). Children’s malnutrition risk also declined with paternal education (primary: AOR = 0.901; secondary or higher: AOR = 0.822) vs. no education. Conversely, malnutrition risk increased with Hindu (AOR = 1.258) or Islam religion (AOR = 1.369) vs. other religions. Conclusions: Child malnutrition remains a critical issue in India, necessitating concerted efforts from both private and public sectors. A ‘Health in All Policies’ approach should guide public health leadership in influencing policies that impact children’s nutritional status.
Sector Formula for Approximation of Spread Option Value & Greeks and Its Applications
Authors: Galeeva Roza , Wang Zi
Published: July 2024

The goal of this paper is to derive closed-form approximation formulas for the spread option value and Greeks by using double integration and investigating the exercise boundary. We have found that the straight-line approximation suggested in previous research does not perform well for curved exercise boundaries. We propose a novel approach: to integrate in a sector and find a closed-form formula expressed in terms of the bivariate normal CDF. We call it the sector formula. Numerical tests show the good accuracy of our sector formula. We demonstrate applications of the formula to the market data of calendar spread options for three major commodities, WTI, Natural Gas, and Corn, listed on the CME site as of May, April, and June 2024.
Apigenin and Phloretin Combination for Skin Aging and Hyperpigmentation Regulation
Authors: Martínez-Gutiérrez Alfredo , Sendros Javier , Noya Teresa , González Mari Carmen
Published: July 2024

Melasma is a pathology with multifactorial causes that results in hyperpigmentation of sun-exposed areas, particularly facial skin. New treatments targeting the different factors regulating this condition need to be effective with and have limited adverse effects. Here, we describe a novel combination of two natural compounds (apigenin and phloretin) that has synergistic effects regulating melanogenesis in vitro. Both compounds inhibit Wnt-stimulated melanogenesis and induce autophagy in melanocytes. Apigenin induces DKK1, a Wnt pathway inhibitor, and reduces VEGF, a melanogenesis and proangiogenic factor, in fibroblasts. Moreover, apigenin induces miR-675, a melanogenesis inhibitor miRNA that is reduced in melasma skin in melanocytes. Both compounds showed senomorphic effects by regulating extracellular-matrix-related genes in senescent fibroblasts. Topical application of the compounds also showed significant melanin reduction in a reconstructed human epidermis after 7 days. Thus, the combination of apigenin and phloretin shows promising results as an effective topical treatment of skin hyperpigmentation conditions.
Focus on Pancreatic Cancer Microenvironment
Authors: Pratticò Fabiana , Garajová Ingrid
Published: July 2024

Pancreatic ductal adenocarcinoma remains one of the most lethal solid tumors due to its local aggressiveness and metastatic potential, with a 5-year survival rate of only 13%. A robust connection between pancreatic cancer microenvironment and tumor progression exists, as well as resistance to current anticancer treatments. Pancreatic cancer has a complex tumor microenvironment, characterized by an intricate crosstalk between cancer cells, cancer-associated fibroblasts and immune cells. The complex composition of the tumor microenvironment is also reflected in the diversity of its acellular components, such as the extracellular matrix, cytokines, growth factors and secreted ligands involved in signaling pathways. Desmoplasia, the hallmark of the pancreatic cancer microenvironment, contributes by creating a dense and hypoxic environment that promotes further tumorigenesis, provides innate systemic resistance and suppresses anti-tumor immune invasion. We discuss the complex crosstalk among tumor microenvironment components and explore therapeutic strategies and opportunities in pancreatic cancer research. Better understanding of the tumor microenvironment and its influence on pancreatic cancer progression could lead to potential novel therapeutic options, such as integration of immunotherapy and cytokine-targeted treatments.
Bootstrap Method as a Tool for Analyzing Data with Atypical Distributions Deviating from Parametric Assumptions: Critique and Effectiveness Evaluation
Authors: Kostanek Joanna , Karolczak Kamil , Kuliczkowski Wiktor , Watala Cezary
Published: July 2024

In today’s research environment characterized by exponential data growth and increasing complexity, the selection of appropriate statistical tests, tailored to research objectives and data distributions, is paramount for rigorous analysis and accurate interpretation. This article explores the growing prominence of bootstrapping, an advanced statistical technique for multiple comparisons analysis, offering flexibility and customization by estimating sample distributions without assuming population distributions, thus serving as a valuable alternative to traditional methods in various data scenarios. Computer simulations were conducted using data from cardiovascular disease patients. Two approaches, spontaneous partly controlled simulation and fully constrained simulation using self-written R scripts, were utilized to generate datasets with specified distributions and analyze the data using tests for comparing more than two groups. The utilization of the bootstrap method greatly improves statistical analysis, especially in overcoming the constraints of conventional parametric tests. Our research showcased its effectiveness in comparing multiple scenarios, yielding strong findings across diverse distributions, even with minor inflation in p values. Serving as a valuable substitute for parametric approaches, bootstrap promotes careful consideration when rejecting hypotheses, thus fostering a deeper understanding of statistical nuances and bolstering analytical rigor.
The Burden of Inpatient Hospitalizations with Cardiac and Cerebrovascular Diseases in Patients with Type 1 Diabetes: Insights from the National Inpatient Sample in the US
Authors: Kwok Chun Shing , Qureshi Adnan I. , Phillips Anne , Lip Gregory Y. H. , Hanif Wasim , Borovac Josip Andelo
Published: July 2024

Background: This study aimed to evaluate the burden and impact of cardiac and cerebrovascular disease (CCD) on hospital inpatients with type 1 diabetes mellitus (T1DM). Methods: This is a retrospective nationwide cohort study of people with T1DM with or without CCD in the US National Inpatient Sample between 2016 and 2019. The in-hospital mortality rates, length of stay (LoS), and healthcare costs were determined. Results: A total of 59,860 T1DM patients had a primary diagnosis of CCD and 1,382,934 did not. The median LoS was longer for patients with CCD compared to no CCD (4.6 vs. 3 days). Patients with T1DM and CCD had greater in-hospital mortality compared to those without CCD (4.1% vs. 1.1%, p < 0.001). The estimated total care cost for all patients with T1DM with CCD was approximately USD 326 million. The adjusted odds of mortality compared to patients with non-CCD admission was greatest for intracranial hemorrhage (OR 17.37, 95%CI 12.68–23.79), pulmonary embolism (OR 4.39, 95%CI 2.70–7.13), endocarditis (OR 3.46, 95%CI 1.22–9.84), acute myocardial infarction (OR 2.31, 95%CI 1.92–2.77), and stroke (OR 1.47, 95%CI 1.04–2.09). Conclusions: The burden of CCD in patients with T1DM is substantial and significantly associated with increased hospital mortality and high healthcare expenditures.
Prognostic Indicators of Morbidity and Mortality in Children with Congestive Hepatopathy Presenting with Ascites
Authors: Spahic Harisa , Wasuwanich Paul , Modanloo Bahareh , Rajborirug Songyos , Kutty Shelby , Cedars Ari , Karnsakul Wikrom
Published: July 2024

Objectives: Congestive hepatopathy is a significant complication for children suffering from right-sided heart disease (RHD). We hypothesize that hospitalized pediatric patients with ascites will have congestive hepatopathy leading to advanced liver disease if their cardiac condition is RHD versus non-right-sided heart disease (NRHD). Methods: This is a retrospective cohort study of pediatric patients who presented with an ascites diagnosis (ICD-10 R18) and at least one cardiac diagnosis. Patient demographics, past medical history, laboratory values, imaging results, calculated clinical scores (e.g., APRI, FIB-4), treatment, length of stay (LOS), and death at hospital discharge were analyzed. Results: Of the 136 patients with ascites, 21 patients presented with a primary cardiac disease (12 in RHD and 9 in NRHD). Of these patients, eight (38%) were female, and nine (43%) were White, seven (33%) were Black, and five (24%) were unknown. The RHD group had a mean age of 5.1 Y (vs. 9.5 Y in NRHD). The mean APRI score in RHD patients was 2.87, and it was 0.85 in NRDH. Treatments were similar, with most patients requiring diuretics (11 RHD (92%) vs. 8 NRDH (89%)); 5 RHD (42%) vs. 4 NRDH (44%) required inotropic support. RHD patients had a longer LOS, with an average of 92 days vs. 52 days for NRDH patients. Overall, each group had one death at discharge (8% RHD vs. 11% NRDH). Conclusions: In the realm of children with ascites, the subset grappling with congestive heart disease paints a unique picture. In this context, ascites stands as an elusive predictor of liver decompensation, defying conventional diagnostic pathways.
EEG-Based Detection of Mild Cognitive Impairment Using DWT-Based Features and Optimization Methods
Authors: Aljalal Majid , Aldosari Saeed A. , AlSharabi Khalil , Alturki Fahd A.
Published: July 2024

In recent years, electroencephalography (EEG) has been investigated for identifying brain disorders. This technique involves placing multiple electrodes (channels) on the scalp to measure the brain’s activities. This study focuses on accurately detecting mild cognitive impairment (MCI) from the recorded EEG signals. To achieve this, this study first introduced discrete wavelet transform (DWT)-based approaches to generate reliable biomarkers for MCI. These approaches decompose each channel’s signal using DWT into a set of distinct frequency band signals, then extract features using a non-linear measure such as band power, energy, or entropy. Various machine learning approaches then classify the generated features. We investigated these methods on EEGs recorded using 19 channels from 29 MCI patients and 32 healthy subjects. In the second step, the study explored the possibility of decreasing the number of EEG channels while preserving, or even enhancing, classification accuracy. We employed multi-objective optimization techniques, such as the non-dominated sorting genetic algorithm (NSGA) and particle swarm optimization (PSO), to achieve this. The results show that the generated DWT-based features resulted in high full-channel classification accuracy scores. Furthermore, selecting fewer channels carefully leads to better accuracy scores. For instance, with a DWT-based approach, the full-channel accuracy achieved was 99.84%. With only four channels selected by NSGA-II, NSGA-III, or PSO, the accuracy increased to 99.97%. Furthermore, NSGA-II selects five channels, achieving an accuracy of 100%. The results show that the suggested DWT-based approaches are promising to detect MCI, and picking the most useful EEG channels makes the accuracy even higher. The use of a small number of electrodes paves the way for EEG-based diagnosis in clinical practice.
Could Ocular Glands Be Infected by SARS-CoV-2?
Authors: Bu Jinghua , Zhang Minjie , Zhang Rongrong , Sun Le , Chen Zhenzong , Wu Yang
Published: July 2024

The aim of the study was to investigate the expression levels of ACE2 in ocular glands and to investigate the effect of S protein on them. Male C57BL/6J mice were used for the experiments. The expression levels of ACE2 are highest in the Meibomian glands, followed by the conjunctiva, the cornea, and the lacrimal glands. Co-immunoprecipitation assays confirmed direct binding between ACE2 and S protein in ocular surface epithelia and Meibomian glands. CD45+ cell infiltration was found in the S protein treatment group, which was accompanied by upregulation of inflammation-related cytokines. There was also prominent cell apoptosis in the S protein treatment group. In conclusion, not only the cornea and the conjunctiva, but also the Meibomian glands express ACE2, and S protein could induce ocular surface epithelial cell and Meibomian gland cell inflammation and apoptosis.
Optimized Tail Bounds for Random Matrix Series
Authors: Gao Xianjie , Zhang Mingliang , Luo Jinming
Published: July 2024

Random matrix series are a significant component of random matrix theory, offering rich theoretical content and broad application prospects. In this paper, we propose modified versions of tail bounds for random matrix series, including matrix Gaussian (or Rademacher) and sub-Gaussian and infinitely divisible (i.d.) series. Unlike present studies, our results depend on the intrinsic dimension instead of ambient dimension. In some cases, the intrinsic dimension is much smaller than ambient dimension, which makes the modified versions suitable for high-dimensional or infinite-dimensional setting possible. In addition, we obtain the expectation bounds for random matrix series based on the intrinsic dimension.
The Road to Safety: A Review of Uncertainty and Applications to Autonomous Driving Perception
Authors: Araújo Bernardo , Teixeira João F. , Fonseca Joaquim , Cerqueira Ricardo , Beco Sofia C.
Published: July 2024

Deep learning approaches have been gaining importance in several applications. However, the widespread use of these methods in safety-critical domains, such as Autonomous Driving, is still dependent on their reliability and trustworthiness. The goal of this paper is to provide a review of deep learning-based uncertainty methods and their applications to support perception tasks for Autonomous Driving. We detail significant Uncertainty Quantification and calibration methods, and their contributions and limitations, as well as important metrics and concepts. We present an overview of the state of the art of out-of-distribution detection and active learning, where uncertainty estimates are commonly applied. We show how these methods have been applied in the automotive context, providing a comprehensive analysis of reliable AI for Autonomous Driving. Finally, challenges and opportunities for future work are discussed for each topic.
sqlFuzz: Directed Fuzzing for SQL Injection Vulnerability
Authors: Yuan Ye , Lu Yuliang , Zhu Kailong , Huang Hui , Chen Yuanchao , Zhang Yifan
Published: July 2024

Fuzz testing technology is an important approach to detecting SQL injection vulnerabilities. Among them, coverage-guided gray-box fuzz testing technology is the current research focus, and has been proved to be an effective method. However, for SQL injection vulnerability, coverage-guided gray-box fuzz testing as a detection method has the problems of low efficiency and high false positives. In order to solve the above problems, we propose a potentially vulnerable code-guided gray-box fuzz testing technology. Firstly, taint analysis technology is used to locate all the taint propagation paths containing potential vulnerabilities as potentially vulnerable codes. Then, the source code of the application program is instrumented according to the location of the potentially vulnerable code. Finally, the feedback of seeds during the run is used to guide seed selection and seed mutation, and a large number of test cases are generated. Based on the above techniques, we implement the sqlFuzz prototype system, and use this system to analyze eight modern PHP applications. The experimental results show that sqlFuzz can not only detect more SQL injection vulnerabilities than the existing coverage-guided gray box fuzz testing technology, but also significantly improve the efficiency, in terms of time efficiency increased by 80 percent.
SSuieBERT: Domain Adaptation Model for Chinese Space Science Text Mining and Information Extraction
Authors: Liu Yunfei , Li Shengyang , Deng Yunziwei , Hao Shiyi , Wang Linjie
Published: July 2024

With the continuous exploration of space science, a large number of domain-related materials and scientific literature are constantly generated, mostly in the form of text, which contains rich and unexplored domain knowledge. Natural language processing technology has made rapid development and pre-trained language models provide promising information extraction tools. However, due to the strong professionalism of space science, there are many domain concepts and technical terms. Moreover, Chinese texts have complex language structures and word combinations, which may yield suboptimal performance by general pre-trained models such as BERT. In this work, we investigate how to adapt BERT to Chinese space science and propose the space science-aware pre-trained language model, namely, SSuieBERT. We validate it through downstream tasks such as named entity recognition, relation extraction, and event extraction, which can perform better than general models. To the best of our knowledge, our proposed SSuieBERT is the first pre-trained language model in space science, which can promote information extraction and knowledge discovery from space science texts.
Pseudo-Normalization via Integer Fast Inverse Square Root and Its Application to Fast Computation without Division
Authors: Kusaka Takashi , Tanaka Takayuki
Published: July 2024

Vector normalization is an important process in several algorithms. It is used in classical physical calculations, mathematical techniques, and machine learning, which has witnessed significant advancements in recent years. Normalization and regularization ensure the stability of solutions and play an important role in algorithm convergence. Normalization typically refers to the division of elements by their norm. Division should not be used in algorithmic implementations because its computational cost is considerably higher than that of multiply–add operations. Based on this, there is a well-known method referred to as the fast inverse square root (FISR) algorithm in floating-point calculations (IEEE754). In deeper-level embedded systems that require fast responses or power efficiency, integer instead of real number arithmetic (floating-point number arithmetic) should be used to increase speed. Conversely, in deeper-level embedded systems that require fast responses or power efficiency, integer arithmetic should be used instead of real number arithmetic (floating-point number arithmetic) to increase speed. Therefore, embedded engineers encounter problems in instances in which they use integer arithmetic for implementation, but real number arithmetic is required to compute vectors and other higher-dimensional algebra. There is no conventional normalization algorithm similar to the FISR algorithm for integer arithmetic; however, the proposed pseudo-normalization achieves vector normalization within a restricted domain using only multiply–add operations and bit shifts. This allows for fast and robust operations, even for low-performance MCUs that do not have power-efficient FPUs. As an example, this study demonstrates the computation of the arctangent (Arctan2 function; atan2(y, x)) with high precision using only integer multiply–add operations. In this study, we proposed a method of vector normalization using only integer arithmetic for embedded systems and confirmed its effectiveness by simulation using Verilog. The research results can contribute to various fields such as signal processing of IMU sensor data, faster artificial intelligence training, and efficient rendering of computer graphics.
Flexible Wearable Antenna for IoT-Based Plant Health Monitoring
Authors: Atanasov Nikolay Todorov , Atanasov Blagovest Nikolaev , Atanasova Gabriela Lachezarova
Published: July 2024

In recent years, the rapid development of wireless technologies has led to the widespread adoption of the Internet of Things (IoT) in various fields. One of the fastest-growing segments of IoT is the “smart” wearables sector. In the next few years, the development of flexible plant-wearable devices that can provide vital information about the physiological characteristics of plants will be essential to support the faster growth of precision agriculture. We propose a small (overall size Ø35 mm × 0.8 mm), ultra-lightweight (0.4 g), and elegant-shaped antenna for unobtrusive integration on a plant surface for application in IoT-based precision agriculture at ISM 2.45 GHz band. The radiating element has a design that resembles a dragonfly, making the antenna visually unnoticeable. We used ZZ Plant leaves as the substrate for the antenna and transparent polymer foil for encapsulating the conductive parts, achieving a highly flexible, waterproof, and chemically resistant antenna for application in harsh environments. The obtained results indicate that the antenna is resilient to changes in substrate relative permittivity up to ±20%. It exhibits high radiation efficiency (between 26% and 40%) and omnidirectional patterns across the ISM 2.45 GHz band. Moreover, the measured results align reasonably well with the simulated ones.