bluuebunny/crossref_metadata_2025 huggingface dataset:
Glycolipid Metabolic Disorders, Metainflammation, Oxidative Stress, and Cardiovascular Diseases: Unraveling Pathways
Authors: de Lima Enzo Pereira , Moretti Renato Cesar , Torres Pomini Karina , Laurindo Lucas Fornari , Sloan Kátia Portero , Sloan Lance Alan , Castro Marcela Vialogo Marques de , Baldi Edgar , Ferraz Bruna Fidencio Rahal , de Souza Bastos Mazuqueli Pereira Eliana , Catharin Virgínia Maria Cavallari Strozze , Mellen Carolina Haber , Caracio Flávia Cristina Castilho , Spilla Caio Sérgio Galina , Haber Jesselina F. S. , Barbalho Sandra Maria
Published: July 2024

Glycolipid metabolic disorders (GLMDs) are various metabolic disorders resulting from dysregulation in glycolipid levels, consequently leading to an increased risk of obesity, diabetes, liver dysfunction, neuromuscular complications, and cardiorenal vascular diseases (CRVDs). In patients with GLMDs, excess caloric intake and a lack of physical activity may contribute to oxidative stress (OxS) and systemic inflammation. This study aimed to review the connection between GLMD, OxS, metainflammation, and the onset of CRVD. GLMD is due to various metabolic disorders causing dysfunction in the synthesis, breakdown, and absorption of glucose and lipids in the body, resulting in excessive ectopic accumulation of these molecules. This is mainly due to neuroendocrine dysregulation, insulin resistance, OxS, and metainflammation. In GLMD, many inflammatory markers and defense cells play a vital role in related tissues and organs, such as blood vessels, pancreatic islets, the liver, muscle, the kidneys, and adipocytes, promoting inflammatory lesions that affect various interconnected organs through their signaling pathways. Advanced glycation end products, ATP-binding cassette transporter 1, Glucagon-like peptide-1, Toll-like receptor-4, and sphingosine-1-phosphate (S1P) play a crucial role in GLMD since they are related to glucolipid metabolism. The consequences of this is system organ damage and increased morbidity and mortality.
Retinal Vascular and Structural Changes in the Murine Alzheimer’s APPNL-F/NL-F Model from 6 to 20 Months
Authors: Sánchez-Puebla Lidia , López-Cuenca Inés , Salobrar-García Elena , González-Jiménez María , Arias-Vázquez Alberto , Matamoros José A. , Ramírez Ana I. , Fernández-Albarral José A. , Elvira-Hurtado Lorena , Saido Takaomi C. , Saito Takashi , Nieto-Vaquero Carmen , Cuartero María I. , Moro María A. , Salazar Juan J. , de Hoz Rosa , Ramírez José M.
Published: July 2024

Alzheimer’s disease (AD) may manifest retinal changes preceding brain pathology. A transversal case-control study utilized spectral-domain OCT angiography (SD-OCTA) and Angio-Tool software 0.6a to assess retinal vascular structures and OCT for inner and outer retina thickness in the APPNL-F/NL-F AD model at 6, 9, 12, 15, 17, and 20 months old. Comparisons to age-matched wild type (WT) were performed. The analysis focused on the three vascular plexuses using AngiooTool and on retinal thickness, which was represented with the Early Treatment Diabetic Retinopathy Study (ETDRS) sectors. Compared to WT, the APPNL-F/NL-F group exhibited both vascular and structural changes as early as 6 months persisting and evolving at 15, 17, and 20 months. Significant vascular alterations, principally in the superficial vascular complex (SVC), were observed. There was a significant decrease in the vessel area and the total vessel length in SVC, intermediate, and deep capillary plexus. The inner retina in the APPNL-F/NL-F group predominantly decreased in thickness while the outer retina showed increased thickness in most analyzed time points compared to the control group. There are early vascular and structural retinal changes that precede the cognitive changes, which appear at later stages. Therefore, the natural history of the APPNL-F/NL-F model may be more similar to human AD than other transgenic models.
Molecular Insight into Acute Limb Ischemia
Authors: Costa Davide , Ielapi Nicola , Perri Paolo , Minici Roberto , Faga Teresa , Michael Ashour , Bracale Umberto Marcello , Andreucci Michele , Serra Raffaele
Published: July 2024

Acute limb ischemia (ALI) is defined as a sudden reduction in blood flow to a limb, resulting in cessation of blood flow and, therefore, cessation of the delivery of nutrients and oxygen to the tissues of the lower limb. Despite optimal treatment to restore blood flow to ischemic tissues, some patients may suffer from ischemia/reperfusion (I/R) syndrome, the most severe complication after a revascularization procedure used to restore blood flow. There are multiple molecular and cellular factors that are involved in each phase of ALI. This review focuses firstly on molecular and cellular factors of arterial thrombosis, highlighting the role of atherosclerotic plaques, smooth muscle cells (SMCs), and cytokine which may alter key components of the extracellular matrix (ECM). Then, molecular and cellular factors of arterial embolism will be discussed, highlighting the importance of thrombi composition. Molecular and cellular factors of ischemia/reperfusion syndrome are analyzed in depth, highlighting several important mechanisms related to tissue damage, such as inflammation, apoptosis, autophagy, necrosis, and necroptosis. Furthermore, local and general complications of ALI are discussed in the context of molecular alterations. Ultimately, the role of novel biomarkers and targeted therapies is discussed.
Elucidating the Transcriptional States of Spermatogenesis—Joint Analysis of Germline and Supporting Cell, Mice and Human, Normal and Perturbed, Bulk and Single-Cell RNA-Seq
Authors: AbuMadighem Ali , Cohen Ofir , Huleihel Mahmoud
Published: July 2024

In studying the molecular underpinning of spermatogenesis, we expect to understand the fundamental biological processes better and potentially identify genes that may lead to novel diagnostic and therapeutic strategies toward precision medicine in male infertility. In this review, we emphasized our perspective that the path forward necessitates integrative studies that rely on complementary approaches and types of data. To comprehensively analyze spermatogenesis, this review proposes four axes of integration. First, spanning the analysis of spermatogenesis in the healthy state alongside pathologies. Second, the experimental analysis of model systems (in which we can deploy treatments and perturbations) alongside human data. Third, the phenotype is measured alongside its underlying molecular profiles using known markers augmented with unbiased profiles. Finally, the testicular cells are studied as ecosystems, analyzing the germ cells alongside the states observed in the supporting somatic cells. Recently, the study of spermatogenesis has been advancing using single-cell RNA sequencing, where scientists have uncovered the unique stages of germ cell development in mice, revealing new regulators of spermatogenesis and previously unknown cell subtypes in the testis. An in-depth analysis of meiotic and postmeiotic stages led to the discovery of marker genes for spermatogonia, Sertoli and Leydig cells and further elucidated all the other germline and somatic cells in the testis microenvironment in normal and pathogenic conditions. The outcome of an integrative analysis of spermatogenesis using advanced molecular profiling technologies such as scRNA-seq has already propelled our biological understanding, with additional studies expected to have clinical implications for the study of male fertility. By uncovering new genes and pathways involved in abnormal spermatogenesis, we may gain insights into subfertility or sterility.
Long- and Short-Term Glucosphingosine (lyso-Gb1) Dynamics in Gaucher Patients Undergoing Enzyme Replacement Therapy
Authors: Dubiela Pawel , Szymanska-Rozek Paulina , Hasinski Piotr , Lipinski Patryk , Kleinotiene Grazina , Giersz Dorota , Tylki-Szymanska Anna
Published: July 2024

Background: Gaucher disease (GD) is a lysosomal storage disorder caused by mutations in the GBA1 gene, leading to β-glucocerebrosidase deficiency and glucosylceramide accumulation. Methods: We analyzed short- and long-term dynamics of lyso-glucosylceramide (lyso-Gb1) in a large cohort of GD patients undergoing enzyme replacement therapy (ERT). Results: Eight-years analysis of lyso-Gb1 revealed statistically insignificant variability in the biomarker across the years and relatively high individual variability in patients’ results. GD type 1 (GD1) patients exhibited higher variability compared to GD type 3 (GD3) patients (coefficients of variation: 34% and 23%, respectively; p-value = 0.0003). We also investigated the short-term response of the biomarker to enzyme replacement therapy (ERT), measuring lyso-Gb1 right before and 30 min after treatment administration. We tested 20 GD patients (16 GD1, 4 GD3) and observed a rapid and significant reduction in lyso-Gb1 levels (average decrease of 17%; p-value < 0.0001). This immediate response reaffirms the efficacy of ERT in reducing substrate accumulation in GD patients but, on the other hand, suggests the biomarker’s instability between the infusions. Conclusions: These findings underscore lyso-Gb1’s potential as a reliable biomarker for monitoring efficacy of treatment. However, individual variability and dry blood spot (DBS) testing limitations urge a further refinement in clinical application. Our study contributes valuable insights into GD patient management, emphasizing the evolving role of biomarkers in personalized medicine.
Unraveling Chylomicron Retention Disease Enhances Insight into SAR1B GTPase Functions and Mechanisms of Actions, While Shedding Light of Intracellular Chylomicron Trafficking
Authors: Levy Emile , Fallet-Bianco Catherine , Auclair Nickolas , Patey Natalie , Marcil Valérie , Sané Alain Théophile , Spahis Schohraya
Published: July 2024

Over the past three decades, significant efforts have been focused on unraveling congenital intestinal disorders that disrupt the absorption of dietary lipids and fat-soluble vitamins. The primary goal has been to gain deeper insights into intra-enterocyte sites, molecular steps, and crucial proteins/regulatory pathways involved, while simultaneously identifying novel therapeutic targets and diagnostic tools. This research not only delves into specific and rare malabsorptive conditions, such as chylomicron retention disease (CRD), but also contributes to our understanding of normal physiology through the utilization of cutting-edge cellular and animal models alongside advanced research methodologies. This review elucidates how modern techniques have facilitated the decoding of CRD gene defects, the identification of dysfunctional cellular processes, disease regulatory mechanisms, and the essential role of coat protein complex II-coated vesicles and cargo receptors in chylomicron trafficking and endoplasmic reticulum (ER) exit sites. Moreover, experimental approaches have shed light on the multifaceted functions of SAR1B GTPase, wherein loss-of-function mutations not only predispose individuals to CRD but also exacerbate oxidative stress, inflammation, and ER stress, potentially contributing to clinical complications associated with CRD. In addition to dissecting the primary disease pathology, genetically modified animal models have emerged as invaluable assets in exploring various ancillary aspects, including responses to environmental challenges such as dietary alterations, gender-specific disparities in disease onset and progression, and embryonic lethality or developmental abnormalities. In summary, this comprehensive review provides an in-depth and contemporary analysis of CRD, offering a meticulous examination of the CRD current landscape by synthesizing the latest research findings and advancements in the field.
Cannabielsoin (CBE), a CBD Oxidation Product, Is a Biased CB1 Agonist
Authors: Haghdoost Mehdi , Young Scott , Roberts Matthew , Krebs Caitlyn , Bonn-Miller Marcel O.
Published: July 2024

Cannabielsoin (CBE) is primarily recognized as an oxidation byproduct of cannabidiol (CBD) and a minor mammalian metabolite of CBD. The pharmacological interactions between CBE and cannabinoid receptors remain largely unexplored, particularly with respect to cannabinoid receptor type 1 (CB1). The present study aimed to elucidate the interaction dynamics of CBE in relation to CB1 by employing cyclic adenosine monophosphate (cAMP) and β-arrestin assays to assess its role as an agonist, antagonist, and positive allosteric modulator (PAM). To our knowledge, this is the first publication to investigate CBE’s receptor activity in vitro. Our findings reveal that S-CBE acts as an agonist to CB1 with EC50 = 1.23 µg/mL (3.7 µM) in the cAMP assay. No agonist activity was observed in the β-arrestin assay in concentrations up to 12 µM, suggesting a noteworthy affinity towards G-protein activation and the cAMP signaling pathway. Furthermore, in silico molecular docking simulations were conducted to provide a structural basis for the interaction between CBE and CB1, offering insights into the molecular determinants of its receptor affinity and functional selectivity.
Ketosis Suppression and Ageing (KetoSAge) Part 2: The Effect of Suppressing Ketosis on Biomarkers Associated with Ageing, HOMA-IR, Leptin, Osteocalcin, and GLP-1, in Healthy Females
Authors: Cooper Isabella D. , Kyriakidou Yvoni , Petagine Lucy , Edwards Kurtis , Soto-Mota Adrian , Brookler Kenneth , Elliott Bradley T.
Published: July 2024

Metabolic dysfunctions are among the best documented hallmarks of ageing. Cardiovascular disease, Alzheimer’s disease, cancer, type 2 diabetes mellitus, metabolic-dysfunction-associated steatosis liver disease, and fragility fractures are diseases of hyperinsulinaemia that reduce life and healthspan. We studied the effect of suppressing ketosis in 10 lean (BMI 20.5 kg/m2 ± 1.4), metabolically healthy, pre-menopausal women (age 32.3 ± 8.9 years) maintaining nutritional ketosis (NK) for an average of 3.9 years (± 2.3) who underwent three 21-day phases: nutritional ketosis (NK; P1), suppressed ketosis (SuK; P2), and returned to NK (P3). Ketosis suppression significantly increased insulin, 1.83-fold (p = 0.0006); glucose, 1.17-fold (p = 0.0088); homeostasis model assessment for insulin resistance (HOMA-IR), 2.13-fold (p = 0.0008); leptin, 3.35-fold (p = 0.0010); total osteocalcin, 1.63-fold (p = 0.0138); and uncarboxylated osteocalcin, 1.98-fold (p = 0.0417) and significantly decreased beta-hydroxybutyrate, 13.50-fold (p = 0.0012) and glucagon-like peptide-1 (GLP-1), 2.40-fold (p = 0.0209). Sustained NK showed no adverse health effects and may mitigate hyperinsulinemia. All biomarkers returned to basal P1 levels after removing the intervention for SuK, indicating that metabolic flexibility was maintained with long-term euketonaemia.
How General and Inflammatory Status Impacts on the Prognosis of Patients Affected by Lung Cancer: State of the Art
Authors: Mazzella Antonio , Orlandi Riccardo , Maiorca Sebastiano , Uslenghi Clarissa , Chiari Matteo , Bertolaccini Luca , Casiraghi Monica , Lo Iacono Giorgio , Girelli Lara , Spaggiari Lorenzo
Published: July 2024

Pulmonary cancer is often associated with systemic inflammation and poor nutritional status and these two aspects are strongly correlated and related to the scarce infiltration of a tumor by immune cells. We reviewed all English literature reviews from 2000 to 2024 from PubMed, Scopus and Google Scholar, including original articles, review articles, and metanalyses. We excluded non-English language articles and case reports/case series. Generally speaking, nutritional and inflammatory status largely affect medium and long-term prognosis in lung cancer patients. A correct stratification of patients could improve their preoperative general functional nutritional and inflammatory status, minimizing, therefore, possible treatment complications and improving long-term prognosis.
Evaluation of Neuroinflammatory Contribution to Neurodegeneration in LRRK2 Drosophila Models
Authors: Nguyen Hoai Nam , Galleri Grazia , Rassu Antonio , Ciampelli Cristina , Bernardoni Roberto , Galioto Manuela , Albani Diego , Crosio Claudia , Iaccarino Ciro
Published: July 2024

Pathological mutations in the LRRK2 gene are the major genetic cause of Parkinson’s disease (PD). Although several animal models with either LRRK2 down- or over-expression have been developed, the physiological function of LRRK2 remains elusive. LRRK2 is constitutively expressed in various tissues including neurons and glial cells, but importantly, it is expressed at low levels in dopaminergic neurons, further contributing to the cryptic function of LRRK2. Significant levels of LRRK2 protein and mRNA have been detected in peripheral blood mononuclear cells, lymph nodes, the spleen, and primary microglia, strongly suggesting the contribution of inflammatory cells to neuronal degeneration. In this research article, using Drosophila LRRK2 models, we were able to demonstrate a significant contribution of glial cells to the LRRK2 pathological phenotype. Furthermore, in Drosophila, neurodegeneration is associated with a significant and important increase in specific inflammatory peptides. Finally, levetiracetam, a compound widely used in human therapy to treat epilepsy, was able to rescue both neuronal degeneration and neuroinflammation.
Anion Effect on Phase Separation of Polyethylene Glycol-8000–Sodium Salt Two-Phase Systems
Authors: Titus Amber R. , Madeira Pedro P. , Uversky Vladimir N. , Zaslavsky Boris Y.
Published: July 2024

Aqueous two-phase systems (ATPSs) are formed when two nonionic polymers, or a single polymer and salt, are mixed in water above a specific concentration, resulting in the emergence of phase separation and the formation of two immiscible aqueous phases. The solvent properties of the aqueous media within the phases of ATPSs rely on the specific composition of the co-solutes and the arrangement of the hydrogen bond network within each phase. Here, we investigate the anion effect of various sodium salts on the enhancement or destabilization of polyethylene glycol (PEG)–salt ATPS formation. Relatively small changes in ATPS ionic composition were shown to result in significant changes in solute partitioning. Additionally, we previously established that the arrangement of hydrogen bonds within the coexisting phases of ATPSs is different, as evidenced by Attenuated Total Reflection—Fourier Transform Infrared (ATR-FTIR) spectroscopic analysis of OH-stretch bands. The hydrogen bond arrangement was shown to abruptly change at concentrations below the threshold of macroscopic phase separation in the ATPSs. Using dynamic light scattering (DLS), we observed a correlation between these abrupt changes in H-bond arrangement and the detection of agglomerate formation in both polymer–polymer and polymer–salt systems.
Comfort for Users of the Educational Center Applying Sustainable Design Strategies, Carabayllo-Peru-2023
Authors: Cuya Nicole , Estrada Paul , Esenarro Doris , Vega Violeta , Vilchez Cairo Jesica , Mancilla-Bravo Diego C.
Published: July 2024

The educational problems in the area, economic disparities, conflict situations, and deficiencies in educational infrastructure directly affect the quality and accessibility of education. Therefore, the present research aims to generate comfort for users of the educational center by applying sustainable design strategies in Carabayllo, Peru. The study started with a literature review, an analysis of flora and fauna, passive design strategies, and climatic analysis applying sustainability strategies supported by digital tools (AutoCAD, Revit Collaborate, Climate Consultant, OpenStreetMap, JOSM, Rhinoceros, and Grasshopper). As a result, the design proposes an educational center that ensures year-round comfort through energy efficiency, the use of eco-friendly materials, and green roofs. Additionally, it includes the implementation of dry toilets, biofilters, and xerophytic vegetation for orchards, promoting food production and enhancing the treatment of nearby public spaces. In conclusion, this proposal enhances the quality of life for users by applying passive design strategies and sustainability principles, adopting clean energy sources, and efficiently managing waste, thereby contributing to the Sustainable Development Goals (SDGs).
Impact of Air Velocity on Mold Growth in High Temperature and Humidity Conditions: An Experimental Approach
Authors: Yang Zhijun , Gao Weijun , Yang Dandan , Hu Xiaotong , Xu Tao
Published: July 2024

To address the challenges of indoor mold in southern China, this study designed and constructed an innovative experimental system to investigate mold growth in buildings under the combined influence of multiple factors. Using Fluent simulation (Ansys Fluent 19.0), we designed a suitably sized experimental chamber to realistically replicate the effects of factors such as temperature, humidity, and air velocity on mold growth. After establishing and fine-tuning the experimental system, we conducted two preliminary experiments, successfully validating the feasibility of our setup. Additionally, we observed that in a high-temperature, high-humidity environment of 28 °C and 80% relative humidity, the mold growth rate in the experimental chamber increased with the rise in inlet air velocity. This experimental system will serve as the foundation for future studies on indoor mold growth in building spaces in southern China.
The Interplay between Spatial Layout and Visitor Paths in Modern Museum Architecture
Authors: Medaković Jelena , Atanacković Jeličić Jelena , Ecet Dejan , Nedučin Dejana , Krklješ Milena
Published: July 2024

This study investigates the transformative potential of contemporary museum architecture, emphasizing the intricate relationship between management requirements and spatial design. Contemporary museum practice must adapt to diverse visitor preferences and secure operational funding beyond public sources by increasing ticket sales through personalized visitor pathways. This necessity has led to a growing trend of reconfiguring permanent collections via temporary exhibitions to enhance performance and revenue. The study aims to demonstrate the strategic utilization of material and technical opportunities within museum structures, underscoring the critical role of spatial organization in optimizing functional arrangements and enriching the visitor experience. Methodologies include integrating museum management needs into architectural design and employing revised spatial configurations to improve accessibility and connectivity. A case study of the City Museum of Belgrade’s central building illustrates these methodologies’ application, enhancing direct access to galleries and expanding potential walking routes. Detailed analysis reveals that redesigned museum layouts can significantly boost efficiency, performance, and visitor satisfaction, thereby supporting the overall sustainability of cultural institutions. This approach enables traditionally resistant public museums to adapt to modern challenges by developing services and programs that attract diverse audiences and enhance visitor experiences, ultimately contributing to their economic, environmental, social, and cultural sustainability.
Experimental and Finite Element Analysis of Reinforced Concrete Beams Using Ferronickel Slag as Partial Replacement for Fine Aggregate under Semi-Cyclic Loading
Authors: Sjah Jessica , Ernawan Eristra , Handika Nuraziz , Astutiningsih Sotya , Vincens Eric
Published: July 2024

The smelting process of Ferronickel in Indonesia produces a significant amount of waste in the form of Ferronickel Slag (FNS), with an annual accumulation of up to 13 million metric tons. Previous studies have shown promising strength results for concrete utilizing FNS as a fine aggregate. This study aims to analyze the mechanical properties of three reinforced concrete (RC) beams measuring 15 cm × 25 cm × 300 cm, each containing FNS as a 50% substitute for fine aggregate. The RC Beams underwent experimental testing using a four-point loading scheme under semi-cyclic loading conditions. Test results show the beams’ capacity had reached up to 8 ton-f and their load–displacement responses show promising results. Digital Image Correlation (DIC) analysis facilitated the observation of surface deformation evolution due to loading, aiding in the identification of concrete crack patterns. Due to semi-cyclic loading, cracks on the beams’ surface were experiencing a crack opening and closing phenomenon, where the propagations of cracks ceased or reclosed throughout the unloading process. Moreover, the opening of residual cracks was also captured by DIC analysis. The experimental finding was validated by finite element analysis. The RC beam numerical model was created using the Timoshenko Multi-fiber element in CAST3M software version 2022. Mazars concrete and elastoplastic steel damage model were used as constitutive laws for numerical modeling. The model’s load–displacement response demonstrated satisfactory agreement compared to the experimental monotonic loading result. However, the model had limitations regarding the simulation of residual displacements of beams due to semi-cyclic loading.
A New Iterative Design Strategy for Steel Frames Modelled by Generalised Multi-Stepped Beam Elements
Authors: Benfratello Salvatore , Caddemi Salvatore , Palizzolo Luigi , Pantò Bartolomeo , Rapicavoli Davide
Published: July 2024

The paper deals with frame steel structures required to ensure sufficient resistance, appropriate ductility and safety against brittle failure. This special aim cannot be reached by utilizing standard procedures and standard beam elements. Therefore, the present study proposes an innovative design strategy devoted to plane steel frames constituted by I-shaped cross-section beam elements and subjected to simultaneous combinations of serviceability limit state conditions and ultimate limit state conditions. Special factory-made I-shaped uniform piecewise steel profiles are utilised to provide the optimal behaviour of the frame. The proposed design strategy consists of two subsequent steps: at first a classical sizing of the frame is performed by utilising standard steel profiles, then a specific optimal design problem is performed to define the optimal geometry of the I-shaped steel profiles that fulfils all the constraints related to the required resistance and the limited deformability as well as special introduced constraints related to the protection against the brittle failure. The reliability of the procedure and the expected optimal behaviour of the frame are checked by performing nonlinear static analyses employing a recently proposed Fibre Smart Displacement-Based (FSDB) beam element model. The proposed beam element is defined by adopting displacement shape functions capable of embedding the cross-section discontinuities by means of the use of generalised functions. Furthermore, the proposed shape functions are addressed to as “smart” since capable of update in accordance with the development of plastic deformations detected by means of fibre discretisation of the cross-section. The results related to a simple steel portal confirmed the expected optimal behaviour of the structure.
Review on the Increasing Role for PSMA-Based Radioligand Therapy in Prostate Cancer
Authors: von Eyben Finn Edler , Virgolini Irene , Baum Richard
Published: July 2024

In 2021, two randomized controlled trials (RCTs), TheraP and VISION, demonstrated that 177Lu-PSMA-617 as monotherapy was more effective for the decline of PSA than the comparator third-line treatments. Methods: Our review summarizes new RCTs that add to the use of radioligand therapy (RLT) for patients with high-risk prostate cancer (PCa). Results: Four past and present RCTs included 1081 patients. An RCT, ENZA-p, studied first-line treatment of patients with metastatic castration-resistant PCa (mCRPC). A combination of enzalutamide (ENZA) and 177Lu-PSMA-617 gave longer progression-free survival than ENZA as monotherapy. Other RCTs of patients with mCRPC, including the PSMAfore, and SPLASH trials, showed 177Lu-PSMA-617 as second-line treatment gave better progression-free survival than androgen receptor pathway inhibitors (combined p value < 6.9 × 10−6). Conclusions: Patients with PCa gain if they are given PSMA-RLT early in the treatment of PCa and as part of combination therapies.
Predictive Risk Factors and Scoring Systems Associated with the Development of Hepatocellular Carcinoma in Chronic Hepatitis B
Authors: Pastras Ploutarchos , Zazas Evaggelos , Kalafateli Maria , Aggeletopoulou Ioanna , Tsounis Efthymios P. , Kanaloupitis Stavros , Zisimopoulos Konstantinos , Kottaridou Eirini-Eleni-Konstantina , Antonopoulou Aspasia , Drakopoulos Dimosthenis , Diamantopoulou Georgia , Tsintoni Aggeliki , Thomopoulos Konstantinos , Triantos Christos
Published: July 2024

Chronic hepatitis B (CHB) infection constitutes a leading cause of hepatocellular carcinoma (HCC) development. The identification of HCC risk factors and the development of prognostic risk scores are essential for early diagnosis and prognosis. The aim of this observational, retrospective study was to evaluate baseline risk factors associated with HCC in CHB. Six hundred thirty-two consecutive adults with CHB (n = 632) [median age: 46 (IQR: 24)], attending the outpatients’ Hepatology clinics between 01/1993–09/2020 were evaluated. Core promoter mutations and cirrhosis-HCC (GAG-HCC), Chinese University-HCC (CU-HCC), risk estimation for hepatocellular carcinoma in chronic hepatitis B (REACH-B), Fibrosis-4 (FIB-4), and Platelet Age Gender–HBV (PAGE-B) prognostic scores were calculated, and receiver operating curves were used to assess their prognostic performance. HCC was developed in 34 (5.38%) patients. In the multivariable Cox regression analysis, advanced age (HR: 1.086, 95% CI: 1.037–1.137), male sex (HR: 7.696, 95% CI: 1.971–30.046), alcohol abuse (HR: 2.903, 95% CI: 1.222–6.987) and cirrhosis (HR: 21.239, 95% CI: 6.001–75.167) at baseline were independently associated with the development of HCC. GAG-HCC and PAGE-B showed the highest performance with c-statistics of 0.895 (95% CI: 0.829–0.961) and 0.857 (95% CI: 0.791–0.924), respectively. In the subgroup of patients with cirrhosis, the performance of all scores declined. When treated and untreated patients were studied separately, the discriminatory ability of the scores differed. In conclusion, HCC development was independently associated with advanced age, male sex, alcohol abuse, and baseline cirrhosis among a diverse population with CHB. GAG-HCC and PAGE-B showed high discriminatory performance to assess the risk of HCC development in these patients, but these performances declined in the subgroup of patients with cirrhosis. Further research to develop scores more specific to certain CHB subgroups is needed.
Vaginal Intraepithelial Neoplasia (VaIN) after Hysterectomy Is Strongly Associated with Persistent HR-HPV Infection
Authors: Bruno Maria Teresa , Panella Marco Marzio , Valenti Gaetano , Di Grazia Salvatore , Sgalambro Francesco , Farina Jessica , Previti Miriam , Mereu Liliana
Published: July 2024

The data from the literature show that women undergoing a LEEP due to CIN3 have a greater risk of having subsequent high-grade anogenital intraepithelial neoplasia or cancer, and the risk is greater for vaginal cancer than for anal and vulvar cancers. It is hypothesized that the laparoscopic hysterectomy procedure may cause a higher incidence of VaIN in hysterectomized women. There are few studies addressing this issue, and they show mixed results. This study aimed to investigate the incidence of high-grade or severe VaIN in the population of women undergoing hysterectomy for CIN3 or benign uterine disease and illustrate the treatment options and follow-up. Methods: This retrospective study was conducted on 170 women who underwent a laparoscopic hysterectomy due to high-grade cervical intraepithelial neoplasia (CIN3) or benign gynecological disease. The follow-up strategy included performing a cotest and colposcopy with biopsy if necessary. The median time between primary treatment and a diagnosis of high-grade VaIN was 18 months. Results: High-grade or severe VaIN was found in eight patients after hysterectomy (4.7%). All cases of high-grade VaIN occurred in women with persistent HPV infection. The most frequent genotype was 16. Women hysterectomized due to CIN3 showed an eight-fold greater risk than women hysterectomized due to benign disease of developing high-grade VaIN. The risk of VaIN is low in women hysterectomized due to benign disease. The risk of developing VaIN is greater in women with viral persistence. Conclusion: All these elements suggest that it is a history of HPV-related disease of the lower genital tract and viral persistence, rather than hysterectomy itself, that should be considered risk factors for the development of high-grade VaIN. After hysterectomy, patients with a history of CIN should undergo annual screening with vaginal dome cytology and HPV testing.
Staphylococcus aureus Alkaline Protease: A Promising Additive for Industrial Detergents
Authors: Alonazi Mona
Published: July 2024

A novel alkaline serine protease, derived from the Staphylococcus aureus strain ALA1 previously isolated from dromedary milk, was subjected to purification and characterization. Optimal protease production occurred under specific culture conditions. The purified protease, designated S. aureus Pr with a molecular mass of 23,662 Da and an N-terminal sequence, showed an approximately 89% similar identity with those of other Staphylococcus strains. It exhibited its highest enzymatic activity at a pH of 10.0 and 60 °C in the presence of 3 mM Ca2+. Remarkable thermostability was observed at temperatures up to 70 °C and within a pH range of 6.0 to 10.0 for 2 h. The presence of Ca2+ or Mg2+ and Zn2+ significantly enhanced both enzymatic activity and thermal stability. Additionally, notable stability was demonstrated in the presence of reducing and chaotropic agents as well as in surfactants, oxidizing agents, and organic solvents commonly found in detergent compositions. This highlights the enzyme’s potential as a versatile biocatalyst, especially in detergents. Its stability and compatibility with laundry detergents matched Alcalase 2.5 L, type Dx, and the Stearothermophilus protease, used as controls. Collectively, this study investigated the potential utilization of S. aureus Pr in industrial detergents as an excellent candidate for incorporation as an additive in detergent formulations.
Post-GWAS Validation of Target Genes Associated with HbF and HbA2 Levels
Authors: Caria Cristian Antonio , Faà Valeria , Porcu Susanna , Marongiu Maria Franca , Poddie Daniela , Perseu Lucia , Meloni Alessandra , Vaccargiu Simona , Ristaldi Maria Serafina
Published: July 2024

Genome-Wide Association Studies (GWASs) have identified a huge number of variants associated with different traits. However, their validation through in vitro and in vivo studies often lags well behind their identification. For variants associated with traits or diseases of biomedical interest, this gap delays the development of possible therapies. This issue also impacts beta-hemoglobinopathies, such as beta-thalassemia and sickle cell disease (SCD). The definitive cures for these diseases are currently bone marrow transplantation and gene therapy. However, limitations regarding their effective use restrict their worldwide application. Great efforts have been made to identify whether modulators of fetal hemoglobin (HbF) and, to a lesser extent, hemoglobin A2 (HbA2) are possible therapeutic targets. Herein, we performed the post-GWAS in vivo validation of two genes, cyclin D3 (CCND3) and nuclear factor I X (NFIX), previously associated with HbF and HbA2 levels. The absence of Ccnd3 expression in vivo significantly increased g (HbF) and d (HbA2) globin gene expression. Our data suggest that CCND3 is a possible therapeutic target in sickle cell disease. We also confirmed the association of Nfix with γ-globin gene expression and present data suggesting a possible role for Nfix in regulating Kruppel-like transcription factor 1 (Klf1), a master regulator of hemoglobin switching. This study contributes to filling the gap between GWAS variant identification and target validation for beta-hemoglobinopathies.
Exploring Enhanced Structural and Dielectric Properties in Ag-Doped Sr(NiNb)0.5O3 Perovskite Ceramic for Advanced Energy Storage
Authors: Tayari Faouzia , Benamara Majdi , Lal Madan , Essid Manel , Thakur Priyanka , Kumar Deepak , Teixeira S. Soreto , Graça M. P. F. , Nassar Kais Iben
Published: July 2024

The ceramic Sr(NiNb)0.5O3, incorporating silver doping in the A site, was synthesized using a sol–gel route and subjected to comprehensive analysis through various experimental techniques. X-ray diffraction data analysis indicates a rhombohedral crystal structure. Scanning electron microscopy (SEM) examination reveals densely packed grains with minimal surface porosity. A thorough investigation of electrical properties, encompassing dielectric constant, loss tangent, electrical impedance, modulus, conductivity, etc., was conducted across a wide frequency range (103–106 Hz) and temperature range (260–340 K). This analysis provided valuable insights into structure–property relationships and conduction mechanisms. The discussion highlights the significance of interface effects, space charge polarization, and Maxwell–Wagner dielectric relaxation in achieving the material’s high dielectric constant at low frequencies and elevated temperatures. Examination of temperature dependence through Nyquist plots elucidates the contributions of grain behavior to the material’s resistive and capacitive properties. The dielectric permittivity, dissipation of energy, and electrical characteristics like impedance, modulus and conductivity are notably influenced by the frequency of the applied electric field and temperature. Overall, the material exhibits promising potential for industrial applications such as energy storage, given its intriguing properties.
Optimizing Photocatalytic Lead Removal from Wastewater Using ZnO/ZrO2: A Response Surface Methodology Approach
Authors: Shakir Hiba Abduladheem , Alsaffar May Ali , Mageed Alyaa K. , Sukkar Khalid A. , Ghany Mohamed A. Abdel
Published: July 2024

One interesting method for environmental remediation is the use of ZnO/ZrO2 composites in the photocatalytic degradation of lead (Pb) in wastewater. Several studies have investigated different types of composites for the removal of heavy metals from wastewater. However, the efficiency of these composites in removing the heavy metals remains debatable. Hence, this study investigated the potential of using a ZnO/ZrO2 composite for the removal of Pb from wastewater. Response surface methodology (RSM) was utilized in this work to maximize the Pb photocatalytic removal over ZnO/ZrO2 in simulated wastewater. Based on a central composite design (CCD), the experimental design included adjusting critical process parameters such as catalyst dosage, initial Pb concentration, and pH. The ZnO/ZrO2 composite was synthesized using a physical mixing technique, and its physicochemical properties were studied by field emission scanning electron microscopy (FESEM), energy dispersive X-ray spectroscopy (EDS), Fourier transform infra-red (FTIR), and X-ray diffraction (XRD). Under visible light irradiation, photocatalytic Pb removal tests were carried out in a batch reactor. The findings showed that a ZnO/ZrO2 dose of 100 mg/L, a pH of 10, and an initial Pb content of 15 ppm were the optimal conditions for maximal Pb removal (above 91.2%). The actual Pb removal obtained from the experimental runs was highly correlated with that predicted using the RSM quadratic model. The usefulness of ZnO/ZrO2 composites for photocatalytic Pb removal is demonstrated in this work, which also emphasizes the significance of RSM in process parameter optimization for improved pollutant degradation. The models that have been proposed offer significant perspectives for the development and scalability of effective photocatalytic systems intended to remove heavy metals from wastewater.
The Effects of a School-Based Physical Activity Program on Physical Fitness in Egyptian Children: A Pilot Study from the DELICIOUS Project
Authors: Abdelkarim Osama , El-Gyar Noha , Shalaby Amira M. , Aly Mohamed
Published: July 2024

Background: Ensuring the physical fitness of Egyptian children is of paramount importance to their overall well-being, given the unique socio-cultural and educational barriers they face that may hinder their active participation. As part of the DELICIOUS project, the “Be Fit Program” aims to increase the level of physical fitness among Egyptian school-aged children. This study explores the effectiveness of a structured, six-week physical activity (PA) program in improving various facets of physical fitness in children, including body composition, speed, coordination, muscular strength, and cardiovascular endurance. With the increasing prevalence of sedentary lifestyles, such efforts are imperative to improve overall health outcomes. Methods: A cohort of 125 children, aged 8.50 to 12.25 y (mean age 10.19 ± 1.03 y), participated in the study. Their body composition, speed, coordination, strength, and aerobic fitness were assessed before and after the Be Fit Program using the revised International Physical Performance Test Profile. Paired t-tests were used to detect changes between the pre- and post-tests. Results: Following the six-week intervention, statistical analyses revealed significant improvements in coordination and lower body strength (p < 0.01). Aerobic endurance showed marginal improvements, approaching statistical significance (p = 0.06). Conversely, there were no statistically significant changes in body composition, speed, or upper body strength (p > 0.05). Conclusions: The study confirms that tailored, non-competitive physical activities can positively influence specific fitness components in Egyptian children. However, achieving holistic improvements across all targeted fitness domains may require further strategic adjustments or a longer program duration. This pilot study underscores the importance of culturally tailored, school-based PA programs and highlights the continued need for research and program refinement to comprehensively improve children’s fitness in the Egyptian context.
An Updated Reappraisal of Dupilumab in Children and Adolescents with Severe Asthma
Authors: Marseglia Gian Luigi , Licari Amelia , Tosca Maria Angela , Miraglia del Giudice Michele , Indolfi Cristiana , Ciprandi Giorgio
Published: July 2024

Severe asthma (SA) is still a demanding challenge in clinical practice. Type 2 inflammation is the most common phenotype in children and adolescents with SA. As a result, anti-inflammatory drugs, mainly corticosteroids (CSs), represent the first choice to reduce type 2 inflammation. However, SA patients may require high inhaled and oral CS doses to achieve and maintain asthma control. Some SA patients, despite the highest CS dosages, can even display uncontrolled asthma. Therefore, the biological era constituted a breakthrough in managing this condition. Dupilumab is a monoclonal antibody directed against the IL-4 receptor α-subunit (IL-4Rα), antagonizing against both IL-4 and IL-13, and has been approved for pediatric severe type 2 asthma. This review presents and discusses the most recent published studies on dupilumab in children and adolescents with SA. There is convincing evidence that dupilumab is a safe and effective option in managing SA as it can reduce asthma exacerbations, reduce CS use, and improve lung function, asthma control, and quality of life, also for caregivers. However, a thorough diagnostic pathway is mandatory, mainly concerning phenotyping. In fact, the ideal eligible candidate is a child or adolescent with a type 2 allergic phenotype.
The Etiology of Neuromuscular Hip Dysplasia and Implications for Management: A Narrative Review
Authors: Presedo Ana , Rutz Erich , Howard Jason J. , Shrader Michael Wade , Miller Freeman
Published: July 2024

This study summarizes the current knowledge of the etiology of hip dysplasia in children with neuromuscular disease and the implications for management. This article is based on a review of development of the hip joint from embryology through childhood growth. This knowledge is then applied to selective case reviews to show how the understanding of these developmental principles can be used to plan specific treatments. The development of the hip joint is controlled by genetic shape determination, but the final adult shape is heavily dependent on the mechanical environment experienced by the hip joint during growth and development. Children with neuromuscular conditions show a high incidence of coxa valga, hip dysplasia, and subluxation. The etiology of hip pathology is influenced by factors including functional status, muscular tone, motor control, child’s age, and muscle strength. These factors in combination influence the development of high neck–shaft angle and acetabular dysplasia in many children. The hip joint reaction force (HJRF) direction and magnitude determine the location of the femoral head in the acetabulum, the acetabular development, and the shape of the femoral neck. The full range of motion is required to develop a round femoral head. Persistent abnormal direction and/or magnitude of HJRF related to the muscular tone can lead to a deformed femoral head and a dysplastic acetabulum. Predominating thigh position is the primary cause defining the direction of the HJRF, leading to subluxation in nonambulatory children. The magnitude and direction of the HJRF determine the acetabular shape. The age of the child when these pathomechanics occur acts as a factor increasing the risk of hip subluxation. Understanding the risk factors leading to hip pathology can help to define principles for the management of neurologic hip impairment. The type of neurologic impairment as defined by functional severity assessed by Gross Motor Function Classification System and muscle tone can help to predict the risk of hip joint deformity. A good understanding of the biomechanical mechanisms can be valuable for treatment planning.
Impact of an Intervention Aimed at Improving Sleep Quality in Hospitalized Children
Authors: Lechosa-Muñiz Carolina , Ruiz-Azcona Laura , Belmonte Elena Pérez , Paz-Zulueta María , Cabero-Pérez María Jesús
Published: July 2024

Background: Hospitalized children need adequate sleep to favor early recovery. Methods: To study the sleep pattern of children admitted to a pediatric inpatient unit, a cross-sectional study was carried out at a reference hospital in northern Spain. The main study variables were medical specialty of admission, sleep-inducing treatment, hours of sleep at home and during admission, number of nocturnal awakenings, and reasons for awakening. Differences in the hours of sleep and nighttime awakenings between the initial period and at six months were calculated using the Student’s t-test. Results: We included 100 baseline patients and 100 post-intervention patients. Up to 4% of the baseline sample and 3% of the six-month sample had been prescribed a sleep-promoting drug. Regarding awakenings, 79% of the children in the baseline sample suffered awakenings, with a mean of 1.98 awakenings (range 1–13). At six months, the percentage of children who experienced awakenings decreased by 17%, with a mean of 1.34 (range 1–5). In the baseline sample, 48% were caused by nursing care, decreasing to 34% after the intervention. Conclusions: An educational intervention with the implementation of targeted evidence-based practices is a useful measure for improving the sleep pattern by decreasing the number of awakenings.