bluuebunny/crossref_metadata_2025 huggingface dataset:
Anti-Cancer Potential of Isoflavone-Enriched Fraction from Traditional Thai Fermented Soybean against Hela Cervical Cancer Cells
Authors: Sukhamwang Amonnat , Inthanon Sirinada , Dejkriengkraikul Pornngarm , Semangoen Tistaya , Yodkeeree Supachai
Published: August 2024

Cervical cancer is a leading cause of gynecological malignancies and cancer-related deaths among women worldwide. This study investigates the anti-cancer activity of Thua Nao, a Thai fermented soybean, against HeLa cervical carcinoma cells, and explores its underlying mechanisms. Our findings reveal that the ethyl acetate fraction of Thua Nao (TN-EA) exhibits strong anti-cancer potential against HeLa cells. High-performance liquid chromatography (HPLC) analysis identified genistein and daidzein as the major isoflavones in TN-EA responsible for its anti-cancer activity. TN-EA and genistein reduced cell proliferation and induced G2/M phase arrest, while daidzein induced G1 arrest. These responses were associated with the downregulation of cell cycle regulators, including Cyclin B1, cycle 25C (Cdc25C), and phosphorylated cyclin-dependent kinase 1 (CDK-1), and the upregulation of the cell cycle inhibitor p21. Moreover, TN-EA and its active isoflavones promoted apoptosis in HeLa cells through the intrinsic pathway, evidenced by increased levels of cleaved Poly (ADP-ribose) polymerase (PARP) and caspase-3, loss of mitochondrial membrane potential, and the downregulation of anti-apoptotic proteins B-cell leukemia/lymphoma 2 (Bcl-2), B-cell lymphoma-extra-large (Bcl-xL), cellular inhibitor of apoptosis proteins 1 (cIAP), and survivin. Additionally, TN-EA and its active isoflavones effectively reduced cell invasion and migration by downregulating extracellular matrix degradation enzymes, including Membrane type 1-matrix metalloproteinase (MT1-MMP), urokinase-type plasminogen activator (uPA), and urokinase-type plasminogen activator receptor (uPAR), and reduced the levels of the mesenchymal marker N-cadherin. At the molecular level, TN-EA suppressed STAT3 activation via the regulation of JNK and Erk1/2 signaling pathways, leading to reduced proliferation and invasion of HeLa cells.
Emerging Roles of Bile Acids and TGR5 in the Central Nervous System: Molecular Functions and Therapeutic Implications
Authors: Romero-Ramírez Lorenzo , Mey Jörg
Published: August 2024

Bile acids (BAs) are cholesterol derivatives synthesized in the liver and released into the digestive tract to facilitate lipid uptake during the digestion process. Most of these BAs are reabsorbed and recycled back to the liver. Some of these BAs progress to other tissues through the bloodstream. The presence of BAs in the central nervous system (CNS) has been related to their capacity to cross the blood–brain barrier (BBB) from the systemic circulation. However, the expression of enzymes and receptors involved in their synthesis and signaling, respectively, support the hypothesis that there is an endogenous source of BAs with a specific function in the CNS. Over the last decades, BAs have been tested as treatments for many CNS pathologies, with beneficial effects. Although they were initially reported as neuroprotective substances, they are also known to reduce inflammatory processes. Most of these effects have been related to the activation of the Takeda G protein-coupled receptor 5 (TGR5). This review addresses the new challenges that face BA research for neuroscience, focusing on their molecular functions. We discuss their endogenous and exogenous sources in the CNS, their signaling through the TGR5 receptor, and their mechanisms of action as potential therapeutics for neuropathologies.
Autoimmune Mast Cell Activation Test as a Diagnostic Tool in Chronic Spontaneous Urticaria
Authors: Koren Ana , Dejanović Luka , Rijavec Matija , Kopač Peter , Bizjak Mojca , Zidarn Mihaela , Košnik Mitja , Korošec Peter
Published: August 2024

Chronic spontaneous urticaria (CSU) is associated with skin mast cell activation, and its triggering mechanisms are not completely elucidated. Evidence suggests an autoimmune component of CSU. Our aim was to assess the usefulness of an autoimmune mast cell activation test (aiMAT) for diagnosing and differentiating CSU into different subtypes. We enrolled 43 patients with active, uncontrolled CSU before starting treatment with omalizumab and 15 controls. Patients were evaluated based on omalizumab response. aiMATs were performed using non-IgE-sensitized (NS) or myeloma IgE-sensitized (S) LAD2 cells, which were then stimulated with CSU/control sera (25 µL and 10 µL). The expression of CD63 was assessed with flow cytometry. CD63 response on NS-LAD2 was significantly increased in CSU patients compared to controls after the stimulation with 25 µL CSU/control sera (p = 0.0007) and with 10 µL CSU/control sera (p = 0.0001). The ROC curve analysis demonstrated an area under the curve (AUC) of 0.82. The cutoff for autoimmune-non-IgE-sensitized-MAT was 40.3% CD63+ LAD2, which resulted in 73.3% sensitivity and 81.4% specificity. CD63 response on S-LAD2 was significantly increased in CSU patients compared to controls after the stimulation with 25 µL CSU/control sera (p = 0.03). The ROC curve analysis demonstrated an AUC of 0.66. The cutoff for the autoimmune-myeloma IgE-sensitized-MAT was 58.4% CD63+ cells, which resulted in 62.8% sensitivity and 66.7% specificity. Overall, 36 out of 43 (84%) patients responded to omalizumab, and 7 (16%) were nonresponders. We found no differences between LAD2 CD63 response and response to omalizumab. In conclusion, aiMAT could represent a new diagnostic tool in CSU. Additional studies are needed to evaluate the potential benefits during omalizumab therapy.
Effects of Oxiris® Therapy on Cytokine Elimination after a LPS Infusion—An Experimental Animal Study
Authors: Kalenka Armin , Arens Philipp , Müllenbach Ralf M. , Weigand Markus A. , Brune Maik , Fiedler-Kalenka Mascha O.
Published: August 2024

The clinical effectiveness of Oxiris®, particularly in reducing cytokines, remains uncertain due to the limited data provided. This study explored and analyzed the application value of Oxiris® endotoxin adsorption technology in a large animal model. Pigs received an intravenous LPS infusion. Six animals were treated 2 h after the infusion with an Oxiris® hemadsorption using a pumpless extracorporeal technique for 6 h. Five animals served as controls. Cardiocirculatory parameters, hyperspectral analysis, and a panel of cytokines were measured. The lipopolysaccharide infusion induced sepsis-like inflammation with tachycardia, elevated pulmonary pressure, elevated lactate level, as well as elevated pro-inflammatory cytokines like interferon (IFN)-γ, interleukin (IL)-1β, IL-2, IL-6, IL-8, IL-12 and tumor necrosis factor alpha (TNF-α). In addition, increases of anti-inflammatory cytokines like IL-1ra and IL-10 were found. After 3 and 6 h in both groups, pro-inflammatory cytokines were significantly reduced. No differences between the intervention and the control group could be detected after 3 and 6 h for IL-1β, IL-2, IL-6, IL-8, IL-12 and TNF-α, suggesting no effect of the Oxiris® filter on the elimination of elevated cytokines with a pumpless extracorporeal hemadsorption technique. The presented large animal model may be a promising option for studying the effects of hemadsorption techniques.
Phase I–IV Drug Trials on Hepatocellular Carcinoma in Asian Populations: A Systematic Review of Ten Years of Studies
Authors: Raghav Alok , Jeong Goo Bo
Published: August 2024

Despite advances in the treatment of hepatocellular carcinoma (HCC) over the last few decades, treatment opportunities for patients with HCC remain limited. HCC is the most common form of liver cancer, accounting for approximately 90% of all cases worldwide. Moreover, apart from the current pharmacological interventions, hepatic resection and liver transplantation are the mainstay curative approaches for patients with HCC. This systematic review included phase I, II, III, and IV clinical trials (CTs) and randomized controlled trials (RCTs) on current treatments for patients with HCC in Asian populations (2013–2023). A total of 427 articles were screened, and 184 non-duplicate publications were identified. After screening the titles and abstracts, 96 publications were excluded, and another 28 were excluded after full-text screening. The remaining 60 eligible RCTs/CTs were finally included. A total of 60 clinical trials fulfilled our inclusion criteria with 36 drugs used as monotherapy or combination therapy for HCC. Most studies used sorafenib alone or in combination with any of the treatment regimens. Lenvatinib or atezolizumab with bevacizumab was used for HCC after initial sorafenib treatment. Eighteen studies compared the efficacy of sorafenib with that of other drugs, including lenvatinib, cabozantinib, tepotinib, tigatuzumab, linifanib, erlotinib, resminostat, brivanib, tislelizumab, selumetinib, and refametinib. This study provides comprehensive insights into effective treatment interventions for HCC in Asian populations. The overall assessment indicates that sorafenib, used alone or in combination with atezolizumab and bevacizumab, has been the first treatment choice in the past decade to achieve better outcomes in patients with HCC in Asian populations.
Impact of Alcalase Hydrolysis and Simulated Gastrointestinal Digestion on the Release of Bioactive Peptides from Erythrina edulis (Chachafruto) Proteins
Authors: Correa Jessica L. , Zapata José Edgar , Hernández-Ledesma Blanca
Published: August 2024

Amidst increasing awareness of diet-health relationships, plant-derived bioactive peptides are recognized for their dual nutritional and health benefits. This study investigates bioactive peptides released after Alcalase hydrolysis of protein from chachafruto (Erythrina edulis), a nutrient-rich South American leguminous plant, focusing on their behavior during simulated gastrointestinal digestion. Evaluating their ability to scavenge radicals, mitigate oxidative stress, and influence immune response biomarkers, this study underscores the importance of understanding peptide interactions in digestion. The greatest contribution to the antioxidant activity was exerted by the low molecular weight peptides with ORAC values for the <3 kDa fraction of HES, GD-HES, and GID-HES of 0.74 ± 0.03, 0.72 ± 0.004, and 0.56 ± 0.01 (μmol TE/mg protein, respectively). GD-HES and GID-HES exhibited immunomodulatory effects, promoting the release of NO up to 18.52 and 8.58 µM, respectively. The findings of this study highlighted the potential of chachafruto bioactive peptides in functional foods and nutraceuticals, supporting human health through dietary interventions.
ZIF-8 as a pH-Responsive Nanoplatform for 5-Fluorouracil Delivery in the Chemotherapy of Oral Squamous Cell Carcinoma
Authors: Hao Jessica , Chen Chider , Pavelic Kresimir , Ozer Fusun
Published: August 2024

5-fluorouracil (5-FU), a chemotherapeutic agent against oral squamous cell carcinoma (OSCC), is limited by poor pharmacokinetics and toxicity. The pH-sensitive zeolite imidazolate framework-8 (ZIF-8) may increase the selectivity and length of 5-FU released into the acidic tumor microenvironment. This study examined the in vitro 5-FU absorption and release profiles of ZIF-8, and then progressed to cytotoxicity assays using the OSCC primary cell line SCC7. The 5-FU loading capacity of ZIF-8 was calculated with UV-vis spectroscopy (λ = 260 nm). 5-FU release was quantified by submerging 5-FU@ZIF-8 in pH 7.4 and 5.5 acetate buffer over 48 h. For the cytotoxicity assays, 5-FU, ZIF-8, and 5-FU@ZIF-8 were added to SCC7 cultures at 25, 50, and 100 μg/mL. Cell viability was assessed through toluidine blue staining and further quantified through transcriptomic RNA sequencing. ZIF-8 stabilized at a maximum absorption of 2.71 ± 0.22 mg 5-FU, and released 0.66 mg more 5-FU at pH 5.5 than 7.4 for at least 72 h. The cytotoxicity assays showed that 5-FU@ZIF-8 had a synergistic inhibitory effect at 50 μg/mL. The RNA sequencing analysis further revealed the molecular targets of 5-FU@ZIF-8 in SCC7. 5-FU@ZIF-8 may release 5-FU based on the pH of the surrounding microenvironments and synergistically inhibit OSCC.
Multi-Omics Analysis Revealed the rSNPs Potentially Involved in T2DM Pathogenic Mechanism and Metformin Response
Authors: Damarov Igor S. , Korbolina Elena E. , Rykova Elena Y. , Merkulova Tatiana I.
Published: August 2024

The goal of our study was to identify and assess the functionally significant SNPs with potentially important roles in the development of type 2 diabetes mellitus (T2DM) and/or their effect on individual response to antihyperglycemic medication with metformin. We applied a bioinformatics approach to identify the regulatory SNPs (rSNPs) associated with allele-asymmetric binding and expression events in our paired ChIP-seq and RNA-seq data for peripheral blood mononuclear cells (PBMCs) of nine healthy individuals. The rSNP outcomes were analyzed using public data from the GWAS (Genome-Wide Association Studies) and Genotype-Tissue Expression (GTEx). The differentially expressed genes (DEGs) between healthy and T2DM individuals (GSE221521), including metformin responders and non-responders (GSE153315), were searched for in GEO RNA-seq data. The DEGs harboring rSNPs were analyzed using the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). We identified 14,796 rSNPs in the promoters of 5132 genes of human PBMCs. We found 4280 rSNPs to associate with both phenotypic traits (GWAS) and expression quantitative trait loci (eQTLs) from GTEx. Between T2DM patients and controls, 3810 rSNPs were detected in the promoters of 1284 DEGs. Based on the protein-protein interaction (PPI) network, we identified 31 upregulated hub genes, including the genes involved in inflammation, obesity, and insulin resistance. The top-ranked 10 enriched KEGG pathways for these hubs included insulin, AMPK, and FoxO signaling pathways. Between metformin responders and non-responders, 367 rSNPs were found in the promoters of 131 DEGs. Genes encoding transcription factors and transcription regulators were the most widely represented group and many were shown to be involved in the T2DM pathogenesis. We have formed a list of human rSNPs that add functional interpretation to the T2DM-association signals identified in GWAS. The results suggest candidate causal regulatory variants for T2DM, with strong enrichment in the pathways related to glucose metabolism, inflammation, and the effects of metformin.
New Variants in the Chloroplast Genome Sequence of Two Colombian Individuals of the Cedar Timber Species (Cedrela odorata L.), Using Long-Read Oxford Nanopore Technology
Authors: Simbaqueba Jaime , Garzón-Martínez Gina A. , Castano Nicolas
Published: August 2024

The plant species Cedrela odorata has been largely exploited in the timber industry due to the high demand for its wood. Therefore, C. odorata has been considered a vulnerable species since 1994, under the Convention on International Trade in Endangered Species of Wild Fauna and Flora (CITES). C. odorata is a key timber species included in the management and conservation plans for the Amazon and Central American rainforests. These plans include the development of genetic and genomic resources to study local populations of the species in Colombia. In this study, two novel chloroplast (cp) genomes were assembled and annotated using the MinION long-read sequencing technology. The new cp genomes were screened for sequence variants (SVs), and a total of 16 SNPs were identified, presumably unique to populations from the Amazon region in Colombia. Comparative genomics with other reported cp genomes from different populations of C. odorata support the hypothesis of intraspecific diversity associated with their place of origin. These cp genome sequences of C. odorata from Colombian individuals represent valuable genomic resources for the species, suitable for identifying novel DNA fingerprinting and barcoding applications.
Apical Sparing in Routine Echocardiography: Occurrence and Clinical Significance
Authors: Leitman Marina , Tyomkin Vladimir
Published: August 2024

Apical sparing is an echocardiographic pattern where myocardial strain is preserved at the apex compared to the basal segments. In a normal heart, longitudinal strain shows a gradient with lower values at the base and higher at the apex. This gradient becomes more pronounced in pathological states, such as cardiac amyloidosis, resulting in a relative apical sparing effect. This study explores cardiac conditions associated with apical sparing and the underlying mechanisms. We reviewed echocardiography examinations reporting apical sparing from 2021 to 2024 in our hospital database. Relevant echo exams and clinical data were retrieved and analyzed. Apical sparing was identified in 74 patients. Cardiac amyloidosis was diagnosed in 12 patients (16.2%). Other cardiac pathologies potentially contributing to apical sparing included hypertrophic cardiomyopathy, left ventricular hypertrophy due to hypertension, end-stage renal disease, coronary artery disease (involving the right coronary artery and left circumflex), reversed Takotsubo syndrome, and chemotherapy-induced cardiomyopathy. The clinical context of echocardiography was crucial in guiding the diagnostic work-up. Apical sparing is a nonspecific echocardiographic finding associated with various cardiac conditions. Its diagnostic value depends heavily on the clinical context. Understanding the broader clinical picture is essential for accurate interpretation and diagnosis.
Evaluation of Pharmacy Intern Interventions on Antimicrobial Use in University-Affiliated Hospitals: A Retrospective Analysis
Authors: Almeleebia Tahani M. , Orayj Khalid M. , Alghamdi Wael A. , Almanasef Mona A. , Hany Omar , Ibrahim Ahmed R. N.
Published: August 2024

Background: Appropriate use of antimicrobials is essential to enhance therapeutic safety and efficacy. Clinical pharmacists play a crucial role in optimizing antimicrobial use; however, the contribution of pharmacy interns in antimicrobial use has not been studied. The objective of this study was to ascertain the quantity and nature of interventions related to antimicrobials documented by pharmacy interns, along with the rates at which physicians accepted these interventions. Methods: From August 2017 to March 2022, this study retrospectively evaluated antimicrobial-related interventions recorded by pharmacy interns during their rotations at King Khalid University. The categories of interventions included medication selection, addition of antimicrobials, dose or frequency adjustments, medication discontinuation, de-escalation, therapeutic drug monitoring, and others. Statistical analysis was conducted to identify patterns and correlations. Results: This study evaluated 1295 antimicrobial-related interventions, with high physician acceptance rates of 91.6% and 4.0% accepted with modifications. The most frequent interventions were dose/frequency adjustments (36.3%) and medication discontinuation (23%). Vancomycin, colistin, and meropenem were the most frequently intervened antimicrobials. Documented clinical outcomes included enhancing treatment efficacy (37.3%), reducing treatment toxicity (26.81%), and avoiding unnecessary antimicrobial exposure (21.8%). Significant correlations were observed between hospital units and intervention types, indicating unit-specific intervention patterns. Conclusions: Theses findings highlight the vital role of pharmacy interns in optimizing antimicrobial therapy. Future research should focus on evaluating the long-term clinical and economic benefits of their involvement.
Total Neoadjuvant Therapy for Locally Advanced Rectal Cancer: How to Select the Most Suitable?
Authors: Bandidwattanawong Chanyoot
Published: August 2024

Rectal cancer shows specific characteristics in terms of pattern of recurrence, which occurs commonly at both local and distant sites. The standard of care for locally advanced rectal cancer (LARC) including neoadjuvant chemoradiotherapy, followed by surgery based on the total mesorectal excision principles leads to a reduction in the rates of local recurrences to 6–7% at 5 years. However, the outcomes among those with high-risk lesions remain unsatisfactory. On the contrary, neoadjuvant chemoradiotherapy results in long-term morbidities among those with low-risk lesions. Furthermore, the overall survival benefit of neoadjuvant therapy is still a subject to be debated, except for patients with complete or near-complete response to neoadjuvant therapy. Total neoadjuvant therapy (TNT) is a new paradigm of management of high-risk rectal cancer that includes early administration of the most effective systemic therapy either before or after neoadjuvant radiotherapy with or without chemotherapy prior to surgery with or without adjuvant chemotherapy. TNT potentially improves disease-free survival, even though whether it can prolong survival has been debatable. Recently, neoadjuvant chemotherapy only has been proved to be non-inferior to neoadjuvant chemoradiotherapy in patients with low-risk lesions. This review intends to review the current evidences of neoadjuvant therapy and propose a more customized paradigm of management of LARC.
Demographic and Injury Characteristics as Potential Risk Factors for Anterior Cruciate Ligament Injuries: A Multicentric Cross-Sectional Study
Authors: Motififard Mehdi , Akbari Aghdam Hossein , Ravanbod Hadi , Jafarpishe Mohammad Saleh , Shahsavan Mahdi , Daemi Amin , Mehrvar Amir , Rezvani Arghavan , Jamalirad Hossein , Jajroudi Mahdie , Shahsavan Mohammad
Published: August 2024

Background: Anterior cruciate ligament (ACL) injuries are prevalent and can have debilitating consequences, with various factors potentially influencing their occurrence. This multicentric study aimed to comprehensively analyze the epidemiological characteristics of ACL injuries. We hypothesized that specific patient characteristics, such as age, sex, body mass index (BMI), and sports involvement, would be associated with distinct injury patterns and risk profiles. Methods: This cross-sectional study analyzed the medical records of 712 patients aged 15–60 diagnosed with ACL rupture. Data on demographics, injury mechanisms, associated injuries, graft type, and sports involvement were collected. Results: The majority of patients were male (93.1%), aged 15–30 years (80.2%), and overweight (66.7%). Autografts were the predominant graft choice (96.07%). Associated injuries were present in 79.5% of cases, with medial meniscus ruptures being the most common (37.36%). Sports-related (49.3%) and non-sports-related (50.7%) injuries were nearly equal, with non-contact injuries more prevalent (71.1%). In the sports-related subgroup, associated injuries emerged as a significant risk factor for ACL rupture (p = 0.014, OR = 1.596, 95% CI: 1.101–2.314), whereas non-contact mechanisms showed borderline significance (OR = 0.75, p = 0.09). Moreover, younger athletes were more susceptible to sports-related injuries (p = 0.024), with football being the primary sport involved. Conclusions: This study identified a high prevalence of concomitant injuries with ACL injury, which increased the risk of ACL injury, particularly in sports-related cases. Age-related differences in injury patterns highlight the need for age-appropriate preventive measures, especially for younger athletes participating in high-risk sports. This underscores the need for comprehensive injury assessment, targeted prevention strategies, and optimized clinical management approaches tailored to different populations’ specific characteristics and risks.
A Pilot Study of Saliva MicroRNA Signatures in Children with Moderate-to-Severe Traumatic Brain Injury
Authors: Ciancaglini Robert , Botash Ann S. , Armijo-Garcia Veronica , Hymel Kent P. , Thomas Neal J. , Hicks Steven D.
Published: August 2024

Background/Objectives: Traumatic brain injury (TBI) is a leading cause of death and disability in children. Currently, no biological test can predict outcomes in pediatric TBI, complicating medical management. This study sought to identify brain-related micro-ribosomal nucleic acids (miRNAs) in saliva associated with moderate-to-severe TBI in children, offering a potential non-invasive, prognostic tool. Methods: A case-control design was used, enrolling participants ≤ 18 years old from three pediatric trauma centers. Participants were divided into moderate-to-severe TBI and non-TBI trauma control groups. Saliva samples were collected within 24 h of injury, with additional samples at 24–48 h and >48 h post-injury from the TBI group. miRNA profiles were visualized with partial least squares discriminant analysis (PLSDA) and hierarchical clustering. Mann–Whitney testing was used to compare miRNAs between groups, and mixed models were used to assess longitudinal expression patterns. DIANA miRPath v3.0 was used to interrogate the physiological functions of miRNAs. Results: Twenty-three participants were enrolled (14 TBI, nine controls). TBI and control groups displayed complete separation of miRNA profiles on PLSDA. Three miRNAs were elevated (adj. p < 0.05) in TBI (miR-1255b-5p, miR-3142, and miR-4320), and two were lower (miR-326 and miR-4646-5p). Three miRNAs (miR-3907, miR-4254, and miR-1273g-5p) showed temporal changes post-injury. Brain-related targets of these miRNAs included the glutamatergic synapse and GRIN2B. Conclusions: This study shows that saliva miRNA profiles in children with moderate-to-severe TBI may differ from those with non-TBI trauma and exhibit temporal changes post-injury. These miRNAs could serve as non-invasive biomarkers for prognosticating pediatric TBI outcomes. Further studies are needed to confirm these findings.
Patch Augmentation in Arthroscopic Rotator Cuff Surgery—Review of Current Evidence and Newest Trends
Authors: Russo Maximilian , Dirkx Gert Karl , Rosso Claudio
Published: August 2024

Background: Rotator cuff tears are a common and debilitating condition requiring surgical intervention. Arthroscopic rotator cuff repair is essential for restoring shoulder function and alleviating pain. Tear classification by size and tendon retraction, along with the grade for fatty infiltration, influence postoperative outcomes, with large tears and higher fatty infiltration grades linked to higher retear rates. Managing complex tears is challenging, with failure rates ranging from 20 to 94%. Patch augmentation has emerged as a promising strategy, using biological or synthetic materials to reinforce tendon repairs, enhancing structural integrity and reducing retear risk. Methods: A review of the recent literature from January 2018 to March 2024 was conducted using PubMed/MEDLINE, Embase, and Web of Science. Keywords included “rotator cuff tear”, “rotator cuff augmentation”, “rotator cuff patch”, “tendon augmentation”, “massive rotator cuff tear”, “patch augmentation”, and “grafts”. Relevant articles were selected based on their abstracts for a comprehensive review. Results: Initial methods used autograft tissues, but advances in biomaterials have led to standardized, biocompatible synthetic patches. Studies show reduced retear rates with patch augmentation, ranging from 17 to 45%. Conclusions: Patch augmentation reduces the retear rates and improves tendon repair, but complications like immune responses and infections persist. Cost-effectiveness analyses indicate that while initial costs are higher, long-term savings from reduced rehabilitation, revision surgeries, and increased productivity can make patch augmentation economically beneficial.
Treatment of Twin Anemia Polycythemia Sequence with Donor Transfusion and Partial Recipient Exchange Transfusion: Procedural Considerations and Outcomes
Authors: Shantz Camille F. , Rosner Mara , Kush Michelle L. , Miller Jena L. , Baschat Ahmet A.
Published: August 2024

Background: Intrauterine transfusion (IUT) of the donor and partial exchange (pET) of the recipient is a temporizing treatment for pregnancies with Twin Anemia Polycythemia Sequence (TAPS). We aimed to provide a detailed description of the procedural approach and outcomes for sequential donor IUT and recipient pET in TAPS. Methods: Retrospective study of spontaneous TAPS referred to the Johns Hopkins Center for Fetal Therapy treated with donor IUT followed by recipient pET utilizing a double-syringe setup. Procedural characteristics and outcomes as well as the accuracy of existing transfusion formulas were analyzed and compared with the literature. Results: 5 of 78 patients with spontaneous TAPS underwent a total of 19 combined IUT/pET procedures (median first procedure to delivery interval 5.6 weeks [interquartile range IQR 1.9–6.0]). One pET was stopped due to fetal deceleration. The patients were delivered at 33.0 weeks [IQR 31.9–33.3] with two survivors and no neonatal transfusion requirements. The IUT volume was 48 mL [IQR 39–63 mL] and the pET volume was 32 mL [IQR 20–50], utilizing aliquots of 5–20 mL for the latter (p = 0.021). For the IUTs, the assumption of a fetal blood volume below 150 mL/kg underestimated the required transfusion volume. For the pETs, all formulas required adjustment of the dilution volume based on bedside testing (p < 0.05 for all). Conclusions: Donor transfusion followed by partial exchange in the recipient can prolong pregnancy in spontaneous TAPS and obviate the need for neonatal transfusion. A double-syringe setup facilitates efficient saline exchange. Because the accuracy of volume formulas is limited, bedside testing is recommended to achieve the target hemoglobin.
Metabolic Imaging of Advanced Basal Cell Carcinoma Treated with Sonidegib: A Retrospective Case Series Study
Authors: Proietti Ilaria , Filippi Luca , Bagni Oreste , Potenza Concetta
Published: August 2024

Background: Positron emission tomography/computed tomography (PET/CT) with 18F-fluorodeoxyglucose (18F-FDG) is a firmly established tool in oncology and is gaining importance in dermato-oncology. However, its use in advanced basal cell carcinoma (BCC) is limited, with only a few case reports and a single study focused on vismodegib. This study evaluates the role of 18F-FDG PET/CT in advanced BCC treated with sonidegib. Methods: We retrospectively assessed the clinical data of patients with advanced BCC who underwent 18F-FDG PET/CT between January 2022 and January 2024. Inclusion criteria included histologically confirmed BCC, FDG-avid lesions on baseline PET/CT, and a minimum follow-up of 6 months. Metabolic response was assessed using the PET Response Criteria in Solid Tumors (PERCIST). Results: Four patients with advanced BCC treated with sonidegib were included, presenting with a total of 10 hypermetabolic lesions at baseline PET/CT. The mean interval between baseline and follow-up scans was 8.7 ± 1.6 months. According to PERCIST, two patients achieved a complete metabolic response (CMR), while the other two had stable metabolic disease (SMD). Low baseline-standardized uptake values (i.e., SUVmax, SUVmean) and reduced total lesion glycolysis (TLG) were associated with CMR. No relapses were observed during follow-up. Conclusions: This study suggests that 18F-FDG PET/CT may help identify advanced BCC patients who are likely to benefit from sonidegib treatment. Further research is needed to fully explore the potential of PET/CT in this specific clinical context.
Obstetric Outcomes of Nighttime Versus Daytime Delivery with Labor Epidural: An Observational Retrospective Study
Authors: Catarci Stefano , Zanfini Bruno Antonio , Capone Emanuele , Di Muro Mariangela , Frassanito Luciano , Maddaloni Giovanni Maria , Lanzone Antonio , Draisci Gaetano
Published: August 2024

Background: Variability in obstetric outcomes in terms of the number and type of deliveries related to the day–night cycle has been described in previous studies. This 11-year retrospective analysis explores the effects of nighttime versus daytime delivery with labor epidural on obstetric outcomes. Methods: Data on deliveries performed between 1 October 2008 and 1 October 2019 were collected and differentiated into daytime, occurring from 8:00 a.m. to 7:59 p.m., and nighttime deliveries, occurring from 8:00 p.m. to 7:59 a.m. of the following day. The data collected included the patient history and maternal and neonatal outcomes. Results: A total of 29831 patients were included in the analysis. A positive and statistically significant correlation between the number of cesarean sections (Odds Ratio 1.35; 95% confidence interval = 1.26–1.44; p < 0.001) and the number of vaginal operative deliveries (Odds Ratio 1.21; 95% confidence interval = 1.01–1.44; p < 0.05) in patients who did not receive an epidural at nighttime was reported. Regarding the labor epidurals, a significantly greater incidence of accidental dural punctures with needles (0,4%; p < 0.05) in the nighttime versus daytime was reported. Conclusions: The absence of labor epidurals was associated with a significant increase in the number of cesarean sections and vaginal operative deliveries occurring at nighttime, without significant differences in labor duration. The incidence of anesthesiologic complications was greater in deliveries performed at nighttime.
Real-World Practices of Pentosan Polysulfate Maculopathy Screening in Various Clinical Settings and Practice-Associated Factors
Authors: Kim Jiyeong , Ahn Seong Joon
Published: August 2024

Objectives: This study investigated the practice patterns of pentosan polysulfate (PPS) maculopathy screening in various clinical settings and demographic and clinical characteristics associated with these screening practices using a health claims database. Methods: In this nationwide population-based study, data from the Health Insurance Review and Assessment database in South Korea were analyzed to identify patients who underwent PPS. The participants were categorized based on whether they had undergone a baseline examination (the first ophthalmic examination since PPS prescription) within one year of PPS use, subsequent monitoring within one year of the baseline examination, or recent monitoring within a 1-year period before the study end date. Demographic and clinical factors were compared between the groups, and factors associated with screening practices were identified using logistic regression analyses. Results: Significant differences in screening practices were observed based on sex, age, residence, the medical specialty of the prescribing physician, indications for PPS use, and hospital type of prescription. Older patients who received PPS prescriptions from urologists were more likely to undergo baseline and monitoring examinations. Logistic regression analyses revealed that older age, female sex, and a longer duration of PPS use were significantly associated with baseline screening. Subsequent and recent monitoring was significantly associated with age, duration of PPS use, and treatment at primary hospitals. Conclusions: This study underscores the variability in screening practices for PPS users based on demographic and clinical factors, emphasizing the need for standardized guidelines. Enhanced awareness and timely referral for maculopathy screening, particularly among non-urological specialties, are essential.
Impact of Spa Therapy on Symptoms and Quality of Life in Post-COVID-19 Patients with Chronic Conditions
Authors: Costantino Maria , Giudice Valentina , Farroni Mario , Marongiu Francesco , De Caro Francesco , Filippelli Amelia
Published: August 2024

Background: With limited pharmacological interventions, post-COVID-19 condition is a clinical challenge, and supplementary therapies are essential for symptom relief and enhancing quality of life (QoL). In our prospective observational study, we aimed to evaluate the impact of Salus per aquam (Spa) therapy on post-COVID-19 symptoms and QoL in individuals who suffer from chronic joint, musculoskeletal, skin, and/or respiratory conditions. Methods: A total of 159 individuals undergoing Spa therapy were enrolled, and 78 of them had post-COVID-19 symptoms, assessed using Visual Analogue Scale (VAS) and modified British Medical Research Council Questionnaire (mMRC-DS scales), as well as the Short Form 36 Health Status Survey (SF-36) questionnaire for QoL. Results: Spa therapy significantly reduced most post-COVID-19 symptoms, especially chronic fatigue, pain, brain fog, and persistent cough (all p < 0.05), as well as physical (+72%) and emotional (+66%) limitations. When stratified by sex, males showed a greater improvement from baseline, while females consistently displayed a higher amelioration in all QoL dimensions. Moreover, full vaccination with 3–4 doses significantly protected against SARS-CoV-2 re-infections and post-COVID-19 development (p < 0.05). Conclusions: Spa therapy demonstrated effectiveness in mitigating post-COVID-19 symptoms and enhancing QoL in patients suffering from chronic diseases.
Investigating the Mechanisms of Discoloration in Modern Dental Materials: A Comprehensive Characterization Approach
Authors: Gawriołek Maria , Varma Naisargi , Hernik Amadeusz , Eliasz Wojciech , Strykowska Marta , Paszyńska Elżbieta , Czarnecka Beata , Sikorski Marek
Published: August 2024

In general, patients’ opinions on reaching ideal esthetics while restoring dental tissues is one of the most important part of the oral treatment. Unfortunately, discoloration of dental materials may occur due to intrinsic and extrinsic factors. The aim of the study was to evaluate the color stability of frequently used dental resin materials and determine the mechanism of their discoloration. The study used various characterization techniques (optical microscopy, Fourier-transform infrared spectroscopy, low-temperature N2 adsorption, diffuse reflectance spectroscopy, and luminescence) to understand the effect of surface defects on discoloration. The adsorption of model liquids on the surface was confirmed to be related to the increase in BET surface area. The study found that the adsorption of discolorants, such as coffee, tea, and wine, on the surface of the dental material follows the multilayer BET model. When the surface is smooth, the discoloration is usually within acceptable limits, with a maximum of ∆E = 3.3. The discoloration made by tea and demineralized water was within acceptable limits even after 7 days of exposure.
Investigating the Role of Artificial Intelligence to Measure Consumer Efficiency: The Use of Strategic Communication and Personalized Media Content
Authors: Binlibdah Saud
Published: August 2024

This study examines the relationships between strategic communication, personalized media content, AI, and consumer service efficiency in social marketing companies in Saudi Arabia. The study used a cluster sampling technique with a quantitative research design. The study targeted 498 responses via distributing the survey links on social media platforms. Using the SEM analysis in Smart PLS 4, this research tested the research hypotheses. The findings showed that strategic communication significantly improves personalized media content and consumer service efficiency, confirming its importance in business customer interactions and outcomes. Customized media content does not significantly improve consumer service efficiency, suggesting other mediating factors may be involved. AI mediates this relationship, bridging strategic inputs and service outcomes. AI boosts strategic communication and personalized content, improving consumer service efficiency. The results showed that AI fully mediates strategic communication and personalized media content into improved service efficiency, demonstrating its transformative potential in business communications and operations. The study shows that AI supports and improves digital marketing communication strategies. It is statistical evidence and confidence intervals that exclude zero, AI-enabled the application of personalized content and strategic directives to improve service efficiency in the mediation analysis.
Are Women Sports Journalists in Spain Truly Progressing or Facing “Pseudo-Progress”?
Authors: Faedo Nahuel Ivan , Corrius Montse , Ginesta Xavier
Published: August 2024

Sports journalism has become one of the news products with the most significant social reach in the press, radio, television and digital media. Despite the significant presence of women in journalism, they continue to face gender-based stereotypes. In Spain, not very many women can effectively access the labour field of sports journalism, and those who do find themselves in a space dominated by men, which results in a perpetuation of the existing imbalances in society. The main objective of this study is to analyse the evolution of the roles developed by women journalists in the article-production aspect of the Spanish sports press between 2010 and 2022. We use quantitative content analysis, studying the articles published in Marca and Mundo Deportivo during the second week of June in 2010, 2014, and 2018, and the third week of November 2022; in each of these years, the men’s FIFA World Cup was played. The results of this study show that: (a) women journalists have an almost invisible role in the production of articles, and (b) rather than progress, women are facing “pseudo-progress”, a more appropriate term for the appearance of a change that is not actually occurring.
Sex Differences in Biochemical Analyses, Cardiometabolic Risk Factors and Their Correlation with CRP in Healthy Mexican Individuals
Authors: Brambila-Tapia Aniel Jessica Leticia , González-Gómez Alejandra Soledad , Carrillo-Delgadillo Laura Arely , Saldaña-Cruz Ana Míriam , Dávalos-Rodríguez Ingrid Patricia
Published: August 2024

Background: Few studies have been undertaken to detect the presence of cardiovascular risk factors (CRFs) in healthy populations (individuals auto-reported as healthy). These risk factors include high body mass index (BMI), high waist-to-hip ratio (WHR), high systolic and diastolic blood pressure (SBP, DBP), high uric acid and high Castelli’s risk index (CRI); this last is the ratio of total cholesterol to HDL cholesterol (TC/HDL-c). In addition, the correlations between CRFs and the biomarker C-reactive protein (CRP) has not been explored in each sex. Aim: Therefore, this study aimed to determine sex differences in the abnormalities in blood and urine analyses, including CRFs and their correlation with CPR in a non-representative sample of healthy Mexican individuals. Results: A total of 238 subjects were included, 123 (51.7%) of whom were women. The main blood alterations detected were high serum lipids, including high total cholesterol, LDL-cholesterol, triglycerides, and the CRI, which were higher in men than in women. The men’s samples had a higher frequency of hypertensives and pre-hypertensives than the women’s sample. The CRP showed positive significant correlations with the CRFs: BMI, WHR, SBP, DBP, uric acid, and the CRI, with a higher correlation for BMI and WHR, and most of these correlations were higher in women than in men. Additionally, all these factors showed a positive correlation among them. Conclusion: In conclusion, the main alterations observed in blood are related to cardiovascular risk and were reported with a higher frequency in men when compared with women. This finding can be related to the higher values of WHR in this sex; additionally, the inflammatory marker CRP was more correlated with the cardiometabolic risk factors in women than in men, which suggests a different relationship between inflammation and cardiometabolic risk factors in each sex.
Adopting Artificial Intelligence to Strengthen Legal Safeguards in Blockchain Smart Contracts: A Strategy to Mitigate Fraud and Enhance Digital Transaction Security
Authors: Louati Hassen , Louati Ali , Almekhlafi Abdulla , ElSaka Maha , Alharbi Meshal , Kariri Elham , Altherwy Youssef N.
Published: August 2024

As blockchain technology increasingly underpins digital transactions, smart contracts have emerged as a pivotal tool for automating these transactions. While smart contracts offer efficiency and security, their automation introduces significant legal challenges. Detecting and preventing fraud is a primary concern. This paper proposes a novel application of artificial intelligence (AI) to address these challenges. We will develop a machine learning model, specifically a Convolutional Neural Network (CNN), to effectively detect and mitigate fraudulent activities within smart contracts. The AI model will analyze both textual and transactional data from smart contracts to identify patterns indicative of fraud. This approach not only enhances the security of digital transactions on blockchain platforms but also informs the development of legal standards and regulatory frameworks necessary for governing these technologies. By training on a dataset of authentic and fraudulent contract examples, the proposed AI model is expected to offer high predictive accuracy, thereby supporting legal practitioners and regulators in real-time monitoring and enforcement. The ultimate goal of this project is to contribute to legal scholarship by providing a robust technological tool that aids in preventing cybercrimes associated with smart contracts, thereby laying a foundation for future legal research and development at the intersection of law, technology, and security.
Strategies for Error Reduction: Why More Stringent Premarket Evaluations Do Little to Prevent Laboratory Errors and Traffic Accidents
Authors: Hortin Glen L.
Published: August 2024

Laboratory testing is a complex process with a significant error rate. Studies of laboratory errors have found that the major causes are preanalytical factors, interferences, and process errors. Efforts by regulatory agencies to improve quality via more stringent premarket evaluations of laboratory tests therefore have poor prospects of reducing laboratory errors and improving test quality. Efforts toward increasing the regulation of laboratory tests are analogous to preventing traffic accidents by increasing the premarket evaluation of automobiles. This analogy illustrates how increased premarket evaluation has limited prospects for quality improvement and, in some cases, actually contributes to errors and lower quality. Tools that are used by laboratories to detect, prevent, and address analytical errors are discussed, and the increased implementation of such tools offers approaches that can be used to improve laboratory quality.
Revisiting Gubbio: Settlement Patterns and Ritual from the Middle Palaeolithic to the Roman Era
Authors: Negro Marianna , Whitehead Nicholas , Malone Caroline , Stoddart Simon
Published: August 2024

The Gubbio Revisited project, initiated to reinterpret the archaeological evidence collected during the 1980s Gubbio Project, primarily by a conversion from a paper to a digital record, has revealed significant insights into the evolving settlement patterns and religious expression in the Gubbio valley in Central Italy. This reanalysis of the survey evidence underscores the rhythms of settlement and ritual practice from the Neolithic through the Bronze and Iron Ages, into Roman times. Key excavations in the 1980s at Monte Ingino, Monte Ansciano, San Marco Romano, and San Marco Neolitico added details not only of settlement activity but also of embedded ritual, evidenced by material culture including pottery, faunal remains, and votive offerings. The foundation myth of indigenous religious practices, even amidst Roman influence, is documented through the Iguvine Tables alongside the introduction of new cults, showcasing a blend of local and imperial religiosity, a common feature in the Roman world. This research enriches the understanding of Gubbio’s historical and cultural landscape, emphasizing the demographic rhythms of the valley alongside the integral role of ritual in its societal evolution.