bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of ABCB1 Gene Polymorphisms and Their Impact on Tacrolimus Blood Levels in Kidney Transplant Recipients
Authors: Rotarescu Corina Andreea , Maruntelu Ion , Rotarescu Ion , Constantinescu Alexandra-Elena , Constantinescu Ileana
Published: October 2024

Tacrolimus (Tc) is an immunosuppressant used in transplant patients, but its therapeutic range is narrow, making precise dosing essential. This study investigates the association of three single nucleotide polymorphisms (SNPs) (ABCB1 3435C>T, 1236C>T, 2677G>T/A) with Tc levels over time to gain better insights into their role in personalized medicine. We conducted the study over four distinct periods: 1–14 days, 15–30 days, 31–60 days, and beyond 60 days post-transplantation. The analysis included allele, genotype, haplotype, and diplotype frequencies of the three SNPs concerning Tc blood levels. Statistical significance was determined, and false discovery rate (PFDR) correction was applied where appropriate. Significant associations were found between the C (ABCB1 C1236T), A alleles (ABCB1 G2677T/A), the CAC haplotype and lower Tc levels. The CAC-TGT and TGT-TGT diplotypes significantly influence how patients metabolize the drug. The TGT haplotype and the AA genotype (ABCB1 G2677T/A) were associated with higher Tc levels, suggesting a long-term genetic influence. Genetic factors, specifically certain SNPs and diplotypes, significantly impact Tc blood levels, with their influence varying over time.
Limited Alleviation of Lysosomal Acid Lipase Deficiency by Deletion of Matrix Metalloproteinase 12
Authors: Buerger Martin , Amor Melina , Akhmetshina Alena , Bianco Valentina , Perfler Bianca , Zebisch Armin , Weichhart Thomas , Kratky Dagmar
Published: October 2024

Lysosomal acid lipase (LAL) is the only known enzyme that degrades cholesteryl esters and triglycerides at an acidic pH. In LAL deficiency (LAL-D), dysregulated expression of matrix metalloproteinase 12 (MMP-12) has been described. The overexpression of MMP-12 in myeloid lineage cells causes an immune cell dysfunction resembling that of Lal knockout (Lal KO) mice. Both models develop progressive lymphocyte dysfunction and expansion of myeloid-derived suppressor (CD11b+ Gr-1+) cells. To study whether MMP-12 might be a detrimental contributor to the pathology of LAL-D, we have generated Lal/Mmp12 double knockout (DKO) mice. The phenotype of Lal/Mmp12 DKO mice closely resembled that of Lal KO mice, while the weight and morphology of the thymus were improved in Lal/Mmp12 DKO mice. Cytological examination of blood smears showed a mildly reversed lymphoid-to-myeloid shift in DKO mice. Despite significant decreases in CD11b+ Ly6G+ cells in the peripheral blood, bone marrow, and spleen of Lal/Mmp12 DKO mice, the hematopoietic bone marrow progenitor compartment and markers for neutrophil chemotaxis were unchanged. Since the overall severity of LAL-D remains unaffected by the deletion of Mmp12, we conclude that MMP-12 does not represent a viable target for treating the inflammatory pathology in LAL-D.
Therapeutic Options for Crigler–Najjar Syndrome: A Scoping Review
Authors: Sambati Vanessa , Laudisio Serena , Motta Matteo , Esposito Susanna
Published: October 2024

Crigler–Najjar Syndrome (CNS) is a rare genetic disorder caused by mutations in the UGT1A1 gene, leading to impaired bilirubin conjugation and severe unconjugated hyperbilirubinemia. CNS presents in the following forms: CNS type 1 (CNS1), the more severe form with the complete absence of UGT1A1 activity, and CNS type 2 (CNS2), with partial enzyme activity. This narrative review aims to provide a detailed overview of CNS, highlighting its clinical significance and the need for new, more effective treatments. By summarizing current knowledge and discussing future treatments, this article seeks to encourage further research and advancements that can improve outcomes for CNS patients. The literature analysis showed that CNS1 requires aggressive management, including phototherapy and plasmapheresis, but liver transplantation (LT) remains the only definitive cure. The timing of LT is critical, as it must be performed before the onset of irreversible brain damage (kernicterus), making early intervention essential. However, LT poses risks such as graft rejection and lifelong immunosuppression. CNS2 is milder, with patients responding well to phenobarbital and having a lower risk of kernicterus. Recent advancements in gene therapy and autologous hepatocyte transplantation offer promising alternatives to LT. Gene therapy using adeno-associated virus (AAV) vectors has shown potential in preclinical studies, though challenges remain in pediatric applications due to liver growth and pre-existing immunity. Autologous hepatocyte transplantation avoids the risk of rejection but requires further research. These emerging therapies provide hope for more effective and less invasive treatment options, aiming to improve the quality of life for CNS patients and reduce reliance on lifelong interventions.
Research on the Mechanism of Growth of Codonopsis pilosula (Franch.) Nannf. Root Responding to Phenolic Stress Induced by Benzoic Acid
Authors: Ma Yantong , Ma Lei , Xu Ling , Wei Ruonan , Chen Guiping , Dang Junhong , Chen Zhen , Ma Shaoying , Li Sheng
Published: October 2024

Soil autotoxic chemosensory substances have emerged as the predominant environmental factors constraining the growth, quality, and yield of Codonopsis pilosula in recent years. Among a vast array of chemosensory substances, benzoic acid constitutes the principal chemosensory substance in the successive cultivation of C. pilosula. However, the exploration regarding the stress exerted by benzoic acid on the growth and development of C. pilosula remains indistinct, and there is a scarcity of research on the mechanism of lobetyolin synthesis in C. pilosula. In the current research, it was discovered that exposure to benzoic acid at a concentration of 200 mmol/L conspicuously attenuated the plant height, root length, total length, fresh weight, root weight, root thickness, chlorophyll content, electrolyte osmolality, leaf intercellular CO2 concentration (Ci), net photosynthesis rate (Pn), transpiration rate (Tr), and leaf stomatal conductance (Gs) of C. pilosula. Benzoic acid (200 mmol/L) significantly enhanced the activity of root enzymes, including superoxide dismutase (SOD), malondialdehyde (MDA), and peroxidase (POD), as well as the accumulation of polysaccharides and lobetyolins (polyacetylene glycosides) in the roots of C. pilosula. In this study, 58,563 genes were assembled, and 7946 differentially expressed genes were discovered, including 4068 upregulated genes and 3878 downregulated genes. The outcomes of the histological examination demonstrated that benzoic acid stress augmented the upregulation of genes encoding key enzymes implicated in the citric acid cycle, fatty acid metabolism, as well as starch and sucrose metabolic pathways. The results of this investigation indicated that a moderate amount of benzoic acid could enhance the content of lobetyolin in C. pilosula and upregulate the expression of key coding genes within the signaling cascade to improve the resilience of C. pilosula lobetyolin against benzoic acid stress; this furnished a novel perspective for the study of C. pilosula lobetyolin as a potential substance for alleviating benzoic acid-induced stress.
Intraperitoneal Injection of the Porphyromonas gingivalis Outer Membrane Vesicle (OMV) Stimulated Expressions of Neuroinflammatory Markers and Histopathological Changes in the Brains of Adult Zebrafish
Authors: Adewoyin Malik , Hamarsha Ahmed , Akinsola Rasaq , Teoh Seong Lin , Azmai Mohammad Noor Amal , Abu Bakar Noraini , Nasruddin Nurrul Shaqinah
Published: October 2024

Porphyromonas gingivalis is the major pathogenic bacteria found in the subgingival plaque of patients with periodontitis, which leads to neuroinflammation. The bacteria destroy periodontal tissue through virulence factors, which are retained in the bacteria’s outer membrane vesicles (OMV). This study aimed to determine the real-time effect of an intraperitoneal injection of P. gingivalis OMV on the production and expression of inflammatory markers and histopathological changes in adult zebrafishes’ central nervous systems (CNS). Following the LD50 (21 µg of OMV), the zebrafish were injected intraperitoneally with 18 µg of OMVs, and the control group were injected with normal saline at seven different time points. Brains of experimental zebrafish were dissected at desired time points for colorimetric assays, ELISA, and histology. This study discovered that nitric oxide and PGE2 were significantly increased at 45 min, while IL-1β and IL-6 were expressed at subsequent 12 h and 24 h time points, respectively. Histopathological changes such as blood coagulation, astrocytosis, edema, spongiosis, and necrosis were observed between the 6hour and 24 h time points. The two apoptotic enzymes, caspases 3 and 9, were not expressed at any point. In summary, the OMV-induced neuroinflammatory responses and histopathological changes in adult zebrafish were time-point dependent. This study will enrich our understanding of the mechanism of P. gingivalis OMVs in neuroinflammation in a zebrafish model, most especially the timing of the expression of inflammatory mediators in relation to observable changes in brain tissues.
Soluble Urokinase-Type Plasminogen Activator Receptor (suPAR), Growth Differentiation Factor-15 (GDF-15), and Soluble C5b-9 (sC5b-9) Levels Are Significantly Associated with Endothelial Injury Indices in CAR-T Cell Recipients
Authors: Gavriilaki Eleni , Demosthenous Christos , Evangelidis Paschalis , Bousiou Zoi , Batsis Ioannis , Vardi Anna , Mallouri Despina , Koravou Eudoxia-Evaggelia , Spyridis Nikolaos , Panteliadou Alkistis , Karavalakis Georgios , Masmanidou Marianna , Touloumenidou Tasoula , Papalexandri Apostolia , Poziopoulos Christos , Yannaki Evangelia , Sakellari Ioanna , Politou Marianna , Papassotiriou Ioannis
Published: October 2024

Endothelial injury indices, such as Endothelial Activation and Stress Index (EASIX), modified EASIX (m-EASIX), and simplified EASIX (s-EASIX) scores, have been previously associated with chimeric antigen receptor-T (CAR-T) cell immunotherapy complications. Soluble urokinase-type plasminogen activator receptor (suPAR), growth differentiation factor-15 (GDF-15), and soluble C5b-9 (sC5b-9) have been described as markers of endothelial injury post-hematopoietic stem cell transplantation. In the current study, we examined whether suPAR, GDF-15, and sC5b-9 levels were associated with endothelial injury indices in adult CAR-T cell recipients. The levels of these markers were measured in patients before CAR-T cell infusion and in healthy individuals with immunoenzymatic methods. We studied 45 CAR-T cell recipients and 20 healthy individuals as the control group. SuPAR, GDF-15, and sC5b-9 levels were significantly higher in the patients’ group compared to the healthy control group (p < 0.001, in all comparisons). SuPAR levels at baseline were associated with the m-EASIX scores calculated at the same time point (p = 0.020), while suPAR and GDF-15 concentrations were correlated with EASIX scores at day 14 post-infusion (p < 0.001 in both comparisons). Moreover, sC5b-9 levels were correlated with the s-EASIX scores at infusion (p = 0.008) and the EASIX scores at day 14 (p = 0.005). In our study, sC5b9, suPAR, and GDF-15 levels were found to reflect endothelial injury in CAR-T cell recipients.
Unveiling the Metabolomic Profile of Oily Sensitive Skin: A Non-Invasive Approach
Authors: Zhang Jiaqi , Wu Fan , Wang Jun , Qin Yi , Pan Yao
Published: October 2024

Skin barrier impairment is becoming increasingly common due to changes in lifestyle and modern living environments. Oily sensitive skin (OSS) is a condition that is characterized by an impaired skin barrier. Thus, examining the differences between OSS and healthy skin will enable a more objective evaluation of the characteristics of OSS and facilitate investigations of potential treatments. Initially, a self-assessment questionnaire was used to identify patients with OSS. Biophysical measurements and LAST scores were used to determine whether skin barrier function was impaired. Epidermal biophysical properties, including skin hydration, transepidermal water loss (TEWL), sebum content, erythema index (EI), and a* value, were measured with noninvasive instruments. We subsequently devised a noninvasive D-square sampling technique to identify changes in the skin metabolome in conjunction with an untargeted metabolomics analysis with an Orbitrap Q ExactiveTM series mass spectrometer. In the stratum corneum of 47 subjects, 516 skin metabolites were identified. In subjects with OSS, there was an increase in the abundance of 15 metabolites and a decrease in the abundance of 48 metabolites. The participants with OSS were found to have the greatest disruptions in sphingolipid and amino acid metabolism. The results revealed that an impaired skin barrier is present in patients with OSS and offers a molecular target for screening for skin barrier damage.
Photoexcitation Dynamics of 4-Aminopthalimide in Solution Investigated Using Femtosecond Time-Resolved Infrared Spectroscopy
Authors: Yoon Hojeong , Park Seongchul , Koninti Raj Kumar , Lim Manho
Published: October 2024

Excited-state intramolecular proton transfer (ESIPT) reactions are crucial in photoresponsive materials and fluorescent markers. The fluorescent compound 4-aminophthalimide (4-AP) has been reported to exhibit solvent-assisted ESIPT in protic solvents, such as methanol, wherein the solvent interacts with 4-AP to form a six-membered hydrogen-bonded ring that is strengthened upon excitation. Although the controversial observation of ESIPT in 4-AP has been extensively studied, the molecular mechanism has yet to be fully explored. In this study, femtosecond infrared spectroscopy was used to investigate the dynamics of 4-AP in methanol and acetonitrile after excitation at 350 and 300 nm, which promoted 4-AP to the S1 and S2 states, respectively. The excited 4-AP in the S1 state relaxed to the ground state, while 4-AP in the S2 state relaxed via the S1 state without the occurrence of ESIPT. The enol form of 4-AP (Enol 4-AP) in the S1 state was calculated to be ~10 kcal/mol higher in energy than the keto form in the S1 state, indicating that keto-to-enol tautomerization was endergonic, ultimately resulting in no observable ESIPT for 4-AP in the S1 state. Upon the excitation of 4-AP to the S2 state, the transition to Enol-4-AP in the S1 state was found to be exergonic; however, ESIPT must compete with an internal conversion from the S2 to the S1 state. The internal S2 → S1 conversion was significantly faster than the solvent-assisted ESIPT, resulting in a negligible ESIPT for the 4-AP excited to the S2 state. The detailed excitation dynamics of 4-AP clearly reveal the molecular mechanism underlying its negligible ESIPT, despite the fact that it forms a favorable structure for solvent-assisted ESIPT.
Anti-Inflammatory and Neuroprotective Polyphenols Derived from the European Olive Tree, Olea europaea L., in Long COVID and Other Conditions Involving Cognitive Impairment
Authors: Papadopoulou Paraskevi , Polissidis Alexia , Kythreoti Georgia , Sagnou Marina , Stefanatou Athena , Theoharides Theoharis C.
Published: October 2024

The European olive tree, Olea europaea L., and its polyphenols hold great therapeutic potential to treat neuroinflammation and cognitive impairment. This review examines the evidence for the anti-inflammatory and neuroprotective actions of olive polyphenols and their potential in the treatment of long COVID and neurodegenerative diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and multiple sclerosis (MS). Key findings suggest that olive polyphenols exhibit antioxidant, anti-inflammatory, neuroprotective, and antiviral properties, making them promising candidates for therapeutic intervention, especially when formulated in unique combinations. Recommendations for future research directions include elucidating molecular pathways through mechanistic studies, exploring the therapeutic implications of olive polyphenol supplementation, and conducting clinical trials to assess efficacy and safety. Investigating potential synergistic effects with other agents addressing different targets is suggested for further exploration. The evidence reviewed strengthens the translational value of olive polyphenols in conditions involving cognitive dysfunction and emphasizes the novelty of new formulations.
Pilot Study on the Effect of Patient Condition and Clinical Parameters on Hypoxia-Induced Factor Expression: HIF1A, EPAS1 and HIF3A in Human Colostrum Cells
Authors: Zarychta Julia , Kowalczyk Adrian , Słowik Karolina , Przywara Dominika , Petniak Alicja , Kondracka Adrianna , Wójtowicz-Marzec Monika , Słyk-Gulewska Patrycja , Kwaśniewska Anna , Kocki Janusz , Gil-Kulik Paulina
Published: October 2024

Hypoxia-inducible factor 1 (HIF-1) may play a role in mammary gland development, milk production and secretion in mammals. Due to the limited number of scientific reports on the expression of HIF genes in colostrum cells, it was decided to examine the expression of HIF1A, HIF3A and EPAS1 in the these cells, collected from 35 patients who voluntarily agreed to provide their biological material for research, were informed about the purpose of the study and signed a consent to participate in it. The expression of HIF genes was assessed using qPCR. Additionally, the influence of clinical parameters (method of delivery, occurrence of stillbirths in previous pregnancies, BMI level before pregnancy and at the moment of delivery, presence of hypertension during pregnancy, presence of Escherichia coli in vaginal culture, iron supplement and heparin intake during pregnancy) on the gene expression was assessed, revealing statistically significant correlations. The expression of HIF1A was 3.5-fold higher in the case of patients with the presence of E. coli in vaginal culture (p = 0.041) and 2.5 times higher (p = 0.031) in samples from women who used heparin during pregnancy. Approximately 1.7-fold higher expression of the EPAS1 was observed in women who did not supplement iron during pregnancy (p = 0.046). To our knowledge, these are the first studies showing the relationship between HIF expression in cells from breast milk and the method of delivery and health condition of women giving birth. The assessment of HIF expression requires deeper examination in a larger study group, and the results of further studies will allow to determine whether HIF can become biomarkers in pregnancy pathology states.
Elevated Temperature Effects on FRP–Concrete Bond Behavior: A Comprehensive Review and Machine Learning-Based Bond Strength Prediction
Authors: Salameh Aseel , Hawileh Rami , Safieh Hussam , Assad Maha , Abdalla Jamal
Published: October 2024

Because of their improved properties, FRP composites are vastly used in the strengthening of aged concrete infrastructures. However, it has been observed that their performance is highly compromised when exposed to high temperatures, as expected during fire incidents, which critically affects FRP–concrete bond behavior, hence affecting the overall efficiency of the strengthening system. This paper critically presents the available literature concerning the degradation of bond strength between FRP systems with concrete substrates due to increased temperatures. Both analytical and numerical bond–slip models developed for the prediction of bond strength degradation under such conditions are reviewed. A generally confirmed fact is that exposure to high temperatures, especially those reaching glass transition temperature (Tg) for epoxy adhesives, leads to bond degradation. Therefore, cement mortar-bonded CFRP textiles display better performance in fire endurance. This present paper also utilizes machine learning algorithms for the prediction of bond strength under elevated temperatures based on an experimental database of 37 beams. The nonlinear relationships and variable interactions in the developed model provide a reliable method for the estimation of bond strength with reduced extensive experimental testing, where the critical role of temperature in bond behavior is identified. This paper emphasizes the use of advanced predictive models to ensure the durability and safety of FRP-strengthened concrete structures in thermally challenging environments.
Effect of Coarse Aggregate Type on the Fracture Toughness of Ordinary Concrete
Authors: Golewski Grzegorz Ludwik
Published: October 2024

This research work aims to compare the strength and fracture mechanics properties of plain concretes, obtained from different coarse aggregates. During the study, mechanical parameters including compressive strength (fcm) and splitting tensile strength (fctm), as well as fracture parameters involving critical stress intensity factor (KIcS) and critical crack tip opening displacement (CTODc) were evaluated. The effect of the aggregates used on the brittleness of the concretes was also analyzed. For better understanding of the crack initiation and propagation in concretes with different coarse aggregates, a macroscopic failure surfaces examination of the tested beams is also presented. Crushed aggregates covered were basalt (BA), granite (GT), and limestone (LM), and natural peeble gravel aggregate (GL) were used in the concrete mixtures. Fracture toughness tests were performed on an MTS 810 testing machine. Due to the high strength of the rock material, the rough surface of the aggregate grains, and good bonding in the ITZ area between the aggregate and the paste, the concretes with crushed aggregates exhibited high fracture toughness. Both of the analyzed fracture mechanics parameters, i.e.,  KIcS and CTODc, increased significantly in the case of concretes which were manufactured with crushed aggregates. They amounted, in comparison to concrete based on gravel aggregate, to levels ranging from 20% for concrete with limestone aggregate to over 30% for concrete with a granite aggregate, and to as much as over 70% for concrete with basalt aggregate. On the other hand, the concrete with gravel aggregate showed the lowest fracture toughness because of the smooth surface of the aggregate grains and poor bonding between the aggregate and the cement paste. However, the fracture process in each series of concrete was quasi-plastic in the case of gravel concrete, semi-brittle in the case of limestone concrete, and clearly brittle in the case of the concretes based on granite and basalt aggregates. The results obtained help to explain how the coarse aggregate type affects the strength parameters and fracture toughness at bending.
Advances in Space Astroparticle Physics: Frontier Technologies for Particle Measurements in Space
Authors: Duranti Matteo , Vagelli Valerio
Published: October 2024

In the last decades, breakthrough advances in understanding the mechanisms of the Universe and fundamental physics have been achieved through the exploitation of data on cosmic rays and high-energy radiation gathered via orbiting experiments, in a synergic and complementary international effort that combines space-based instrument data with ground-based space observatories, accelerator, and collider experiments [...]
Prognostic Value of Coronary Artery Calcification in Patients with COVID-19 and Interstitial Pneumonia: A Case-Control Study
Authors: Dall’Ara Gianni , Piciucchi Sara , Carletti Roberto , Vizzuso Antonio , Gardini Elisa , De Vita Maria , Dallaserra Chiara , Campacci Federica , Di Giannuario Giovanna , Grosseto Daniele , Rinaldi Giovanni , Vecchio Sabine , Mantero Federica , Mellini Lorenzo , Albini Alessandra , Giampalma Emanuela , Poletti Venerino , Galvani Marcello
Published: October 2024

Background: Patients suffering from coronavirus disease-19 (COVID-19)-related interstitial pneumonia have variable outcomes, and the risk factors for a more severe course have yet to be comprehensively identified. Cohort studies have suggested that coronary artery calcium (CAC), as estimated at chest computed tomography (CT) scan, correlated with patient outcomes. However, given that the prevalence of CAC is gender- and age-dependent, the influence of baseline confounders cannot be completely excluded. Methods: We designed a retrospective, multicenter case-control study including patients with COVID-19, with severe course cases selected based on death within 30 days or requiring invasive ventilation, whereas controls were age- and sex-matched patients surviving up to 30 days without invasive ventilation. The primary outcome was the analysis of moderate-to-severe CAC prevalence between cases and controls. Results: A total of 65 cases and 130 controls were included in the study. Cases had a significantly higher median pulmonary severity score at chest CT scan compared to controls (10 vs. 8, respectively; p = 0.0001), as well as a higher CAC score (5 vs. 2; p = 0.009). The prevalence of moderate-to-severe CAC in cases was significantly greater (41.5% vs. 23.8%; p = 0.013), a difference mainly driven by a higher prevalence in those who died within 30 days (p = 0.000), rather than those requiring invasive ventilation (p = 0.847). White blood cell count, moderate-to-severe CAC, the need for antibiotic therapy, and severe pneumonia at CT scan were independent primary endpoint predictors. Conclusions: This case-control study demonstrated that the CAC burden was higher in COVID-19 patients who did not survive 30 days or who required mechanical ventilation, and CAC played an independent prognostic role.
The Influence of Age and Exercise Training Status on Left Ventricular Systolic Twist Mechanics in Healthy Males—An Exploratory Study
Authors: Beaumont Alexander J. , Campbell Amy K. , Unnithan Viswanath B. , Oxborough David , Grace Fergal , Knox Allan , Sculthorpe Nicholas F.
Published: October 2024

Age-related differences in twist may be mitigated with exercise training, although this remains inconclusive. Moreover, temporal left ventricular (LV) systolic twist mechanics, including early-systolic (twistearly), and beyond peak twist (twistpeak) alone, have not been considered. Therefore, further insights are required to ascertain the influence of age and training status on twist mechanics across systole. Forty males were included and allocated into 1 of 4 groups based on age and training status: young recreationally active (YRA, n = 9; 28 ± 5 years), old recreationally active (ORA, n = 10; 68 ± 6 years), young trained (YT, n = 10; 27 ± 6 years), and old trained (OT, n = 11, 64 ± 4 years) groups. Two-dimensional speckle-tracking echocardiography was performed to determine LV twist mechanics, including twistearly, twistpeak, and total twist (twisttotal), by considering the nadir on the twist time-curve during early systole. Twisttotal was calculated by subtracting twistearly from their peak values. LV twistpeak was higher in older than younger men (p = 0.036), while twistpeak was lower in the trained than recreationally-active (p = 0.004). Twistpeak is underestimated compared with twisttotal (p < 0.001), and when early-systolic mechanics were considered, to calculate twisttotal, the age effect (p = 0.186) was dampened. LV twist was higher in older than younger age, with lower twist in exercise-trained than recreationally-active males. Twistpeak is underestimated when twistearly is not considered, with novel observations demonstrating that the age effect was dampened when considering twistearly. These findings elucidated a smaller age effect when early phases of systole are considered, while lower LV systolic mechanics were observed in older aged trained than recreationally-active males.
First Worldwide Report of a Total Colectomy with the Hugo RAS Platform
Authors: Santos Marisa Domingues dos , Brandão Pedro
Published: October 2024

Background: Compared with the da Vinci platform, there is limited experience with the Hugo RAS® platform for colorectal surgery in Europe. This difference is especially notable when considering complex procedures such as total colectomy. Aim: To demonstrate the feasibility and safety of using the Hugo RAS® (Medtronic, Minneapolis, MN, USA) platform for total colectomy. Clinical case: An 18-year-old female patient with Familial Adenomatous Polyposis (FAP) and a BMI of 19 underwent a total colectomy with ileorectal anastomosis using the Hugo RAS® platform. The procedure lasted 253 min without complications. The postoperative period was uneventful, and she was discharged from the hospital on the third postoperative day. Conclusion: The Hugo RAS® platform is an emerging minimally invasive robotic that can be used even for total colectomy with proper patient selection. The placement and choice of arms and trocars were crucial to obtaining a similar operative time to the standard laparoscopic approach. The certification of Hugo’s new instruments, such as energy devices and staplers, will make this platform even more competitive.
Artificial Intelligence in Aesthetic Dentistry: Is Treatment with Aligners Clinically Realistic?
Authors: Mourgues Thomas , González-Olmo María José , Huanca Ghislanzoni Luis , Peñacoba Cecilia , Romero-Maroto Martín
Published: October 2024

Smile aesthetics are increasingly prioritized in dental practice, with accurate orthodontic assessment and treatment planning being crucial for optimal outcomes. This study evaluates Invisalign® SmileView™ (SV), an AI-based tool that simulates post-treatment smiles, focusing on its ability to present potential orthodontic outcomes to patients. Background/Objectives: This research aims to study whether SV can simulate predictable orthodontic results and if it makes anatomical modifications to the teeth. Additionally, it will evaluate whether SV displays smiles that conform to the orthodontic criteria described in the literature. Finally, the study will analyze whether the software can align the dental with the facial midline. Methods: A total of 51 subjects were recruited in Madrid, Spain. The operator took a frontal photograph of the subjects with a social smile (T0), following the application’s instructions. Subsequently, the subjects followed the steps to modify their smile (T1), resulting in a new image of the subject with a different smile. The following variables were collected, analyzed, and compared with the standards defined in the literature: smile width, vertical exposure of the maxillary central incisor, width of the maxillary central and lateral incisors, proportion of the maxillary lateral incisor width to the central incisor, anterior gingival exposure level, position of the upper and lower dental midlines relative to the facial midline. Results: 58% of the sample showed dental expansion, with an excessive expansion (>5 mm) observed in 8%. In the maxillary arch, 5.9% of incisors exceeded predictable aligner movement (>1.5 mm), with 3.9% showing excessive extrusion and 2% excessive intrusion. For the lateral incisors, the mesiodistal size was reduced less than 0.5 mm in 31.4% of cases, with excessive interproximal reduction (>0.5 mm) in 5.9%. Additionally, 62.7% of cases would require multidisciplinary treatment due to an increase in size. SV centered the upper midline in 77.9% of these cases. Among the sample, the upper midline was initially centered in 74.5% of subjects, and SV maintained it centered in 84.2% of these subjects. Conclusions: SV tends to generate simulations of broader smiles, which are mostly achievable through aligner treatments, from an orthodontic perspective, and showed high predictability regarding the vertical movements of the incisors that can be achieved with aligners. Moreover, it adjusted the mesiodistal size of the upper incisors in its simulations and demonstrated the ability to identify and correct deviations of the dental midlines relative to the facial midline.
Increased Prevalence of Attention Deficit Hyperactivity Disorder in Individuals with Selective Immunoglobulin A Deficiency: A Nationwide Case–Control Study
Authors: Merzon Eugene , Farag Reem , Ashkenazi Shai , Magen Eli , Manor Iris , Weizman Abraham , Green Ilan , Golan-Cohen Avivit , Genshin Akim , Vinker Shlomo , Israel Ariel
Published: October 2024

Background: Selective Immunoglobulin A Deficiency (SIgAD) is one of the most prevalent immunodeficiencies, characterized by an increased risk of mucosal infections. Attention deficit hyperactivity disorder (ADHD) is among the most common neurodevelopmental disorders and is associated with significantly higher rates of various infectious diseases, white blood cell abnormalities, and considerable morbidity. This study aimed to evaluate the prevalence of ADHD among patients with SIgAD. Methods: We conducted a retrospective, observational, population-based case–control study, within Leumit Health Services, by comparing individuals diagnosed with SIgAD to a matched control group. Data were extracted from electronic health records. Results: Of the >700,000 registered individuals, 772 aged ≥4 years with SIgAD were identified (mean age 22.0 ± 17.5 years; male/female ratio 1:1). The 5:1 matched control group consisted of 3860 subjects without SIgAD, with no significant differences between the groups regarding age, gender, ethnicity, and socioeconomic status. ADHD prevalence was significantly higher in the SIgAD group (16.2%) than in the control group (12.9%), with an odds ratio of 1.30 (95% confidence interval 1.05–1.61, p = 0.017), as was the use of methylphenidate (6.6% vs. 4%). Additionally, respiratory and intestinal infections were significantly more common in the SIgAD group (p < 0.001). Conclusion: A significantly higher prevalence of ADHD was observed in patients with SIgAD compared to strictly matched controls without SIgAD. These findings enhance our understanding of the pathophysiology of ADHD and its associated health complications.
Effectiveness of Osteopathic Treatment in Adults with Short Hamstring Syndrome: A Systematic Review
Authors: Ogando-Berea Hugo , Leirós-Rodríguez Raquel , Hernandez-Lucas Pablo , Rodríguez-González Óscar
Published: October 2024

Background/Objective: Short hamstring syndrome is common in the general population and can lead to impaired balance, function, and posture, and increased risk of injuries. Local treatments have obtained controversial results, so it is necessary to evaluate the effectiveness of other types of therapy such as osteopathic treatment. To evaluate the efficacy of osteopathic techniques in increasing the elasticity of the hamstring musculature in short hamstring syndrome. Methods: A systematic review of randomised controlled trials was conducted in PubMed, Medline, Cinhal, Scopus, WOS, SPORTDiscuss, and PEDro. The PEDro scale was used to evaluate the methodological quality and the RoB2 for the evaluation of biases. Results: A total of eight articles were selected. Most of the participants were assessed with the Active Knee Extension or Straight Leg Raise tests. The osteopathic techniques used were the muscle energy technique, suboccipital inhibition, and vertebral mobilisations. As for the control interventions, they mainly included passive stretching and placebo. Conclusions: The results suggest that osteopathic techniques are more effective than placebo or other interventions in increasing flexibility in adult patients with short hamstring syndrome. This effect can be explained by neurophysiological (Golgi apparatus, neuromuscular spindle activity, and Hoffmann reflex) and structural factors (dura mater, posture, and myofascial chains). Nevertheless, the evidence suggests that it would be beneficial to incorporate this type of treatment into flexibility improvement programmes.
Association between Diverticulosis and Colorectal Neoplasia: Analysis from a Large Austrian Database
Authors: Völkerer Andreas , Wernly Sarah , Semmler Georg , Flamm Maria , Ausserwinkler Mathias , Datz Leonora , Götz Nikolaus , Hofer Hannah , Aigner Elmar , Datz Christian , Wernly Bernhard
Published: October 2024

Background: Colorectal neoplasia and diverticulosis are common findings on colonoscopies. While adenomas are precursors to colorectal cancer, diverticulosis is usually asymptomatic but can lead to diverticulitis. Despite their prevalence and coexistence, the relationship between these conditions remains unclear. This study investigates whether diverticulosis is associated with adenomas, considering shared risk factors and potential inflammation-driven mechanisms. Methods: We examined 6154 asymptomatic individuals undergoing colorectal cancer screening in Austria. Diverticulosis and colorectal neoplasia were documented during screenings based on macroscopic definitions. Advanced neoplasia was defined as polyps >1 cm or high-grade dysplasia. Associations between diverticulosis and neoplastic findings were assessed using univariate and multivariable logistic regression models. Results: Although the overall incidence of any polypoid lesion was higher in the diverticulosis group (37% vs. 30%), statistical analysis revealed a comparable rate of advanced neoplasms in both groups. Importantly, no significant link between diverticulosis and advanced neoplasms was found (OR 1.125; 95% CI: 0.933 to 1.357, p = 0.218) even after adjusting for confounding factors. In a univariate analysis, a statistically significant association between diverticulosis and the presence of any colorectal polyps was identified (OR 1.388; 95% CI: 1.244–1.549, p < 0.0001). However, after adjusting for confounding factors in model 2 (OR 1.065, 95% CI: 0.942 to 1.204, p = 0.314) and model 3 (OR 1.071, 95% CI: 0.925 to 1.239, p = 0.360), this effect was also not statistically significant. Conclusions: Patients with diverticulosis share demographic and clinical features with those at risk of colorectal neoplasia, such as older age, male gender, and higher cardiometabolic risk. However, diverticulosis does not independently increase the risk of advanced colorectal neoplasia or unspecified polypoid lesions.
A 2024 Update on Growth Hormone Deficiency Syndrome in Adults: From Guidelines to Real Life
Authors: Aversa Luigi Simone , Cuboni Daniela , Grottoli Silvia , Ghigo Ezio , Gasco Valentina
Published: October 2024

Background: Adult growth hormone deficiency (GHD) has been recognized since the late 1980s. The clinical manifestations of adult GHD are often nonspecific, and diagnosis relies on GH stimulation tests, which are intricate, costly, time-consuming, and may carry the risk of adverse effects. Diagnosis is further complicated by factors like age, sex, and BMI, which affect GH response during testing. Therefore, GH replacement therapy remains challenging, requiring careful individualized evaluation of risks and benefits. The aim of this review is to provide an update on diagnosing and treating adult GHD, addressing current limitations and challenges based on recent studies. Methods: We conducted a comprehensive review of the literature regarding the diagnosis and management of adult GHD by searching PubMed and EMBASE. Only articles in English were included, and searches were conducted up to August 2024. Results: A review of guidelines and literature up to 2024 highlights the significant heterogeneity in the data and reveals various protocols for managing GHD, covering both diagnostic and therapeutic approaches. Conclusions: Despite diagnostic and treatment advances, managing adult GHD remains challenging due to variable presentation and the need for personalized GH therapy. Future efforts should aim to improve and standardize diagnostic and treatment protocols.
Sedentary Lifestyle Is a Modifiable Risk Factor for Cognitive Impairment in Patients on Dialysis and after Kidney Transplantation
Authors: Golenia Aleksandra , Olejnik Piotr , Maciejewska Oliwia , Wojtaszek Ewa , Żebrowski Paweł , Małyszko Jolanta
Published: October 2024

Background: Chronic kidney disease (CKD) is a risk factor for cognitive impairment (CI), and this risk is the highest in patients with end-stage kidney disease (ESKD). As a multifactorial disease, CI may be influenced by several potentially modifiable lifestyle and behavioral factors that may reduce or increase the risk of dementia. The aim of this study was to evaluate the associations between the known modifiable risk factors for dementia and the risk of CI in patients with ESKD treated with renal replacement therapy. The Charlson Comorbidity Index and the risk of CI in patients with ESKD were also assessed. Methods: In this cross-sectional study, 225 consecutive patients with ESKD treated with different modalities of renal replacement therapy were assessed for cognitive decline using the Addenbrooke’s Cognitive Examination (ACE III) test. Information was also collected on modifiable risk factors for dementia, medical history and demographics. Results: This study included 117 patients after kidney transplantation (KT) and 108 patients with ESKD undergoing peritoneal dialysis and hemodialysis. The prevalence of modifiable risk factors for dementia differed between the groups; KT patients were more likely to be physically active, residing in cities with populations of less than 500,000 inhabitants, and were less likely to suffer from depression. Furthermore, the KT group had a lower Charlson Comorbidity Index score, indicating less severe comorbidities, and a lower risk of CI (3.6 ± 1.67 vs. 5.43 ± 2.37; p = 0.001). In both the KT and dialysis groups, patients with CI were more likely to have a sedentary lifestyle (45% vs. 9%, p = 0.001 and 88% vs. 48%, p = 0.001, respectively), whereas lower educational attainment and depression had a significant negative impact on ACE III test results, but only in KT patients. Finally, cognitive function in dialysis patients was negatively affected by social isolation and living in urban areas. Conclusions: Modifiable risk factors for dementia, particularly a sedentary lifestyle, are associated with a higher risk of CI in patients treated with different renal replacement therapy modalities. As CI is an irreversible condition, it is important to identify lifestyle-related factors that may lead to dementia in order to improve or maintain cognitive function in patients with ESKD.
Semaglutide Treatment Effects on Liver Fat Content in Obese Subjects with Metabolic-Associated Steatotic Liver Disease (MASLD)
Authors: Dusilová Tereza , Kovář Jan , Laňková Ivana , Thieme Lenka , Hubáčková Monika , Šedivý Petr , Pajuelo Dita , Burian Martin , Dezortová Monika , Miklánková Denisa , Malínská Hana , Svobodová Šťastná Petra , Poledne Rudolf , Hájek Milan , Haluzík Martin
Published: October 2024

Background: Metabolic-dysfunction-associated steatotic liver disease (MASLD) represents a major clinical complication of obesity. Methods: In this study, we used magnetic resonance (MR) methods to determine the effect of obesity treatment with semaglutide, a GLP-1 receptor agonist, on the liver fat content and selected metabolic variables. We investigated whether treatment would affect the acute response of liver fat to glucose and fructose administration and whether it would affect the fatty acid profile of VLDL-triglycerides. Sixteen obese non-diabetic men underwent a 16-week dietary intervention and 16-week treatment with subcutaneous semaglutide in a crossover design without a washout period. The order of the interventions was randomized. Results: After treatment, body weight of the subjects decreased by 5% and liver fat by a third, whereas dietary intervention had no impact on these parameters. The decrease in liver fat with semaglutide did not correlate with changes in body weight and other measures of adiposity and was unrelated to improved insulin sensitivity. Conclusions: The proportion of palmitic and palmitoleic acids in VLDL-triglycerides decreased after treatment, suggesting that the beneficial effects of semaglutide on liver fat are mediated by the suppression of de novo lipogenesis.
On the Fabrication Processes of Structural Supercapacitors by Resin Transfer Molding and Vacuum-Assisted Resin Transfer Molding
Authors: Wu Chien-Chih , Young Wen-Bin
Published: October 2024

This study investigated the manufacturing processes for structural supercapacitors (SSCs) using smear molding (RS), resin transfer molding (RTM), and vacuum-assisted resin transfer molding (VARTM). Woven carbon fibers were used as the electrode, woven glass fibers as an insulating layer, and an alkaline/epoxy compound as the electrolyte. In the RTM process, due to the vacuum and the high-pressure injection of the electrolyte, the electrochemical and mechanical properties of the SSC can be greatly improved, and the void contents in the SSC can be reduced. The balanced electrochemical performance and mechanical properties of SSCs were observed in the range of epoxy content from 15 wt% to 30 wt%. This study contributes to the development of SSCs through the establishment of the fabrication process for improvements in part quality. The fabrication method demonstrated here can be directly applied by industries to produce even larger-scale SSCs, opening up new possibilities for practical implementation and scalability.
The Impact of Activated Carbon–MexOy (Me = Bi, Mo, Zn) Additives on the Thermal Decomposition Kinetics of the Ammonium Nitrate–Magnesium–Nitrocellulose Composite
Authors: Yelemessova Zhanerke , Yerken Ayan , Zhaxlykova Dana , Milikhat Bagdatgul
Published: October 2024

This research investigates the impact of additives such as activated carbon (AC) combined with metal oxides (Bi2O3, MoO3, and ZnO) on the thermal decomposition kinetics of ammonium nitrate (AN), magnesium (Mg), and nitrocellulose (NC) as a basic AN–Mg–NC composite. To study the thermal properties of the AN–Mg–NC composite with and without the AC–MexOy (Me = Bi, Mo, Zn) additive, a differential scanning calorimetry (DSC) analysis was conducted. The DSC results show that the AC–MexOy (Me = Bi, Mo, Zn) additive catalytically affects the basic AN–Mg–NC composite, lowering the peak decomposition temperature (Tmax) from 534.58 K (AN–Mg–NC) to 490.15 K (with the addition of AC), 490.76 K (with AC–Bi2O3), 492.17 K (with AC–MoO3), and 492.38 K (with AC–ZnO) at a heating rate of β equal to 5 K/min. Based on the DSC data, the activation energies (Ea) for the AN–Mg–NC, AN–Mg–NC–AC, and AN–Mg–NC–AC–MexOy (Me = Bi, Mo, Zn) composites were determined using the Kissinger method. The results suggest that incorporating AC and AC–MexOy (Me = Bi, Mo, Zn) additives reduce the decomposition temperatures and activation energies of the basic AN–Mg–NC composite. Specifically, Ea decreased from 99.02 kJ/mol (for AN–Mg–NC) to 93.63 kJ/mol (with addition of AC), 91.45 kJ/mol (with AC–Bi2O3), 91.65 kJ/mol (with AC–MoO3), and 91.76 kJ/mol (with AC–ZnO). These findings underscore the potential of using AC–MexOy (Me = Bi, Mo, Zn) as a catalytic additive to enhance the performance of AN–Mg–NC-based energetic materials, increasing their efficiency and reliability for use in solid propellants.