bluuebunny/crossref_metadata_2025 huggingface dataset:
Transcription Factors Sox8 and Sox10 Contribute with Different Importance to the Maintenance of Mature Oligodendrocytes
Authors: Jörg Lisa Mirja , Schlötzer-Schrehardt Ursula , Lefebvre Véronique , Sock Elisabeth , Wegner Michael
Published: August 2024

Myelin-forming oligodendrocytes in the vertebrate nervous system co-express the transcription factor Sox10 and its paralog Sox8. While Sox10 plays crucial roles throughout all stages of oligodendrocyte development, including terminal differentiation, the loss of Sox8 results in only mild and transient perturbations. Here, we aimed to elucidate the roles and interrelationships of these transcription factors in fully differentiated oligodendrocytes and myelin maintenance in adults. For that purpose, we conducted targeted deletions of Sox10, Sox8, or both in the brains of two-month-old mice. Three weeks post-deletion, none of the resulting mouse mutants exhibited significant alterations in oligodendrocyte numbers, myelin sheath counts, myelin ultrastructure, or myelin protein levels in the corpus callosum, despite efficient gene inactivation. However, differences were observed in the myelin gene expression in mice with Sox10 or combined Sox8/Sox10 deletion. RNA-sequencing analysis on dissected corpus callosum confirmed substantial alterations in the oligodendrocyte expression profile in mice with combined deletion and more subtle changes in mice with Sox10 deletion alone. Notably, Sox8 deletion did not affect any aspects of the expression profile related to the differentiated state of oligodendrocytes or myelin integrity. These findings extend our understanding of the roles of Sox8 and Sox10 in oligodendrocytes into adulthood and have important implications for the functional relationship between the paralogs and the underlying molecular mechanisms.
Research on Bone Cells in Health and Disease
Authors: Győri Dávid S.
Published: August 2024

Bone-forming osteoblasts, osteocytes, and bone-resorbing osteoclasts are responsible for life-long skeletal remodeling [...]
Hepatic Amyloid Beta-42-Metabolizing Proteins in Liver Steatosis and Metabolic Dysfunction-Associated Steatohepatitis
Authors: Gross Simon , Danielyan Lusine , Buechler Christa , Kubitza Marion , Klein Kathrin , Schwab Matthias , Melter Michael , Weiss Thomas S.
Published: August 2024

Amyloid beta (Aβ) plays a major role in the pathogenesis of Alzheimer’s disease and, more recently, has been shown to protect against liver fibrosis. Therefore, we studied Aβ-42 levels and the expression of genes involved in the generation, degradation, and transport of Aβ proteins in liver samples from patients at different stages of metabolic dysfunction-associated liver disease (MASLD) and under steatotic conditions in vitro/in vivo. Amyloid precursor protein (APP), key Aβ-metabolizing proteins, and Aβ-42 were analyzed using RT-PCR, Western blotting, Luminex analysis in steatotic in vitro and fatty liver mouse models, and TaqMan qRT-PCR analysis in hepatic samples from patients with MASLD. Hepatocytes loaded with palmitic acid induced APP, presenilin, and neprilysin (NEP) expression, which was reversed by oleic acid. Increased APP and NEP, decreased BACE1, and unchanged Aβ-42 protein levels were found in the steatotic mouse liver compared to the normal liver. Aβ-42 concentrations were low in MASLD samples of patients with moderate to severe fibrosis compared to the livers of patients with mild or no MASLD. Consistent with the reduced Aβ-42 levels, the mRNA expression of proteins involved in APP degradation (ADAM9/10/17, BACE2) and Aβ-42 cleavage (MMP2/7/9, ACE) was increased. In the steatotic liver, the expression of APP- and Aβ-metabolizing proteins is increased, most likely related to oxidative stress, but does not affect hepatic Aβ-42 levels. Consistent with our previous findings, low Aβ-42 levels in patients with liver fibrosis appear to be caused by the reduced production and enhanced non-amyloidogenic processing of APP.
A Need to Preserve Ejection Fraction during Heart Failure
Authors: Akinterinwa Oluwaseun E. , Singh Mahavir , Vemuri Sreevatsa , Tyagi Suresh C.
Published: August 2024

Heart failure (HF) is a significant global healthcare burden with increasing prevalence and high morbidity and mortality rates. The diagnosis and management of HF are closely tied to ejection fraction (EF), a crucial parameter for evaluating disease severity and determining treatment plans. This paper emphasizes the urgent need to maintain EF during heart failure, highlighting the distinct phenotypes of HF with preserved ejection fraction (HFpEF) and HF with reduced ejection fraction (HFrEF). It discusses the complexities of HFrEF pathophysiology and its negative impact on patient outcomes, stressing the importance of ongoing research and the development of effective therapeutic interventions to slow down the progression from preserved to reduced ejection fraction. Additionally, it explores the potential role of renal denervation in preserving ejection fraction and its implications for HFrEF management. This comprehensive review aims to offer valuable insights into the critical role of EF preservation in enhancing outcomes for patients with heart failure.
Structural Characterization of Heat Shock Protein 90β and Molecular Interactions with Geldanamycin and Ritonavir: A Computational Study
Authors: Lima Carlyle Ribeiro , Antunes Deborah , Caffarena Ernesto , Carels Nicolas
Published: August 2024

Drug repositioning is an important therapeutic strategy for treating breast cancer. Hsp90β chaperone is an attractive target for inhibiting cell progression. Its structure has a disordered and flexible linker region between the N-terminal and central domains. Geldanamycin was the first Hsp90β inhibitor to interact specifically at the N-terminal site. Owing to the toxicity of geldanamycin, we investigated the repositioning of ritonavir as an Hsp90β inhibitor, taking advantage of its proven efficacy against cancer. In this study, we used molecular modeling techniques to analyze the contribution of the Hsp90β linker region to the flexibility and interaction between the ligands geldanamycin, ritonavir, and Hsp90β. Our findings indicate that the linker region is responsible for the fluctuation and overall protein motion without disturbing the interaction between the inhibitors and the N-terminus. We also found that ritonavir established similar interactions with the substrate ATP triphosphate, filling the same pharmacophore zone.
Genome-Wide Characterization and Haplotypic Variation Analysis of the IDD Gene Family in Foxtail Millet (Setaria italica)
Authors: Wu Hongpo , Zhang Renliang , Diao Xianmin
Published: August 2024

The indeterminate domain proteins (IDD proteins) play essential roles in the growth and development of various plant tissues and organs across different developmental stages, but members of this gene family have not yet been characterized in foxtail millet (Setaria italica). To have a comprehensive understanding of the IDD gene family in foxtail millet, we performed a genome-wide characterization and haplotypic variation analysis of the IDD gene family in foxtail millet. In this study, sixteen IDD genes were identified across the reference genome of Yugu1, a foxtail millet cultivar. Phylogenetic analysis revealed that the Setaria italica IDD (SiIDD) proteins were clustered into four groups together with IDD proteins from Arabidopsis thaliana (dicot) and Oryza sativa (monocot). Conserved protein motif and gene structure analyses revealed that the closely clustered SiIDD genes were highly conserved within each subgroup. Furthermore, chromosomal location analysis showed that the SiIDD genes were unevenly distributed on nine chromosomes of foxtail millet and shared collinear relationships with IDD genes of other grass species. Transcriptional analysis revealed that the SiIDD genes differed greatly in their expression patterns, and paralogous genes shared similar expression patterns. In addition, superior haplotypes for two SiIDD genes (SiIDD8 and SiIDD14) were identified to correlate with traits of early heading date, and high thousand seed weight and molecular markers were designed for SiIDD8 and SiIDD14 to distinguish different haplotypes for breeding. Taken together, the results of this study provide useful information for further functional investigation of SiIDD genes, and the superior haplotypes of SiIDD8 and SiIDD14 will be particularly beneficial for improving heading date and yield of foxtail millet in breeding programs.
Intra-Phenotypic and -Genotypic Variations of Beauveria bassiana (Bals.) Vuill. Strains Infecting Aedes aegypti L. Adults
Authors: Zamora-Avilés Norma , Orozco-Flores Alonso A. , Cavazos-Vallejo Teodora , Romo-Sáenz César I. , Cuevas-García David A. , Gomez-Flores Ricardo , Tamez-Guerra Patricia
Published: August 2024

Beauveria bassiana has potential for Aedes aegypti biological control. However, its efficacy depends on the strain’s geographic location, host susceptibility, and virulence. The present study aimed to evaluate the effectiveness of B. bassiana strain BBPTG4 conidia in controlling Ae. aegypti adults and its detection via introns profile on exposed mosquito corpses. Morphologic characteristics among strains were highly similar. Comprehensive testing of these strains demonstrated that BBPT4 exhibited the ideal biological activity for Ae. aegypti control, with a median lethal time (TL50) of 7.5 d compared to ~3 d and ~10 d for BB01 and BB37 strains, respectively. Infected mosquitoes died after GHA and BBPTG4 exposure, and corpses were analyzed for infecting strains detection. Differences among the seven evaluated strains were determined, assessing five different insertion group I intron profiles in BBTG4, BB01, GHA, BB37, and BB02 strains. Mosquitoes infected by BBPTG4 and non-exposed (negative control) intron profiles were obtained. We detected the presence of introns in the BBPTG4 strain, which were not present in non-exposed mosquitoes. In conclusion, B. bassiana strains showed similarities in terms of their cultural and microscopic morphological characteristics and biologicals virulence level, but different intron profiles. BBPTG4 strain-infected Ae. aegypti adult corpses, showing specific amplicons, enabled us to identify B. bassiana at the strain level among infected mosquitoes. However, monitoring and detection of field-infected insects is essential for further verification.
Repetitive Sequence Stability in Embryonic Stem Cells
Authors: Shi Guang , Pang Qianwen , Lin Zhancheng , Zhang Xinyi , Huang Kaimeng
Published: August 2024

Repetitive sequences play an indispensable role in gene expression, transcriptional regulation, and chromosome arrangements through trans and cis regulation. In this review, focusing on recent advances, we summarize the epigenetic regulatory mechanisms of repetitive sequences in embryonic stem cells. We aim to bridge the knowledge gap by discussing DNA damage repair pathway choices on repetitive sequences and summarizing the significance of chromatin organization on repetitive sequences in response to DNA damage. By consolidating these insights, we underscore the critical relationship between the stability of repetitive sequences and early embryonic development, seeking to provide a deeper understanding of repetitive sequence stability and setting the stage for further research and potential therapeutic strategies in developmental biology and regenerative medicine.
Temperature-Dependent tRNA Modifications in Bacillales
Authors: Hoffmann Anne , Lorenz Christian , Fallmann Jörg , Wolff Philippe , Lechner Antony , Betat Heike , Mörl Mario , Stadler Peter F.
Published: August 2024

Transfer RNA (tRNA) modifications are essential for the temperature adaptation of thermophilic and psychrophilic organisms as they control the rigidity and flexibility of transcripts. To further understand how specific tRNA modifications are adjusted to maintain functionality in response to temperature fluctuations, we investigated whether tRNA modifications represent an adaptation of bacteria to different growth temperatures (minimal, optimal, and maximal), focusing on closely related psychrophilic (P. halocryophilus and E. sibiricum), mesophilic (B. subtilis), and thermophilic (G. stearothermophilus) Bacillales. Utilizing an RNA sequencing approach combined with chemical pre-treatment of tRNA samples, we systematically profiled dihydrouridine (D), 4-thiouridine (s4U), 7-methyl-guanosine (m7G), and pseudouridine (Ψ) modifications at single-nucleotide resolution. Despite their close relationship, each bacterium exhibited a unique tRNA modification profile. Our findings revealed increased tRNA modifications in the thermophilic bacterium at its optimal growth temperature, particularly showing elevated levels of s4U8 and Ψ55 modifications compared to non-thermophilic bacteria, indicating a temperature-dependent regulation that may contribute to thermotolerance. Furthermore, we observed higher levels of D modifications in psychrophilic and mesophilic bacteria, indicating an adaptive strategy for cold environments by enhancing local flexibility in tRNAs. Our method demonstrated high effectiveness in identifying tRNA modifications compared to an established tool, highlighting its potential for precise tRNA profiling studies.
Morphology-Dependent Photocatalytic Activity of Nanostructured Titanium Dioxide Coatings with Silver Nanoparticles
Authors: Shakeel Nasir , Piwoński Ireneusz , Kisielewska Aneta , Krzywiecki Maciej , Batory Damian , Cichomski Michał
Published: August 2024

This study aims to improve the photocatalytic properties of titanium dioxide nanorods (TNRs) and other related nanostructures (dense nanorods, needle-like nanorods, nanoballs, and nanoflowers) by modifying them with silver nanoparticles (AgNPs). This preparation is carried out using a two-step method: sol–gel dip-coating deposition combined with hydrothermal crystal growth. Further modification with AgNPs was achieved through the photoreduction of Ag+ ions under UV illumination. The investigation explores the impact of different growth factors on the morphological development of TiO2 nanostructures by modulating (i) the chemical composition, the water:acid ratio, (ii) the precursor concentration involved in the hydrothermal process, and (iii) the duration of the hydrothermal reaction. Morphological characteristics, including the length, diameter, and nanorod density of the nanostructures, were analyzed using scanning electron microscope (SEM). The chemical states were determined through use of the X-ray photoelectron spectroscopy (XPS) technique, while phase composition and crystalline structure analysis was performed using the Grazing Incidence X-ray Diffraction (GIXRD) method. The results indicate that various nanostructures (dense nanorods, needle-like nanorods, nanoballs, and nanoflowers) can be obtained by modifying these parameters. The photocatalytic efficiency of these nanostructures and Ag-coated nanostructures was assessed by measuring the degradation of the organic dye rhodamine B (RhB) under both ultraviolet (UV) irradiation and visible light. The results clearly show that UV light causes the RhB solution to lose its color, whereas under visible light RhB changes into rhodamine 110, indicating a successful photocatalytic transformation. The nanoball-like structures’ modification with the active metal silver (TNRs 4 Ag) exhibited high photocatalytic efficiency under both ultraviolet (UV) and visible light for different chemical composition parameters. The nanorod structure (TNRs 2 Ag) is more efficient under UV, but under visible-light photocatalyst, the TNRs 6 Ag (dense nanorods) sample is more effective.
Expression of Growth Hormone-Releasing Hormone and Its Receptor Splice Variants in a Cohort of Hungarian Pediatric Patients with Hematological and Oncological Disorders: A Pilot Study
Authors: Juhász Éva , Szabó Zsuzsanna , Schally Andrew V. , Király József , Fodor Petra , Kónya Gábor , Dezső Balázs , Szabó Erzsébet , Halmos Gábor , Kiss Csongor
Published: August 2024

Hematological and oncological diseases are still among the leading causes of childhood mortality. Expression of growth hormone-releasing hormone (GHRH) and its receptors (GHRH-R) has been previously demonstrated in various human tumors, but very limited findings are available about the presence and potential function of GHRH-Rs in oncological and hematological disorders of children. In this study, we aimed to investigate the expression of mRNA for GHRH and splice variant 1 (SV) of GHRH-R in 15 pediatric hematological/oncological specimens by RT-PCR. The presence and binding characteristics of GHRH-R protein were also studied by Western blot and ligand competition assays. Of the fifteen specimens studied, eleven pediatric samples (73%) showed the expression of mRNA for GHRH. These eleven samples also expressed mRNA for GHRH receptor SV1. GHRH-R protein was found to be expressed in two benign tumor samples and five malignant tumors examined by Western blot. The presence of specific, high affinity binding sites on GHRH-R was demonstrated in all of the seven human pediatric solid tumor samples investigated. Our results show that the expression of GHRH and SV1 of GHRH-R in hemato-oncological diseases in children can pave the way for further investigation of GHRH-Rs as potential molecular targets for diagnosis and therapy.
The Food Additive Benzaldehyde Confers a Broad Antibiotic Tolerance by Modulating Bacterial Metabolism and Inhibiting the Formation of Bacterial Flagella
Authors: Xiao Xia , Ma Can , Zhang Han , Liu Wei , Huang Yanhu , Meng Chuang , Wang Zhiqiang
Published: August 2024

The rise of antibiotic tolerance in bacteria harboring genetic elements conferring resistance to antibiotics poses an increasing threat to public health. However, the primary factors responsible for the emergence of antibiotic tolerance and the fundamental molecular mechanisms involved remain poorly comprehended. Here, we demonstrate that the commonly utilized food additive Benzaldehyde (BZH) possesses the capacity to induce a significant level of fluoroquinolone tolerance in vitro among resistant Escherichia coli. Our findings from animal models reveal that the pre-administration of BZH results in an ineffective eradication of bacteria through ciprofloxacin treatment, leading to similar survival rates and bacterial loads as observed in the control group. These results strongly indicate that BZH elicits in vivo tolerance. Mechanistic investigations reveal several key factors: BZH inhibits the formation of bacterial flagella and releases proton motive force (PMF), which aids in expelling antibiotics from within cells to reducing their accumulation inside. In addition, BZH suppresses bacterial respiration and inhibits the production of reactive oxygen species (ROS). Moreover, exogenous pyruvate successfully reverses BZH-induced tolerance and restores the effectiveness of antibiotics, highlighting how crucial the pyruvate cycle is in combating antibiotic tolerance. The present findings elucidate the underlying mechanisms of BZH-induced tolerance and highlight potential hazards associated with the utilization of BZH.
TMEM132C rs7296262 Single-Nucleotide Polymorphism Is Significantly Associated with Nausea Induced by Opioids Administered for Cancer Pain and Postoperative Pain
Authors: Kang Yuna , Nishizawa Daisuke , Ohka Seii , Terui Takeshi , Ishitani Kunihiko , Morino Ryozo , Yokota Miyuki , Hasegawa Junko , Nakayama Kyoko , Ebata Yuko , Koshika Kyotaro , Ichinohe Tatsuya , Ikeda Kazutaka
Published: August 2024

Opioids are almost mandatorily used for analgesia for cancer pain and postoperative pain. Opioid analgesics commonly induce nausea as a side effect. However, the genetic factors involved are still mostly unknown. To clarify the genetic background of individual differences in the occurrence of nausea during opioid administration, the incidence of nausea was investigated in 331 patients (Higashi-Sapporo Hospital [HS] group) who received morphine chronically for cancer pain treatment and in 2021 patients (Cancer Institute Hospital [CIH] group) who underwent elective surgery under general anesthesia. We conducted a genome-wide association study of nausea in HS samples. Among the top 20 candidate single-nucleotide polymorphisms (SNPs), we focused on the TMEM132C rs7296262 SNP, which has been reportedly associated with psychiatric disorders. The rs7296262 SNP was significantly associated with nausea in both the HS and CIH groups (TT+TC vs. CC; HS group, p = 0.0001; CIH group, p = 0.0064). The distribution of nausea-prone genotypes for the rs7296262 SNP was reversed between HS and CIH groups. These results suggest that the TMEM132C rs7296262 SNP is significantly associated with nausea during opioid use, and the effect of the SNP genotype on nausea is reversed between chronic and acute phases of opioid use.
Ribosome Profiling and RNA Sequencing Reveal Translation and Transcription Regulation under Acute Heat Stress in Rainbow Trout (Oncorhynchus mykiss, Walbaum, 1792) Liver
Authors: Zhao Guiyan , Liu Zhe , Quan Jinqiang , Lu Junhao , Li Lanlan , Pan Yucai
Published: August 2024

Rainbow trout (Oncorhynchus mykiss, Walbaum, 1792) is an important economic cold-water fish that is susceptible to heat stress. To date, the heat stress response in rainbow trout is more widely understood at the transcriptional level, while little research has been conducted at the translational level. To reveal the translational regulation of heat stress in rainbow trout, in this study, we performed a ribosome profiling assay of rainbow trout liver under normal and heat stress conditions. Comparative analysis of the RNA-seq data with the ribosome profiling data showed that the folding changes in gene expression at the transcriptional level are moderately correlated with those at the translational level. In total, 1213 genes were significantly altered at the translational level. However, only 32.8% of the genes were common between both levels, demonstrating that heat stress is coordinated across both transcriptional and translational levels. Moreover, 809 genes exhibited significant differences in translational efficiency (TE), with the TE of these genes being considerably affected by factors such as the GC content, coding sequence length, and upstream open reading frame (uORF) presence. In addition, 3468 potential uORFs in 2676 genes were identified, which can potentially affect the TE of the main open reading frames. In this study, Ribo-seq and RNA-seq were used for the first time to elucidate the coordinated regulation of transcription and translation in rainbow trout under heat stress. These findings are expected to contribute novel data and theoretical insights to the international literature on the thermal stress response in fish.
Pramipexole Hyperactivates the External Globus Pallidus and Impairs Decision-Making in a Mouse Model of Parkinson’s Disease
Authors: Kubota Hisayoshi , Zhou Xinzhu , Zhang Xinjian , Watanabe Hirohisa , Nagai Taku
Published: August 2024

In patients with Parkinson’s disease (PD), dopamine replacement therapy with dopamine D2/D3 receptor agonists induces impairments in decision-making, including pathological gambling. The neurobiological mechanisms underlying these adverse effects remain elusive. Here, in a mouse model of PD, we investigated the effects of the dopamine D3 receptor (D3R)-preferring agonist pramipexole (PPX) on decision-making. PD model mice were generated using a bilateral injection of the toxin 6-hydroxydopamine into the dorsolateral striatum. Subsequent treatment with PPX increased disadvantageous choices characterized by a high-risk/high-reward in the touchscreen-based Iowa Gambling Task. This effect was blocked by treatment with the selective D3R antagonist PG-01037. In model mice treated with PPX, the number of c-Fos-positive cells was increased in the external globus pallidus (GPe), indicating dysregulation of the indirect pathway in the corticothalamic-basal ganglia circuitry. In accordance, chemogenetic inhibition of the GPe restored normal c-Fos activation and rescued PPX-induced disadvantageous choices. These findings demonstrate that the hyperactivation of GPe neurons in the indirect pathway impairs decision-making in PD model mice. The results provide a candidate mechanism and therapeutic target for pathological gambling observed during D2/D3 receptor pharmacotherapy in PD patients.
Combined-Step-Size Affine Projection Andrew’s Sine Estimate for Robust Adaptive Filtering
Authors: Wan Yuhao , Wang Wenyuan
Published: August 2024

Recently, an affine-projection-like M-estimate (APLM) algorithm has gained popularity for its ability to effectively handle impulsive background disturbances. Nevertheless, the APLM algorithm’s performance is negatively affected by steady-state misalignment. To address this issue while maintaining equivalent computational complexity, a robust cost function based on the Andrew’s sine estimator (ASE) is introduced and a corresponding affine-projection Andrew’s sine estimator (APASE) algorithm is proposed in this paper. To further enhance the tracking capability and accelerate the convergence rate, we develop the combined-step-size APASE (CSS-APASE) algorithm using a combination of two different step sizes. A series of simulation studies are conducted in system identification and echo cancellation scenarios, which confirms that the proposed algorithms can attain reduced misalignment compared to other currently available algorithms in cases of impulsive noise. Meanwhile, we also establish a bound on the learning rate to ensure the stability of the proposed algorithms.
The Effect of Maternal Parity on Preterm Birth Risk in Women with Short Mid-Trimester Cervical Length: A Retrospective Cohort Study
Authors: Kremer Einav , Bitton Elyasaf , Ezra Yossef , Alter Roie , Kabiri Doron
Published: August 2024

Objectives: To evaluate the effect of maternal parity on the association between mid-trimester cervical length and preterm birth to elucidate the potential intricacies of this relationship. Methods: A retrospective cohort study using Electronic Medical Records (EMR) data. The study population included pregnant women with a singleton fetus and a short mid-trimester cervical length, recorded in the EMR system at a large health maintenance organization. Women were categorized by parity in the current pregnancy, and a statistical analysis was conducted to examine the relationship between parity and premature delivery. Results: Data were collected from 1144 records of cervical length measurements of 738 pregnancies obtained from the HMO database. The study population consisted of 259 nulliparous women (35.1%), 451 multiparous women (61.1%), and 28 grand multiparous women (3.8%). The results from the multivariate analysis of the primary outcome showed that nulliparity was significantly associated with an increased risk of premature delivery, with a risk of 1.557 for nulliparous women compared to parous women. Conclusions: In this study, a statistically significant association was found between nulliparity and preterm birth among women with a short mid-trimester cervical length. Nulliparous women were found to have a higher risk of preterm birth in the current pregnancy compared to parous women. Further research is needed to understand the underlying mechanisms and to develop targeted interventions to reduce the risk of premature birth in this population. These findings highlight the need to consider nulliparity as a potential risk factor in the management of pregnancies with a shortened cervix.
Evaluating the Protective Role of Vitamin A Supplementation in Periodontal Health: A Comprehensive Systematic Review and Meta-Analysis
Authors: Luca Magda Mihaela , Buzatu Roxana , Bumbu Bogdan Andrei
Published: August 2024

Background: Recent studies suggest a potential role for vitamin A supplementation in improving periodontal health, though evidence remains inconclusive. This systematic review and meta-analysis aimed to evaluate the protective role of vitamin A supplementation on periodontal health, focusing on outcomes such as gingival inflammation, pocket depth reduction, and alveolar bone preservation. Methods: A literature search was conducted in PubMed, Scopus, and Web of Science up until May 2024, adhering to strict inclusion criteria that required studies to involve human participants diagnosed with periodontal diseases and to assess the impact of vitamin A through dietary intake or supplementation. This review excluded studies not explicitly focused on vitamin A and those lacking clear, quantifiable outcomes. The risk of bias was assessed using the Newcastle–Ottawa Scale for observational studies and the Cochrane Collaboration’s tool for randomized controlled trials. Meta-analysis was performed to synthesize data and quantify the effectiveness of vitamin A on periodontal health outcomes. Results: A total of six studies were included in the final analysis with a total of 50,722 participants. The meta-analysis revealed a pooled odds ratio (OR) of 0.97 (95% CI: 0.94–1.00) for the association between vitamin A supplementation and periodontal health, indicating a slight protective effect. Notably, two high-quality studies reported ORs of 0.92 (95% CI: 0.85–1.00) and 0.83 (95% CI: 0.69–1.00), respectively, suggesting a potential reduction in periodontal disease risk with sufficient vitamin A levels. However, high heterogeneity (I2 = 86.93%) across studies indicates variability in outcomes, possibly influenced by demographic and lifestyle factors. Conclusions: Vitamin A supplementation may offer a marginal protective effect against periodontal disease, although results vary significantly across different populations and study designs. Further research is needed to clarify these relationships and to explore the mechanisms through which vitamin A influences periodontal health, considering the high degree of observed heterogeneity.
Accuracy of Autonomous Artificial Intelligence-Based Diabetic Retinopathy Screening in Real-Life Clinical Practice
Authors: Riotto Eleonora , Gasser Stefan , Potic Jelena , Sherif Mohamed , Stappler Theodor , Schlingemann Reinier , Wolfensberger Thomas , Konstantinidis Lazaros
Published: August 2024

Background: In diabetic retinopathy, early detection and intervention are crucial in preventing vision loss and improving patient outcomes. In the era of artificial intelligence (AI) and machine learning, new promising diagnostic tools have emerged. The IDX-DR machine (Digital Diagnostics, Coralville, IA, USA) represents a diagnostic tool that combines advanced imaging techniques, AI algorithms, and deep learning methodologies to identify and classify diabetic retinopathy. Methods: All patients that participated in our AI-based DR screening were considered for this study. For this study, all retinal images were additionally reviewed retrospectively by two experienced retinal specialists. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were calculated for the IDX-DR machine compared to the graders’ responses. Results: We included a total of 2282 images from 1141 patients who were screened between January 2021 and January 2023 at the Jules Gonin Eye Hospital in Lausanne, Switzerland. Sensitivity was calculated to be 100% for ‘no DR’, ‘mild DR’, and ‘moderate DR’. Specificity for no DR’, ‘mild DR’, ‘moderate DR’, and ‘severe DR’ was calculated to be, respectively, 78.4%, 81.2%, 93.4%, and 97.6%. PPV was calculated to be, respectively, 36.7%, 24.6%, 1.4%, and 0%. NPV was calculated to be 100% for each category. Accuracy was calculated to be higher than 80% for ‘no DR’, ‘mild DR’, and ‘moderate DR’. Conclusions: In this study, based in Jules Gonin Eye Hospital in Lausanne, we compared the autonomous diagnostic AI system of the IDX-DR machine detecting diabetic retinopathy to human gradings established by two experienced retinal specialists. Our results showed that the ID-x DR machine constantly overestimates the DR stages, thus permitting the clinicians to fully trust negative results delivered by the screening software. Nevertheless, all fundus images classified as ‘mild DR’ or greater should always be controlled by a specialist in order to assert whether the predicted stage is truly present.
Pathogenesis of Pachyvein Formation in Central Serous Chorioretinopathy: A Hydrodynamic Analysis
Authors: Nishi Okihiro , Nishi Yutaro , Tatsumichi Miki , Yasukawa Tsutomu
Published: August 2024

Objectives: To attain an understanding of pachyvein formation seen with central serous chorioretinopathy (CSC) by measuring the choroidal blood flow (CBF) velocity and to apply the findings to existing hydrodynamic theorems. Methods: Nineteen subjects with monocular CSC (mean age 51.8 ± 12.7 years) were included. Laser speckle flowgraphy measured the mean blur rate (MBR) in the foveal and perifoveal regions, and the findings were applied to the Equation of Continuity (Q = AV) and Bernoulli’s theorem (1/2V2 + P/ρ = constant). Results: The mean foveal/perifoveal MBRs in the CSC eyes were 6.4 ± 3.2/9.6 ± 3.2 (p < 0.001). The mean MBRs in the non-CSC eyes were 8.3 ± 3.2/7.9 ± 2.4 (p = 0.37). The significant foveal CBF velocity decrease in CSC eyes occurs because of exudation from the hyperpermeable choriocapillaris. The subsequent decrease in blood volume due to the exudation elicits a decrease in the blood flow velocity in the inferior venules in accordance with the Equation of Continuity. The decrease in the blood flow velocity may result in an elevated blood flow pressure in the inferior venules and veins at the exudation site, in accordance with Bernoulli’s theorem. Conclusion: A significant decrease in the foveal MBR may result from exudation from the hyperpermeable macular choriocapillaris. This decreased velocity may elicit a blood pressure elevation that can expand the inferior venules and veins at the exudation site, so-called pachyvein and pachychoroid formation. The application of hydrodynamic theorems to the measurement of ocular blood flow can provide new insights into the understanding of the pathogenesis of chorioretinal disease.
Management and Treatment Outcomes of Hemolytic Disease of the Fetus and Newborn (HDFN)—A Retrospective Cohort Study
Authors: Drozdowska-Szymczak Agnieszka , Łukawska Sabina , Mazanowska Natalia , Ludwin Artur , Krajewski Paweł
Published: August 2024

Background: Hemolytic disease of the fetus and newborn (HDFN) is caused by maternal antibodies attacking fetal blood cell antigens. Despite routine antenatal anti-D prophylaxis, intrauterine transfusions (IUTs) are still needed in some HDFN cases. Methods: We conducted a retrospective cohort study on newborns with HDFN born in the 1st Department of Obstetrics and Gynecology of the Medical University of Warsaw. We analyzed 274 neonates with HDFN, identifying 46 who required IUT due to fetal anemia and 228 who did not. The laboratory results, management, and outcomes were compared between these groups. Results: Comparative analysis showed that newborns treated with IUT were more likely to have significant anemia, hyperbilirubinemia, and iron overload, indicated by a high ferritin concentration. These neonates more often required top-up transfusions, phototherapy, intravenous immunoglobulin infusions, and exchange transfusions. The length of stay was longer for newborns who received IUT. Conclusions: HDFN requiring IUT is associated with a greater number of complications in the neonatal period and more often requires additional treatment compared to HDFN not requiring IUT.
Impact of Baseline Anti-ABO Antibody Titer on Biliary Complications in ABO-Incompatible Living-Donor Liver Transplantation
Authors: Yu Se-Hyeon , Jo Hye-Sung , Yu Young-Dong , Park Pyoung-Jae , Han Hyung-Joon , Kim Sang-Jin , Kamarulzaman Syahrul Hadi , Kim Dong-Sik
Published: August 2024

Background: Although advancements in desensitization protocols have led to increased ABO-incompatible (ABOi) living-donor liver transplantation (LDLT), a higher biliary complication rate remains a problem. This study evaluated the effect of baseline anti-ABO antibody titers before desensitization on biliary complications after ABOi LDLT. Methods: The study cohort comprised 116 patients in the ABO-compatible group (ABOc), 29 in the ABOi with the low titer (<1:128) group (ABOi-L), and 14 in the high titer (≥1:128) group (ABOi-H). Results: Biliary complications occurred more frequently in the ABOi-H group than in the ABOi-L and ABOc groups (7 [50.0%] vs. 8 [27.6%] and 24 [20.7%], respectively, p = 0.041). Biliary complication-free survival was significantly worse in the ABOi-H group than in the other groups (p = 0.043). Diffuse intrahepatic biliary strictures occurred more frequently in the ABOi-H group than in the other groups (p = 0.005). Multivariable analysis revealed that the high anti-ABO antibody titer (≥1:128) is an independent risk factor for biliary complications (hazard ratio 3.943 [1.635–9.506]; p = 0.002). Conclusions: A high baseline anti-ABO antibody titer (≥1:128), female sex, and hepatic artery complications are significant risk factors for biliary complications.
Reconstructive Surgery of the Head and Neck in Organ Transplant Recipients: A Case Report and a Review of the Literature
Authors: Rampi Andrea , Comini Lara Valentina , Galli Andrea , Howardson Bright Oworae , Tettamanti Alberto , Luparello Paolo , Redaelli Gabriele , Di Santo Davide , Bondi Stefano
Published: August 2024

The number of solid organ transplant recipients (SOTRs) is growing as a consequence of an increase in transplantations and longer survival; these patients, thus, frequently suffer various comorbidities and are subjected to the detrimental effects of immunosuppressive agents, which expose them to a higher risk of developing malignancies. These drugs also complicate the surgical treatment of neoplasms, as they can hinder wound healing, especially when associated with other unfavorable factors (e.g., previous radiotherapy, diabetes, etc.). We herein present our experience with a 74-year-old SOTR who underwent a radical extended parotidectomy and reconstruction with a submental island flap for a persistent cutaneous squamous carcinoma after radiotherapy; his complicated clinical course was characterized by incredibly slow wound healing. The current literature was reviewed to provide a succinct overview of the main difficulties of head and neck surgery in SOTRs. In particular, the immunosuppressive regimen can be tapered considering the individual risk and other elements should be carefully assessed, possibly prior to surgery, to prevent cumulative harm. New developments, including intraoperative monitoring of flap vascularization through indocyanine green fluorescence video-angiography and the prophylactic application of negative pressure wound therapy, when feasible, may be particularly beneficial for high-risk patients.
Metamizole in the Management of Musculoskeletal Disorders: Current Concept Review
Authors: Jeyaraman Naveen , Migliorini Filippo , Murugan Shrideavi , Ramasubramanian Swaminathan , Balaji Sangeetha , Maffulli Nicola , Jeyaraman Madhan
Published: August 2024

Metamizole, or dipyrone, has been used for decades as a non-narcotic analgesic, providing pain relief from musculoskeletal disorders and antipyretic and antispasmolytic properties. Despite being in use since the 1920s, its mechanism of action still needs to be discovered. Despite causing fewer adverse effects when compared to other analgesics, its harmful effects on the blood and lack of evidence regarding its teratogenicity make the usage of the drug questionable, which has led to it being removed from the drug market of various countries. This narrative review aims to provide a detailed insight into the mechanism of action and efficacy, comparing its effectiveness and safety with other classes of drugs and the safety profile of metamizole.
Use & Abuse of Personal Information, Part II: Robust Generation of Fake IDs for Privacy Experimentation
Authors: Kolenbrander Jack , Husmann Ethan , Henshaw Christopher , Rheault Elliott , Boswell Madison , Michaels Alan J.
Published: August 2024

When personal information is shared across the Internet, we have limited confidence that the designated second party will safeguard it as we would prefer. Privacy policies offer insight into the best practices and intent of the organization, yet most are written so loosely that sharing with undefined third parties is to be anticipated. Tracking these sharing behaviors and identifying the source of unwanted content is exceedingly difficult when personal information is shared with multiple such second parties. This paper formulates a model for realistic fake identities, constructs a robust fake identity generator, and outlines management methods targeted towards online transactions (email, phone, text) that pass both cursory machine and human examination for use in personal privacy experimentation. This fake ID generator, combined with a custom account signup engine, are the core front-end components of our larger Use and Abuse of Personal Information system that performs one-time transactions that, similar to a cryptographic one-time pad, ensure that we can attribute the sharing back to the single one-time transaction and/or specific second party. The flexibility and richness of the fake IDs also serve as a foundational set of control variables for a wide range of social science research questions revolving around personal information. Collectively, these fake identity models address multiple inter-disciplinary areas of common interest and serve as a foundation for eliciting and quantifying personal information-sharing behaviors.
A Wave Drift Force Model for Semi-Submersible Types of Floating Wind Turbines in Large Waves and Current
Authors: Fonseca Nuno , Dadmarzi Fatemeh H.
Published: August 2024

The correct prediction of slowly varying wave drift loads is important for the mooring analysis of floating wind turbines (FWTs). However, present design analysis tools fail to correctly predict these loads in conditions with current and moderate and large waves. This paper presents a semi-empirical method to correct zero-current potential-flow quadratic transfer functions (QTFs) of horizontal wave drift loads in conditions with current and moderate and large waves. The method is applicable to column-stabilized types of substructures or semi-submersibles. In the first step, the potential-flow QTF is corrected for potential-flow wave–current effects by applying a heuristic method. Second, the generalized Exwave formula corrects for viscous drift effects. Viscous drift effects become important for moderate and large waves. Conditions with current in the same direction as the waves increase the viscous drift contribution further. The method is validated by comparing QTF predictions with empirical QTFs identified from model test data for the INO Windmoor semi. While potential-flow QTFs agree well with the empirical data for small seastates without current, they underestimate the wave drift loads for moderate and large seastates. Conditions with current increase the underestimation. The semi-empirical correction method significantly improves predictions.
Development of an Extensional Fault System and Its Control on Syn-Rift Sedimentation: Insights from 3D Seismic Interpretation of the Weixinan Depression, Northern South China Sea
Authors: He Jie , Qin Chunyu , Liao Yuantao , Jiang Tao , Liu Entao , Chen Si , Wang Hua
Published: August 2024

The impacts of the growth and linkage of fault segments on sedimentation in a lacustrine rift basin, the Weixinan Depression, the Beibuwan Basin, in the northern South China Sea, which has been demonstrated to have huge petroleum potential, are elucidated on the basis of well-constrained 3D seismic data. Two main fault systems, the No. 1 boundary fault system and the No. 2 fault system, were developed in the Weixinan Depression. The evolution of the lower basement is based on the No. 1 fault system, which controls the distribution of depocenters (ranging from 450–800 m) within the lower structural layer. It includes the five fault segments isolated at the initial stage, the interaction and propagation stage, the linkage stage, and the decline stage. The No. 2 fault system governs the deposition of the upper structural layer with a series of discrete depocenters in the hangingwall. Initially, it comprises several right-order echelon branching faults. Each branch fault rapidly reached the existing length and maintained a constant length while establishing soft links with each other in the subsequent displacement accrual. The development of topographic slopes, transition zones, transverse anticlines, and related fault troughs and gullies related to the activity of the No. 1 boundary fault system is the main controlling factor that induces the differential development of the western, middle, and eastern sections of steep slope fans. The differential subsidence effect along the No. 2 fault system is responsible for the multiple ‘rising-stable’ stage changes in the relative lake level during the development of axial delta deposits. This study will help elucidate the different controls of extensional fault systems on associated sedimentation, as well as rift basin development in the South China Sea and similar areas throughout the world.
Trends and Perspectives on Nuclear Waste Management: Recovering, Recycling, and Reusing
Authors: Terranova Maria Letizia , Tavares Odilon A. P.
Published: August 2024

This paper focuses on the highly radioactive, long-lasting nuclear waste produced by the currently operating fission reactors and on the sensitive issue of spent fuel reprocessing. Also included is a short description of the fission process and a detailed analysis of the more hazardous radioisotopes produced either by secondary reactions occurring in the nuclear installations or by decay of the fission fragments. The review provides an overview of the strategies presently adopted to minimize the harmfulness of the nuclear waste to be disposed, with a focus on the development and implementation of methodologies for the spent fuel treatments. The partitioning-conditioning and partitioning-transmutation options are analyzed as possible solutions to decrease the presence of long-lived highly radioactive isotopes. Also discussed are the chemical/physical approaches proposed for the recycling of the spent fuel and for the reusing of some technologically relevant isotopes in industrial and pharmaceutical areas. A brief indication is given of the opportunities offered by innovative types of reactors and/or of new fuel cycles to solve the issues presently associated with radioactive waste.
Invasive Pulmonary Aspergillosis in Patients with HBV-Related Acute on Chronic Liver Failure
Authors: Yuan Man , Han Ning , Lv Duoduo , Huang Wei , Zhou Mengjie , Yan Libo , Tang Hong
Published: August 2024

Background: We aim to investigate the characteristics of invasive pulmonary aspergillosis (IPA) in patients with HBV-related acute on chronic liver failure (HBV-ACLF). Methods: A total of 44 patients with probable IPA were selected as the case group, and another 88 patients without lung infections were chosen as the control group. Results: HBV-ACLF patients with probable IPA had more significant 90-day mortality (38.6% vs. 15.9%, p = 0.0022) than those without. The white blood cell (WBC) count was the independent factor attributed to the IPA development [odds ratio (OR) 1.468, p = 0.027]. Respiratory failure was associated with the mortality of HBV-ACLF patients with IPA [OR 26, p = 0.000]. Twenty-seven patients received voriconazole or voriconazole plus as an antifungal treatment. Plasma voriconazole concentration measurements were performed as therapeutic drug monitoring in 55.6% (15/27) of the patients. The drug concentrations exceeded the safe range with a reduced dosage. Conclusions: The WBC count might be used to monitor patients’ progress with HBV-ACLF and IPA. The presence of IPA increases the 90-day mortality of HBV-ACLF patients mainly due to respiratory failure. An optimal voriconazole regimen is needed for such critical patients, and voriconazole should be assessed by closely monitoring blood levels.