bluuebunny/crossref_metadata_2025 huggingface dataset:
Signal Peptides and Their Fragments in Post-Translation: Novel Insights of Signal Peptides
Authors: Ono Kenji
Published: December 2024

Signal peptides (SPs), peptide sequences located at the N-terminus of newly synthesized proteins, are primarily known for their role in targeting proteins to the endoplasmic reticulum (ER). It has traditionally been assumed that cleaved SPs are rapidly degraded and digested near the ER. However, recent evidence has demonstrated that cleaved SP fragments can be detected in extracellular fluids such as blood flow, where they exhibit bioactivity. In addition, SP fragments are delivered to extracellular fluids via extracellular vesicles such as exosomes and microvesicles, which are important mediators of intercellular communication. These findings suggest that SPs and their fragments may have physiological roles beyond their classical function. This review aims to provide a comprehensive overview of these novel roles and offer new insights into the potential functions of SPs and their fragments in post-translational regulation and intercellular communication.
Evaluation of Cellulase, Pectinase, and Hemicellulase Effectiveness in Extraction of Phenolic Compounds from Grape Pomace
Authors: Stanek-Wandzel Natalia , Krzyszowska Alicja , Zarębska Magdalena , Gębura Katarzyna , Wasilewski Tomasz , Hordyjewicz-Baran Zofia , Tomaka Magdalena
Published: December 2024

Grape pomace, the solid residue from winemaking, is a rich source of polyphenolic compounds with significant antioxidant properties. However, the efficient extraction of these valuable compounds remains a challenge. This study focuses on optimizing the conditions for the enzyme-assisted extraction of polyphenolic compounds from red grape pomace using cellulase, hemicellulase, and pectinase. The key variables investigated in this study were enzyme concentration, extraction time, and solid/liquid ratio. The results highlight the importance of selecting enzymes based on target compounds, as different enzymes were found to be more effective for specific phenolic fractions. Hemicellulase was most effective for phenolic acids, cellulase for catechins, and pectinase for anthocyanins. Enzyme-assisted extraction significantly increased the yield of phenolic compounds and resulted in higher total phenolic content and antioxidant activity compared to control samples treated with solid/liquid extraction without enzyme addition. These findings confirm that enzyme-assisted extraction is a promising approach for enhancing the recovery of polyphenolic compounds from grape pomace.
Cannabichromene as a Novel Inhibitor of Th2 Cytokine and JAK/STAT Pathway Activation in Atopic Dermatitis Models
Authors: Kim Ki Chan , Jeong Ga Hee , Bang Chul Hwan , Lee Ji Hyun
Published: December 2024

Cannabichromene (CBC) is one of the main cannabinoids found in the cannabis plant, and although less well known than tetrahydrocannabinol (THC) and cannabidiol (CBD), it is gaining attention for its potential therapeutic benefits. To date, CBC’s known mechanisms of action include anti-inflammatory, analgesic, antidepressant, antimicrobial, neuroprotective, and anti-acne effects through TRP channel activation and the inhibition of inflammatory pathways, suggesting that it may have therapeutic potential in the treatment of inflammatory skin diseases, such as atopic dermatitis (AD), but its exact mechanism of action remains unclear. Therefore, in this study, we investigated the effects of CBC on Th2 cytokines along with the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathways involved in AD pathogenesis. We used a 2,4-Dinitrochlorobenzene (DNCB)-induced BALB/c mouse model to topically administer CBC (0.1 mg/kg or 1 mg/kg). The results showed that skin lesion severity, ear thickness, epithelial thickness of dorsal and ear skin, and mast cell infiltration were significantly reduced in the 0.1 mg/kg CBC-treated group compared with the DNCB-treated group (p < 0.001). In addition, real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis showed a significant decrease in the mRNA expression of Th2 cytokines (TSLP, IL-4, IL-13) and inflammatory mediators (IFN-γ, IL-1β, IL-6, IL-17, IL-18, and IL-33) (p < 0.05). Western blot analysis also revealed a significant decrease in JAK1, JAK2, STAT1, STAT2, STAT3, and STAT6 protein expression (p < 0.05). These results suggest that CBC is a promising candidate for the treatment of AD and demonstrates the potential to alleviate AD symptoms by suppressing the Th2 immune response.
Precise and Accurate DNA-3′/5-Ends Polishing with Thermus thermophilus Phage vb_Tt72 DNA Polymerase
Authors: Dorawa Sebastian , Kaczorowski Tadeusz
Published: December 2024

Tt72 DNA polymerase is a newly characterized PolA-type thermostable enzyme derived from the Thermus thermophilus phage vB_Tt72. The enzyme demonstrates strong 3′→5′ exonucleolytic proofreading activity, even in the presence of 1 mM dNTPs. In this study, we examined how the exonucleolytic activity of Tt72 DNA polymerase affects the fidelity of DNA synthesis. Using a plasmid-based lacZα gene complementation assay, we determined that the enzyme’s mutation frequency was 2.06 × 10−3, corresponding to an error rate of 1.41 × 10−5. For the exonuclease-deficient variant, the mutation frequency increased to 6.23 × 10−3, with an associated error rate of 4.29 × 10−5. The enzyme retained 3′→5′ exonucleolytic activity at temperatures up to 70 °C but lost it after 10 min of incubation at temperatures above 75 °C. Additionally, we demonstrated that Tt72 DNA polymerase efficiently processes 3′/5′-overhangs and removes a single-nucleotide 3′-dA overhang from PCR products at 55 °C. These characteristics make Tt72 DNA polymerase well suited for specialized molecular cloning applications.
Repetitive Overuse Injury Causes Entheseal Damage and Palmar Muscle Fibrosis in Older Rats
Authors: Patel Parth R. , Tamas Istvan P. , Van Der Bas Megan , Kegg Abby , Hilliard Brendan A. , Lambi Alex G. , Popoff Steven N. , Barbe Mary F.
Published: December 2024

Overuse injury is a frequent diagnosis in occupational medicine and athletics. Using an established model of upper extremity overuse, we sought to characterize changes occurring in the forepaws and forelimbs of mature female rats (14–18 months of age). Thirty-three rats underwent a 4-week shaping period, before performing a high-repetition low-force (HRLF) task for 12 weeks, with the results being compared to 32 mature controls. HRLF animals showed a reduced grip strength versus controls. ELISAs carried out in the HRLF rats, versus controls, showed elevated levels of IL1-α in tendons, IL1-α and TNF-α in distal bones/entheses, and TNF-α, MIP1-α/CCL3, and CINC-2/CXCL-3 in serum, as well as IL-6 in forelimb muscles and tendons, and IL-10 in serum. HRLF rats had elevated collagen deposition in the forepaw intrinsic muscles (i.e., fibrosis), entheseal microdamage, and articular cartilage degradation versus the control rats. CD68/ED1+ osteoclasts and single-nucleated cells were elevated in distal forelimb metaphyses of the HRLF animals, versus controls. Declines in grip strength correlated with muscle fibrosis, entheseal microdamage, articular cartilage damage, distal bone/enthesis IL1-α, and serum IL-6. These data demonstrate inflammatory and persistent degradative changes in the forearm/forepaw tissues of mature female animals exposed to prolonged repetitive tasks, changes with clinical relevance to work-related overuse injuries in mature human females.
Au@109Pd Core–Shell Nanoparticles Conjugated to Panitumumab for the Combined β−—Auger Electron Therapy of Triple-Negative Breast Cancer
Authors: Gharibkandi Nasrin Abbasi , Majkowska-Pilip Agnieszka , Walczak Rafał , Wierzbicki Mateusz , Bilewicz Aleksander
Published: December 2024

Apart from HER2-positive, triple-negative breast cancer (TNBC) is the second most highly invasive type of breast cancer. Although TNBC does not overexpress HER2 receptors, it has been observed that EGFR protein expression is present in this specific type of tumor, making it an attractive target for immune and radiopharmaceutical treatments. In our current study, we used 109Pd (T1/2 = 13.7 h) in the form of a 109Pd/109mAg in vivo generator as a source of β− particles and Auger electrons in targeted radionuclide therapy for TNBC. 109Pd, obtained through neutron irradiation of the 108Pd target, was deposited onto 15 nm gold nanoparticles to form Au@109Pd core–shell nanoparticles, which were then conjugated to the panitumumab antibody. Au@109Pd-PEG-panitumumab nanoparticles were bound, internalized, and partially routed to the nucleus in MDA-MB-231 human breast cancer cells overexpressing EGFR receptors. The Au@109Pd-panitumumab radioconjugate significantly reduced the metabolic activity of MDA-MB-231 cells in a dose-dependent manner. In conclusion, we have found that Au@109Pd-PEG-panitumumab nanoparticles show potential as a therapeutic agent for combined β−–Auger electron targeted radionuclide therapy of TNBC. The simultaneous emission of β−, conversion, and Auger electrons from the 109Pd/109mAg generator, similar to 161Tb conjugates, significantly enhances the therapeutic effect. The partial localization of these nanoparticles into the cell nucleus, provided by the panitumumab vector, ensures effective therapy with Auger electrons. This is particularly important for the treatment of drug-resistant TNBC cells.
The Motility of Mouse Spermatozoa Changes Differentially After 30-Minute Exposure Under Simulating Weightlessness and Hypergravity
Authors: Ogneva Irina V. , Zhdankina Yulia S. , Gogichaeva Ksenia K. , Malkov Artyom A. , Biryukov Nikolay S.
Published: December 2024

Research into the mechanisms by which gravity influences spermatozoa has implications for maintaining the species in deep space exploration and may provide new approaches to reproductive technologies on Earth. Changes in the speed of mouse spermatozoa after 30 min exposure to simulated weightlessness (by 3D-clinostat) and 2 g hypergravity (by centrifugation) were studied using inhibitory analysis. Simulated microgravity after 30 min led to an increase in the speed of spermatozoa and against the background of an increase in the relative calcium content in the cytoplasm. This effect was prevented by the introduction of 6-(dimethylamino) purine, wortmannin, and calyculin A. Hypergravity led to a decrease in the speed of spermatozoa movement, which was prevented by sodium orthovanadate and calyculin A. At the same time, under microgravity conditions, there was a redistribution of proteins forming microfilament bundles between the membrane and cytoplasmic compartments and under hypergravity conditions—proteins forming networks. The obtained results indicate that even a short exposure of spermatozoa to altered gravity leads to the launch of mechanotransduction pathways in them and a change in motility.
Subchronic Treatment with CBZ Transiently Attenuates Its Anticonvulsant Activity in the Maximal Electroshock-Induced Seizure Test in Mice
Authors: Banach Monika , Borowicz Kinga K.
Published: December 2024

The objective of this study is to evaluate the anticonvulsant efficacy of carbamazepine (CBZ) following acute and chronic administration across four treatment protocols in a murine model of maximal electroshock-induced seizures. A single dose of the drug was utilized as a control. The neurotoxic effects were evaluated in the chimney test and the passive avoidance task. Furthermore, plasma and brain concentrations of CBZ were quantified across all treatment protocols. The subchronic administration of CBZ (7 × 2 protocol) resulted in an attenuation of its antielectroshock effect. In the three remaining treatment regimens (7 × 1, 14 × 1, and 14 × 2) the median effective doses of CBZ were comparable to the control. Neither acute nor chronic treatment with CBZ resulted in a discernible impact on motor coordination or long-term memory. The plasma and brain concentrations of CBZ were significantly lower in most chronic protocols when compared to a single-dose application. This may explain the transient attenuation of CBZ effectiveness in the 7 × 2 protocol, but not the return to the previous level. The anticonvulsant and neurotoxic profiles of CBZ did not differ after single and chronic administration. Therefore, experimental chronic studies with CBZ are not prerequisites for concluding and possibly translating results to clinical conditions.
Prenatal Stress Modulates Placental and Fetal Serotonin Levels and Determines Behavior Patterns in Offspring of Mice
Authors: Melnikova Victoria , Lifantseva Nadezhda , Voronova Svetlana , Bondarenko Nadezhda
Published: December 2024

Available evidence from animal studies suggests that placental serotonin plays an important role in proper fetal development and programming by altering brain circuit formation, which later translates into altered abnormal adult behaviors. Several environmental stimuli, including stress and maternal inflammation, affect placental and, hence, fetal serotonin levels and thus may disturb fetal brain development. We investigated the effect of prenatal stress of varying intensities on the formation of adaptive behaviors in mouse offspring and the role of placental serotonin in these processes. Mild prenatal stress increased placental serotonin synthesis, whereas exposure to moderate stress decreased it. Prenatal stress of varying intensities also resulted in multidirectional changes in animal behavior in progeny, consistent with changes in serotonin levels in the placenta and fetal tissues. Mice exposed to mild prenatal stress showed higher sociality and exploratory activity, whereas, after moderate stress, in contrast, they avoided contact with other individuals of their species and had reduced exploratory activity, with no effect on locomotor activity. Thus, in mice, stressors of varying intensities during the critical period of intrauterine development can affect the synthesis of serotonin by the placenta and lead to multidirectional changes in animal behavior in postnatal life.
The RAGE Pathway in Skin Pathology Development: A Comprehensive Review of Its Role and Therapeutic Potential
Authors: Radziszewski Marcin , Galus Ryszard , Łuszczyński Krzysztof , Winiarski Sebastian , Wąsowski Dariusz , Malejczyk Jacek , Włodarski Paweł , Ścieżyńska Aneta
Published: December 2024

The receptor for advanced glycation end-products (RAGE), a member of the immunoglobulin superfamily, is expressed in various cell types and mediates cellular responses to a wide range of ligands. The activation of RAGE triggers complex signaling pathways that drive inflammatory, oxidative, and proliferative responses, which are increasingly implicated in the pathogenesis of skin diseases. Despite its well-established roles in conditions such as diabetes, cancer, and chronic inflammation, the contribution of RAGE to skin pathologies remains underexplored. This review synthesizes current findings on RAGE’s involvement in the pathophysiology of skin diseases, including conditions such as psoriasis, atopic dermatitis, and lichen planus, focusing on its roles in inflammatory signaling, tissue remodeling, and skin cancer progression. Additionally, it examines RAGE-modulating treatments investigated in dermatological contexts, highlighting their potential as therapeutic options. Given RAGE’s significance in a variety of skin conditions, further research into its mediated pathways may uncover new opportunities for targeted interventions in skin-specific RAGE signaling.
Aging-Related Gene-Based Prognostic Model for Lung Adenocarcinoma: Insights into Tumor Microenvironment and Therapeutic Implications
Authors: Wang Jin , Zhang Hailong , Feng Yaohui , Gong Xian , Song Xiangrong , Wei Meidan , Hu Yaoyu , Li Jianxiang
Published: December 2024

Lung cancer remains the leading cause of cancer-related mortality globally, with a poor prognosis primarily due to late diagnosis and limited treatment options. This research highlights the critical demand for advanced prognostic tools by creating a model centered on aging-related genes (ARGs) to improve prediction and treatment strategies for lung adenocarcinoma (LUAD). By leveraging datasets from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), we developed a prognostic model that integrates 14 ARGs using the least absolute shrinkage and selection operator (LASSO) alongside Cox regression analyses. The model exhibited strong predictive performance, achieving area under the curve (AUC) values greater than 0.8 for one-year survival in both internal and external validation cohorts. The risk scores generated by our model were significantly correlated with critical features of the tumor microenvironment, including the presence of cancer-associated fibroblasts (CAFs) and markers of immune evasion, such as T-cell dysfunction and exclusion. Higher risk scores correlated with a more tumor-promoting microenvironment and increased immune suppression, highlighting the model’s relevance in understanding LUAD progression. Additionally, XRCC6, a protein involved in DNA repair and cellular senescence, was found to be upregulated in LUAD. Functional assays demonstrated that the knockdown of XRCC6 led to decreased cell proliferation, whereas its overexpression alleviated DNA damage, highlighting its significance in tumor biology and its potential therapeutic applications. This study provides a novel ARG-based prognostic model for LUAD, offering valuable insights into tumor dynamics and the tumor microenvironment, which may guide the development of targeted therapies and improve patient outcomes.
Promoter of Vegetable Pea PsPIP2-4 Responds to Abiotic Stresses in Transgenic Tobacco
Authors: Feng Zhijuan , Liu Na , Bu Yuanpeng , Zhang Guwen , Wang Bin , Gong Yaming
Published: December 2024

Plasma membrane intrinsic proteins (PIPs), one sub-family of aquaporins (AQPs), are responsible for plant abiotic stress responses. However, little information is currently available about the stress responsiveness of the PIP promoter in vegetable pea. In the present study, one novel promoter of PsPIP2-4 which shared high similarity to the PIP2-type AQPs from other plants, was isolated. Quantitative real-time PCR (qRT-PCR) assays suggested that PsPIP2-4 was predominantly expressed in leaves and abundantly induced by abiotic stress treatments (polyethylene glycol (PEG) 6000, NaCl, and methyl jasmonate (MeJA)). Further, the promoter activity of PsPIP2-4 was verified in transgenic tobacco plants. Beta-glucuronidase (GUS) staining driven by the PsPIP2-4 promoter confirmed that it was mainly detected in the leaves of transgenic seedlings, especially in the guard cells. Exposure of transgenic seedlings to various environmental stimuli proved that the promoter activity of PsPIP2-4 was abundantly strengthened by osmotic, salt, and MeJA stresses. This research provides one stress-inducible promoter enabling targeted gene expression under abiotic stresses and demonstrates its usefulness in the genetic improvement of plant stress resistance.
Genome Studies in Amaranthus cruentus L. and A. hypochondriacus L. Based on Repeatomic and Cytogenetic Data
Authors: Amosova Alexandra V. , Yurkevich Olga Yu. , Semenov Alexey R. , Samatadze Tatiana E. , Sokolova Diana V. , Artemyeva Anna M. , Zoshchuk Svyatoslav A. , Muravenko Olga V.
Published: December 2024

Amaranthus cruentus L. and Amaranthus hypochondriacus L. are valuable and promising food crops for multi-purpose use that are distributed worldwide in temperate, subtropical, and tropical zones. However, their karyotypes and genomic relationships still remain insufficiently studied. For the first time, a comparative repeatome analysis of A. cruentus and A. hypochondriacus was performed based on the available NGS data; bioinformatic analyses using RepeatExplorer/TAREAN pipelines; and chromosome FISH mapping of 45S rDNA, 5S rDNA, and the most abundant satellite DNAs. In the repeatomes of these species, interspecific variations in the amount of Ty3/Gypsy and Ty1/Copia retroelements, DNA transposons, ribosomal, and satellite DNA were detected. In the repeatomes of both species, shared satDNAs with high sequence similarity were identified. The chromosome distribution patterns of four effective molecular markers, 45S rDNA, 5S rDNA, AmC4, and AmC9, allowed us to identify all chromosome pairs in the species karyotypes, construct unique karyograms of A. cruentus and A. hypochondriacus, and confirm the close relationship between their genomes. These results are important for comparative karyotypic studies within the genus Amaranthus. Our findings demonstrated that cytogenomic analyses might provide important data on genomic relationships within Amaranthus and increase knowledge on genome organization in these valuable crops.
Enhancing Personalized Mental Health Support Through Artificial Intelligence: Advances in Speech and Text Analysis Within Online Therapy Platforms
Authors: Jelassi Mariem , Matteli Khouloud , Ben Khalfallah Houssem , Demongeot Jacques
Published: December 2024

Automatic speech recognition (ASR) and natural language processing (NLP) play key roles in advancing human–technology interactions, particularly in healthcare communications. This study aims to enhance French-language online mental health platforms through the adaptation of the QuartzNet 15 × 5 ASR model, selected for its robust performance across a variety of French accents as demonstrated on the Mozilla Common Voice dataset. The adaptation process involved tailoring the ASR model to accommodate various French dialects and idiomatic expressions, and integrating it with an NLP system to refine user interactions. The adapted QuartzNet 15 × 5 model achieved a baseline word error rate (WER) of 14%, and the accompanying NLP system displayed weighted averages of 64.24% in precision, 63.64% in recall, and an F1-score of 62.75%. Notably, critical functionalities such as ‘Prendre Rdv’ (schedule appointment) achieved precision, recall, and F1-scores above 90%. These improvements substantially enhance the functionality and management of user interactions on French-language digital therapy platforms, indicating that continuous adaptation and enhancement of these technologies are beneficial for improving digital mental health interventions, with a focus on linguistic accuracy and user satisfaction.
Pregnancy in Inflammatory Bowel Disease: Data from a Real-World Cohort in Germany
Authors: Ayoub Mousa , Muzalyova Anna , Ebigbo Alanna , Nagl Sandra , Römmele Christoph , Classen Johanna , Wanzl Julia , Fleischmann Carola , Ayoub Sami , Tadic Vidan , Schlottmann Jakob , Schnoy Elisabeth
Published: December 2024

Background: Inflammatory bowel disease (IBD) frequently manifests at a young age, during the peak fertility years. Understanding the risks of negative pregnancy outcomes associated with IBD is crucial for effective pregnancy management and support. Additionally, it is essential to provide patients with the necessary knowledge to make informed choices and foster their confidence in navigating pregnancy while maintaining effective disease management. Although IBD frequently appears during the peak fertility years, knowledge about managing pregnancy in the context of IBD remains limited and often inaccurate among both physicians and patients. Our study aims to assess the complications occurring during pregnancy in patients with IBD, considering the level of disease activity, and to evaluate the standard of care provided to patients with chronic inflammatory conditions through a cohort analysis. Methods: Patients with IBD who had children were included in this single-center mixed-method (retrospective and prospective) study. Clinical data, disease progression, course of pregnancy, and complications were examined in women. Outcomes for children of men with IBD were also analyzed. To supplement the data, a survey addressing various pregnancy-related topics, including all patients from the university outpatient clinic for IBD, was conducted over a period of six months. Results: A total of 410 patients were screened retrospectively between 2010 and 2021. In total, 134 patients who had children were included in the study: 51.4% (n = 69) had Crohn’s disease, 44% (n = 59) had ulcerative colitis, and 4.6% (n = 6) had unclassified inflammatory bowel disease. Of the women, 85% (n = 34) were in remission for at least three months before pregnancy, 14.6% (n = 6) experienced an acute flare-up during pregnancy, and 10.3% (n = 4) and 7.7% (n = 3) had active disease at the time of delivery and during breastfeeding, respectively. Patients with IBD who were in remission before pregnancy did not experience a higher risk of pregnancy complications (no cases of pre-eclampsia or placental abruption were reported in this group). However, the rates of gestational diabetes and fever during pregnancy were 10% for those in remission, compared to 25% for those with active disease. Conclusions: Patients with IBD in remission did not present an increased risk of pregnancy complications. However, our survey indicates that those with active disease at conception were more likely to experience complications such as gestational diabetes and fever. These findings underscore the importance of adequate patient education regarding the safety of various IBD medications during pregnancy in order to avoid pregnancy-related complications.
The Role of SHBG as a Marker in Male Patients with Metabolic-Associated Fatty Liver Disease: Insights into Metabolic and Hormonal Status
Authors: Fodor Duric Ljiljana , Belčić Velimir , Oberiter Korbar Anja , Ćurković Sanja , Vujicic Bozidar , Gulin Tonko , Muslim Jelena , Gulin Matko , Grgurević Mladen , Catic Cuti Edina
Published: December 2024

Background: Metabolic-associated fatty liver disease (MAFLD) is a spectrum of liver diseases linked to insulin resistance (IR), type 2 diabetes, and metabolic disorders. IR accelerates fat accumulation in the liver, worsening MAFLD. Regular physical activity and weight loss can improve liver function, reduce fat, and lower cardiovascular risk. This study examines the role of sex hormone-binding globulin (SHBG) in MAFLD, focusing on its potential as a biomarker and its relationship with insulin resistance. Methods: The study included 98 male patients (ages 30–55) with MAFLD, identified through systematic examinations, and 74 healthy male controls. All participants underwent abdominal ultrasound and blood tests after fasting, assessing markers such as glucose, liver enzymes (AST, ALT, γGT), lipids (cholesterol, triglycerides), insulin, SHBG, estradiol, and testosterone. SHBG levels were analyzed in relation to body mass index (BMI) and age. Results: A significant association was found between low SHBG levels and the presence of fatty liver. Individuals with MAFLD had lower SHBG levels compared to controls. BMI and age were key factors influencing SHBG, with higher BMI linked to lower SHBG in younger men, while SHBG remained stable in older individuals regardless of BMI. Conclusion: SHBG may serve as a valuable biomarker for early detection and risk assessment of MAFLD. The complex relationship between SHBG, BMI, and age highlights the importance of considering both hormonal and metabolic factors when assessing fatty liver risk. Our findings support the need for comprehensive metabolic evaluations in clinical practice.
Challenges in Obstructive Sleep Apnea Management in Elderly Patients
Authors: Joskin Aude , Bruyneel Marie
Published: December 2024

With the aging of the population, obstructive sleep apnea (OSA) in elderly patients is now more commonly seen in clinical practice. In older people, sleepiness is less marked than in younger patients, but insomnia symptoms are more common. Comorbidities are numerous and related to cardiometabolic and cognitive conditions. Polygraphy can be used to establish the diagnosis in the vast majority of cases, but polysomnography is indicated in cases of comorbid sleep disorders. Continuous positive airway pressure (CPAP) remains the cornerstone of treatment, but compliance decreases with age, especially in those over 80, and when cognitive disorders are also present. In these patients, CPAP can be beneficial in terms of nighttime symptoms, sleepiness, mood, and cognition but can also prevent cardiovascular and cerebrovascular disorders, especially in severeOSA patients. For this reason, we should offer this treatment to elderly patients and devise strategies to support them with treatment difficulties (e.g., therapeutic education, adapted masks, and telemonitoring). In the future, we need prospective studies to help identify elderly patients who will gain the greatest long-term benefit from treatment. Dedicated sleep testing, OSA severity markers, and specific questionnaires need to be developed in this older, but large, OSA population.
Two-Dimensional and Point Shear-Wave Elastography to Predict Esophageal Varices and Clinically Significant Portal Hypertension in Patients with Chronic Liver Disease
Authors: Heilani Myriam W. , Bolender Max , Mücke Victoria T. , Schwarzkopf Katharina M. , Kubesch-Grün Alica , Abedin Nada , Dultz Georg , Zeuzem Stefan , Welsch Christoph , Friedrich-Rust Mireen , Bojunga Jörg , Herrmann Eva , Mücke Marcus M.
Published: December 2024

Introduction: The non-invasive assessment of disease severity remains pivotal in patients with chronic liver disease (CLD) as it has wide implications in predicting liver-related complications or death. Shear-wave elastography (SWE) is an emerging ultrasound-based method to non-invasively measure liver stiffness. The aim of our study was to evaluate two-dimensional (2D) and point (p) SWE to predict the presence of esophageal varices (EV) or clinically significant portal hypertension (CSPH). Methods: This was a retrospective analysis of a prospectively performed cohort study of patients with CLD treated in the outpatient clinic of the Frankfurt University Hospital. PSWE using the Hitachi HI Vision ASCENDUS system and the Siemens ACUSON S2000TM system or 2D-SWE using the Toshiba APLIO500 system were analyzed at baseline and during follow-up to predict EV or surrogate parameters of CSPH. ROC curves were calculated for pooled liver stiffness measurements (LSMs) using a bootstrap approach. A combined model of SWE and platelet count was created and a mixed-effect logistic regression analysis using log-transformed values was performed. Results: Overall, 511 patients with CLD and 919 consecutive LSMs were included and 315 patients (61.6%) had signs of CSPH. 2D-SWE performed best to predict EV and CSPH, and the addition of platelet count to the predictive model significantly increased test results for EV (AUC 0.83, 95%-CI: 0.76–0.89; difference in AUC 0.11, 95%-CI: 0.03–0.19, p = 0.004), but only marginally for CSPH (AUC 0.75, 95%-CI: 0.64–0.85; difference in AUC 0.06, 95%-CI: 0.02–0.14, p = 0.150). LSM > 18.5 and >20 kPa were indicative of CSPH and EV, while LSM < 10 kPa and <11 kPa ruled out CSPH and EV, respectively. Conclusions: Our study found that 2D-SWE in combination with platelet count performed best (in comparison to the other SWE methods) to predict EV or CSPH in patients with CLD. Future prospective trials are needed to validate our results.
Cardiovascular Outcomes in Patients with Atrial Flutter and Oral Anticoagulation: The Predictive Role of Left Atrial Appendage Thrombus in a Long-Term, Prospective, Observational Cohort Study
Authors: Turek Łukasz , Sadowski Marcin , Kurzawski Jacek , Janion Marianna
Published: December 2024

Background/Objectives: The risks of blood clot formation, stroke, heart failure (HF), and cardiovascular death are enhanced in individuals with atrial flutter (AFL). However, it remains unclear whether left atrial appendage thrombus (LAAT) in individuals with AFL with anticoagulation enhances the risk of cardiovascular morbidity and mortality. Thus, in the current trial, we aimed to evaluate the predictive role of LAAT for cardiovascular outcomes in individuals with AFL who were receiving anticoagulation and admitted for electrical cardioversion. Methods: Ninety patients were included in this prospective observational cohort study. The primary endpoint was the identification of LAAT by transesophageal echocardiographic examination. All participants were observed for a median of 2114.5 (interquartile range, 1487.5–2591) days to identify the secondary endpoints: cardiovascular death, transient ischemic attack (TIA), stroke, systemic thromboembolic complications, hospitalization due to HF, or myocardial infarction. Results: LAAT was identified in nine (10%) patients. No differences in cardiovascular outcomes between patients with and without LAAT were documented. However, a higher CHA2DS2-VASc score, previous myocardial infarction, and previous stroke/TIA/systemic thromboembolism were associated with significantly higher rates of hospitalization due to HF. Decreased left ventricular ejection fraction (LVEF) was associated with significantly higher rates of cardiovascular death, underscoring the significance of this marker in disease prognosis. Conclusions: The impact of LAAT on cardiovascular outcomes was insignificant. Higher CHA2DS2-VASc scores, previous myocardial infarction, previous stroke/TIA/systemic thromboembolism, and lower LVEF significantly affected long-term prognosis and were associated with a poor prognosis.
Online vs. Supervised Training in Relieving Urinary Incontinence and Diastasis Recti Abdominis in Early Postpartum
Authors: Tim Sabina , Mazur-Bialy Agnieszka
Published: December 2024

Background/Objectives: The postpartum period is marked by numerous physical changes, often leading to pelvic floor disorders (PFD) such as urinary incontinence (UI) and diastasis recti abdominis (DRA). This study aimed to assess the occurrence of UI and DRA in postpartum women and evaluate the effectiveness of physiotherapy in managing UI and DRA. Methods: A total of 396 women, between the 3rd and 5th postpartum day, were randomized into three groups: control (GrCon), online exercise group (GrOnl), and supervised group (GrSup). GrCon received only education, whereas GrOnl and GrSup had three sessions with exercises with physiotherapist—online or supervised. Data were collected through questionnaires, ICIQ FLUTS, body posture assessments, and DRA measurements. Results: The results showed a significant reduction in UI and DRA symptoms across all groups, with the GrSup group showing the greatest improvement. UI symptoms decreased from 49% during pregnancy to 36.9% postpartum, with GrSup women reporting fewer urological complaints compared to the GrOnl and GrCon groups (p < 0.001). DRA incidence dropped from 76.2% in the early postpartum days to 23.4% at six weeks, with GrSup showing the lowest rates (9.8%). Notably, supervised physiotherapy resulted in a higher frequency (94.7%) and correct performance of PFME (72.2%) compared to the online and control groups. Conclusions: The study concludes that supervised physiotherapy is more effective than online sessions in managing postpartum UI and DRA, emphasizing the importance of guided exercise for better outcomes.
The Role of Therapeutic Endoscopic Ultrasound in Management of Malignant Double Obstruction (Biliary and Gastric Outlet): A Comprehensive Review with Clinical Scenarios
Authors: Dell’Anna Giuseppe , Nunziata Rubino , Delogu Claudia , Porta Petra , Grassini Maria Vittoria , Dhar Jahnvi , Barà Rukaia , Bencardino Sarah , Fanizza Jacopo , Mandarino Francesco Vito , Fasulo Ernesto , Barchi Alberto , Azzolini Francesco , Albertini Petroni Guglielmo , Samanta Jayanta , Facciorusso Antonio , Dell’Anna Armando , Fuccio Lorenzo , Massironi Sara , Malesci Alberto , Annese Vito , Pagano Nico , Donatelli Gianfranco , Danese Silvio
Published: December 2024

Endoscopic ultrasound (EUS)-guided interventions have revolutionized the management of malignant biliary obstruction (MBO) and gastric outlet obstruction (GOO), providing minimally invasive alternatives with improved outcomes. These procedures have significantly reduced the need for high-risk surgical interventions or percutaneous alternatives and have provided effective palliative care for patients with advanced gastrointestinal and bilio-pancreatic malignancies. EUS-guided biliary drainage (EUS-BD) techniques, including hepaticogastrostomy (EUS-HGS), choledochoduodenostomy (EUS-CDS), and antegrade stenting (EUS-AS), offer high technical and clinical success rates, with a good safety profile particularly when Endoscopic Retrograde Cholangiopancreatography (ERCP) is not feasible. EUS-HGS, which allows biliary drainage by trans-gastric route, is primarily used for proximal stenosis or in case of surgically altered anatomy; EUS-CDS with Lumen-Apposing Metal Stent (LAMS) for distal MBO (dMBO), EUS-AS as an alternative of EUS-HGS in the bridge-to-surgery scenario or when retrograde access is not possible and EUS-guided gallbladder drainage (EUS-GBD) with LAMS in case of dMBO with cystic duct patent without dilation of common bile duct (CDB). EUS-guided gastroenterostomy (EUS-GE) has already established its role as an effective alternative to surgical GE and enteral self-expandable metal stent, providing relief from GOO with fewer complications and faster recovery times. However, we do not yet have strong evidence on how to combine the different EUS-guided drainage techniques with EUS-GE in the setting of double obstruction. This comprehensive review aims to synthesize growing evidence on this topic by randomized controlled trials, cohort studies, and case series not only to summarize the efficacy, safety, and technical aspects of these procedures but also to propose a treatment algorithm based essentially on the anatomy and stage of the neoplasm to guide clinical decision-making, incorporating the principles of personalized medicine. This review also highlights the transformative impact of EUS-guided interventions on the treatment landscape for MBO and GOO. These techniques offer safer and more effective options than traditional approaches, with the potential for widespread clinical adoption. Further research is needed to refine these procedures, expand their applications, and improve patient care and quality of life.
Ablative Five-Fraction Stereotactic Radiotherapy in Elderly Patients with Pancreatic Cancer: A Single Institution Experience
Authors: Fiore Michele , Petrianni Gian Marco , D’Ercole Gabriele , Onorati Elena , Trecca Pasquale , Alaimo Rita , Carlotti Daniele , Ippolito Edy , D’Angelillo Rolando Maria , Ramella Sara
Published: December 2024

Background: Pancreatic cancer, with its poor prognosis, is frequently diagnosed in elderly patients who may be ineligible for surgery or chemoradiation due to age or comorbidities. Stereotactic body radiotherapy (SBRT) offers a targeted approach by delivering precise, high-dose radiation to a limited volume in few fractions. This study aims to evaluate the efficacy and safety of SBRT in elderly pancreatic cancer patients. Methods: Patients with pancreatic cancer received SBRT using Volumetric Modulated Arc Therapy in schedules of five dose fractions tailored to the tolerance of adjacent tissues. Progression-free survival (PFS), local progression-free survival (LPFS), metastasis-free survival (MFS) and overall survival (OS) were analysed. Toxicities were graded according to the Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Results: Median follow-up was 9.5 months (range, 4–37.2 months). The 1-year, 2-year and 3-year LPFS rates were 88%, 73% and 54%, respectively (median not reached). Median PFS, MFS and OS were 29.6 months, 32.6 months, and 24.1 months, respectively. SBRT was well tolerated with acute and late toxicity rates of 6% and 9%, respectively. Conclusionsd: SBRT appears to be an effective and safe option for elderly pancreatic cancer patients, achieving high local control with minimal toxicity.
Towards Accurate Biocompatibility: Rethinking Cytotoxicity Evaluation for Biodegradable Magnesium Alloys in Biomedical Applications
Authors: De Luca Angela , Ruggiero Roberta , Cordaro Aurora , Marrelli Benedetta , Raimondi Lavinia , Costa Viviana , Bellavia Daniele , Aiello Elisabetta , Pavarini Matteo , Piccininni Antonio , Tatullo Marco , Boanini Elisa , Paduano Francesco , Giavaresi Gianluca
Published: December 2024

Magnesium and its alloys represent promising candidates for biomedical implants due to their biodegradability and mechanical properties, which are similar to natural bone. However, their rapid degradation process characterized by dynamic pH fluctuations and significant hydrogen gas evolution during biocorrosion adversely affects both in vitro and in vivo assessments. While the ISO 10993-5 and 12 standards provide guidelines for evaluating the in vitro biocompatibility of biodegradable materials, they also introduce testing variability conditions that yield inconsistent results. To address these inherent characteristics of Mg alloys, developing improved methods that accurately simulate the physiological environment for in vitro biocompatibility testing is essential. This study introduces two novel extraction approaches for evaluating Mg alloys: a buffered solution utilizing PBS/DMEM with quaternary dilutions and a modified ISO standard protocol employing decuple dilution of conventional unbuffered extracts. The present findings establish that controlled optimization of extraction conditions, specifically buffer composition and dilution parameters, enables reliable in vitro cytotoxicity assessment of Mg alloys, providing a robust methodology that advances the preclinical evaluation of these promising biodegradable materials.
Enhancement of Machining Performance of Ti-6Al-4V Alloy Though Nanoparticle-Based Minimum Quantity Lubrication: Insights into Surface Roughness, Material Removal Rate, Temperature, and Tool Wear
Authors: Mehmood Tahir , Khalil Muhammad Shahid
Published: December 2024

In competitive industry, economical and environmentally friendly production techniques are essential. In this sense, cleaner and more sustainable machining techniques are the industry’s focus. In addition to green methods, effective parametric control is necessary for hard-to-cut materials, particularly titanium Ti-6Al-4V, which is extensively used in a diversity of industries, including aerospace, medical, and military applications. Therefore, the current study aims to improve the machining performance of Ti-6Al-4V alloy using sustainable lubrication conditions. The effect of Al2O3 nanoparticles based on the minimum quantity lubrication (N-MQL) condition on surface quality and productivity are compared with minimum quantity lubrication (MQL). The performance measures, including surface roughness (Ra), material removal rate (MRR), and temperature, are evaluated at three machining variables, i.e., cutting speed (Vc), feed rate (f), and depth of cut (ap). These performance measures are further assessed by tool wear and surface morphology analysis. ap, f, and Vc are the most influencing parameters for Ra, MRR, and temperature, regardless of lubrication mode. The optimized values of RA of 0.728443 µm, MRR of 2443.77 m3/min, and temperature of 337 °C are achieved at N-MQL. For the N-MQL state, the optimized values of Ra of 0.55 µm, MRR of 2579.5 m3/min, and temperature of 323.554 °C are attained through a multi-response optimization desirability approach. Surface morphology analysis reveals a smooth machined surface with no obvious surface flaws, such as feed marks and adhesion, under N-MQL conditions, which significantly enhances the surface finish of the parts. The machining performance under the N-MQL condition has been enhanced considerably in terms of an improvements in surface finish of 32.96% and MRR of 11.56%, along with a decrease in temperature (17.22%) and higher tool life (326 s) than MQL. Furthermore, Al2O3 is advised over MQL because it uses less energy and has reduced tool wear and improved surface quality, and it is a cost-effective and sustainable fluid.
Effects of Several Bile Acids on the Production of Virulence Factors by Pseudomonas aeruginosa
Authors: Lomri Noureddine , Hulen Christian
Published: December 2024

The presence of bile acids in the cystic fibrosis patient’s lungs contributes to an increase in the inflammatory response, in the dominance of pathogens, as well as in the decline in lung function, increasing morbidity. The aim of this study is to determine the effects of exposure of Pseudomonas aeruginosa to primary and secondary bile acids on the production of several virulence factors which are involved in its pathogenic power. The presence of bile acids in the bacterial culture medium had no effect on growth up to a concentration of 1 mM. However, a slight decrease in the adhesion index as well as a reduction in the virulence of the bacteria on the HT29 cell line could be observed. In this model, exposure of P. aeruginosa to bile acids showed a significant decrease in the production of LasB and AprA proteases due to the reduction in the expression of their genes. A decrease in pyocyanin production was also observed in relation to the effects of bile acids on the quorum sensing regulators. In order to have an effect on gene expression, it is necessary for bile acids to enter the bacteria. P. aeruginosa harbors two potential homologs of the eukaryotic genes encoding the bile acid transporters NTCP1 and NTCP2 that are expressed in hepatocytes and enterocytes, respectively. By carrying out a comparative BLAST-P between the amino acid sequences of the PAO1 proteins and those of NTCP1 and NTCP2, we identified the products of the PA1650 and PA3264 genes as the unique homologs of the two eukaryotic genes. Exposure of the mutant in the PA1650 gene to chenodeoxycholic acid (CDCA) and lithocholic acid (LCA) showed a less significant effect on pyocyanin production than with the isogenic PAO1 strain. Also, no effect of CDCA on the PA3264 gene mutant was observed. This result indicated that CDCA should enter the bacteria by the transporter produced by this gene. The entry of LCA into bacteria seemed more complex and rather responded to a multifactorial system involving the product of the PA1650 gene but also the products of other genes encoding potential transporters.
Efficacy of Fractional CO2 Laser Therapy in Improving Symptoms and Quality of Life in Women with Refractory Vulvar Lichen Sclerosus: A Prospective Observational Study
Authors: Gil-Villalba Ana , Ayén-Rodríguez Ángela , Naranjo-Díaz María José , Linares-González Laura , Ruiz-Villaverde Ricardo
Published: December 2024

Lichen sclerosus (LS) is a chronic inflammatory condition predominantly affecting the anogenital region of postmenopausal women. It is associated with considerable aesthetic and functional impairments and an increased risk of squamous cell carcinoma. While high-potency topical corticosteroids remain the cornerstone of treatment, therapeutic options for patients with refractory LS are scarce. Fractional CO2 laser therapy has emerged as a potential second-line intervention aiming to mitigate symptoms and improve quality of life. This prospective observational study investigated the short-term efficacy and safety of fractional CO2 laser therapy in 75 women with refractory LS who underwent four treatment sessions between January 2022 and February 2024. Sixty-nine patients completed the protocol, demonstrating significant reductions in key symptoms, including pruritus (VAS score from 7.53 ± 3.02 to 4.08 ± 3.07), pain (5.83 ± 3.84 to 2.42 ± 2.85), and dyspareunia (8.26 ± 2.82 to 6.34 ± 3.30). Quality of life, sexual function, and psychological well-being also improved, as evidenced by reductions in Dermatology Life Quality Index (DLQI) scores (10.72 ± 7.25 to 5.94 ± 5.16), enhancements in sexual function (FSFI scores from 10.48 ± 8.46 to 15.52 ± 9.59), and decreased depression severity (BDI scores from 16.66 ± 12.64 to 5.94 ± 5.16). Importantly, no adverse effects were reported during the study period. Although these findings highlight the potential of fractional CO2 laser therapy as a safe and effective adjunct for refractory LS, it is essential to acknowledge the study’s limitations, particularly the relatively short follow-up period. Longer-term studies are warranted to confirm sustained benefits and to evaluate the broader applicability of this approach.