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14 pages, 777 KiB  
Article
Effectiveness of a Flossing Protocol and Manual Therapy in Improving the Clinical and Functional Status of Subjects with Recurrent Ankle Sprains; A Double-Blind Randomized Clinical Trial
by Mario Bermúdez-Egidos, Raúl Pérez-Llanes and Rubén Cuesta-Barriuso
Med. Sci. 2025, 13(3), 149; https://doi.org/10.3390/medsci13030149 - 20 Aug 2025
Abstract
Introduction: Recurrent ankle sprains can lead to chronic ankle instability. The flossing technique aims to modify the function and characteristics of fascial tissue. The objective was to evaluate the effectiveness of flossing and sliding techniques in improving subjects with previous ankle sprains. [...] Read more.
Introduction: Recurrent ankle sprains can lead to chronic ankle instability. The flossing technique aims to modify the function and characteristics of fascial tissue. The objective was to evaluate the effectiveness of flossing and sliding techniques in improving subjects with previous ankle sprains. Methods: Randomized, double-blind clinical study with a follow-up period. Twenty-six subjects were assigned to two study groups: experimental (flossing technique and passive manual therapy techniques) and placebo control group (flossing technique without compression and manual therapy techniques without sliding). The intervention lasted three weeks, with two sessions per week. The study variables were dorsiflexion under load (Leg Motion®), ankle mobility under unloaded conditions (goniometer), pressure pain threshold (algometer), and stability (Rs Scan® pressure platform). Three measurements were taken: pre-treatment (T0), post-treatment (T1), and after 3 weeks of follow-up (T2). Results: There were significant intergroup differences in dorsiflexion under load (F = 4.90; p = 0.02). Range of motion in plantar flexion without load (F = 3.78; p = 0.04), in the ellipse area (F = 4.72; p = 0.01), left stability (F = 3.74; p = 0.03), and right stability (F = 3.73; p = 0.03) without visual support. Conclusions: A physiotherapy protocol using flossing and manual sliding therapy can increase loaded dorsal flexion in young adults with previous ankle sprains. This intervention can also improve ankle plantar flexion under unloaded conditions. The area of the ellipse without visual support can improve in young adults with a history of ankle sprains following a program of flossing and manual therapy. Full article
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15 pages, 8312 KiB  
Review
Equine Pituitary Pars Intermedia Dysfunction
by Nicola J. Menzies-Gow
Vet. Sci. 2025, 12(8), 780; https://doi.org/10.3390/vetsci12080780 (registering DOI) - 20 Aug 2025
Abstract
Pituitary pars intermedia dysfunction (PPID) is a common, slowly progressive, neurodegenerative disorder of the older horse. Oxidative damage to the hypothalamic periventricular neurons results in loss of dopaminergic inhibition of the pars intermedia region of the pituitary gland. Consequently, there is increased production [...] Read more.
Pituitary pars intermedia dysfunction (PPID) is a common, slowly progressive, neurodegenerative disorder of the older horse. Oxidative damage to the hypothalamic periventricular neurons results in loss of dopaminergic inhibition of the pars intermedia region of the pituitary gland. Consequently, there is increased production of the pro-opiomelanocortin (POMC)-derived hormones normally produced by this region, as well as initial melanocyte hypertrophy and hyperplasia, followed by adenomatous change. Clinical signs that are highly suggestive of the disease are generalised and regional hypertrichosis and delayed/abnormal coat shedding. Numerous clinical signs provide a moderate clinical suspicion, including hyperhidrosis, abnormal fat distribution/regional adiposity, epaxial muscle atrophy/loss of topline, laminitis, weight loss, recurrent infections, behavioural changes/lethargy, polyuria and polydipsia, a pot-bellied appearance, bulging supraorbital fat pads, reduced wound healing, lordosis and infertility. In all animals, a diagnosis of PPID is made based on the signalment, clinical signs and results of further diagnostic tests, with age being a crucial factor to consider. Currently recommended further diagnostic tests are measurement of basal adrenocorticotrophic hormone (ACTH) concentrations (all year) and evaluation of the ACTH response to thyrotrophin-releasing hormone (TRH) using seasonally adjusted references intervals (non-autumn). Animals should also be tested for insulin dysregulation, as laminitis risk in PPID is associated with hyperinsulinaemia. PPID can be managed but not cured; it is a lifelong condition. The individual clinical signs can be managed, e.g., clipping the excessive haircoat and providing unrestricted access to water for individuals with polydipsia. Alternatively, pharmacological management can be employed, and the dopamine-2 receptor agonist pergolide is licensed/approved for the treatment of equine PPID. This should be prescribed in combination with dietary recommendations based on the body condition score and insulin sensitivity status of the individual animal. Full article
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48 pages, 3298 KiB  
Article
Do Stop Words Matter in Bug Report Analysis? Empirical Findings Using Deep Learning Models Across Duplicate, Severity, and Priority Classification
by Jinfeng Ji and Geunseok Yang
Appl. Sci. 2025, 15(16), 9178; https://doi.org/10.3390/app15169178 (registering DOI) - 20 Aug 2025
Abstract
As software systems continue to increase in complexity and scale, the number of reported bugs also grows. Bug reports are essential artifacts in software maintenance, supporting critical tasks such as detecting duplicate reports, predicting bug severity, and assigning priority levels. Although stop word [...] Read more.
As software systems continue to increase in complexity and scale, the number of reported bugs also grows. Bug reports are essential artifacts in software maintenance, supporting critical tasks such as detecting duplicate reports, predicting bug severity, and assigning priority levels. Although stop word removal is a common text preprocessing step in natural language processing, its effectiveness in deep learning-based bug report analysis has not been thoroughly evaluated. This study investigates the impact of stop word removal on three core bug report classification tasks. The analysis uses a dataset containing over 1.9 million bug reports from eight large-scale open-source projects, including Eclipse, FreeBSD, GCC, Gentoo, Kernel, RedHat, Sourceware, and WebKit. Five deep learning models are applied: convolutional neural networks, long short-term memory networks, gated recurrent units, Transformers, and BERT. Each model is evaluated on its performance with and without stop word removal during preprocessing. The results show that the F1 score difference was less than 0.01 in over 85% of comparisons, so stop word removal has little to no effect on predictive performance in eight open-source projects. Average F1-scores remain consistent across all tasks and models, with 0.36 for duplicate detection, 0.33 for severity prediction, and 0.33 for priority prediction. Statistical significance tests confirm that the observed differences are not meaningful across datasets or model types. The findings suggest that stop word removal is not necessary in deep learning-based bug report analysis. Removing this step may simplify preprocessing pipelines without reducing accuracy, particularly in large-scale and real-world software engineering applications. Full article
12 pages, 541 KiB  
Article
Efficacy of Non-Invasive Monopolar Radiofrequency for Treating Genitourinary Syndrome of Menopause: A Prospective Pilot Study
by Mariachiara Palucci, Marta Barba, Alice Cola, Clarissa Costa, Desirèe De Vicari and Matteo Frigerio
Clin. Pract. 2025, 15(8), 155; https://doi.org/10.3390/clinpract15080155 - 20 Aug 2025
Abstract
Introduction: The decline of serum estrogen in postmenopausal women leads to several changes in the vulvovaginal and vesicourethral areas, resulting in the genitourinary syndrome of menopause (GSM), characterized by bothersome symptoms such as vaginal atrophy, lack of lubrication, dyspareunia, urgency, dysuria, and recurrent [...] Read more.
Introduction: The decline of serum estrogen in postmenopausal women leads to several changes in the vulvovaginal and vesicourethral areas, resulting in the genitourinary syndrome of menopause (GSM), characterized by bothersome symptoms such as vaginal atrophy, lack of lubrication, dyspareunia, urgency, dysuria, and recurrent urinary tract infections. Nevertheless, this condition could also be experienced by younger women affected by hormone-dependent tumors. Although topical estrogens are considered “the gold standard”, hormonal treatments cannot be indicated in cancer survivors. As a result, energy-based devices using radiofrequency and laser technologies have emerged as alternative options. This prospective study aimed to evaluate the benefits of non-invasive monopolar radiofrequency (RF) in women affected by GSM who have contraindications to, did not respond to, or declined local estrogen therapy. Methods: The patients underwent five weekly sessions of second-generation monopolar RF. At baseline and at the fifth session, two validated questionnaires were administered to the patients: the Visual Analogue Scale (VAS) and the Female Sexual Function Index (FSFI-19). On the other hand, the vaginal mucosa status was evaluated by clinicians through the Vaginal Health Index (VHI). At the end of the cycle, the Patient Global Impression of Improvement (PGI-I) questionnaire was collected. Results: Based on 44 patients who completed five sessions of radiofrequency, a significant improvement was observed in sexual function according to the FSFI scale (22.9 vs. 38.6; p < 0.001) and in VVA atrophy symptoms, as documented by the VAS score (223 vs. 125; p < 0.001). The mean VHI score increased by 3 points (p < 0.001). Moreover, according to PGI-I, 96% of patients reported a perceived improvement (PGI-I score ≤ 3). Conclusions: Radiofrequency could provide an innovative and safe therapeutic approach for patients suffering from GSM and VVA, especially when hormonal strategies are unsuitable. Full article
21 pages, 5608 KiB  
Article
Wildfires and Climate Change as Key Drivers of Forest Carbon Flux Variations in Africa over the Past Two Decades
by Lianglin Zhang and Zhenke Zhang
Fire 2025, 8(8), 333; https://doi.org/10.3390/fire8080333 - 20 Aug 2025
Abstract
Forests play a vital role in the global carbon cycle; however, the carbon sink capacity of African forests is increasingly threatened by wildfires, rising temperatures, and ecological degradation. This study analyzes the spatiotemporal dynamics of forest carbon fluxes across Africa from 2001 to [...] Read more.
Forests play a vital role in the global carbon cycle; however, the carbon sink capacity of African forests is increasingly threatened by wildfires, rising temperatures, and ecological degradation. This study analyzes the spatiotemporal dynamics of forest carbon fluxes across Africa from 2001 to 2023, based on multi-source remote sensing and climate datasets. The results show that wildfires have significantly disrupted Africa’s carbon balance over the past two decades. From 2001 to 2023, fire activity was most intense in the woodland–savanna transition zones of Central and Southern Africa. In countries such as the Democratic Republic of the Congo, Angola, Mozambique, and Zambia, each recorded burned areas exceeding 500,000 km2, along with high recurrence rates (e.g., up to 0.7584 fires per year in South Sudan). These fire-affected regions often exhibited high ecological sensitivity and carbon density, which led to pronounced disturbances in carbon fluxes. Nevertheless, the Democratic Republic of the Congo maintained an average annual net carbon sink of 74.2 MtC, indicating a high potential for ecological recovery. In contrast, Liberia and Eswatini exhibited net carbon emissions in fire-affected areas, suggesting weaker ecosystem resilience. These findings underscore the urgent need to incorporate wildfire disturbances into forest carbon management and climate mitigation strategies. In addition, climate variables such as temperature and soil moisture also influence carbon fluxes, although their effects display substantial spatial heterogeneity. On average, a 1 °C increase in temperature leads to an additional 0.347 (±1.243) Mt CO2 in emissions, while a 1% increase in soil moisture enhances CO2 removal by 1.417 (±8.789) Mt. However, compared to wildfires, the impacts of these climate drivers are slower and more spatially variable. Full article
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28 pages, 1169 KiB  
Article
Uropathogenic Escherichia coli in a Diabetic Dog with Recurrent UTIs: Genomic Insights and the Impact of Glucose and Antibiotics on Biofilm Formation
by Inês C. Rodrigues, Marisa Ribeiro-Almeida, Joana Campos, Leonor Silveira, Liliana Leite-Martins, Jorge Ribeiro, Paula Martins da Costa, Joana C. Prata, Ângela Pista and Paulo Martins da Costa
Microorganisms 2025, 13(8), 1946; https://doi.org/10.3390/microorganisms13081946 - 20 Aug 2025
Abstract
Recurrent urinary tract infections (UTIs) pose a significant clinical challenge in both human and veterinary medicine, due to antibiotic-resistant and biofilm-forming bacteria. We hypothesized that high glucose levels in diabetic animals enhance biofilm formation and reduce antibiotic efficacy, promoting infection persistence. This study [...] Read more.
Recurrent urinary tract infections (UTIs) pose a significant clinical challenge in both human and veterinary medicine, due to antibiotic-resistant and biofilm-forming bacteria. We hypothesized that high glucose levels in diabetic animals enhance biofilm formation and reduce antibiotic efficacy, promoting infection persistence. This study analyzed Escherichia coli from a diabetic female Labrador Retriever with recurrent UTIs over 18 months, focusing on antimicrobial resistance, biofilm-forming capacity, and genomic characterization. Most isolates (9/11) were resistant to ampicillin and fluoroquinolones. Whole genome sequencing of six selected isolates revealed that they belonged to the multidrug-resistant ST1193 lineage, a globally emerging clone associated with persistent infections. Phylogenetic analysis revealed clonal continuity across six UTI episodes, with two distinct clones identified: one during a coinfection in the second episode and another in the last episode. High-glucose conditions significantly enhanced biofilm production and dramatically reduced antibiotic susceptibility, as evidenced by a marked increase in minimum biofilm inhibitory concentrations (MBICs), which were at least 256-fold higher than the corresponding minimum inhibitory concentration (MIC). Sulfamethoxazole–trimethoprim demonstrated the strongest antibiofilm activity, though this was attenuated in glucose-supplemented environments. This research highlights the clinical relevance of glucosuria in diabetic patients and emphasizes the need for therapeutic strategies targeting biofilm-mediated antibiotic tolerance to improve the management of recurrent UTIs. Full article
(This article belongs to the Special Issue Antimicrobial Resistance and the Use of Antibiotics in Animals)
17 pages, 814 KiB  
Review
Optimization of Photodynamic Therapy in Dermatology: The Role of Light Fractionation
by Luis Alonso-Mtz de Salinas, Emilio Garcia-Mouronte, Jorge Naharro-Rodriguez, Luis Alfonso Perez-Gonzalez and Montserrat Fernández-Guarino
Int. J. Mol. Sci. 2025, 26(16), 8054; https://doi.org/10.3390/ijms26168054 (registering DOI) - 20 Aug 2025
Abstract
Photodynamic therapy (PDT) has become a widely used modality for treating actinic keratosis (AK) and non-melanoma skin cancers (NMSC), as well as other inflammatory or infectious diseases. Despite its efficacy, limitations such as incomplete responses and pain have motivated the exploration of protocol [...] Read more.
Photodynamic therapy (PDT) has become a widely used modality for treating actinic keratosis (AK) and non-melanoma skin cancers (NMSC), as well as other inflammatory or infectious diseases. Despite its efficacy, limitations such as incomplete responses and pain have motivated the exploration of protocol enhancements. This review examines the clinical and biological rationale for light fractionation—dividing the total light dose into two separate exposures with a dark interval—as a strategy to improve PDT outcomes. We reviewed preclinical and clinical studies evaluating fractionated illumination using 5-aminolevulinic acid (ALA) or methyl aminolevulinate (MAL). The findings consistently demonstrate superior efficacy of fractionated schemes, particularly with ALA, showing higher complete response rates in AK, superficial basal cell carcinoma (sBCC), and Bowen’s disease (BD), and improved long-term tumor control compared to single illumination. The better outcomes are attributed to increased reactive oxygen species (ROS) generation following tissue reoxygenation during the dark interval and greater susceptibility of partially damaged cells to subsequent illumination. Fractionated PDT also shows a favorable safety and cosmetic profile. These results support considering light fractionation protocols as a standard approach for optimizing PDT efficacy in dermatologic oncology, particularly in lesions with limited depth and high recurrence risk. Full article
(This article belongs to the Special Issue Dermatology: Advances in Pathophysiology and Therapies (2nd Edition))
29 pages, 686 KiB  
Review
Targeted Screening Strategies for Head and Neck Cancer: A Global Review of Evidence, Technologies, and Cost-Effectiveness
by Orlando Guntinas-Lichius, Claudio Bücking, Sweet Ping Ng, Fernando López, Juan Pablo Rodrigo, Karthik N. Rao, Andrés Coca Pelaz, Luiz P. Kowalski, Cesare Piazza, Alessandra Rinaldo and Alfio Ferlito
Diagnostics 2025, 15(16), 2095; https://doi.org/10.3390/diagnostics15162095 - 20 Aug 2025
Abstract
Head and neck cancer (HNC) is the seventh most common cancer worldwide, with rising incidence particularly in oropharyngeal cancer subsites. Despite well-known risk factors, such as tobacco and alcohol consumption as well as human papillomavirus (HPV) infection, most HNCs are diagnosed at an [...] Read more.
Head and neck cancer (HNC) is the seventh most common cancer worldwide, with rising incidence particularly in oropharyngeal cancer subsites. Despite well-known risk factors, such as tobacco and alcohol consumption as well as human papillomavirus (HPV) infection, most HNCs are diagnosed at an advanced stage, resulting in poor prognosis. Early detection and screening are critical, especially in high-risk populations. Nevertheless, there is a lack of guidelines for a stratified HNC screening. A systematic literature review was conducted following PRISMA guidelines, using PubMed and ScienceDirect databases up to 30 June 2025. Search terms included “screening”, “early diagnosis”, and specific HNC subsites. A total of 199 records were screened, and 160 studies were included based on relevance and scientific rigor. The review concentrates on contemporary screening modalities, stratification of high-risk cohorts, emerging technologies, and cost-effectiveness evidence. Visual inspection and panendoscopy remain the standard tools for HNC screening, but have limited effectiveness and cost-efficiency. Opportunistic screening in high-risk individuals, especially in regions with high HNC prevalence, has shown benefits. Liquid biopsy techniques targeting HPV- and Epstein-Barr virus-related HNC demonstrate high sensitivity for early detection and recurrence monitoring. Novel imaging technologies like narrow-band imaging and Raman spectroscopy show promising diagnostic accuracy but require further validation. Most broad-based screening programs lack cost-effectiveness, while targeted strategies in high-risk groups appear more viable. Screening for HNC should be stratified by individual risk profiles and regional disease prevalence. Emerging technologies, particularly liquid and optical biopsy techniques, offer transformative potential. Future screening strategies must integrate technological advances into tailored, evidence-based protocols to improve early detection and patient outcomes in HNC. Full article
33 pages, 2196 KiB  
Review
Redefining Chemoresistance: Natural Bioactives as Molecular Modulators at the Cancer–Tumor Microenvironment Interface
by Claudia Reytor-González, Emilia Jiménez-Flores, Natalí González and Daniel Simancas-Racines
Int. J. Mol. Sci. 2025, 26(16), 8037; https://doi.org/10.3390/ijms26168037 (registering DOI) - 20 Aug 2025
Abstract
Therapeutic resistance remains a critical barrier in effective cancer treatment, contributing to disease recurrence, progression, and reduced patient survival. In recent years, natural bioactive compounds have emerged as promising adjuncts in oncology due to their ability to modulate multiple biological processes involved in [...] Read more.
Therapeutic resistance remains a critical barrier in effective cancer treatment, contributing to disease recurrence, progression, and reduced patient survival. In recent years, natural bioactive compounds have emerged as promising adjuncts in oncology due to their ability to modulate multiple biological processes involved in resistance. This review explores current evidence on the role of natural compounds in influencing cancer cell behavior and their interactions with the tumor microenvironment. By organizing these compounds into chemical families, we provide a structured overview of their potential to enhance the efficacy of standard chemotherapy and reduce resistance-related mechanisms. We also highlight innovative strategies, including combination therapies and advanced drug delivery systems, that aim to improve their clinical applicability. Overall, this work underscores the relevance of integrating natural bioactives into modern cancer therapy and calls for further translational research to bridge preclinical findings with clinical implementation. Full article
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12 pages, 1250 KiB  
Case Report
Robotic Treatment of Adrenal Sclerosing PEComa: A Case Report with 13 Years of Follow-Up and a Literature Review
by Alessio Paladini, Raffaele La Mura, Michele Del Zingaro, Luca Lepri, Andrea Vitale, Jessica Pagnotta, Matteo Mearini, Guido Massa, Ettore Mearini and Giovanni Cochetti
Appl. Sci. 2025, 15(16), 9161; https://doi.org/10.3390/app15169161 (registering DOI) - 20 Aug 2025
Abstract
Background: Sclerosing perivascular epithelioid cell tumors (PEComas) are rare mesenchymal neoplasms, typically benign but occasionally exhibiting aggressive behavior. This study reports a case of sclerosing PEComa of the adrenal gland that was treated with robotic partial adrenalectomy, with 13 years of follow-up and [...] Read more.
Background: Sclerosing perivascular epithelioid cell tumors (PEComas) are rare mesenchymal neoplasms, typically benign but occasionally exhibiting aggressive behavior. This study reports a case of sclerosing PEComa of the adrenal gland that was treated with robotic partial adrenalectomy, with 13 years of follow-up and a review of the literature. Methods: A 48-year-old woman presented with abdominal pain. Imaging revealed a 10 × 9 cm adrenal mass displacing adjacent structures. MRI and 18F-FDG PET-CT suggested angiomyolipoma. Robotic partial adrenalectomy was performed. Intraoperative frozen section analysis identified the mass as angiomyolipoma, while final histopathology confirmed it as a sclerosing PEComa. Results: This case highlights the advantages of robotic surgery in the management of large adrenal tumors, allowing complete tumor removal while preserving functional adrenal tissue. The extended 13-year follow-up is significant, given the potential for recurrence or malignant transformation reported in other cases. A literature review identified 39 reported cases of sclerosing PEComas, with few documenting long-term outcomes. Conclusions: This is a documented case of robotic partial adrenalectomy for sclerosing PEComa. The findings support robotic surgery as a safe effective approach for managing this rare tumor, with excellent functional and oncological results. Extended follow-up reinforces the tumor’s benign behavior and the importance of long-term monitoring in PEComas. Full article
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19 pages, 9171 KiB  
Article
Long-Term Cotton Node Count Prediction Using Feature Selection, Data Augmentation, and Multivariate Time-Series Forecasting
by Vaishnavi Thesma, Glen C. Rains and Javad Mohammadpour Velni
Appl. Sci. 2025, 15(16), 9159; https://doi.org/10.3390/app15169159 (registering DOI) - 20 Aug 2025
Abstract
In this paper, we present an approach to performing long-term cotton node count prediction using feature selection, data augmentation, and forecasting using a multivariate long short-term memory (LSTM) model. Specifically, we used in situ measurement data that was collected from a cotton research [...] Read more.
In this paper, we present an approach to performing long-term cotton node count prediction using feature selection, data augmentation, and forecasting using a multivariate long short-term memory (LSTM) model. Specifically, we used in situ measurement data that was collected from a cotton research field from Tifton, GA, USA, to perform feature selection to select the most important input measurements and enable random data generation using Gaussian distribution to increase the size of our dataset. We concatenated the generated data to create longer, usable time-series and trained a multivariate LSTM model to predict average cotton node count. Our model’s prediction results on both the training and testing data had a low RMSE of less than 3, low MAE of less than 2.5, and high R2 score of at least 0.85. Our model also showed promise in accurately forecasting cotton node count in subsequent seasons via transfer learning. In particular, our transfer learned model maintained a low RMSE of less than 7.5 and MAE of less than 3.5, despite the subsequent season data having a shorter temporal scale. Moreover, we validated our results by performing hypothesis testing against a similar time-series forecasting model, namely, the gated recurrent unit (GRU) model. Full article
(This article belongs to the Special Issue Deep Learning and Data Mining: Latest Advances and Applications)
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15 pages, 1806 KiB  
Article
Acute HSV-1 Ocular Infection Is Impaired in KLF15 Knockout Mice but Stress-Induced Reactivation from Latency Is Prolonged in Male KLF15 Knockout Mice
by Kelly S. Harrison and Clinton Jones
Pathogens 2025, 14(8), 823; https://doi.org/10.3390/pathogens14080823 (registering DOI) - 20 Aug 2025
Abstract
Acute human alpha-herpesvirus 1 (HSV-1) infection culminates in a latent infection of neurons in trigeminal ganglia (TG) and the central nervous system. Following infection of mucosal epithelial cells, certain neurons survive infection and life-long latency is established. Periodically, stressful stimuli trigger reactivation from [...] Read more.
Acute human alpha-herpesvirus 1 (HSV-1) infection culminates in a latent infection of neurons in trigeminal ganglia (TG) and the central nervous system. Following infection of mucosal epithelial cells, certain neurons survive infection and life-long latency is established. Periodically, stressful stimuli trigger reactivation from latency, which result in virus shedding, transmission to other people, and, occasionally, recurrent disease. The glucocorticoid receptor (GR) and Krüppel-like factor 15 (KLF15) comprise a feed-forward transcriptional loop that cooperatively transactivate key HSV-1 promoters that drive expression of infected cell protein 0 (ICP0), ICP4, and ICP27. Silencing KLF15 significantly reduces HSV-1 replication in cultured mouse neuroblastoma cells. Consequently, we hypothesized that KLF15 mediates certain aspects of reactivation from latency. To test this hypothesis, we compared HSV-1 replication in KLF15−/− mice versus wild-type (wt) parental C57BL/6 mice. Virus shedding during acute infection was reduced in KLF15−/− mice. Male KLF15−/− mice shed higher titers of virus during late stages of reactivation from latency compared to KLF15−/− females and wt mice regardless of sex. At 15 d after explant-induced reactivation, virus shedding was higher in male KLF15−/− mice relative to wt mice and female KLF15−/− mice. These studies confirm KLF15 expression enhances viral replication during acute infection and reactivation from latency. Full article
(This article belongs to the Section Viral Pathogens)
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12 pages, 1547 KiB  
Article
Effects of Photodynamic Therapy and Glucocorticosteroids on Salivary Oxidative Stress in Oral Lichen Planus: A Randomized Clinical Trial
by Patryk Wiśniewski, Magdalena Sulewska, Jagoda Tomaszuk, Anna Zalewska, Sara Zięba, Aleksandra Pietruska, Emilia Szymańska, Katarzyna Winnicka, Mateusz Maciejczyk, Małgorzata Żendzian-Piotrowska and Małgorzata Pietruska
Antioxidants 2025, 14(8), 1017; https://doi.org/10.3390/antiox14081017 - 20 Aug 2025
Abstract
Objective: This study aimed to assess the impact of photodynamic therapy (PDT) and topical glucocorticosteroids (GKS) on total oxidant status (TOS), total antioxidant capacity (TAC), and oxidative stress index (OSI) in the saliva of patients with oral lichen planus (OLP). Methods: Ninety patients [...] Read more.
Objective: This study aimed to assess the impact of photodynamic therapy (PDT) and topical glucocorticosteroids (GKS) on total oxidant status (TOS), total antioxidant capacity (TAC), and oxidative stress index (OSI) in the saliva of patients with oral lichen planus (OLP). Methods: Ninety patients with histopathologically confirmed OLP were randomly assigned to either the PDT group (n = 50) or the GKS group (n = 40). Unstimulated saliva samples were collected before treatment and at 1, 3, and 6 months post-therapy. TOS, TAC, and OSI were determined using colorimetric assays. Results: Both PDT and GKS significantly reduced TOS over the entire observation period. TAC decreased persistently after GKS but remained stable after PDT except for an initial decline. OSI was significantly lower immediately after PDT but did not show sustained differences. Overall, PDT more effectively and durably restored redox balance compared to GKS. Conclusions: Photodynamic therapy demonstrates superior long-term efficacy in modulating oxidative stress markers in saliva, supporting its role as a promising alternative to topical corticosteroids in managing OLP. Clinically, these findings suggest that PDT may offer a non-invasive, recurrence-reducing, and steroid-sparing treatment alternative for OLP, potentially improving long-term patient outcomes and reducing side effects associated with prolonged corticosteroid use. Full article
(This article belongs to the Special Issue Oxidative Stress in Human Diseases—4th Edition)
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13 pages, 1310 KiB  
Protocol
PREDICT-H Protocol: A Multicenter Prospective Cohort Study on Preoperative Anatomical Determinants and Postoperative Complications in Primary Hypospadias Repair
by Tariq Abbas
Diagnostics 2025, 15(16), 2087; https://doi.org/10.3390/diagnostics15162087 - 20 Aug 2025
Abstract
Background: Hypospadias is a common congenital anomaly in boys, marked by ectopic urethral meatus and a wide range of anatomical variants such as chordee and atypical glans morphology. Despite advancements in surgical techniques, complication rates remain high and unpredictable due to heterogeneity [...] Read more.
Background: Hypospadias is a common congenital anomaly in boys, marked by ectopic urethral meatus and a wide range of anatomical variants such as chordee and atypical glans morphology. Despite advancements in surgical techniques, complication rates remain high and unpredictable due to heterogeneity in anatomy and a lack of standardized preoperative assessments. Retrospective studies suggest associations between specific anatomical features and postoperative complications; however, high-quality prospective, multicenter evidence is currently lacking. Methods: The PREDICT-H (Prospective Research on Essential Determinants Influencing Complication Trends in Hypospadias) study is a multicenter, prospective cohort study aiming to enroll approximately 1450 boys aged 1–12 years undergoing primary hypospadias repair at ten or more tertiary pediatric urology centers. A standardized preoperative assessment protocol will document detailed anatomical parameters, including urethral plate width and length, glans size, meatal location, chordee severity, and GMS score. Intraoperative variables and surgical techniques will be recorded. Postoperative outcomes, including urethrocutaneous fistula, meatal stenosis, and recurrent chordee, will be assessed at ≥6 months follow-up. Statistical analyses will include multivariate logistic regression and advanced modeling to identify independent predictors and develop a validated risk prediction nomogram. Interobserver reliability of anatomical assessments will also be evaluated. Results: As this is a study protocol, results are not yet available. Data collection is ongoing and will be analyzed upon completion of the planned follow-up period. The primary outcome will be the incidence of postoperative complications and the development of a predictive nomogram for individualized risk estimation. Conclusions: The PREDICT-H study is designed to provide robust, prospective evidence on the anatomical determinants of postoperative complications in hypospadias surgery. The development of a validated, clinically applicable risk prediction tool could standardize preoperative assessment and enhance individualized surgical planning. Findings from this study are expected to support evidence-based practice and inform future clinical guidelines. Full article
(This article belongs to the Section Clinical Diagnosis and Prognosis)
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13 pages, 638 KiB  
Article
Conditional Survival in Patients with Locally Advanced Rectal Cancer and Pathologic Complete Response: Results from an Observational Retrospective Multicenter Long-Term Follow-Up Study
by Carlos Cerdán Santacruz, Oscar Cano-Valderrama, Laura Melina Fernández, Ramón Sanz-Ongil, Rocío Santos Rancaño, Miquel Kraft Carre, Francisco Blanco Antona, Inés Aldrey Cao, Alba Correa Bonito, Jesús Cifuentes, Antoni Codina-Cazador, Eloy Espín-Basany, Eduardo García-Granero and Blas Flor Lorente
Cancers 2025, 17(16), 2707; https://doi.org/10.3390/cancers17162707 - 20 Aug 2025
Abstract
Introduction/Background: Patients with locally advanced rectal cancer (LARC) with pathological complete response (pCR) after neoadjuvant chemo-radiotherapy (NCRT) are a privileged group because of the favorable progression of their disease. However, their follow-up patterns after surgery are similar to those of other groups [...] Read more.
Introduction/Background: Patients with locally advanced rectal cancer (LARC) with pathological complete response (pCR) after neoadjuvant chemo-radiotherapy (NCRT) are a privileged group because of the favorable progression of their disease. However, their follow-up patterns after surgery are similar to those of other groups with worse prognosis, with the consequent psychological and economic impact. Methods: This is a retrospective observational multicenter study with data obtained from the Spanish Rectal Cancer Project. Patients with LARC who underwent surgery with curative intent after NCRT and achieved pCR were selected. The last follow-up update was conducted in December 2021. A conditional survival model was used to analyze oncological outcomes during follow-up. Recurrence-free survival (RFS) was analyzed for the entire cohort of patients and for those who survived at one, two, and three years. Results: A total of 815 patients from 32 hospitals were included. Their mean age was 65.1 years, and 36.1% of them were women. Of the 815 patients, 35 died or experienced recurrence (local or systemic) in the first postoperative year, and 780 were included in the conditional survival analysis one year after surgery. The probability of RFS at 5 years was 86.5% in the whole cohort and 89.4%, 92.9%, and 95.2% for survivors at one, two, and three years, respectively. The probability of recurrence in these same groups was 6.5%, 4.3%, 1.8%, and 0.6%. Conclusions: Follow-up of patients with LARC and pCR after NCRT followed by surgery could be adapted based on conditional survival data showing that the probability of RFS increases as patients remain recurrence-free, and recurrences more than 3 years after treatment are exceptional. Full article
(This article belongs to the Section Cancer Survivorship and Quality of Life)
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