Search Results (22,633)

Background: Breast cancer remains the most common malignancy among women worldwide. Current systemic treatment strategies include chemotherapy, immunotherapy, bone-stabilizing agents, endocrine therapy for hormone receptor-positive disease, anti-HER2 therapy for HER2-positive disease, and poly (ADP-ribose) polymerase (PARP) inhibitors for BRCA mutation cases. However, effectively overcoming drug resistance and reducing recurrence and metastasis rates remain major therapeutic challenges. Methods: To investigate the underlying mechanism of RSL3 in PARPi-resistant breast cancer cells, we treated several PARPi-resistant breast cancer cells with varying doses of RSL3. The regulatory proteins of STAT3 were analyzed using real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot analysis. Immunoprecipitation and ubiquitination assay were performed to identify the STAT3 ubiquitination levels. Results: Recently, we identified that RSL3, a ferroptosis activator, exhibits potent antitumor activity against PARPi-resistant breast cancer. Yet, its underlying mechanism remains unclear. Here, we demonstrate that RSL3 directly targets STAT3 and promotes its degradation via the ubiquitination pathway, leading to increased LC3-II levels and decreased p62 expression. These changes ultimately enhance autophagy, which at least partially contributes to elevated apoptosis. Rescue experiments confirmed that STAT3 overexpression reverses RSL3-induced autophagy and apoptosis. Conclusions: Our findings highlight RSL3 as a promising therapeutic agent and STAT3 as a potential target for treating PARPi-resistant breast cancer. Full article

Background/Objective: The standard approach for managing suspected basal cell carcinoma (BCC) involves performing a biopsy to confirm the diagnosis before treatment. This process often leads to multiple visits and increased healthcare costs. We aimed to evaluate the effectiveness of direct surgical excision of BCCs diagnosed clinically and dermoscopically, without the need for prior biopsy. Methods: We conducted a retrospective case–control study at a tertiary cancer center. Lesions suspected to be BCC, based on clinical and dermoscopic criteria, were divided into two groups: (1) a streamlined treatment group (cases), in which lesions were treated without a confirmatory biopsy (either excised with a 4 mm margin or managed with curettage and electrodesiccation); (2) and a biopsied group (controls). Clinical and histopathological data were analyzed and compared between groups to assess diagnostic accuracy, margin status, and treatment outcomes. Results: Of 389 BCCs, 167 (42.9%) were streamlined, while 222 (57.1%) underwent a biopsy before definitive treatment. The streamlined group demonstrated higher diagnostic accuracy, with 94.6% of excised lesions confirmed as BCC, compared with 73.4% in the biopsy group (p < 0.001). Among lesions excised with 4 mm margins, 97.9% achieved clear margins with the streamlined approach. Margin involvement was associated with high-risk BCC (p = 0.048), particularly with recurrent BCCs (p = 0.023). Conclusions: Streamlined management of BCC through direct excision without prior biopsy is an efficient and cost-effective strategy that reduces patient visits, costs, and waiting times, particularly for low-risk BCCs and older patients. Advances in dermoscopy and non-invasive tools support their accuracy, making it a feasible option in resource-limited settings. Full article

Background: The present study aimed to identify the differences between experiences, in terms of oral health-related quality of life, pain, side effects and/or other complications, of adults undergoing orthodontic treatment using removable aligners and fixed labial or lingual appliances. Methods: The review was registered with PROSPERO, and a comprehensive electronic search was undertaken without language or date restrictions. Randomised and non-randomised trials and prospective cohort and cross-sectional studies along with case series were included. The Cochrane Collaboration’s Risk of Bias 2 Tool, Newcastle–Ottawa Scale and The Risk Of Bias In Non-Randomized Studies—of Interventions tools were used to assess quality. Data were grouped in terms of oral health-related quality of life, pain side effects and/or other complications. Results: Data from 35 studies were included; 9 were eligible for meta-analysis. Thus 2611 participants were included related to removable aligners (n = 513), fixed labial (n = 1816) and lingual (n = 218) appliances or a combination (n = 64) of appliances. The standardised mean differences in visual analogue scale pain reports between 24 h and 7 days were −10.02 (95% CI: −11.13, −8.91) for aligners and −6.40 (95%CI: −10.42, −2.38) for labial appliances (p = 0.09). There was a significant improvement in dental self-confidence following fixed labial appliance treatment (p = 0.001). Conclusions: No difference was detected in short-term pain with aligners and labial appliances. Aligners may have less impact on oral health-related quality of life measures compared to labial appliances. Lingual appliances have a persistent impact on speech, despite some adaptability. Any deterioration in oral health-related quality of life measures during treatment appears temporary. Further randomised trials using validated assessment tools and comparing aligners and labial and lingual appliances are required. Full article

Background: Respiratory syncytial virus (RSV) pneumonia is an underrecognized cause of critical illness in adults. However, the influence of biological sex on intensive care unit (ICU) outcomes in this population remains unclear. Due to limited case numbers and incomplete covariate data, this study was designed as exploratory and hypothesis-generating. Methods: We conducted a retrospective exploratory cohort study using the MIMIC-IV database and identified 105 adult ICU patients with laboratory-confirmed RSV pneumonia. Clinical variables included sex, age, ICU length of stay, use of mechanical ventilation, and weaning status. Exploratory multivariable logistic regression was performed to assess associations with in-hospital mortality and weaning success, acknowledging substantial missingness of comorbidity data, severity scores, and treatment variables. This limited adjustment for confounding and statistical power. Results: Overall, in-hospital mortality was 33.3%. Mortality was significantly higher among women than men (51.6% vs. 7.0%; p < 0.001), although the absolute number of deaths in men was very small. In adjusted models, female sex (OR 14.6, 95% CI 1.58–135.3, p = 0.018), reflecting model instability due to sparse events, as well as longer ICU stay (OR 1.22 per day, p = 0.001) were independently associated with higher mortality. Female sex was also associated with lower odds of successful weaning (OR 0.07, 95% CI 0.01–0.63, p = 0.018). These effect estimates must be interpreted cautiously due to the very small number of deaths in men and the resulting wide confidence intervals. Age and ventilation duration were not significant predictors. Conclusions: In this preliminary ICU cohort, female sex and prolonged ICU stay were linked to higher mortality and lower weaning success in adults with RSV pneumonia. However, given the very small number of events—particularly among male patients—together with the modest sample size, limited covariate availability, and unstable effect estimates, the findings should be viewed as exploratory rather than confirmatory. Larger, well-powered, prospective multicenter studies are needed to validate and further characterize potential sex-related differences in outcomes of RSV-associated critical illness. Full article

Aflatoxin M1 (AFM1), a hydroxylated metabolite of aflatoxin B1, is a persistent food safety hazard in the dairy production chain. This study investigated AFM1 occurrence in fermented dairy products collected from the Croatian market in spring 2025 and assessed associated dietary exposure risks. A total of 81 samples were analyzed using ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) following immunoaffinity column clean-up. AFM1 was detected in 48.1% of samples, with a mean concentration of 0.015 µg/kg. Products with thermophilic and probiotic bacterial cultures showed the lowest incidence rates, at 33.3% and 40.0%, respectively. Significantly higher AFM1 occurrence was found in Croatian samples than in imported ones (p < 0.05). Exposure assessment, based on estimated daily intake (EDI), hazard index (HI), and margin of exposure (MOE), identified toddlers and children as the most at-risk groups, with EDI ranging from 0.21 to 0.93 ng/kg bw/day, depending on AFM1 concentration. HI exceeded 1 even at mean AFM1 levels, while MOE fell below the safety threshold of 10,000 in worst-case scenarios, indicating potential health concerns. These findings underscore the need for continuous monitoring and targeted risk mitigation strategies for vulnerable populations, and support expanding regulatory limits to include processed dairy products. Full article

Background: Appendiceal neoplasms are rare, but recent data indicate a rising trend, particularly in patients under the age of 50. These tumours are often diagnosed incidentally during histopathological examination. This study has aimed to examine the incidence and histological subtypes of appendiceal neoplasms in a Southern Hungarian population. Methods: Our study included neoplastic appendix specimens processed at the University of Szeged between 2014 and 2023. Results: Neoplasms were identified in 71 cases from 3640 appendectomies (1.9%). Benign lesions were present in 37% of cases (n = 26), with the most common subtype being the sessile serrated lesion (n = 20). Mucinous and malignant neoplasms were found in 63% of cases (n = 45), most frequently low-grade appendiceal mucinous neoplasm (n = 19), followed by neuroendocrine tumour (n = 17). Notably, colorectal neoplasm was identified in 50% of benign, and 42.2% of mucinous and malignant cases during a mean follow-up of 33.4 months. Significant associations were found between histological subtype and age (p = 0.022), complete resection (p = 0.012), presence of vascular invasion (p = 0.007), and localisation of potentially associated colorectal carcinoma (p = 0.018). Additionally, tumour dignity showed significant correlations with tumour, node, metastasis (TNM) stage (p < 0.001), vascular invasion (p = 0.017), and lastly, occurrence (p = 0.031) and localisation (p = 0.003) of associated colorectal carcinoma. Conclusions: The prevalence and characteristics observed in this Southern Hungarian population were consistent with international data, although raw case numbers suggested an upward trend. The high rate of associated colorectal neoplasms underscores the importance of thorough pathological evaluation and long-term surveillance. Full article

Objective: To evaluate the clinical and biochemical differences between pediatric patients with suspected foreign body aspiration (FBA) who had foreign bodies detected on bronchoscopy and those who did not. Methods: Patients undergoing bronchoscopy for suspected FBA were retrospectively divided into two groups: Group 1 (n = 59), with confirmed foreign body; Group 2 (n = 50), without foreign body. Age, blood gas parameters (pCO₂, pO₂, SpO₂), and type and localization of foreign bodies were recorded and statistically compared. Results: The mean age was significantly lower in Group 1 (24.63 ± 12.32 months) than in Group 2 (37.12 ± 32.98 months; p = 0.014). Group 1 had significantly higher pCO₂ levels (41.24 ± 13.37 mmHg vs. 31.53 ± 6.44 mmHg; p < 0.001) and lower pO₂ levels (45.78 ± 12.18 mmHg vs. 53.98 ± 13.24 mmHg; p = 0.001). Oxygen saturation values showed no significant difference between groups (p = 0.19). Among confirmed cases, foreign bodies were located in the right bronchial system (56%), left bronchial system (41%), and trachea (3.4%). Conclusions: Children diagnosed with FBA were younger and exhibited greater abnormalities in blood gas parameters compared to those without FBA. While bronchoscopy remains essential for the definitive diagnosis and treatment of suspected FBA, our findings suggest that these results may play a significant role in reducing unnecessary bronchoscopies. Full article

Background/Objectives: Reconstructive urology is critically underrepresented in global surgery initiatives, despite its essential role in managing congenital and acquired urogenital conditions. In response, a multinational Global Surgery Collaborative was launched in 2022 by a faculty from the University of Toronto, aiming to enhance reconstructive urology capacity in the Philippines, among other low- to low-middle-income countries through longitudinal mentorship and skills transfer. This report presents early experience from 2022 to 2024. Methods: This collaboration delivered annual in-person surgical missions from 2022 to 2024 at two major Philippine healthcare institutions. Training focused on pediatric and adult reconstructive urologic procedures. Local mentees participated in structured preoperative planning, intraoperative teaching, and postoperative debriefing. We conducted a prospective service evaluation comprising a prospective registry of consecutive cases and paired pre/post trainee surveys. Data were collected on patient demographics and surgical metrics. Primary clinical endpoints included operative time, length of stay, and complications (Clavien–Dindo), with standardized follow-up windows. Mentee educational outcomes were assessed through pre- and post-training trainee-reported (Likert) measures, evaluating comfort and technical understanding. Statistical analysis used the Wilcoxon signed-rank test to assess changes. Results: Over three years, 33 surgical cases were performed with 45 surgical resident mentees (Post-graduate year (PGY)4–PGY6) engaged. The median patient age was 23 (inter-quartile range [IQR] 12.5–41.5) years, with 33.3% pediatric and 84.8% of cases classified as major. The complication rate was 15.1%, with only one major event (3%). Across 45 mentees, comfort increased from a median 4.0 (IQR 2.5–5.0) to 7.0 (5.5–8.0) and technique understanding from 5.0 (4.0–6.5) to 9.0 (8.0–10.0), with large Wilcoxon effects (r = 0.877 and r = 0.875; both p < 0.001). Year-by-year analyses showed the same pattern with large effects. Conclusions: In this early three-year experience (33 cases, 84.8% major), this multi-institutional collaboration longitudinal mentorship model was feasible and safe, and was associated with significant trainee-reported improvements in comfort and technical understanding. This demonstrates a replicable model for global surgery in reconstructive urology, successfully enhancing surgical skills and fostering sustainable capacity in low- and middle-income countries (LMIC) settings. Full article

Background/Objectives: Krabbe disease (KD) is a hereditary lysosomal disorder whose hallmark is progressive demyelination, with variable involvement of the central nervous system. It is caused by pathogenic variants in the GALC gene that disrupt the function of its gene product, the lysosomal enzyme galactosylceramidase. We analyzed two unrelated cases (one early infantile and one adult) with a clinical suspicion of KD. Methods: We used a combination of biochemical techniques (high-performance liquid chromatography–tandem mass spectrometry), NGS (resequencing gene panels), splicing assays, and molecular modeling to identify and analyze the pathogenicity of the variants underlying the disorder. Results: The two probands were compound heterozygotes for disease-causing variants in the GALC gene, encoding the lysosomal hydrolase galactosylceramidase. Three of the variants were novel and caused aberrant splicing, either by exon skipping (c.908+5G>A and c.1034-1G>C) or by inclusion of a cryptic, deep intronic pseudoexon (c.621+772G>C). The fourth variant was a known missense change (c.956A>G, p.(Tyr319Cys)) with conflicting interpretations of pathogenicity in the databases. Conclusions: We demonstrated the pathogenicity of the three novel splicing variants, all with strong impact on galactosylceramidase function. We also concluded that the c.956A>G missense variant is a hypomorph usually underlying the later-onset, milder phenotypes of KD. Our results stress the importance of integrated approaches combining clinical, biochemical, and genetic testing to obtain a definitive diagnosis of lysosomal diseases. Full article

In the context of healthy and sustainable alternatives to fishmeal, insect meal asserts itself as a potentially healthy ingredient in aquafeeds. The aim of this study was to determine the possibility of successfully replacing fishmeal with Hermetia illucens larvae meal in the diet of the hetero-clarias hybrid, and to improve the overall bioavailability of the meal by supplementation with an enzyme complex (Hostazyme X). There were eight treatments: 0, 40, 50, and 60% replacement of fishmeal with larvae meal in the diet, with and without the enzyme supplement. In total, 240 fish with a mean weight of 11.43 ± 0.32 g were employed in the treatments for 80 days. Growth parameters (specific growth rate, feed conversion ratio, daily feed intake, daily weight gain, percentage weight gain, survival rate, production index, metabolic grow rate), hematological parameters and blood serum biochemistry were determined and analyzed. There was an improvement (p < 0.05) in most growth parameters for fish fed experimental diets. Blood parameters, although significantly different (p < 0.05) in some cases, were within a normal range for fish physiology. Thus, the partial replacement (40%) of fishmeal with larvae meal and supplementation with an enzyme complex produced the best growth performance compared to other treatments and controls. Full article

This study was designed to assess the effectiveness of neonatal congenital adrenal hyperplasia (CAH) screening in Guangzhou, China. A total of 818,417 newborns were screened for CAH by measuring 17-hydroxyprogesterone (17-OHP) concentrations. Cut-off values were stratified based on gestational age (GA) and the timing of sample collection. Neonates with initial positive results (17-OHP ≥ cut-off value) were recalled for a second dried blood spot sample to reassess 17-OHP levels. Confirmatory testing involved biochemical analyses, Sanger sequencing, and multiplex ligation-dependent probe amplification of the CYP21A2 gene. From 2018 to 2024, a total of 40 patients with classical 21-hydroxylase deficiency were identified, including 28 cases (70%) of the salt-wasting form and 12 cases (30%) of the simple virilizing form. The overall incidence of CAH was 1 in 20,653 (95% confidence interval: 1:34,928, 1:14,661). No statistically significant differences in prevalence were observed between sexes or between preterm and full-term infants (p > 0.05). 17-OHP concentrations are influenced by GA and the timing of sample collection. The screening efficiency for CAH could be improved by adopting a multitiered cut-off value system adjusted for GA and collection time. Full article

Background: The uterocervical angle (UCA) is a promising ultrasound parameter for predicting preterm birth. Transvaginal ultrasound (TVUS) is the gold standard for cervical assessment; however, some patients may decline the procedure due to discomfort or embarrassment. Although transperineal ultrasound (TPUS) offers an alternative associated with less discomfort, comparative data on UCA measurements between these two methods are limited. Objective: We aimed to evaluate the consistency and agreement between UCA measurements obtained using TVUS and TPUS in pregnant women between 24 and 34 weeks of gestation. Methods: In this prospective cross-sectional study, UCA and CL measurements of 189 pregnant women between 24 and 34 weeks of gestation were performed using TVUS and TPUS by a single specialist. Of these, 25 women (13.2%) were excluded due to inadequate TPUS image quality. A total of 164 women were included in the statistical analysis. Pearson correlation analysis, intraclass correlation coefficient (ICC), Lin’s concordance correlation coefficient (CCC), and Bland–Altman analysis were performed. Results: UCA measurements showed a high positive correlation between TVUS and TPUS (r = 0.833, p < 0.001). The ICC was 0.827 (95% CI: 0.77–0.87), indicating good consistency, and the CCC was 0.81 (95% CI: 0.76–0.86). The Bland–Altman analysis demonstrated a median difference of 3° between UCA measurements obtained via TVUS and TPUS. The non-parametric limits of agreement, represented by the 2.5th and 97.5th percentiles, ranged from −20.9° to 34.8°. Conclusions: TPUS shows insufficient agreement to be used interchangeably with TVUS for UCA measurement. Although the level of consistency is high, inadequate image quality in a subset of cases and the uncertainty regarding the clinical utility of TPUS-derived measurements for predicting preterm birth limit its current clinical applicability. Full article

We present the case of a Vipera ammodytes ammodytes (Vaa, nose-horned viper)-bitten patient with recurrent thrombocytopenia. A 53-year-old patient envenomated by Vaa experienced three episodes of venom-dependent thrombocytopenia (4, 57 and 11 × 10⁹/L), all of which we managed with antivenom Fab fragments. Despite these three severe episodes of thrombocytopenia within 24 h, platelet function remained intact, as demonstrated by normal thromboelastometry and aggregometry (96, 126, and 150 U) results after antivenom was administered and the platelet count normalized. Furthermore, flow cytometry showed only 0.3–1.7% expression of P-selectin on platelets, indicating that platelets did not activate but remained functional during and after thrombocytopenia. We assessed platelet function using rotational thromboelastometry, which evaluates the overall kinetics of hemostasis, including clot formation and stability. We performed aggregometry, which also reflects platelet function, only when the platelet count was within the normal range. Flow cytometry quantified P-selectin expression as a key marker of platelet activation. This case demonstrates that a component of Vaa venom can repeatedly induce venom-dependent thrombocytopenia, which is reversible by intervention, while platelet function remains intact. Full article

Background/Objectives: Human papillomavirus (HPV) is one of the most common sexually transmitted infections, yet its role in female infertility remains uncertain. This study aimed to compare HPV prevalence and genotype distribution between infertile and fertile women and to evaluate demographic and clinical factors, together with HPV vaccine coverage, in both groups. Methods: Cervical samples from 200 infertile and 200 fertile women aged 18–45 years were analyzed for 28 HPV genotypes using multiplex real-time polymerase chain reaction (PCR). Results: HPV DNA was detected in 13.5% (27/200) of infertile women and 18.0% (36/200) of fertile women (p = 0.272). The most frequent genotypes were HPV-82 (5/200, 2.5%) and HPV-16 (5/200, 2.5%) in infertile women, and HPV-45 (8/200, 4.0%) and HPV-16 (7/200, 3.5%) in fertile women. Single HPV infections were more common in infertile women (81.5%, 22/27) than in fertile women (63.9%, 23/36). HPV positivity was not associated with reproductive, clinical, or lifestyle factors, and age-stratified analyses revealed no statistically significant differences (all p > 0.05). Among women aged 30–45 years, atypical squamous cells of undetermined significance (ASC-US) cytology was identified in eight infertile women, all of whom were HPV-negative, whereas one of nine fertile women with ASC-US was HPV-positive. No low-grade squamous intraepithelial lesion (LSIL) cases were detected in the infertile group. The 9-valent HPV vaccine covered 56.2% (18/32) of genotypes detected in infertile women and 45.1% (23/51) of those detected in fertile women. Conclusions: In this study, no significant differences were observed between the groups in terms of HPV prevalence, genotype distribution, or cytology findings. These results suggest that HPV is not an independent risk factor for infertility and highlight the need for further studies focusing on genotype-specific patterns, viral persistence, and biological mechanisms that may influence reproductive outcomes. Full article

Background: Cervical cancer remains a major global health challenge, ranking fourth among malignancies in women, with an estimated 660,000 new cases and 350,000 deaths in 2022. Despite advances in vaccination and screening, incidence and mortality remain disproportionately high in low- and middle-income countries. The disease is strongly linked to persistent infection with high-risk human papillomavirus (HPV) types, predominantly HPV 16 and 18, whose E6 and E7 oncoproteins drive cervical intraepithelial neoplasia (CIN) and invasive cancer. This review summarizes current evidence on clinically relevant biomarkers in HPV-associated CIN and cervical cancer, emphasizing their role in screening, risk stratification, and disease management. Methods: We analyzed the recent literature focusing on validated and emerging biomarkers with potential clinical applications in HPV-related cervical disease. Results: Biomarkers are essential tools for improving early detection, assessment of progression risk, and personalized management. Established markers such as p16 immunostaining, p16/Ki-67 dual staining, and HPV E6/E7 mRNA assays increase diagnostic accuracy and reduce overtreatment. Prognostic indicators, including squamous cell carcinoma antigen (SCC-Ag) and telomerase activity, provide information on tumor burden and recurrence risk. Novel approaches—such as DNA methylation panels, HPV viral load quantification, ncRNAs, and cervico-vaginal microbiota profiling—show promise in refining risk assessment and supporting non-invasive follow-up strategies. Conclusions: The integration of validated biomarkers into clinical practice facilitates more effective triage, individualized treatment decisions, and optimal use of healthcare resources. Emerging biomarkers, once validated, could further improve precision in predicting lesion outcomes, ultimately reducing the global burden of cervical cancer and improving survival. Full article