Heliyon

Objective: Hyperthyroidism and hypothyroidism related to iodine deficiency are major public health concerns in Afghanistan. This study aimed to assess the frequency of thyroid dysfunction among male patients referred for thyroid testing and its association with age, and to examine monthly trends in thyroid dysfunction at Asia Med Laboratory in Herat, Afghanistan, from July 2021 to January 2022. Methods: A retrospective analysis was conducted on 250 male patients aged 0-69 years. We measured Serum TSH, total T4, and total T3 levels, and thyroid status was classified using age specific reference ranges. In addition, the frequency of thyroid dysfunction was analyzed across age groups with monthly trends of thyroid state. Results: Overall, the euthyroid state consisted of 69.2% of participants, 24.8% with overt hypothyroidism, 3.2% with overt hyperthyroidism, and 2.8% with subclinical hyperthyroidism. Thyroid status differed significantly by age (p = 0.0135), with hypothyroidism increasing in older age groups and reaching its highest proportion among men aged 60-69 years (55.6%). Euthyroidism predominated in patients aged 10-39 years, while hyperthyroidism across age groups remained relatively infrequent. After September 2021, a threefold increase was observed in the total number of male patients referred for thyroid testing. During this period, the proportion of hyperthyroidism increased slightly, whereas hypothyroidism cases declined. Conclusion: In conclusion, hypothyroidism was more frequent with older age. The rise in absolute case numbers after September 2021 likely reflects increased patient referrals, underscoring the need for ongoing monitoring of thyroid function. The study may assist in the early management of thyroid disorders and in reducing their complications.

Bangladesh's agricultural sector remains heavily dependent on pesticides and chemical inputs, yet limited attention has been paid to how farmers' knowledge of occupational health and environmental sustainability translates into actual practice across the full agricultural value chain. This study aimed to assess the knowledge and practices of farmers in Pabna District, Bangladesh, regarding occupational health, pesticide handling, environmentally sustainable farming, and market sanitation. A cross-sectional survey was conducted among 301 farmers in 2024 using a structured questionnaire covering socio-demographic characteristics, sustainable farming knowledge and adoption, soil testing and organic farming practices, pesticide handling and occupational health and safety behaviours, post-harvest waste management, and market sanitation conditions. Data were analysed using descriptive statistics. The majority of respondents were male (87.04%) and had no formal education (63.46%). Although most farmers reported knowledge of environmentally sustainable farming practices (97.70%) and pesticide label instructions (98.00%), corresponding safety practices were poor: only 10.63% reported wearing any personal protective equipment and 1.33% reported using a mask during pesticide application. Eye irritation was the most commonly self-reported health symptom following pesticide exposure (92.69%). Market sanitation infrastructure was similarly inadequate, with 89.00% of respondents reporting an absence of sanitary toilets. These findings indicate a consistent gap between farmers' knowledge and their actual practices across multiple domains of the agri-food system. Strengthening extension services, delivering practical hands-on occupational safety training, and investing in market sanitation infrastructure are recommended to close this gap and support safer, more sustainable farming practices in Bangladesh.

Introduction: Acute gastroenteritis (AGE) is a global public health problem and a major cause of mortality in low- and lower-middle-income countries. Human bocavirus (HBoV) is among the viral agents associated with this condition. Therefore, investigating the presence of HBoV in cases of AGE in Salvador, Bahia, as well as its prevalence and circulating strains, is important. Objective: To investigate the occurrence of HBoV infection during an AGE outbreak in Salvador. Methods: A total of 178 samples were analyzed for HBoV using nested polymerase chain reaction (nested PCR), and the amplification products were visualized by agarose gel electrophoresis. HBoV was detected in 5.7% of the samples analyzed. Conclusion: This study contributes to the understanding of HBoV epidemiology as a secondary agent associated with acute gastroenteritis during a norovirus outbreak in Salvador. Continued investigation and identification of the etiological agents involved in outbreaks are essential for evaluating the causes of AGE. These findings also highlight the need for broader diagnostic approaches and the importance of phylogenetic analysis for monitoring and controlling viral infections.

Introduction: Lichen sclerosus (LS) is a chronic inflammatory dermatosis predominantly affecting the anogenital region of both women and men. Sexual dysfunction remains among the most debilitating and overlooked consequences of the disease, as available patient-reported outcome measures are either restricted to one sex or capture sexual health only partially. The aim of the present work is to validate the Qualisex questionnaire (in its the Italian version) in patients with LS and to evaluate its psychometric properties, factor structure, convergent, discriminant validity, and sex symmetry. Methods: A cross-sectional study was conducted on 211 patients (167 women, 44 men; mean age 52.9 years) with a confirmed diagnosis of LS. Participants completed the Italian Qualisex, Skindex-29, DASS-21, and sexual-health-specific scales, the Female Sexual Function Index (FSFI) for women, and the International Index of Erectile Function (IIEF) for men. Construct validity was assessed via Principal Component Analysis (PCA), and reliability via Cronbach's alpha. Convergent and discriminant validities were evaluated against standard psychometric batteries. Results: Item 2 was removed due to low communality (0.167). PCA on the remaining 9 items revealed a two-factor structure accounting for 72.5% of total variance: Component 1 (Sexual Functioning and Satisfaction, 59.89%) and Component 2 (Partner Devaluation, 12.66%). Internal consistency was high (alpha= 0.911 overall; alpha= 0.841 in women; alpha= 0.899 in men). Qualisex scores correlated strongly with Skindex-29 Social Functioning (r = 0.582) and Emotions (r = 0.531) subscales, as well as FSFI (r = -0.391) and IIEF (alpha= -0.566). Discriminant validity was supported by low-to-moderate correlations with DASS-21 domains (r < 0.38). While FSFI and IIEF showed significant negative correlations with age (p = 0.002), Qualisex remained age-independent across sexes (p > 0.05). Conclusion. The 9-item Italian Qualisex is a reliable, sex-symmetrical, and age-independent patient-reported outcome measure for assessing sexual health impairment in LS, successfully isolating disease-specific distress from physiological aging and general distress.

Abstract Background: Large language models (LLMs) are increasingly explored as adjunct tools in graduate medical education, but their reliability for answering discipline-specific certification examinations remains incompletely characterized. In dentistry in China, the national dental examination serves as a milestone for stomatology trainees. Prior studies predominantly rely on single metric, limiting reproducibility and granularity. Objective: To systematically evaluate the performance of five LLMs in answering the national standardized training examination for dental residents. Method: A total of 1,318 questions covering the six dentistry disciplines were selected. Five LLMs (DeepSeek-V3, DeepSeek-R1, Qwen3-32B, Claude 3.5, and GPT-4o) were evaluated via a single-response protocol on the Dify-based Chatflow framework. Performance combined human verification with automated scoring using the Retrieval-Augmented Generation Systems (RAGAS) framework across seven dimensions. Tasks involving question classification, key-point categorization, and instructional requirement summarization were designed to enable a horizontal comparison of models' cognitive capabilities, assessed using inter-model consistency scores. Results: DeepSeek-R1 achieved the highest correct choice rate (80.90%, p < 0.001) and answer correctness score (0.853, p < 0.001), significantly outperforming the others. All models exhibited limitations, including information insufficiency, redundancy, and hallucination-related issues (lowest 44.20% in DeepSeek-R1). In classification and summarization tasks, Claude 3.5 showed higher consistency scores (186/181) than Qwen3-32B (152/151). Conclusion: Evaluated LLMs demonstrated good performance on dental examination questions and in executing tasks. DeepSeek-R1 consistently outperformed the others. While LLMs showed potential as supportive tools in dental education, further refinement and validation are needed before formal adoption in graduate medical educational and clinical training settings.

Predicting implantation outcomes in vitro fertilization (IVF) is challenging because clinically relevant information becomes available at different points during treatment. In this study, we developed a stage-aware, leakage-conscious, and explainable machine-learning framework to predict implantation using a public IVF dataset. {beta}-HCG was excluded to avoid potential downstream target leakage. The data were divided into training, validation, and independent test sets. Several machine-learning models, including Logistic Regression, Random Forest (RF), Extra Trees, XGBoost, and Hist Gradient Boosting, were optimized using stratified cross-validation. A fixed RF model was then evaluated at three stages of the IVF process, using baseline couple characteristics, gamete and fertilization variables, and embryological variables, respectively. Model performance improved as additional treatment-related information became available, with the largest improvement observed after the inclusion of embryological variables. The final RF model showed good predictive performance on the independent test set. The number of embryos was consistently identified as the most important predictor across RF, permutation, and SHAP analyses. Overall, the findings suggest that IVF implantation prediction becomes more accurate as later-stage treatment information is incorporated, particularly information related to embryological characteristics. The proposed approach also provides interpretable predictions while reducing the risk of information leakage. Further evaluation using independent clinical datasets is needed before the framework can be considered for clinical use.

Introduction: Acute gastroenteritis (AGE) is a cause of childhood morbidity and may be associated with human adenovirus (HAdV) infection. This study aimed to investigate the occurrence of HAdV in fecal samples from children with AGE in Salvador, Bahia, Brazil, as well as to molecularly characterize the identified strains and evaluate their cytopathic effects in cell culture. Methods: A total of 131 samples were analyzed using the nested polymerase chain reaction (Nested-PCR) technique. Molecular characterization was performed through Sanger sequencing and phylogenetic analysis, while Vero cell cultures were used to investigate the occurrence of cytopathic effects. Results: Of the samples analyzed, 13 (9.9%) tested positive for HAdV, while 118 (90.1%) were negative. The highest detection frequency was observed in children aged three years or younger, particularly those under one year of age. Phylogenetic analysis identified variants related to HAdV-F41 and HAdV-B3, revealing genetic differences and distinct clustering patterns compared with reference sequences. In cell culture, cytopathic effects were observed four days after inoculation, although further analyses are required to confirm productive viral replication. Conclusion: These findings demonstrate the presence of HAdV in the samples studied and contribute to understanding its genetic diversity and circulation in Salvador, highlighting the importance of epidemiological surveillance and further studies on its role in the etiology of childhood AGE.

Introduction: Thyroid diseases are major health problems and among the most common endocrine disorders worldwide, including in Ethiopia. They are characterized by alterations in hormone secretion, enlargement of the thyroid gland, or both. Fine needle aspiration cytology is an important initial screening tool, and histopathologic examination is essential for the definitive diagnosis of thyroid disease. This study aimed to compare the diagnostic accuracy of fine needle aspiration cytology with histopathology in identifying thyroid diseases. Methods: A cross-sectional study was conducted at three health facilities in Hawassa City, Ethiopia, involving 304 patients who underwent both thyroid fine needle aspiration cytology and histopathologic examination of the same site between 30th October 2024 and 29th October 2025. FNAC results were classified using the Bethesda system, with histopathology as the gold standard. Data were entered into Kobo Toolbox, exported to SPSS version 27, and analyzed using cross-tabulation and chi-square ({chi}{superscript 2}) tests to determine diagnostic accuracy. Result: 304 patient records were included in the study. The fine needle aspiration cytology was determinate/diagnostic in 81.6% of cases. The study revealed the sensitivity and specificity of fine needle aspiration cytology to be 88.2% (CI 77.6-95.1%) and 94.4% (CI 90.6-97.1%), respectively. The false negative and false positive rates in this study were 2.4% and 4.4%, respectively. The positive predictive value was 80.3% (CI 68.7-89.3%), and the negative predictive value was 96.8% (CI 93.8-98.7%). The accuracy of fine needle aspiration cytology in differentiating benign from malignant thyroid lesions was 93.1%. Conclusion: FNAC demonstrated strong agreement with histopathology and remains a reliable, cost-effective first-line diagnostic tool for thyroid disease, particularly in resource-limited settings. Strengthening sample handling, ultrasound guidance, and adherence to Bethesda criteria may further improve diagnostic precision

Background. Lead crosses the placenta and harms the developing brain, and no safe level is known. Bangladesh lacks national estimates of lead exposure in pregnancy. Objectives. We estimated blood lead in pregnant women nationally, described where and in whom it was raised, and examined links with child lead and haemoglobin. Methods. In the Bangladesh Multiple Indicator Cluster Survey 2025, 1,932 of 2,711 eligible pregnant women (71%) had valid venous blood results. Survey-weighted modified Poisson models estimated prevalence ratios (PR) for blood lead of 3.5 microgram/dL or more, an analytical cut-off. We also studied 540 households with a tested child aged 12 to 59 months. Results. Among tested women, geometric mean blood lead was 2.05 microgram/dL (95% CI 1.99 to 2.12). In all, 17.7% (15.7 to 19.9) had 3.5 microgram/dL or more and 7.6% (6.1 to 9.3) had 5 microgram/dL or more. Greater Dhaka, defined after inspecting district estimates, held 12% of pregnant women but 64% (54 to 73) of those at 5 microgram/dL or more. The richest quintile had a crude PR of 3.06 (2.02 to 4.63, P<0.001), attenuated to 1.09 (0.72 to 1.67, P=0.678) after adjustment for place. No clear association was seen with cosmetics, indoor smoking or nearby battery sites. A woman's lead of 3.5 microgram/dL or more was associated with child lead of 5 microgram/dL or more (adjusted PR 1.50, 1.16 to 1.96, P=0.002). This cut-off identified only 23% (16 to 30) of them. Conclusions. Raised blood lead in pregnancy varied sharply by place and was highest in greater Dhaka. The crude wealth association was markedly attenuated after adjustment for place. Maternal lead was linked with child lead, but most exposed children lived with women below the cut-off. These findings support source investigation in greater Dhaka and evaluation of targeted lead assessment for women and children.

Preeclampsia is a multisystem hypertensive disorder of pregnancy that emerges after 20 weeks of gestation, and remains a leading cause of maternal and perinatal morbidity and mortality globally, yet evidence on its predictors and outcomes in Kenya remains limited. This prospective cohort study compared pregnant women with and without preeclampsia who attended selected hospitals in Kiambu County, to determine the predictors of preeclampsia and its associated maternal and neonatal outcomes. The results indicated a very strong statistical association between preeclampsia and the following i.e parity, time taken to reach the hospital, hypertension and diabetes mellitus (p-value <0.001) and religion (p-value <0.013). Women with preeclampsia had nearly twice the risk and six times the odds of delivering low-birth-weight infants compared with women without preeclampsia (RR = 1.97; OR = 6.25). A strong statistically significant association was observed between multiparity and prematurity (RR = 5.3, OR = 8.4, p < 0.001). Multiparous women with preeclampsia had approximately 5.3 times the risk and 8.4 times the odds of experiencing a premature birth compared with women without preeclampsia. In conclusion preeclampsia significantly increased adverse maternal and neonatal outcomes, highlighting the need for early high-risk pregnancies identification and strengthened antenatal care to improve both maternal and neonatal outcomes.

BACKGROUND: Zinc inhibits energy production, growth, and proliferation in normal prostate cells while suppressing the malignant potential and angiogenesis that are essential to prostate cancer aggressiveness. The study aimed to determine the correlation of serum zinc with Gleason score as a marker for prostate cancer aggressiveness METHODOLOGY: We conducted a hospital-based cross-sectional analytical study carried out on forty-two (42) eligible participants with newly diagnosed histologically confirmed prostate adenocarcinoma over one year. Spearman's rank correlation was used to assess the relationship between serum zinc and prostate cancer aggressiveness as measured by the Gleason score. The impact of serum zinc level on the aggressiveness of severe prostate cancer was assessed using a binary regression model, adjusting for age as a confounder in the logistic regression model. A statistically significant P value was set at 0.05. RESULTS: The mean age of participants was 67.12 years, with a range of 45- 90 years. High-grade disease (Gleason 8) was the most common, representing 57.1% of patients. The median serum zinc concentration was 71.5 microgram/dL (IQ: 47.6 to 88.5 microgram/dL). Serum zinc and Gleason score showed a statistically significant inverse correlation (Spearman r = -0.514, p < 0.001). Reduced zinc levels were significantly associated with higher Gleason scores (MannWhitney; 140.0, p = 0.002). Low serum zinc independently predicted high-grade disease after adjusting for age. CONCLUSION: This study found a statistically significant inverse correlation between serum zinc concentrations and Gleason score in men with prostate cancer. This finding indicates that reduced serum zinc levels are associated with higher Gleason scores

Background: Neuroanatomy poses a significant challenge for Psychology students due to its spatial and conceptual complexity. Educational approaches that enhance the relevance and visualization of neuroanatomical content may improve students learning experiences. This study implemented a tractography-based activity focused on the virtual dissection of the arcuate fasciculus, a major white matter pathway, in undergraduate Psychology students and examined the relationships between perceived learning and students perceptions of utility, difficulty and handling, and organizational aspects of the activity. Methods: First-year undergraduate Psychology students participated in a two-session tractography-based activity combining instruction on white matter anatomy and diffusion tractography with a hands-on virtual dissection of the arcuate fasciculus using research-grade software routinely employed in neuroscience research. Following the activity, students completed an anonymous questionnaire assessing perceived learning, utility, difficulty and handling, and organizational aspects of the activity. Pearson correlations, multiple regression analyses, and relative importance analyses were performed. Results: Sixty-eight students completed the questionnaire. Students reported generally positive perceptions of the activity across the evaluated dimensions, with perceived learning receiving the highest mean score (M = 3.44, SD = .85). Perceived utility showed the strongest association with perceived learning (r = .64, p < .001). The regression model explained 41% of the variance in perceived learning (R2 = .41, adjusted R2 = .38, p < .001). Perceived utility was the only significant predictor in the model ({beta} = .59, p = .001), accounting for 67.9% of the explained variance. Conclusions: The findings support the feasibility of integrating authentic neuroimaging tools into undergraduate neuroanatomy teaching. Students who perceived the activity as more useful also reported higher perceived learning outcomes, with perceived utility emerging as the strongest predictor of perceived learning. In contrast, perceived difficulty and handling, and organizational aspects did not make significant independent contributions. These results suggest that students perceptions of educational relevance may play an important role in technology-enhanced STEM learning experiences.

Abstract Background: Cyprus has transitioned into a high-alert zone for mosquito-borne viruses. This necessitates a proactive assessment of its future physicians. Following the 2022 re-establishment of Aedes aegypti in Larnaca and Aedes albopictus in Limassol, Cyprus, the island is now biologically primed for local outbreaks of dengue, Zika, and chikungunya, alongside Culex-borne West Nile virus. The study assessed medical students' knowledge and risk perception. Methods: A cross-sectional online survey administered the validated MosquitoWise Health Belief Model instrument to undergraduate-entry and graduate-entry students at a university in Cyprus in mid-2026. Results: Of 1023 students, 119 responded (11.6%), with pre-clinical students overrepresented (p<0.001). Mean knowledge was 5.43/9, stronger on mosquito biology (72.5%) than virus knowledge (54.2%). Median severity was 6.00/7 against susceptibility 4.25/7. Knowledge differed by study stage (p<0.001), correlated with severity (rs = 0.399) but not susceptibility. Conclusions: The study establishes a critical baseline for pre-clinical medical students in Cyprus. Overall, participants performed better on mosquito biology when compared to mosquito-borne viruses and how they spread. Our findings highlight the value of integrating theoretical microbiology with clinical practice in medical education to enhance physicians' preparedness for the changing landscape of newly emerging infections in Cyprus and across Europe as a whole. Key Words: Arboviruses, Cross-Sectional Studies, Cyprus, Health Belief Model, Medical Students, Risk Perception.

Objective: Current guidelines recommend different adjuvant treatment strategies for women with endometrioid early stage endometrial cancer exhibiting a p53 abnormal pattern. We aimed to evaluate recurrence patterns and explore the clinical implications for adjuvant therapy in this population. Materials and methods: This multicenter retrospective study included 86 patients with endometrioid, p53 abnormal, FIGO stage I, II endometrial cancer treated between 2013 and 2023 at six hospitals in the Republic of Korea. Clinicopathologic data were collected through medical record review. Progression free survival (PFS) was estimated using the Kaplan Meier method, and prognostic factors were analyzed using Cox proportional hazards regression models. Results: The 12, 24, and 36 month PFS rates were 91%, 78%, and 76%, respectively. Among the 16 patients who experienced recurrence, 12 (75%) had distant metastases. Adjuvant chemotherapy showed a trend toward improved PFS compared with adjuvant radiation therapy with or without chemotherapy (p=0.10). In multivariable analysis, the p53 overexpression pattern was independently associated with worse PFS compared with the p53 null pattern (HR 8.59, 95% CI 1.61 to 45.79, p=0.01). Conclusion: Given the poor PFS, the predominance of distant recurrence and the observed trend toward improved PFS with chemotherapy, adjuvant chemotherapy may be considered in women with endometrioid early stage endometrial cancer exhibiting a p53 abnormal pattern. Further studies are warranted to clarify the prognostic impact of p53 abnormality subtypes.

Introduction: Hospitals face increasing financial pressures. Hospital reimbursement is tied to the Case Mix Index (CMI). The CMI is a measure of complexity of care provided by the hospital and the total reimbursement is the CMI multiplied by a base pay factor, multiplied by the total number of discharges from the hospital. The few studies in the literature have involved logistically complex attempts to improve documentation. We sought to determine whether limited, structured chart review by surgeons can improve CMI in a multihospital system. Methods: We performed a prospective, observational study in a four-hospital academic medical system on all surgical patients from 10/2022 to 7/2026. Two clinically busy trauma surgeons performed limited structured chart reviews for select surgical patients. In the limited intervention period (1/2024-9/2024) this focused only on the trauma division. In the full intervention period (10/2024-7/2026) expanded to all surgical patients across the system. The main outcome was surgical case mix index (CMI). Results: A total of 35,695 patients were included (13,811 pre-intervention, 9,337 limited intervention, 12,547 full intervention). CMI increased significantly among surgical patients across the whole system (2.68 (95%CI 2.65-2.71) to 2.87 (95%CI 2.82-2.92) to 2.97 (95%CI 2.93-3.01), ANOVA p <0.001). Overall length of stay was unchanged among surgical patients across the whole system. The estimated increase in revenue per patient attributable to this intervention was $3,912 in surgical patients across the system. Conclusion: Having trauma surgeons review targeted surgical patients for high value documentation capture significantly enhanced the CMI and estimated revenue of surgical services across a multi-hospital integrated health system. Such documentation reviews may represent a practical method to improve hospital documentation and revenue.

Gamete donation may widen access to assisted reproductive technology, but donor gametes remain difficult to obtain in Ghana. This institution-based cross-sectional survey assessed knowledge, attitudes and willingness to donate among 380 undergraduate students at Ho Technical University. The sample was allocated proportionately across 24 strata defined by six faculties and four academic levels; within each stratum, students who were present during scheduled classes were recruited consecutively. Data were collected using a self-administered questionnaire and analysed using descriptive statistics, exact tests and exploratory logistic regression. Although 88.2% of participants had heard of gamete donation and 72.4% supported it, only 42.1% said they would donate if approached. Among the 220 participants who were unwilling, 210 (95.5%) selected the response that donation felt wrong to them. Participants who perceived societal attitudes as positive had higher odds of reported willingness than those who perceived them as negative (adjusted odds ratio [aOR] 3.08, 95% confidence interval [CI] 1.34-7.08). Belief that donation could exhaust ones gametes was associated with lower odds of willingness (aOR 0.27, 95% CI 0.15-0.48). The conditional statement that payment would increase willingness was also associated with direct willingness (aOR 7.16, 95% CI 4.25-12.06), but the two measures overlapped conceptually. The findings identify fertility misconceptions, concerns about donation and differing views on compensation that should be considered when developing donor information, counselling and protection measures.

Discourse analysis can reliably predict real-world communicative success, yet is rarely implemented clinically, due to challenges in manually generating stimulus-specific main concept inventories (MCIs) and scoring patient narratives. We evaluated whether automatically derived macrolinguistic (main concept, sentiment) and microlinguistic (fluency, lexical, syntactic) features extracted from movie clip narrations can augment the clinical assessment of discourse in aphasia. The MCIs generated directly from each clip's video, audio and subtitles using a vision-language model approximated the main concepts healthy controls produced. Group classification (control: n=51; aphasia: n=54) based on the discourse features was excellent (AUC=0.95, 95% CI [0.90, 0.99]), with macrolinguistic features showing the largest group differences (main concept completeness: d=-1.84, 95% CI [-2.30, -1.38]) and strongest associations with aphasia severity (semantic distance to inventory: r=-0.79, 95% CI [-0.87, -0.66]). Findings support the feasibility and scalability of automated criterion-based discourse assessment using ecological stimuli, and highlight its potential for clinical implementation.

Kaposi's sarcoma (KS) is an angioproliferative tumor associated with infection by human herpesvirus 8 (HHV-8), also known as Kaposi's sarcoma-associated herpesvirus (KSHV). Among the viral genes involved in KS pathogenesis, the viral G protein-coupled receptor (vGPCR) plays a key role in oncogenic transformation and angiogenesis, and its sustained activity contributes to tumor development and maintenance. Quercetin (QUE), a naturally occurring flavonoid with well-recognized anticancer properties, has been shown to reduce cell viability and proliferation and to induce apoptosis in vGPCR-transformed endothelial cells. This study further investigated the mechanisms underlying the antineoplastic effects of QUE in vGPCR cells, an in vitro model of Kaposi's sarcoma. Initially, QUE promoted the activation of MAPK signaling pathways in vGPCR cells, increasing the phosphorylation levels of ERK1/2, JNK1/2, and p38, without affecting AKT phosphorylation. In parallel, QUE increased intracellular oxidant levels, followed by lipid peroxidation and DNA damage, supporting a link between oxidative imbalance and genotoxicity. However, increased total glutathione content, and unaltered Gpx4 mRNA expression, suggest the induction of oxidative stress and compensatory antioxidant responses. Furthermore, increased intracellular oxidant levels were associated with MAPK signaling activation, particularly JNK1/2, whereas ERK1/2 and p38 activation may reflect a compensatory response that is insufficient to overcome QUE-induced cytotoxicity. Taken together, these findings indicate that QUE exerts antiproliferative effects in vGPCR cells through a mechanism involving oxidative stress, MAPK activation, and DNA damage, supporting its potential relevance in the study of therapeutic strategies for virus-associated malignancies.

Background: Alpha-mannosidosis (AM) is a debilitating lysosomal storage disorder (LSD) caused by insufficient activity of alpha-mannosidase, an enzyme responsible for cleavage of alpha-linked mannose residues from N-glycan-type oligosaccharides during their degradation. As a result, specific oligosaccharides accumulate in tissues and are also detectable in body fluids. AM is a progressive multi-organ disease for which hematopoietic stem cell transplantation (HSCT) and enzyme replacement therapy (ERT) are therapeutic options, however, treatment results depend considerably on early diagnosis. Therefore, inclusion of AM into newborn screening panels would significantly contribute to improving therapeutic outcome. Methods: A rapid and fully quantitative method for the specific AM oligosaccharide biomarker Man2GlcNAc in dried blood spots (DBS) using ultra-performance liquid chromatography coupled to tandem-mass spectrometry was developed. DBS from 420 controls, 27 AM patients (including five newborn screening samples), and 35 patients with other LSDs were analyzed. Results: A distinct separation in biomarker concentrations was observed between unaffected individuals and untreated AM patients (0.1 - 0.8 vs 3.2 - 11.3 mol Man2GlcNAc/L, p<0.0001). Furthermore, Man2GlcNAc concentrations significantly differed between untreated patients and those on ERT (n = 17, p<0.0001) or after HSCT (n = 15, p<0.0001), and between both treatment groups (p<0.0001). Moreover, we demonstrated that this method is appropriate for monitoring treatment efficacy by analysis of samples from individual patients before and after initiation of therapy. We retrospectively analyzed residual samples of dried blood spots (DBS) from routine newborn screening that had been stored from patients with later-confirmed AM, which resulted in clear separation from the concentrations observed in a newborn screening control cohort (7.7 - 11.3 vs 0.1 - 0.8 mol Man2GlcNAc/L, p=0.0001). Conclusion: We present a simple and rapid method for quantitative analysis of the specific AM oligosaccharide biomarker Man2GlcNAc, which is remarkably stable compared to enzymatic assays. Thus, the method is useful for selective screening in suspected cases as well as for monitoring the response to different forms of treatment. Furthermore, Man2GlcNAc has the potential to serve as a useful biomarker for newborn screening offering the prospect of earlier treatment initiation, improved therapeutic outcome and higher quality of life for AM patients.

Background: Cervical cancer (CC), mostly associated with high-risk human papillomaviruses (hrHPV) infection, is the most common cancer that disproportionately affects women in developing countries, including Ethiopia. Early detection of CC and initiation of treatment are key to positive health outcomes. Identifying factors associated with delayed CC diagnosis is essential for effective prevention and control efforts. This study assessed the stage at diagnosis and examined associated clinical and sociodemographic factors. Methods: An institution-based cross-sectional study was conducted among 284 women newly diagnosed with CC who attended Tibebe Ghion Specialized Hospital (TGSH) between 1st January 2021 and 31st December 2022. A structured questionnaire was used to collect data on the participants' demographic, reproductive, and gynaecologic history, and clinical profiles. The CC stage at diagnosis was categorised as early (stage I-IIA) or late (stage IIB-IV). Logistic regression models (unadjusted and adjusted) were used to examine associations of sociodemographic or clinical factors with stage at CC diagnosis. Results: The mean age ({+/-}standard deviation) at presentation was 53.2 {+/-} 11.3 years, with an age range of 18 - 80 years. Most of the patients (73.6%) were from rural areas, and three-fifths (58.1%) had no medical insurance. Among participants, 74.6% (95% CI: 69.4, 79.6%) had late-stage CC. The odds of late-stage CC diagnosis were higher for women from rural areas (AOR: 2.21; 95% CI:1.18, 4.12; p<0.013), and those with anaemia (defined as <12 mg/dl haemoglobin) (AOR: 3.42; 95% CI: 1.88, 6.23; p<0.001). On the other hand, the odds of late-stage CC diagnosis were lower in HIV positive women (AOR:0.41; 95%CI:0.19, 0.88; p<0.021). Conclusion: The proportion of late-stage diagnosis among CC patients was high. Residential area, anaemia status, and HIV serostatus were factors associated with stage at CC diagnosis. These findings can inform screening efforts of CC and call for expanding of the screening services to the rural setting in order to reduce the burden of late-stage CC diagnosis.