INTRODUCTION:This systematic review and meta-analysis evaluated artificial intelligence (AI) and radiomics applied to renal ultrasound for the diagnosis, staging, and prognosis of degenerative kidney disorders. METHODS:PubMed/MEDLINE, Embase, Scopus, Web of Science, the Cochrane Library, and gray-literature sources were searched without date or language restrictions. Eligible studies applied AI or radiomics to renal ultrasound and reported diagnostic, staging, or prognostic outcomes. Risk of bias and methodological quality were assessed using the Prediction model Risk Of Bias Assessment Tool (PROBAST), Checklist for Artificial Intelligence in Medical Imaging (CLAIM 2024), and Radiomics Quality Score 2.0 (RQS 2.0). Random-effects models were used for diagnostic accuracy synthesis. RESULTS:Thirty-one studies were included. Machine-learning models achieved pooled sensitivity of 0.86 (95% confidence interval 0.82-0.90) and specificity of 0.83 (0.79-0.87); deep-learning models achieved sensitivity of 0.89 (0.84-0.93) and specificity of 0.85 (0.81-0.91). Heterogeneity was substantial and external validation was uncommon. CONCLUSIONS:AI-augmented renal ultrasound shows promising diagnostic performance, but heterogeneous populations, limited calibration, and predominantly internal validation constrain clinical generalizability. Prospective multicenter external validation is required.
Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest solid malignancies despite advances in surgery, perioperative care, and systemic therapies. Pretherapeutic radiological sarcopenia has emerged as a clinically relevant body-composition phenotype associated with poor outcomes in oncology. This imaging-based concept differs from contemporary geriatric definitions of sarcopenia, which require impaired muscle strength and incorporate low muscle quantity and/or quality. This narrative review critically examines radiological assessment, biological context, prognostic implications, artificial intelligence (AI)-enabled quantification, and interventional evidence in PDAC. A structured narrative search of PubMed/MEDLINE, Embase, and Google Scholar was conducted from database inception through July 31, 2026. Computed tomography (CT)-based skeletal muscle index remains the most widely validated imaging biomarker, although substantial heterogeneity persists in methods and diagnostic thresholds. Low muscle mass is most consistently associated with reduced survival, whereas associations with postoperative morbidity and systemic treatment toxicity are more heterogeneous. Exercise, nutritional, and multimodal cachexia interventions appear feasible and may provide functional or nutritional benefits, but evidence remains insufficient to establish a survival benefit from improving muscle status. AI-based approaches enable scalable body-composition analysis, although external validation, methodological standardization, and prospective clinical integration remain necessary. Overall, radiological sarcopenia is a promising prognostic and potentially actionable phenotype in PDAC.
INTRODUCTION:Improvement of knowledge and attitude helps to improve the prevention of breast cancer (BC). AIM:This study aimed to determine the level of knowledge of early signs and risk factors, and attitude toward BC. MATERIALS AND METHODS:This was a cross-sectional study that was conducted in Dodoma city, Tanzania among women aged ≥18 years. Mean values were used as cutoff points for adequate knowledge and positive attitude. Multivariable analysis was used to determine the predictors of knowledge and attitude. p < 0.05 was considered statistically significant. RESULTS:A total of 354 women were analyzed. Having 35-49 years was associated with increased chance of having adequate knowledge of early signs and risk factors for BC compared to having ≥50 years of age (adjusted odds ratio (AOR) = 2.11, 95% CI = 1.87-5.09, p = 0.040) and positive attitude toward BC (AOR = 2.87, 95% CI = 1.14-7.27, p = 0.040). Having secondary education had a reduced chance of having adequate knowledge compared to having a tertiary level of education (AOR = 0.84, 95% CI = 0.14-0.97, p = 0.032). CONCLUSION:This study has shown a moderately low level of adequate knowledge of early signs and risk factors for BC. Also, younger age was associated with adequate knowledge and positive attitude toward BC.
AIMS:To compare the effectiveness and safety of ultrasound-guided botulinum toxin injection at the plantar fascia origin with the two-point Babcock technique in patients with chronic plantar fasciitis. MATERIALS AND METHODS:This randomized clinical trial compared two ultrasound-guided botulinum toxin injection techniques. Pain intensity, foot function, pressure-pain threshold, and ultrasonographic plantar fascia thickness were assessed at baseline and at 6 and 24 weeks. Between-group comparisons were adjusted for baseline values, and treatment effects were reported with 95% confidence intervals. RESULTS:Sixty participants were randomized, and 53 completed follow-up. At 24 weeks, the Babcock group showed a greater improvement in Foot Function Index-Revised scores than the plantar-fascia-origin group (adjusted mean difference, -14.18; 95% CI, -20.70 to -7.66; p < 0.001). Pressure-pain threshold was also higher in the Babcock group at 6 weeks (adjusted mean difference, 4.86; 95% CI, 2.65-7.08; p < 0.001) and 24 weeks (7.97; 95% CI, 5.23-10.72; p < 0.001). No significant between-group differences were found for pain intensity at 6 weeks (p = 0.191) or 24 weeks (p = 0.529). No serious intervention-related adverse events occurred. CONCLUSIONS:Both techniques were associated with improvement. The Babcock technique may provide additional functional and pressure-pain benefits, although larger multicenter trials are needed.Clinical trial registration: www.irct.ir; registration number: IRCT20130523013442N33 Registration date: 2023-09-17, https://irct.ir/trial/72584.
AIMS:To describe a giant ulcerating fibroadenoma mimicking malignancy and highlight diagnostic uncertainty from discordant clinical, imaging, and biopsy findings. PATIENTS AND METHODS:A 22-year-old woman presented with an approximately 10 cm fungating, ulcerated right-breast mass complicated by methicillin-resistant Staphylococcus aureus infection. Multiple core biopsies showed fibroadenoma, despite rapid progression raising concern for phyllodes tumor or malignancy. Multidisciplinary review supported a staged breast-preserving approach. RESULTS:The mass was enucleated with preservation of the nipple-areolar complex. Histopathology confirmed giant fibroadenoma with multiple epidermal inclusion cysts, cyst rupture, keratin-associated inflammation, and a foreign-body giant-cell reaction. Earlier biopsy material showed an epidermal component before clinical deterioration. Biopsy-related disruption of this preexisting component, together with inflammation, infection, cyst rupture, and wound breakdown, was considered a possible contributor to the fungating presentation; the exact sequence was uncertain. Histology showed focal superficial-margin involvement at the ulcerated/fungating surface. At six months, there was no clinical or ultrasonographic evidence of recurrence. CONCLUSIONS:Giant fibroadenomas may mimic phyllodes tumor or breast malignancy. Clinicoradiological-pathological correlation and multidisciplinary planning can support breast-preserving management despite an alarming presentation when tissue diagnosis remains benign.
BACKGROUND:Dementia incidence is rising globally with population aging and improved survival from chronic diseases. Cancer incidence may reflect longevity, diagnostic capacity, socioeconomic development, and demographic transition, but sex-specific population-level evidence on its association with dementia incidence remains limited. METHODS:Country-level associations between cancer incidence in 2019 and dementia incidence in 2023 were examined separately for females and males across 204 countries. Analyses included bivariate correlations, principal component analysis, partial correlations, and forced-entry regression models adjusted for gross domestic product per capita adjusted for purchasing power parity, urbanization, reduced selection opportunity, and sex-specific life expectancy at age 60. RESULTS:Cancer incidence was positively associated with dementia incidence in both sexes. Globally, cancer incidence correlated strongly with dementia incidence among females (r = 0.765, p < 0.001) and males (r = 0.781, p < 0.001). In adjusted models, cancer incidence remained associated with dementia incidence in females (β = 0.496, p < 0.001; adjusted R2 = 0.693) and males (β = 0.526, p < 0.001; adjusted R2 = 0.709). Incremental explained variance was larger among males. CONCLUSIONS:Cancer incidence is a sex-specific country-level correlate of dementia incidence. Findings indicate population-level co-variation, not individual-level risk or causality in aging populations worldwide.
RESULTS:The review further examines mechanisms underlying treatment resistance and the limitations of current targeted therapies. Although many pathway-directed treatments have demonstrated promising preclinical activity, clinical translation remains challenging because of compensatory signaling, blood-brain barrier limitations, and molecular heterogeneity.Conclusion: Future progress will likely depend on biomarker-driven patient stratification, improved CNS drug delivery, and rational combination therapies capable of simultaneously targeting multiple tumor-promoting mechanisms.
Aim To report a case of Adebrelimab-related liver injury and emphasize the role of the updated RUCAM in causality assessment for suspected immune checkpoint inhibitor-induced hepatotoxicity.Observation A 51-year-old male with small-cell lung cancer developed severe jaundice four days after his last dose of etoposide/carboplatin combined with adebrelimab, occurring after nine cycles of therapy (at 5 months) and later than the onset time described in the drug label. Baseline liver function was normal, and there was no history of hepatobiliary disease. Physical examination revealed jaundice and scleral icterus. The updated RUCAM score was 8, indicating a highly probable relationship between the regimen and liver injury, while the simplified AIH score (<6) ruled out autoimmune hepatitis. The patient’s liver enzymes and bilirubin normalized, and clinical symptoms improved following treatment with low-dose methylprednisolone (1 mg/kg/d) and other supportive measures.Conclusion This case highlights the value of applying the updated RUCAM to reliably distinguish drug-induced liver injury from other etiologies in immune checkpoint inhibitor recipients, thereby guiding appropriate clinical management.
BACKGROUND:Off-label underdosing of direct oral anticoagulants (DOACs) is common among Asian patients with atrial fibrillation (AF), partly reflecting concerns about bleeding, yet Southeast Asian data remain limited. This study aimed to characterize DOAC dosing patterns, identify predictors of off-label underdosing, and evaluate associated effectiveness and safety outcomes. METHODS:We conducted a retrospective cohort using electronic health records (EHRs) from two tertiary hospitals in Thailand (2015-2023). Incident AF patients initiating dabigatran, rivaroxaban, apixaban, or edoxaban were included. Doses were classified as on-label, underdosed, or overdosed based on guideline criteria. Propensity score-based inverse probability of treatment weighting (PS-IPTW) Cox proportional hazards regression models was used to evaluate ischemic stroke or systemic embolism (ISSE) and bleeding outcomes. RESULTS:Among 553 patients, 20.4% were underdosed, 6.3% overdosed, and 73.2% received on-label dosing. Rivaroxaban was most frequently underdosed. Older age and diabetes mellitus independently predicted underdosing. Compared to on-label dosing, underdosing was not associated with ISSE (adjusted hazard ratio [aHR] 0.48, 95% CI 0.11-2.16; p = 0.336) or bleeding (aHR 1.06, 95% CI 0.30-3.73; p = 0.924). CONCLUSIONS:Off-label underdosing occurred in one-fifth of patients but was not associated with significant differences in ISSE or bleeding. Larger, prospective studies in broader Asian and non-Asian populations are warranted.
INTRODUCTION:Post-acute coronavirus disease 2019 syndrome (PACS) is a multisystemic clinical condition that clinically starting weeks or even months after acute SARS-CoV-2 (COVID 19) infections. The objective of this study was to explore change in quality of life, mechanical force and metabolic activity after ozone therapy treatment. METHODS:A preliminary clinical open label study was carried out. Twenty-three patients diagnosed with PACS more than 5 months ago participated in the study. Thermography, Handgrip test and Quality of life scale SF12 were used to analyze the effects of ozone therapy on these patients. RESULTS:Related to the Handgrip test, a significant improvement was recorded in T0-T1 time interval (p = 0.0003; d 0.88), but in T1-T2 time variation was not statistically significant (p = 0.957). About the SF-12 test, a significant difference was also found in both the PCS (p = 0.0038; d = 0.67) and the MCS (p = 0.0088, d = 0.60) in T0-T1 time, but not in T1-T2 for either the PCS (p = 0.5933) or the MCS (p = 0.3917). Finally, regarding temperature, statistically significant differences were observed in the T0-T1 time interval (p = 0.0465, d = 0.44) but not between T1 and T2 (p = 0.1038). No significant differences between the sexes were observed for any of the four parameters. CONCLUSION:Our results confirmed that clinical ozone could be a potentially useful drug in improving the strength, quality of life and basal metabolism in patients with long COVID. However, we believe that further studies and larger sample sizes are needed to corroborate and support the results obtained in this preliminary trial.
Aim To identify novel substrates of USP14 and elucidate the molecular mechanisms by which USP14 promotes head and neck squamous cell carcinoma (HNSCC) progression.Materials and methods USP14 expression patterns were examined in HNSCC tissues and cell lines. Functional effects were assessed using genetic knockout and overexpression models in vitro and in vivo. USP14-CFL2 interactions were evaluated by co-immunoprecipitation and GST pull-down assays. Deubiquitination activity was measured in vitro. Transcriptomic analysis and bioinformatics were used to identify downstream pathways and clinical relevance.Results USP14 was significantly overexpressed in HNSCC and correlated with poor prognosis. Genetic knockout of USP14 markedly suppressed HNSCC cell proliferation, migration, and tumor growth, while USP14 overexpression exerted opposite effects. Mechanistically, we identified CFL2 as a novel substrate of USP14; USP14 directly interacted with and deubiquitinated CFL2, thereby enhancing its stability by preventing proteasomal degradation. Clinically, CFL2 was also overexpressed in HNSCC and its elevated levels correlated with reduced overall survival. Functionally, CFL2 overexpression significantly rescued the anti-tumor effects of USP14 knockout, including impaired cell proliferation and migration.Conclusion In summary, our findings identify a novel USP14-CFL2 regulatory axis and establish USP14 as a critical promoter of HNSCC progression, acting through CFL2 deubiquitination and stabilization.
Aims E3112 is a recombinant human hepatocyte growth factor (HGF) intended for the treatment of acute liver failure. As the presence of anti-drug antibody (ADA) against E3112 could pose a significant risk in clinical settings if it cross-reacts with the body’s natural HGF, we have developed assays for E3112 and its ADA in human serum.Methods Assays of E3112 and its ADA developed by ligand binding assays were validated in accordance with bioanalytical guidelines and applied to clinical pharmacokinetic (PK) and immunogenicity assessments.Results These assays demonstrated the ability to detect E3112 at a concentration as low as 0.156 ng/mL, whereas the sensitivity of ADA was determined to be 42.3 ng/mL. The validation studies, incorporating quality control for the PK assay and positive control of ADA, substantiated the reproducibility of the assays. The ADA and PK assays were applied to the real sample assays supporting a clinical trial of E3112. Following the intravenous administration of E3112, serum E3112 levels declined with a half-life of 19.3 h. No ADA was detected in predose or postdose samples.Conclusion These findings collectively indicate that E3112 exhibited a favorable PK profile with minimal immunogenicity within the clinical context.
Aims This study aimed to characterize cyclin-dependent kinase 1 (CDK1) expression in bladder cancer (BC), elucidate its role in intercellular signaling and mitosis, and identify small-molecule inhibitors targeting CDK1.Methods RNA sequencing data from multiple databases were integrated, with immunohistochemistry on tissue microarrays validating protein expression. Single-cell RNA sequencing (scRNA-seq), spatial transcriptomics (ST), gene set enrichment analysis (GSEA), and molecular docking with molecular dynamics (MD) simulations were performed.Results CDK1 mRNA and protein were significantly overexpressed in BC tissues. CDK1 expression correlated with patient age and race. CDK1 was predominantly expressed in epithelial cells and central to pleiotrophin (PTN) pathway-mediated intercellular communication; virtual CDK1 knockout markedly reduced PTN signaling strength. ST confirmed CDK1 enrichment in tumor regions. GSEA linked CDK1 to mitosis and chromosome segregation, and scRNA-seq analyses revealed a PTN-CDK1-mitosis regulatory axis active specifically in epithelial cells. Dinaciclib showed favorable MD stability as a CDK1 inhibitor.Conclusion CDK1 is significantly overexpressed in BC with good discriminatory ability. Predominantly expressed in BC epithelial cells, CDK1 may be activated by PTN signaling to drive mitosis. MD simulations support Dinaciclib as a promising CDK1-targeting inhibitor.
BACKGROUND:Adalimumab is the first biologic approved for moderate-to-severe hidradenitis suppurativa (HS). Considering potential cost savings, real-world data evaluating the prescribing patterns following a switch from the originator in HS remain limited. METHODS:We conducted a retrospective multicenter observational study (2019-2025) at two hospitals in Saudi Arabia. Adult HS patients who received originator adalimumab for ≥3 months, and then switched to its biosimilar for non-medical reasons for ≥3 months were included. Descriptive statistics summarized baseline characteristics. A Wilcoxon paired test compared treatment durations, and a Sankey diagram illustrated treatment pathways. RESULTS:A total of 40 patients were included (median age: 26 years; 62.5% male; median BMI: 31.6). Most presented with nodules (55.0%), abscesses (47.5%), and sinus tracts (37.5%). Among all treatment actions/pathways, 22.6% represented treatment escalation to an alternative biologic, specifically secukinumab or ustekinumab. Patients who were switched from biosimilar therapy demonstrated more severe disease involvement. Median duration of originator therapy was 6.0 months versus 21.0 months for biosimilar (p = 0.477), with no significant difference in treatment persistence. CONCLUSION:In this small real-world cohort, treatment escalation after switching to biosimilar adalimumab was observed in a subset of patients with more complex HS features. Larger studies using standardized severity measures are needed to confirm these observations.
BACKGROUND AND OBJECTIVES:We characterized fine-scale geographic variation in serum trace metals across Campania (southern Italy). MATERIALS AND METHODS:In 2016-2017, the SPES programme sampled residents aged 20-49 years from municipal registries across Campania. Municipalities were stratified using an environmental-pressure index into three broad impact strata: high-impact, medium-impact and low-impact. For higher spatial resolution, municipalities were also grouped into 21 predefined municipal clusters. We measured 20 serum trace metals by ICP-MS and estimated age- and sex-adjusted geometric mean ratios (GMRs) comparing each stratum or cluster with the study-wide geometric mean. RESULTS:Of 4205 enrolled participants, 4188 were included. Medium-impact areas showed higher mercury (GMR 1.87, 95% CI 1.73-2.02) and antimony (1.95, 1.71-2.23) relative to the cohort average. At the municipal-cluster scale, the Irno Valley clusters around the Fonderie Pisano foundry (Baronissi-Pellezzano and Salerno) had about six-fold higher mercury (GMR 5.71 and 6.10) and about three-fold higher antimony (3.45 and 2.93), whereas the Valle del Sabato cluster showed about ten-fold higher antimony (GMR 10.5) and about seven-fold higher nickel (7.16) and cadmium (7.67). CONCLUSIONS:Overall serum metal concentrations were broadly comparable with European general-population ranges, but pronounced small-area heterogeneity indicates localized hotspots that provincial or regional averages can obscure.
BACKGROUND:Deep learning for mammographic image classification yields impressive performance metrics, but inconsistent evaluation methodologies-specifically whether results are reported at the independent side level or the bilateral patient level-make cross-study comparisons unreliable. The aim of this study was to quantify, on a single dataset and with a uniform training recipe, how much of the reported performance is determined by evaluation granularity rather than by model architecture. MATERIALS & METHODS:We benchmarked six backbone architectures (ResNet-18, ResNet-50, EfficientNet-B0, DenseNet-121, ConvNeXt-Tiny, ViT-B/16) crossed with three multi-view fusion strategies (concatenation, bilateral asymmetry, cross-view spatial attention) on the biopsy-confirmed Chinese Mammography Database (CMMD; 706 four-view patients), using five-fold patient-level stratified cross-validation. Sixteen configurations completed training for both binary malignancy diagnosis and five-class BI-RADS assessment. We report side-level and patient-level metrics; statistical analyses include 5-fold Wilcoxon signed-rank tests, DeLong's paired AUC test on pooled per-case scores, and bootstrap 95% confidence intervals. RESULTS:Side-level AUC exceeded patient-level AUC by an average of 17.5 percentage points (range 12.7-22.4), an effect that dwarfs the absolute differences observed between CNN backbones (<3 AUC points). DeLong tests resolved approximately half of all CNN-vs-CNN pairwise comparisons at p<0.05 despite small effect sizes, whereas ViT-B/16 underperformed every CNN variant by 8-10% AUC despite having 6-10× more parameters. Patient-level multi-class BI-RADS evaluation under the standard probability-averaging aggregation rule returned a degenerate macro-AUC of exactly 0.000-a property of the metric/aggregation pair, not of the models-and three concrete alternative aggregators are proposed. The extreme patient-level malignancy prevalence intrinsic to this biopsy-confirmed cohort (96.2%) rendered all models unable to identify non-malignant patients at the patient level. CONCLUSION:Reporting methodology, evaluation granularity, and dataset composition are compounding confounds in mammography classification research. Absolute performance numbers reported on CMMD should not be extrapolated to population screening settings, where prevalence is several orders of magnitude lower; studies should report both side-level and patient-level metrics with mutually consistent label/aggregation rules, and characterise performance using confidence intervals or paired statistical tests rather than fold-level Wilcoxon alone.
OBJECTIVE:To evaluate associations between environmental toxicant (ET) exposures and obstructive sleep apnea (OSA) using an exposome-wide approach. METHODS:This cross-sectional analysis included 13,161 participants from two NHANES cycles (2015-2016 and 2017-March 2020). Fifty-six toxicants across six classes (arsenic species, ethylene oxide, heavy metals, nicotine metabolites, VOC metabolites, and thyroid-disrupting compounds) were measured. OSA status was defined using a validated questionnaire based on self-reported symptoms. Exposome-wide association analysis (ExWAS) adjusted for sociodemographic, lifestyle, and clinical covariates, and restricted cubic spline (RCS) analysis characterized nonlinear exposure-response relationships. RESULTS:The overall prevalence of OSA was 49% (n = 6,443). Nine ETs showed significant associations with OSA, including blood and urinary cadmium, seven volatile organic compound metabolites (e.g., 2,5-dimethylfuran, ethylbenzene, furan, o-xylene), and three urinary cysteine-derived metabolites (N-acetylcysteine derivatives). Subgroup analyses revealed higher susceptibility among women and individuals aged <65 years. RCS analyses demonstrated nonlinear, nonmonotonic relationships for cadmium and cysteine-derived metabolites with OSA prevalence. CONCLUSIONS:Nine ETs were significantly associated with OSA prevalence, with evidence of differential susceptibility by sex and age. These findings highlight environmental factors associated with OSA, which may serve as potential targets for future mechanistic research and public health interventions.
INTRODUCTION:In response to the increasing prevalence of online behavioral addictions, researchers have investigated various treatment approaches, including pharmacotherapies. This systematic review aimed to summarize pharmacotherapeutic studies of online behavioral addictions. METHODS:PubMed, MEDLINE, and Embase were searched to identify randomized controlled trials or quasi-experimental studies of pharmacotherapy for online behavioral addictions. Studies were excluded if they only targeted offline behavioral addictions. Study findings were summarized, and the Effective Public Health Practice Project Quality Assessment Tool was used for quality assessment. RESULTS:This systematic review included 20 studies (1016 participants). Bupropion, selective serotonin reuptake inhibitors (SSRIs), and opioid receptor antagonists were most frequently studied and showed preliminary promise in reducing symptom severity. Many pharmacotherapeutic studies addressed co-occurring concerns, such as depression. CONCLUSIONS:Pharmacotherapies for online behavioral addictions appear promising, but the evidence base was limited by small samples, few randomized controlled trials, and short follow-up periods. Given preliminary support for psychotherapy + pharmacotherapy for problematic gaming, future research may evaluate the efficacy of combined treatment for a broader range of online behavioral addictions. Future research should also investigate pharmacotherapies for emerging problematic online behaviors, such as AI-based sexual engagement and problematic cryptocurrency trading.
INTRODUCTION:Healthcare-associated infections (HAIs) are a global challenge, exacerbated by multidrug-resistant pathogens. This study systematically maps antimicrobial surface formulations (1995-2024), analyzing gaps in regulatory readiness, toxicological validation, and sustainability. AREAS COVERED:Using the Espacenet database and PRISMA guidelines, 49 patents were analyzed. Innovation surged post-2015, led by private corporations (72.09%) in the USA, Canada, and China (67.35%). Synthetic actives, primarily quaternary ammonium compounds, dominated (71.43%), while natural (16.33%) and hybrid (10.20%) approaches were less frequent. Key targets included S. aureus, K. pneumoniae, and E. coli. Although 38.77% of patents claimed sustainability (biodegradability/low toxicity), only 40.82% disclosed mechanisms of action, and 34.69% provided toxicological data. EXPERT OPINION:A significant gap exists between technological innovation and regulatory/safety validation. Future developments must integrate life-cycle assessments and robust toxicological testing. Harmonized regulatory pathways and public-private partnerships are essential to translate these innovations into scalable, sustainable, and safer disinfectant solutions for healthcare environments.
