Search Results (1,019)

Background: This cross-sectional study compared immunoassay urine drug screening with LC–MS/MS confirmation in individuals with substance use disorder undergoing probation monitoring, focusing on samples with results close to assay cutoff values. Methods: The study was conducted between January and March 2026 in Şanlıurfa, Türkiye, and included 110 individuals followed at an Addiction Treatment Center (AMATEM). Urine samples with at least one analyte result within ±20% of the cutoff value were analyzed. Immunoassay screening was performed using a Beckman Coulter AU480 analyzer, whereas confirmation was performed by LC–MS/MS using a SCIEX Triple Quad 5500+ system. Agreement was evaluated using Cohen’s kappa and McNemar’s test, while diagnostic performance was assessed using 2 × 2 contingency tables. Results: Agreement varied substantially among analyte groups. Buprenorphine showed the highest agreement (κ = 0.47), followed by amphetamines (κ = 0.33), whereas opioids showed very low agreement (κ = 0.081). Benzodiazepines, cocaine, and cannabinoids showed no meaningful agreement; however, benzodiazepine and cocaine findings were limited by very low numbers of positive cases. Immunoassay screening produced notable false-positive results for amphetamines and opioids and false-negative results for cannabinoids and opioids. Conclusions: Immunoassay performance was analyte-dependent and appeared limited in samples with results close to cutoff values. LC–MS/MS confirmation remains important for reliable toxicological interpretation in probation monitoring settings. Full article

Urinary biomarkers are promising tools in urological oncology because urine can be collected non-invasively and repeatedly during diagnosis, treatment, and surveillance. Despite extensive biomarker discovery, their adoption in routine practice remains limited. Biomarker performance depends not only on analytical accuracy but also on the clinical decision, anatomical route into urine, biological source of the signal, specimen fraction, and timing and conditions of sampling. This review evaluates urinary biomarkers across bladder cancer, upper-tract urothelial carcinoma, prostate cancer, and renal cell carcinoma using a biologically grounded, decision-oriented framework. It considers tumor-derived nucleic acids, epigenetic alterations, proteins, immune and inflammatory mediators, extracellular vesicles, metabolites, microbiome-associated signals, and multiparametric models. Bladder cancer represents the most anatomically direct and clinically mature setting, with potential applications in hematuria evaluation, cystoscopy triage, recurrence surveillance, molecular residual disease assessment, and monitoring of response to bacillus Calmette–Guérin therapy. In upper-tract urothelial carcinoma, distinguishing voided from selectively collected urine is essential because dilution, transit, obstruction, and limited localization affect interpretation. Prostate urine assays are best positioned for biopsy triage and refinement of active surveillance rather than general population screening. Renal cell carcinoma biomarkers remain exploratory because the sources and mechanisms of urinary signal release are insufficiently resolved. Clinical translation should be assessed using decision-specific outcomes, including incremental value, calibration, net clinical benefit, procedures avoided, significant cancers missed, reproducibility, and feasibility, rather than diagnostic accuracy or area under the receiver operating characteristic curve alone. Full article

Liquid biopsy enables minimally invasive detection and longitudinal monitoring of tumor-derived material in blood and urine. In genitourinary cancers, most applications have focused on genomic alterations in circulating tumor DNA (ctDNA), together with circulating tumor cells (CTCs), extracellular vesicles (EVs), and cell-free RNAs. These measurements are clinically informative but are often interpreted as isolated, predominantly descriptive biomarkers and therefore incompletely represent the adaptive processes that determine progression and treatment response. We propose circulating tumor function (CTF) as a systems biology framework for integrating tumor-derived and host-derived genomic, regulatory, metabolic, redox, and immune signals obtained through serial liquid biopsy. CTF is not a single analyte or assay; rather, it is an inference model intended to generate interpretable functional states, including proliferative activity, immune evasion, metastatic potential, metabolic stress, and therapeutic adaptation. We review the contributions and limitations of ctDNA, ncRNA networks, EV-mediated signaling, redox biomarkers, and tumor–host crosstalk in prostate, bladder, renal, and testicular cancers. We also outline the analytical and clinical validation required to determine whether integrated CTF models provide incremental value over established single-analyte approaches. This framework may help reposition liquid biopsy from molecular detection toward functional precision oncology. Full article

Microbiologically induced calcium carbonate precipitation (MICP) links microbial metabolism with carbonate biomineralization and offers a platform for environmental protection and a circular bioeconomy. This critical review synthesizes ureolytic and non-ureolytic pathways, including denitrification, sulfate reduction, photosynthesis, ammonification and carbonic-anhydrase-mediated routes, and evaluates their efficiency, scalability, environmental impacts and field applicability. MICP can immobilize heavy metals and metalloids, stabilize soils and mine wastes, reduce permeability, control erosion and dust, seal cracks in cementitious materials, and support brine or wastewater treatment. Representative studies report >90% Cd²⁺ removal in selected wastewater systems, 50–90% hydraulic-conductivity reduction at about 10–15% CaCO₃, 2.7 MPa compressive strength in urine-based bio-bricks, 31.87% calcium-source cost reduction using waste-limestone-derived calcium acetate, and geothermal-brine treatment removing 96% Ca, 88% Mn, and 91% Sr while retaining >96% Li. The review emphasizes that circular MICP requires more than waste input substitution; it must include nitrogen management, feedstock quality control, long-term contaminant stability, LCA/TEA, regulatory readiness, biosafety, field monitoring, and technology-readiness assessment. Future research should develop low-ammonia, waste-fed and data-guided MICP systems with standardized quantitative performance metrics. Full article

Post-hemorrhagic hydrocephalus (PHH) is a serious neurological sequela of severe intraventricular hemorrhage (IVH) in premature infants and remains one of the leading indications for ventriculoperitoneal (VP) shunt placement. Evaluating possible VP shunt-related complications can be challenging because clinical manifestations are often nonspecific, neuroimaging may initially appear unchanged, and microbiological cultures may remain negative. We report the case of a 19-month-old male born at 28 weeks’ gestation who developed Grade IV germinal matrix/intraventricular hemorrhage with bilateral intraparenchymal extension, early periventricular cystic leukomalacia, and post-hemorrhagic communicating hydrocephalus requiring multiple cerebrospinal fluid diversion procedures culminating in long-term VP shunt dependence. His medical history was notable for recurrent neonatal meningitis, secondary epilepsy with previous episodes of status epilepticus, secondary adrenal insufficiency, and severe global developmental delay. He presented with fever, recurrent coffee-ground vomiting, abdominal distension, progressive lethargy, reduced responsiveness, and localized erythematous swelling over the cranial VP shunt reservoir, raising concern for possible shunt-related pathology. During hospitalization, he deteriorated with status epilepticus and respiratory failure, with clinical concern for increased intracranial pressure, requiring admission to the Pediatric Intensive Care Unit (PICU). Laboratory investigations demonstrated leukocytosis, elevated C-reactive protein, cerebrospinal fluid pleocytosis, markedly elevated CSF protein, and CSF glucose of 2.0 mmol/L, for which a paired serum glucose value was unavailable, while repeated blood, urine, wound, and CSF cultures remained negative. Initial computed tomography (CT) demonstrated no significant interval change in the chronic hydrocephalus despite progressive neurological deterioration; however, serial neuroimaging later revealed progressive bilateral extra-axial fluid collections with radiological features suggestive of an evolving subacute subdural hemorrhage. The patient was managed with empirical broad-spectrum intravenous antibiotics, aggressive seizure control, stress-dose corticosteroids, respiratory support, and continuous multidisciplinary monitoring. His neurological and respiratory status subsequently improved, and he returned to his pre-admission neurological baseline before discharge with planned further evaluation at a tertiary pediatric neurosurgical center. This case highlights the diagnostic uncertainty surrounding acute neurological deterioration in a child with shunt-dependent PHH. VP shunt-related infection or malfunction remained important but unconfirmed diagnostic considerations, alongside competing or potentially overlapping contributors including status epilepticus, evolving extra-axial collections, respiratory infection, and endocrine or metabolic decompensation. No single etiology was definitively established. The case emphasizes the importance of serial neurological assessment, consideration of alternative diagnoses, repeat neuroimaging, and multidisciplinary evaluation when initial investigations do not establish the cause of deterioration. Full article

Background/Objectives: Type 2 diabetes (T2D) is a major risk factor for cardiovascular disease and chronic kidney disease (CKD), yet the extent of longitudinal CKD screening in routine clinical practice remains unclear. This study aimed to assess long-term cardiorenal outcomes and CKD screening practices in patients with T2D managed across primary care and endocrinology settings, evaluating the feasibility of risk stratification in real-world practice. Methods: We conducted a retrospective cohort study using anonymized data from the Telotrón database (2.2 million patients). Adults with T2D attended across primary and endocrinology care were followed from 1 January 2018 to 31 December 2022. Frequency of estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR) measurements, and cumulative proportion of kidney and cardiovascular events, hospitalizations, and mortality were assessed. Results: Among 13,600 individuals, 31.1% experienced a kidney event and 18.6% a cardiovascular event over 5 years. All-cause hospitalization occurred in 24.9% and 16.1% died. First occurrence of an abnormal eGFR or UACR measurement occurred in 37.0% of participants without baseline CKD, and 45.4% with baseline CKD showed progression. Annual monitoring was limited, with 39.1% and 16.6% undergoing at least one yearly assessment, and 2.9 and 1.5 mean number of measurements per patient for eGFR and UACR, respectively. Conclusions: Despite receiving endocrinology care, kidney disease progression and cardiovascular events remain a major concern in T2D, and yet suboptimal albuminuria and eGFR assessment limit early detection and risk stratification, thereby hindering risk-directed management. Full article

The widespread use of neonicotinoids (NEOs) poses a significant risk to school-aged children. However, critical knowledge gaps remain regarding their comprehensive exposure profiles and associated health risks. This study assessed the co-exposure levels and non-carcinogenic risks of 16 NEOs (including both traditional and emerging compounds) in 184 school-aged children recruited from a typical rural and urban area of South China. The sum concentrations of 16 NEOs (∑₁₆NEOs) ranged from 0.648 to 227 μg/L (median: 8.99 μg/L). The predominant compounds were clothianidin (CLO, 1.93 μg/L), N-desmethyl-acetamiprid (N-dm-ACE, 1.64 μg/L), thiamethoxam (THM, 0.792 μg/L), and dinotefuran (DIN, 0.222 μg/L). To our knowledge, this is the first report of emerging NEOs—paichongding (IPP), sulfoxaflor (SUL), and flonicamid (FLO)—in children urine, with detection frequencies of 11.4%, 68.2%, and 53.4%, respectively. Significant rural–urban disparities in urinary concentrations were observed. The metabolite-to-parent ratios (e.g., N-dm-ACE/ACE, 5-OH-IMI/IMI, and THCP-AM/THCP) may serve as a useful biomarker for assessing human exposure to NEOs, as it provides valuable insight into the metabolic fate of the target compounds and aids in distinguishing exposure pathways. The median estimated daily intake (EDI) values for CLO, N-dm-ACE, THM, and ∑₁₂NEOs were 0.127, 0.117, 0.046, and 0.696 μg/kg-bw/day, respectively. Although the hazard quotient for individual compounds was below 1 for vast majority of school-aged children, cumulative exposure assessment indicated that 1.09% of participants had a hazard quotient exceeding 1 for both IMI_eq and ∑₁₂NEOs, suggesting potential health concerns under co-exposure scenarios. Using a multi-criteria Toxicological Priority Index (ToxPi) model, CLO, THM, thiacloprid-amid (THCP-AM), and N-dm-ACE were identified as the high-priority compounds requiring regulatory attention in children’s environmental health. This study provides the first comprehensive biomonitoring and ToxPi-based prioritization of both traditional and emerging NEOs in school-aged children in South China. The findings highlight the urgent need for continued monitoring, refined mixture risk assessment, and regulatory consideration of emerging substitutes and their metabolites, which are not adequately covered by current safety guidelines. Full article

Renal cell carcinoma (RCC) is frequently detected incidentally, and no widely adopted noninvasive biomarkers are available for RCC diagnosis or prognosis. In this regard, cell-free microRNAs (cfmiRs) have emerged as promising candidates due to their stability in biological fluids. In this narrative review, we summarize translational studies published from 2010 to 2025 that evaluated serum, plasma, or urinary cfmiRs for RCC diagnosis, prognosis, recurrence surveillance, or treatment-response monitoring. Forty-two studies met inclusion criteria, comprising 3454 patients with RCC and 2445 healthy donors. Twenty-nine studies assessed diagnostic performance, fewer evaluated prognostic applications, and none examined treatment-response monitoring. Multi-miRNA panels generally reported higher performance than single-miRNA assays. Serum was the most frequently studied biofluid in this review (n = 26), followed by urine (n = 12) and plasma (n = 4). Urinary biomarkers demonstrated high specificity and the practical advantage of noninvasive collection. Although limited in number, prognostic studies identified associations between cfmiRs and overall survival, recurrence-free survival, metastasis-free survival, and other clinically relevant outcomes. However, substantial heterogeneity in study design, assay methods, and reporting limited comparisons across studies. Current evidence supports continued evaluation of cfmiRs as adjunctive biomarkers alongside imaging or histopathology, but multicenter validation, standardized methods, and more robust evidence are required before clinical implementation. Full article

Diuretics remain indispensable for the treatment of congestion in cardiovascular disease, particularly in acute and chronic heart failure. Their principal clinical value is rapid symptom relief, reduction in filling pressures and facilitation of decongestion; however, a mortality benefit has not been consistently demonstrated. This distinction is clinically important because long-term diuretic exposure in patients without objective congestion may promote hypotension, renal dysfunction, electrolyte instability, neurohormonal activation, falls, cognitive impairment and avoidable polypharmacy. The challenge is therefore not whether diuretics should be used, but how intensively, for how long and under which monitoring strategy. In this narrative review, we summarize the pharmacology of major diuretic classes, the mechanisms of diuretic resistance, and the clinical consequences of potassium, sodium and magnesium disorders. We also discuss drug interactions, frailty, chronic kidney disease, pregnancy, heart failure with preserved ejection fraction and the emerging role of sodium–glucose cotransporter 2 inhibitors and adjunctive proximal-tubule strategies. A practical approach is proposed: use loop diuretics promptly when congestion is present, reassess response with symptoms, weight, urine output, renal function, electrolytes and congestion markers, and reduce or discontinue therapy once euvolemia is achieved and maintained. Deprescribing should be individualized, gradual and reversible, with explicit thresholds for restarting treatment. Optimized diuretic care requires the same discipline applied to disease-modifying heart failure therapy: phenotype recognition, dose minimization, close follow-up and avoidance of treatment inertia. Full article

Background: Fibroblast Growth Factor Receptor 3 (FGFR3) mutations are common and clinically relevant alterations in bladder cancer, with implications for diagnosis, monitoring, and patient selection for targeted therapies. Tissue-based testing is often limited by sample availability, invasiveness, and the need for repeated sampling. This study aimed to develop and analytically validate a sensitive double drop-off droplet digital polymerase chain reaction (ddPCR) assay for simultaneous detection of four FGFR3 hotspot mutations in tissue and liquid biopsy samples. Methods: The assay targeted four FGFR3 mutations (S249C, R248C, Y373C, G370C) using reference probes that generate a constant fluorescence signal and wild-type-specific drop-off probes that lose binding when a mutation is present, thereby distinguishing wild-type double-positive droplets from mutant droplets with reduced drop-off fluorescence. Analytical validation was performed using synthetic mutant oligonucleotides, wild-type genomic DNA, and cell-free DNA (cfDNA) from healthy donors (HDs). Specificity, limit of blank (LOB), limit of detection (LOD), and assay precision were evaluated. Performance was compared with next-generation sequencing (NGS) in formalin-fixed paraffin-embedded (FFPE) tissue DNA. FGFR3 mutations were also assessed in matched plasma and urinary cfDNA from bladder cancer patients. Results: The assay demonstrated clear cluster separation, no cross-reactivity, and reliable detection of all mutations down to 0.2% mutant allele frequency (MAF). Strong agreement was observed with a mutation-specific singleplex ddPCR assay for S249C. Concordance with NGS in tissue DNA was 74.2%, with ddPCR identifying additional low-abundance mutations not reported by NGS. FGFR3 mutations were detected in plasma and urinary cfDNA, with complete concordance between matched plasma and urine samples. Conclusions: This ddPCR assay provides a rapid, sensitive, and cost-effective method for detecting clinically relevant FGFR3 mutations and may complement sequencing-based approaches for molecular monitoring using tissue, plasma, and urine specimens. Full article

Background/Objectives: BK polyomavirus (BKPyV) establishes lifelong, asymptomatic persistence but frequently reactivates in renal transplant recipients, contributing to significant post-transplant morbidity. Although humoral responses are routinely monitored, the role of cellular immunity in viral control remains incompletely characterized. This study aimed to characterize BKPyV-specific T-cell responses and IgG-binding levels in healthy adults and renal transplant recipients and to explore their association with active BKPyV viruria. Methods: BKPyV DNA was screened and quantified in urine samples from eighty-two healthy adults and thirty-three renal transplant recipients, who were categorized into active, no, historical, and pre-transplant infection groups. BKPyV-specific cellular immunity was assessed in peripheral blood mononuclear cells using IFN-γ ELISPOT and T-cell proliferation assays, and IgG binding levels were measured in plasma using semi-quantitative ELISA. Results: Healthy BKPyV-positive individuals had significantly higher IFN-γ-secreting T-cell frequencies than BKPyV-negative individuals, with no significant difference in IgG levels. Transplant recipients with detectable viruria had markedly diminished IFN-γ responses compared with all other groups, whereas IgG levels remained comparable except in the pre-transplant group (n = 2). A strong negative correlation was observed between IgG levels and urine viral load in actively infected patients. Proliferation assays showed no detectable antigen-specific proliferation despite measurable cytokine secretion. Conclusions: Cellular immunity, rather than total binding IgG levels, may be more closely associated with BKPyV activity, particularly in transplant recipients. Given the exploratory cross-sectional design, prospective validation is needed. These findings support integrating cell-mediated immune assays into BKPyV monitoring to improve post-transplant risk assessment. Full article

Endometrial and cervical cancers can recur from subclinical disease not evident on routine surveillance. This narrative review critically evaluates liquid biopsy for minimal residual disease (MRD) assessment and recurrence monitoring. Post-treatment human papillomavirus (HPV) circulating tumor DNA (ctDNA) in cervical cancer has the strongest disease-specific prospective evidence of clinical validity; persistent detection is strongly associated with recurrence, but moderate sensitivity and false-negative results do not support treatment de-escalation on negativity alone. With regard to endometrial cancer, perioperative ctDNA has prognostic support from an 11-study, 1298-patient meta-analysis and additional cohorts, although assay heterogeneity and limited independent replication constrain clinical readiness. Postoperative positivity generally shows stronger associations than preoperative detection. Cervicovaginal and urine DNA-methylation studies provide preliminary evidence for detecting established recurrence, especially local recurrence, but not prospective molecular lead time or clinical utility. Digital PCR, disease-specific fixed panels, tumor-informed assays, and error-corrected sequencing serve distinct settings; broad pan-cancer plasma profiling remains mainly an advanced-disease tool. Circulating tumor cells, extracellular vesicles, microRNAs, tumor-educated platelets, and fragmentomics remain exploratory. Liquid biopsy should remain an investigational adjunct until prospective trials show that acting on molecular findings improves outcomes. Full article

Kindergarten environments combine high microbial exposure with increased immunological vulnerability, yet antibiotic resistance genes (ARGs) in kindergarten dust remain poorly characterized. This systematic review synthesized evidence on the occurrence and potential health relevance of ARGs in kindergarten dust. Following PRISMA 2020 guidelines, PubMed, Scopus, and Web of Science were searched. Four studies from China, Hong Kong, and Norway (2018–2024) met the inclusion criteria. ARGs were detected in all kindergarten dust samples, indicating that dust is a consistent reservoir of antibiotic resistance determinants. A consensus resistome (classes detected in ≥2 studies) encompassed sulfonamide, macrolide–lincosamide–streptogramin B (MLSB), tetracycline, beta-lactam, aminoglycoside, and multidrug resistance genes; beta-lactam resistance genes were the only class reported in all four studies. Clinically important ARGs associated with last-resort antibiotics, including mecA, vanA, bla_NDM, and mcr-5, were reported in three studies. Class 1 integron-integrase genes (intI1) frequently co-occurred with ARGs, suggesting potential horizontal gene transfer. Limited evidence indicated higher ARG abundance in urban and winter samples. One study reported antibiotic-resistant bacteria carrying resistance markers concordant with those in kindergarten dust in the urine of children attending the same facilities; however, this cross-sectional, single-site evidence is consistent with, but not sufficient to establish, a dust-to-child exposure pathway. The available evidence supports the plausibility that kindergarten dust may contribute to children’s exposure to ARGs and ARG-carrying bacteria, but current studies do not establish causal transmission from dust to child colonization or infection. Standardized monitoring and longitudinal studies are needed to assess health risks and guide mitigation strategies in early childhood educational settings. Full article

Carbon nanotube (CNT)-based biosensors have emerged as promising platforms for non-invasive biofluid analysis because of their high electrical conductivity, large surface area, tunable optical properties, and versatile surface chemistry, enabling miniaturized, flexible sensing devices. Sweat, saliva, tears, and urine are increasingly recognized as attractive alternatives to blood for point-of-care diagnostics because they enable repeated, non-invasive sampling while containing clinically relevant metabolites, electrolytes, proteins, hormones, nucleic acids, pathogens, and other biomarkers. However, the low abundance of many analytes, matrix complexity, biofouling, and biofluid-specific variability present significant analytical challenges. This review critically examines the different CNT-based sensor architectures, and their recent advances in non-invasive analysis of sweat, saliva, tears, and urine. It integrates sensor architecture, biofluid-specific analytical challenges, sample-validation level, and translational readiness within a single comparative framework. Representative applications are discussed for metabolic monitoring, renal health assessment, infectious disease testing, and other clinically relevant uses. Beyond clinical diagnostics, emerging non-clinical applications, including drug-of-abuse detection, forensic body-fluid identification, and occupational or environmental exposure assessment, are also highlighted. Finally, we discuss key barriers limiting real-world translation of CNT biosensors, including material reproducibility issues, biofouling, physiological interpretation of biofluid biomarkers, scalable manufacturing, and long-term operational stability, and outline future strategies to advance these platforms toward robust, reliable, and widely deployable biosensing technologies. Full article

Background/Objectives: Hypoxic–ischemic encephalopathy (HIE) remains a leading cause of neonatal death and long-term neurodisability. Cardiovascular dysfunction commonly accompanies HIE and influences neurological recovery, yet it is difficult to recognize because conventional clinical signs correlate poorly with the myocardial function. This review summarizes the current evidence on cardiac dysfunction in neonates with HIE, with particular attention to the diagnostic tools used to evaluate cardiovascular function and the clinical outcomes associated with myocardial injury. Methods: We conducted a narrative review informed by a systematic, reproducible search of four databases (PubMed, Embase, Cochrane Library, and Web of Science) from 2000 to 2026, using a Population–Concept–Context framework to identify studies of term and near-term neonates (≥35 weeks gestation) with HIE or perinatal asphyxia reporting a measure of cardiac dysfunction (electrocardiographic, biomarker, echocardiographic, or clinical hemodynamic). Records were screened and selected using Covidence systematic review software; eligible studies were original, primary-data reports with a minimum sample size of 20 neonates. Findings were synthesized narratively and grouped thematically by diagnostic modality and clinical outcome. Results: Eighty-one studies met the pre-specified eligibility criteria following a systematic multi-database search and structured screening process. As a subset of included studies are secondary analyses or overlapping cohorts, an aggregate patient count is not reported. Reported prevalence of cardiac dysfunction varied widely with the definition applied, reaching 70–90% when multimodal assessment was used. Blood pressure, heart rate, urine output, and lactate were inconsistently reliable indicators of myocardial function, and ejection fraction and fractional shortening often remained normal despite injury. Tissue Doppler imaging and speckle-tracking strain appeared to be more sensitive, with impaired left ventricular global longitudinal strain associated with brain injury. The right ventricle was more commonly and severely affected, with reduced TAPSE, RV fractional area change, and RV strain associated with death or MRI-defined injury. Each additional 24 h of inotropic support was associated with increased odds of adverse short- and long-term outcomes by 14% and 12%, respectively. Conclusions: Cardiac dysfunction is common and prognostically important but remains underrecognized by the routine clinical assessment and cardiovascular monitoring. Multimodal monitoring centered on TnECHO, near infra-red spectroscopy, and specific biomarkers may enable earlier, physiology-based management. Full article