This study aims to synthesise and interpret evidence relating to fluoride-free toothpaste alternatives for caries prevention, examining how these products have been studied, the outcomes used to evaluate them, and how this evidence may inform discussions with children and families. A scoping review was undertaken. Electronic searches of major bibliographic databases identified peer-reviewed studies published between January 2020 and March 2026 evaluating fluoride-free toothpaste formulations. Data were extracted on intervention type, study design, outcome measures, and population characteristics and synthesised narratively with emphasis on patterns of evidence generation rather than comparative effectiveness. A total of 122 studies were included, comprising predominantly laboratory and mechanistic investigations, with only 20 studies providing direct paediatric evidence. Fluoride-free formulations were associated with antimicrobial activity, biofilm modulation, and surrogate remineralisation outcomes. Direct assessment of clinical caries outcomes was uncommon, and substantial heterogeneity was observed in formulation composition, study design, and outcome selection.  Fluoride-free toothpaste formulations demonstrate measurable biological effects, but evidence is dominated by surrogate outcomes and short-term study designs. While hydroxyapatite-based products have the most consistent evidence base, no fluoride-free category currently has evidence comparable to fluoride for long-term caries prevention in children. • Fluoride toothpaste has strong evidence for long-term caries prevention. • Fluoride-free alternatives are increasingly used, but existing evidence is largely based on surrogate or short-term outcomes. • Across formulations, observed effects are driven more by study design, delivery context, and outcome selection than by specific ingredients. • No fluoride-free category shows equivalent clinical evidence to fluoride for long-term caries prevention, although hydroxyapatite demonstrates relatively more consistent, yet still limited data.
Digital Protein A Membrane Chromatography (DMCPrA) introduces an innovative antibody purification method that enables gentle elution using electrical fields rather than conventional low-pH buffers. By eliminating acidic conditions, DMCPrA mitigates antibody degradation and aggregation associated with traditional Protein A chromatography. In this study, we investigated electrically driven elution in preparative Protein A membrane chromatography with the i3 DMCPrA device (i3 Membrane GmbH, Radeberg, Germany). The effects of applied voltage, buffer composition, and salt type and concentration were systematically evaluated to clarify the underlying elution mechanisms. Effective elution occurred only with low-conductivity buffers and solutions, requiring specific salts at appropriate concentrations, for example 0.15 mM Na₂SO₄ or 1.0 mM NaCl, which yielded high antibody recovery. Applying voltage to induce elution, showed consistent pH shifts. When the electric field was oriented from anode to cathode, the pH increased, representing the optimal condition for voltage-driven elution; reversing polarity decreased the pH. The results support the hypothesis that the elution mechanism is primarily driven by electrochemical reactions at the electrodes, leading to water electrolysis. Hydroxide ions resulting from cathodic hydrogen evolution reactions (HER) increase pH, while protons from anodic oxygen evolution reactions (OER) likely induce conformational changes in Protein A and IgG, initiating elution. These reactions are strongly influenced by the applied voltage as well as the chemical composition and ionic properties of the buffers. Collectively, these parameters exert a significant impact on elution efficiency and reproducibility. This work demonstrates that electrically driven elution provides a promising alternative to low-pH based methods, enabling milder purification of antibodies through electrochemical modulation.
Live cell-based assay (LCBA) is the gold standard for sensitive detection of aquaporin-4 (AQP4) and myelin oligodendrocyte glycoprotein (MOG) autoantibodies in neuromyelitis optica spectrum disorder (NMOSD) and MOG antibody-associated disorder (MOGAD). However, LCBA is less practical, standardisable and cost-effective than fixed cell-based assay (FCBA). We developed a high-performance untransfected vector cells lysate, named AbFine, to process patients' sera to pre-bind and deplete interferents before FCBA, and examined its rationality. We then conducted a multicentre, double-blind, prospective discovery study to compare the diagnostic accuracy of conventional FCBA, FCBA-AbFine, and LCBA in detecting AQP4-IgG and MOG-IgG. A retrospective validation cohort was used to assess generalisability. Participants included patients with NMOSD, MOGAD, and seronegative inflammatory demyelination syndromes, and controls with other neurological disorders. 818 participants were recruited, including 410 in the discovery and 408 in the validation cohorts with good consistency. Among 205 patients with NMOSD, AQP4-IgG was detected in 165, 185, and 178 by FCBA, FCBA-AbFine, and LCBA, yielding sensitivity of 80.5% (95% CI, 74.4-85.7), 90.2% (95% CI, 85.3-93.9), and 86.8% (95% CI, 81.4-91.1), respectively. Among 171 patients with MOGAD, MOG-IgG was found in 134, 155, and 158 by FCBA, FCBA-AbFine, and LCBA, with sensitivity of 78.4% (95% CI, 71.4-84.3), 90.6% (95% CI, 85.3-94.6), and 92.4% (95% CI, 87.4-95.9), respectively. All assays achieved specificity greater than 99.5%. The area under the curve for FCBA-AbFine was higher than that for FCBA for both AQP4-IgG (0.950 vs. 0.902; p < 0.0001) and MOG-IgG (0.935 vs. 0.888; p < 0.05), and was comparable to LCBA (AQP4-IgG 0.950 vs. 0.934; MOG-IgG 0.935 vs. 0.940; p > 0.05 for both). AbFine enables the use of FCBA as an alternative to LCBA in AQP4-IgG and MOG-IgG detection with operationally practical and cost-efficient characteristics and could be extended to other fixed cellular assays. Beijing Precigen Biopharma Co., Ltd., Beijing, China.
The past decade has seen increased research interest on the possible alternatives to cement in concrete and mortar, with materials that are environmentally friendly, economical, and socially inherent. However, recycling, reusing, and regenerating methods may be used to harness the potential benefits of agricultural/industrial wastes as alternatives. The utilization of these recyclables as supplementary and alternative resources yields notable energy conservation and a reduction in cement consumption, thus contributing to the mitigation of carbon dioxide (CO₂) emissions in the environment. Moreover, groundnut shell ash (GSA) is utilized as a substitution for cement in the mixture. The proportion of cement substitution with GSA ranged from 0% to 20% in order to examine the characteristics of concrete and mortar. Concrete samples were cast and tested at 7th, 14th, 28th, and 90th days. Cube, cylinder, and prism specimens were cast for assessing the compressive, flexural, and splitting tensile strengths of concrete consistently. It was discovered that the highest compressive and splitting tensile strengths were 13.39% and 12.69%, respectively, over the control at 90 days, and the flexural strength was 10.64% at 28 days of curing over the control for 10% GSA cement replacement. Also, the water absorption, and drying shrinkage dropped with the increased content of GSA. Besides, the utilization of GSA in the mixture has reduced the embodied carbon. Furthermore, utilizing ANOVA, response prediction approaches were produced at a 95% significance level. The models demonstrated R² ranging from 96 to 99%. Therefore, the research study's findings indicate that the addition of GSA in concrete positively affects the concrete and mortar properties and recommends a 10% substitution of cement in the mixture.
Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome is a rare multisystem paraneoplastic disorder. The syndrome presents unique perioperative challenges, including sclerotic bone changes that may preclude conventional neuraxial techniques. The ultrasound-guided sacral erector spinae plane (SESP) block represents a novel interfacial plane block that offers an alternative approach for sacral region analgesia. We describe a 58-year-old man with POEMS syndrome who presented with an acute perianal abscess requiring surgical drainage. The patient exhibited multiple high-risk features: sacrococcygeal sclerosis preventing identification of the sacral hiatus, severe hyperkalemia (6.54 mmol/L), stage 3 chronic kidney disease, pericardial effusion, and previous ischemic stroke. These comorbidities rendered traditional caudal epidural block contraindicated and general anesthesia high risk. Under ultrasound guidance, a single-shot SESP block was performed at the S3-S4 level using 25 mL of 0.2% ropivacaine with 25 µg dexmedetomidine. The block provided complete intraoperative analgesia (visual analog scale [VAS] score of 0) and effective postoperative pain control (VAS score <2 for 24 hours), facilitating successful surgery and discharge on postoperative day 1. This case demonstrates that the SESP block is a feasible and effective alternative for patients with complex conditions such as POEMS syndrome, where neuraxial techniques are anatomically precluded or clinically contraindicated. Based on this experience and supporting literature, the SESP block warrants consideration as a valuable component of multimodal analgesic strategies for anorectal and pelvic floor surgery, particularly in high-risk patients with challenging anatomy or significant comorbidities.
Subcutaneous antibiotic administration is increasingly considered an alternative to intravenous therapy in selected patients. It can facilitate early discharge and outpatient management when oral treatment is not possible. We retrospectively evaluated the effectiveness and tolerability of subcutaneous ceftriaxone, teicoplanin, and ertapenem in adults treated in a tertiary care infectious diseases center between January 2017 and February 2023. A total of 136 patients were included. The median age was 64 years (interquartile range 53-78), and 38% were older than 75 years. Bone and joint infections (45.6%), urinary tract infections (25.7%), and pulmonary infections (22.1%) were the most frequent indications. Overall clinical cure was achieved in 126/136 patients (92.6%). Cure rates reached 100% for urinary tract and cardiovascular infections and 96.7% for pulmonary infections. Twenty-one adverse events were reported, including injection site pain in 11 patients (8.1%). No severe local complication occurred. Teicoplanin trough concentrations, available in three patients with adverse events, remained within the therapeutic range. These findings support subcutaneous ceftriaxone, teicoplanin, and ertapenem administration as a safe and effective alternative when oral or intravenous therapy is not feasible.
Coordination between the deltoid and rotator cuff (including subscapularis) muscles is critical to maintain dynamic stability of the glenohumeral joint. Organisation of the primary motor cortex (M1) might provide insight into how this coordination is controlled. Task specific organisation of the motor cortex would imply that individual muscles are controlled by multiple cortical regions subserving different functions, and that multiple muscles involved in a task are controlled by a common region. Alternatively, the cortex might be organised in a muscle-specific manner. This study compared these alternatives. Transcranial Magnetic Stimulation (TMS) was used to investigate the motor cortex representations of the middle deltoid and subscapularis muscles during two tasks (isometric abduction and internal rotation) in nineteen pain-free adults. Muscle-specific hotspots and active motor thresholds were identified. TMS maps were generated for each muscle during the tasks. Novel measures were used to quantify the extent of overlap between TMS map pairs. Overlap was observed between deltoid and subscapularis maps during the same task - consistent with TASK-specific organization. Overlap was also evident within the same muscle between tasks - aligning with a MUSCLE-specific organization. Subscapularis had a greater bias to MUSCLE-specific organisation. Results suggest coexisting principles of MUSCLE- and TASK-specific representations in M1 for the control of shoulder muscles. Differences between organisation of the rotator cuff and deltoid muscles might have functional relevance. This study provides insight into the M1 cortical organization principles underlying shoulder motor control.
Mosquito larval source management remains a critical strategy for malaria control, but traditional methods for mapping breeding sites are labor-intensive and slow. While drones offer a promising tool, their application is often hindered by reliance on costly orthomosaic generation (stitching drone images into precise, georeferenced maps) and multispectral sensors, creating significant barriers for resource-limited health programs. This study developed an alternative workflow using a deep learning approach for water body segmentation. We utilized the DeepLabV3 + architecture with an EfficientNetV2 backbone on still RGB and Grayscale drone imagery, bypassing the need for orthomosaics by directly georeferencing individual images using GPS metadata. The model was trained and evaluated on a dataset of over 4,400 images from Pangandaran Regency, Indonesia, with performance assessed via the Intersection over Union (IoU) metric. Predictions were validated through field inspections to confirm water presence and larval abundance. The model achieved a mean IoU of 0.86 on RGB images and 0.80 on Grayscale data, demonstrating robust performance even with minimal spectral information. Field validation of 47 predicted sites confirmed water presence in all cases (100% confirmation of water presence), with 31.9% found to contain mosquito larvae, including the primary local vectors Anopheles vagus and An. sundaicus. The entire workflow, from cloud-based processing to field localization, was executed without specialized hardware or software. Our findings demonstrate that a deep learning-based analysis of still drone imagery provides a scalable, cost-effective, and rapid alternative to multispectral and orthomosaic-dependent methods for larval habitat mapping. This approach democratizes advanced surveillance technology, significantly shortens the delay between data collection and intervention, and holds great promise for enhancing the efficiency of vector control programs in malaria-endemic regions.
This study explores the role of the Monash Health Disability Liaison Officer program in supporting people with disability to access appropriate care pathways and avoid unnecessary emergency department (ED) presentations where possible. Using data from July to December 2024, we analysed 123 referrals with recorded ED-relevant outcomes. Associations between ED diversion and referral characteristics were examined using chi-squared or Fisher's exact tests for categorical variables, and Mann-Whitney U tests for continuous variables. At the referral level, 62.6% of referrals had at least one episode of ED diversion to alternative care pathways, such as general practice, Medicare Urgent Care Clinics or direct hospital admission. Significant associations were observed between ED diversion and referrals related to the management of chronic conditions requiring coordinated care and barriers to healthcare access (P = 0.005 and P < 0.001). These findings suggest that the Disability Liaison Officer model may support access to alternative care pathways and facilitate ED diversion for some people with disability who require coordinated supports across health and social care systems.
Neovascular age-related macular degeneration (nAMD) is a leading cause of blindness worldwide. Anti-VEGF agents are very beneficial for nAMD, with intravitreal (IVT) delivery becoming the gold standard for treatment of nAMD and other retinal conditions. Incomplete response remains a major challenge, as does the requirement for high-frequency, repeat IVT injections, which pose a significant burden on patients. Many potential drug candidates have attractive pharmacodynamic profiles but are limited by their insolubility, precluding IVT administration. These include tyrosine kinase inhibitors (TKIs), which target multiple receptors regulating angiogenesis, including the VEGF receptors. Thus, there is a great need for alternative treatment approaches. To this end, we developed a crystallization formulation approach for sorafenib (SFB), a very hydrophobic anti-angiogenic, multi-receptor TKI, for sustained intraocular release. We evaluated the efficacy of this formulation in two mouse models of nAMD: laser-induced choroidal neovascularization (LI-CNV) and Vldlr knockout (Vldlr-/-). Crystalline sorafenib ("Crystal SFB") exhibited controlled, prolonged drug release across both an accelerated release assay in vitro and in C57BL/6 mice, with ~13% remaining in the eye after 28 days in vivo. Further, a single IVT injection effectively suppressed both neovascularization and vascular leakage, two critical clinical parameters in nAMD, for at least 28 days. IVT administration of Crystal SFB did not have discernible adverse effects on intraocular pressure, retinal morphology assessed by OCT, or neuroretinal function as measured by ERG. These results suggest that Crystal SFB offers a promising alternative for long-term nAMD management and a proof-of-concept for ocular utilization of other crystallized drugs.
Rituximab combined with short-term corticosteroids is the standard first-line treatment for pemphigus, but a subset of patients remains refractory, with limited effective alternatives. Daratumumab, an anti-CD38 monoclonal antibody targeting plasma cells, has emerged as a potential option in severe autoimmune diseases. We report two cases of life-threatening pemphigus refractory to rituximab and alternative therapies, successfully treated with daratumumab, with longitudinal clinical and immunological monitoring of anti-desmoglein responses. Rituximab failure was associated with incomplete B-cell depletion, with persistence of memory B cells and plasmablasts. Daratumumab induced rapid clinical improvement, depletion of CD38+ plasma cells, and reduction of anti-desmoglein antibodies. In one patient, relapse occurred after daratumumab discontinuation, with subsequent rituximab inefficacy due to anti-rituximab antibodies; combined daratumumab and belimumab led to sustained complete remission, likely through complementary targeting of plasma cells and prevention of autoreactive B-cell reconstitution. In the second patient, remission induced by daratumumab was consolidated with additional rituximab. No treatment-related adverse events were observed. These findings suggest that daratumumab, alone or in combination with B-cell-targeting agents, may represent a promising therapeutic strategy for rituximab-refractory pemphigus.
Adsorbed natural gas storage using porous materials at ambient temperature and relatively low pressure promises to address safety and cost concerns of conventional natural gas storage technologies (liquefaction and compression), but its utility is hindered by low deliverable capacity. Flexible porous materials such as metal-organic frameworks can exhibit isotherms with the potential to afford enhanced deliverable capacity. However, prototypal flexible adsorbed natural gas sorbents, exemplified by the metal-organic framework cobalt benzenedipyrazolate, Co(bdp), suffer from hydrolytic instability and are unsuitable for pelletization. Here we report a family of metal-bipyrazolate frameworks, including hydrophobic sorbents, Zn(dpt) and Co(dpt) (H2dpt = 2,5-di(1H-pyrazol-4-yl)thiophene), that exhibit methane-induced reversible transformations between narrow-pore and large-pore phases. Zn(dpt) shows exceptionally high methane deliverable capacities for 5-35 and 5-65 bar, that is, 173 cm3 (STP) cm-3 and 225 cm3 (STP) cm-3, respectively, but, unlike Co(bdp), is hydrolytically stable. In situ structural characterization, high-pressure gas sorption and modelling provide an insight into the narrow-pore-large-pore transformations, whereas testing with 250-ml tanks reveals that Zn(dpt) retains high deliverable capacity over multiple cycles. We demonstrate a practical alternative to pelletization through a formulation approach that is probably generally suitable for flexible sorbents.
Neoadjuvant dual HER2 blockade with trastuzumab and pertuzumab plus chemotherapy represents the current standard-of-care for HER2-positive breast cancer. However, treatment responses remain heterogeneous, underscoring the lack of clinically practical tools for predicting treatment efficacy and informing personalized therapy. Here, we developed HER2-LADDER (Layered AI-based Dual-targeteD anti-HER2 Recommendation), a spatially interpretable and clinically accessible artificial intelligence framework that integrates clinicopathological and spatial topological features from routine hematoxylin and eosin (H&E) and HER2 immunohistochemistry (IHC) slides. Using these spatially derived features, HER2-LADDER accurately predicted response to neoadjuvant TCbHP/PCbHP, achieving AUCs of 0.944 in the model construction cohort (N = 276), 0.917 in the temporal validation cohort (N = 82), and 0.869 in the trial-based validation cohort (N = 85). On the basis of HER2-LADDER scores, patients were stratified into Low (highly responsive), Medium (responsive), and High (resistant) groups, identifying candidates for treatment de-escalation (THP or TCbH/PCbH), standard-of-care (TCbHP/PCbHP), or alternative regimens (e.g., next-generation anti-HER2 antibody-drug conjugates), respectively. Importantly, Xenium in situ profiling further revealed biological correlates underlying model predictions, including HER2-enriched tumor cell aggregation and neutrophil-helper T-cell interactions, thereby highlighting the mechanistic interpretability of the model. Collectively, HER2-LADDER unites digital pathology and high-resolution spatial profiling into a clinically accessible AI framework, offering a robust, transparent, and biologically grounded tool to tailor individualized HER2-targeted therapy optimization.
Pseudomonas aeruginosa is a major opportunistic pathogen associated with high morbidity in hospitalized patients due to its intrinsic and acquired resistance mechanisms. Carbapenem resistance, often mediated by the production of carbapenemase, poses a critical therapeutic challenge worldwide. This study investigated the genomic organization, molecular diversity, and plasmid-mediated dissemination of carbapenemase genes in P. aeruginosa isolates from hospitals in Paraná and Santa Catarina, Brazil, and explored their correlation with phenotypic resistance profiles. Eight isolates (80%) were classified as extensively drug-resistant (XDR), showing broad resistance to β-lactams, carbapenems, and β-lactam/β-lactamase inhibitor combinations. Multi-Locus Sequence Typing revealed a heterogeneous clonal structure, with ST1560 being the predominant type (30%). Multiple β-lactamase genes were identified, including chromosomal blaPDC variants, blaOXA-50, and carbapenemase genes blaSPM-1, blaIMP-16, blaIMP-1, blaVIM-2, blaKPC-2, and blaNDM-1. Notably, 40% of isolates carried plasmid-borne carbapenemase genes, indicating a potential for horizontal gene transfer. Isolate 20,783 exhibited high resistance despite lacking additional carbapenemase genes, suggesting alternative mechanisms such as efflux or porin loss. The predominance of XDR P. aeruginosa,which harbors diverse carbapenemases, including plasmid-mediated determinants, underscores the complexity of antimicrobial resistance in Brazilian hospitals. The coexistence of multiple resistance mechanisms, coupled with clonal heterogeneity, highlights the urgent need for integrated genomic surveillance and targeted infection control strategies to mitigate the spread of multidrug-resistant P. aeruginosa in clinical settings.
The superior temporal cortex has long been implicated in the perception of vocal sounds, yet most evidence remains correlational. Establishing causal necessity requires demonstrating that disruption of specific neural circuits produces selective perceptual deficits. Here, we report a pediatric patient who underwent intracranial EEG following resection of a left temporal pilocytic astrocytoma that removed anterior and middle superior temporal cortex but spared posteromedial Heschl's gyrus (pmHG) and posterior superior temporal gyrus (pSTG). During an auditory task, broadband high-gamma activity revealed voice-selective responses in pSTG, whereas pmHG showed robust auditory responses without category sensitivity. During a two-alternative forced-choice voice-nonvoice discrimination task, direct electrical stimulation of either pmHG or pSTG produced acute, reversible knockouts of categorization, whereas control-site stimulation did not. Cortico-cortical evoked potentials, Granger causality, and diffusion tractography demonstrated preserved bidirectional connectivity between pmHG and pSTG, indicating an intact posterior auditory circuit despite extensive anterior temporal loss. Together, these findings provide causal evidence that categorical voice perception depends on coordinated activity across posterior primary and nonprimary posterior auditory cortex.
Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) are widely used for resecting large, laterally spreading colorectal polyps. While ESD offers higher en bloc resection rates, its comparative efficacy and safety relative to EMR remain uncertain, particularly in Western practice. This systematic review and meta-analysis aimed to evaluate the recurrence and adverse event rates of EMR versus ESD in adult patients with colorectal polyps  ≥ 20 mm. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing EMR and ESD for colorectal polyps. Ovid MEDLINE and Embase were searched from inception to April 2024. The primary outcome was recurrence rate; secondary outcomes included total adverse events, bleeding, and perforation. Certainty of evidence was assessed using the GRADE framework. In this meta-analysis of three randomized controlled trials including 484 patients, ESD was associated with significantly lower recurrence rates compared to EMR (OR 3.24, 95% CI: 1.58-6.64), with high certainty of evidence. There were no significant differences between EMR and ESD in total adverse events (OR 0.96, 95% CI: 0.43-2.17), bleeding (OR 0.96, 95% CI: 0.41-2.27), or perforation rates (OR 0.96, 95% CI: 0.14-6.65), though certainty for these outcomes was moderate due to heterogeneity and imprecision. ESD is associated with significantly lower recurrence rates compared to EMR in the treatment of large colorectal polyps, with high-certainty evidence. These findings support the use of ESD when recurrence risk is a primary concern, while EMR remains a feasible alternative with comparable safety. CRD420251048732.
Histopathological diagnosis of cutaneous drug eruptions (CDEs) presents a challenge in dermatopathology due to morphological overlap and high inter-observer variability. This retrospective study systematically compares the diagnostic performance of modern convolutional neural networks (ConvNeXt, ResNet 152, EfficientNet), hierarchical vision transformers (Swin Transformer), and traditional machine learning algorithms (HGBT, XGBoost) on whole-slide images (WSIs) of CDEs and validates decisions using explainable artificial intelligence (XAI). We analyzed 443 WSIs collected between 2014 and 2024, encompassing three diagnostic classes: CDE (n = 194), Atopic Dermatitis (n = 187), and histologically normal skin controls (n = 62), thereby better reflecting real-world clinical diagnostic challenges. Following controlled data augmentation to 600 images (200 per class), all models were evaluated on a held-out 20% test set (n = 120) using accuracy, sensitivity, specificity, precision, and F1-score across all three classes. Each WSI was processed as a single resized (512 × 512 pixels) sample; no sub-patch tessellation or patch-level aggregation was performed. Gradient-weighted Class Activation Mapping (Grad-CAM) was applied to visualize the histological regions influencing model decisions. ConvNeXt emerged as the highest-performing model, achieving the highest accuracy rate (88.98%) and demonstrating strong multi-class differential diagnosis capability. ResNet 152 and Hybrid Feature Fusion models also achieved highly competitive results (86.44% accuracy). ConvNeXt demonstrated a statistically significant advantage over traditional methods and legacy architectures (p < 0.05). Histogram-Based Gradient Enhancement Classification Tree (HGBT) and XGBoost were effective among traditional models, with accuracies of 77.97% and 77.12%, respectively. Grad-CAM confirmed that models focused on clinically meaningful histological features, including basal vacuolar degeneration and eosinophilic infiltration. These findings suggest that advanced deep learning architectures, particularly ConvNeXt, may assist pathologists as a decision-support and triage tool in multi-class CDE diagnosis; ensemble methods offer a viable alternative in resource-constrained settings. Pending external validation, these XAI-supported models have the potential to provide transparent, reproducible diagnostic assistance in dermatopathology.
Approximately 25% of sexually transmitted infections (STIs) in Philadelphia involve teens and birth rates among underserved youth is more than double the national average. Proud Teens of Philly (PTOP), a community-based youth-oriented sexual-health education program, aims to mitigate disparities among underserved youth, including Latino/Hispanic and Black youth. This study assessed the impact of PTOP on sexual-health education and behaviors among Philadelphia youth. Participants were recruited from schools, churches, and community-based organizations, to attend eight one-hour-long virtual synchronous sessions. Evidence-based sexual-health curricula, Positive Potential and Making Proud Choices, were administered to 650 Philadelphia students aged 12-18 during the 2021-2022 academic year. Pre- and post-surveys were administered electronically to collect data on demographics, sexual attitudes, HIV/STI knowledge, contraception knowledge and access, confidence in consent and condom use, and life skills. Paired t-tests comparing pre- and post-survey responses were conducted. Participants demonstrated significant improvement in knowledge (t = 10.48, p < 0.0001) regarding STI transmission, HIV pre-exposure prophylaxis, and birth control. They felt more prepared to reject unprotected sex (t = 4.81, p < 0.0001) and better understood the efficacy of condoms. PTOP curricula increased exposure to alternative forms of contraception. In addition, students gained valuable skills in communication, goal setting, and emotion management. Engagement in a comprehensive sexual-health education program can significantly improve STI knowledge, sexual attitudes, and consent among underserved youth populations. Increased knowledge and emotion management empower teens to make safer choices, potentially limiting engagement in and adverse outcomes of risky sexual behaviors. Future studies should explore longitudinal impacts of youth-oriented sexual-health educational programs.
During the Medically Assisted Reproduction (MAR) pathway, the treatment termination is a critical phase. This study aims to explore the lived experiences of patients discontinuing homologous reproduction by a) examining how they perceive the clinician relationship in the decision‑making process, and b) exploring the factors that motivate patients to pursue third‑party reproduction or permanently forgo the treatment. This qualitative study employed Interpretative Phenomenological Analysis. Through convenience and purposive sampling, the study engaged patients who 1) have completed at least one cycle of homologous reproduction without live birth; 2) are currently awaiting third-party reproduction treatment or have permanently discontinued treatment within the past 36 months; (3) are Italian-speaking adults. Participants completed an online questionnaire to gather sociodemographic and clinical data and were involved in semi-structured interviews. The sample included 21 participants. Of the 13 interviews conducted, five interviews were conducted with the woman alone, and eight were conducted with both partners present. The analysis yielded five overarching themes: 1) The MAR pathway: from diagnosis to the end of homologous treatment; 2) the clinician-patient relationship throughout the MAR journey and at treatment conclusion; 3) the dyadic decision-making process and couple communication; 4) the decision to transition to third-party reproduction; 5) the decision to permanently discontinue treatment. The findings highlight the communicative and relational dimensions of care as critical determinants of patients' experiences and decisions. Patients provide specific indications for improving the planning of MAR pathway, establishing goals and potential alternatives in advance. Healthcare professionals should share timely, evidence-based information and actively engage patients. The integration of these practices into routine MAR care has the potential to improve not only patients' satisfaction and their psychological wellbeing, but also the quality of care and appropriateness of decisions.
Tyrosine kinase inhibitors (TKIs) have improved outcomes in Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) and are increasingly incorporated into treatment protocols of Philadelphia chromosome-like (Ph-like, ABL-class) ALL. However, central nervous system (CNS) relapse remains a significant challenge. Imatinib, a first-generation TKI, demonstrates limited CNS penetration in adults, yet data in children are sparse. This prospective, multicenter study investigated cerebrospinal fluid (CSF) and matched plasma concentrations of imatinib and its primary bioactive metabolite (N-desmethyl-imatinib) in children and young adults with Ph + or Ph-like (ABL-class) ALL. Plasma and CSF samples were analyzed with liquid chromatography tandem mass spectrometry (LC-MS/MS). Linear mixed-effects models were used to assess concentrations across compartments and over time. Between January 2023 and June 2025, 32 paired plasma and CSF samples were collected from ten patients (range 1-8 samples/patient; median: 3). In total, 78% of plasma imatinib concentrations were above 1,000 ng/mL. On average, plasma imatinib concentrations were 189-fold higher than in CSF (geometric mean ratio, 95% CI: 142-249, p < 0.001), which was even more profound for N-desmethyl-imatinib (geometric mean ratio 273, 95% CI: 218-339, p < 0.001). The highest measured CSF-imatinib concentration was 63 ng/mL. During therapy, both plasma and CSF imatinib concentrations declined at an average of 0.32% per day (p < 0.001), resulting in stable CSF-to-plasma ratio over a median follow-up of 5.7 months (range: 0-14 months). The very low CSF concentrations support the rationale for alternative TKIs with improved CNS distribution in patients at risk of CNS relapse.