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Community pharmacists' perspectives on resupplying and prescribing contraceptives: a descriptive qualitative study in Australia.

OBJECTIVES: Australia has commenced implementing contraceptive resupply and prescribing by community pharmacists to improve equity in method access. This study aimed to investigate pharmacist's acceptability of hormonal contraceptive resupply and prescribing. METHODS: Participants were recruited via convenience sampling and had provided contraceptive counseling consistent with the ALLIANCE intervention (i.e. structured, patient-centered, effectiveness-based care) to women seeking the emergency contraceptive pill or presenting prescriptions for medical abortion medicines. This qualitative descriptive study was embedded within the ALLIANCE trial, whose process evaluation included semi-structured interviews with pharmacist participants. The interview guide, containing questions on pharmacists' views of the resupply and prescribing service, was reviewed by the ALLIANCE Trial Chief Investigators and piloted in June 2024 with the SPHERE Pharmacy Advisory Circle. Thirteen questions were developed using the Theoretical Framework of Acceptability (TFA). Two researchers conducted line-by-line coding using an iteratively refined codebook, with codes mapped to TFA constructs to examine operationalization in pharmacists' delivery of hormonal contraception. KEY FINDINGS: Although pharmacists (n = 24) perceived that the service could be cost- and time-saving to patients, they raised concerns of unintentionally removing general practitioner (GP)-led monitoring of patients and overstepping GPs' roles. While pharmacists felt confident in their expertise and generally supported the service, they expressed hesitation about initiating contraceptive prescriptions, for which they felt further training and access to comprehensive medical records were required. Additional barriers included increased workload pressures, lack of reimbursement, and inadequate staffing. CONCLUSIONS: Overall, providing a resupply service appears to be acceptable to community pharmacists because it relies on the GP's initial assessment but prescribing less so. However, evaluation is needed post-implementation to explore sustainability, feasibility, and long-term impact on patient outcomes.

contraception

Simultaneous determination of imiquimod and terbinafine in skin permeation studies: Validation of a liquid chromatography method with fluorescence detection.

Chromoblastomycosis is a chronic, neglected subcutaneous mycosis posing significant therapeutic challenges. A topical strategy combining terbinafine (TBF), an antifungal, with imiquimod (IMQ), a TLR-7/8 agonist immunomodulator, has emerged a promising alternative. However, no validated analytical method is currently available to simultaneously quantify both drugs in skin, which is crucial for novel formulation development. This study reports the development and validation of a simple HPLC method with fluorescence detection (excitation 236 nm, emission 340 nm) for the simultaneous determination of TBF and IMQ extracted from porcine skin. Separation was achieved on a C8 reversed-phase column (125 × 4.0 mm, 5 μm) using a mobile phase of methanol and water (60,40, v/v), both containing 0.1% formic acid at a flow rate of 0.8 mL/min. The method showed excellent linearity (r > 0.999) over 0.01-1.0 μg/mL for IMQ and 0.1-2.0 μg/mL for TBF. Intra- and inter-day precision demonstrated coefficients of variation below 5%, and recovery rates from skin (79-105%) confirmed accuracy. Limits of detection were 0.001 μg/mL for IMQ and 0.004 μg/mL for TBF, with quantification limits of 0.02 μg/mL and 0.16 μg/mL, respectively. This selective, sensitive, and reproducible method represents a valuable analytical tool for supporting the development and quality control of topical formulations for chromoblastomycosis and other fungal skin diseases.

Animals

Impact of adenosine in controlled aortic root reperfusion on clinical outcomes among patients undergoing valvular heart surgery.

BACKGROUND: Adenosine is a vital medication in cardiac surgery, particularly in valvular heart procedures. While its use has been linked to improved postoperative cardiac function in some studies, there remains significant uncertainty regarding the adenosine usage in aortic reperfusion phase. This lack of consensus poses challenges for surgeons, perfusionists, and anesthesiologists alike. This study aims to explore the impact of adenosine on clinical outcomes in patients undergoing valvular heart surgery. METHOD: This prospective randomized controlled trial was conducted over a three-month period. Sixty patients undergoing valvular heart surgery were enrolled using a continuous sampling method and randomly allocated into two equal groups of 30 patients each. The intervention group received adenosine-enriched aortic root reperfusion immediately prior to aortic declamping, while the control group underwent standard warm blood aortic root reperfusion. Both groups were matched for demographic and clinical characteristics to ensure comparability. RESULTS: Results indicated no significant differences in mean cardiopulmonary bypass (CPB) time, aortic cross-clamping duration, or mechanical ventilation between the intervention and control groups. However, the intervention group that received adenosine had a higher rate of antiarrhythmic agent usage in the operating room (P&#xa0;<&#xa0;0.05). Inotropic agent usage was similar in both groups during surgery and in the ICU. Additionally, laboratory parameters on the first day of ICU admission were comparable between groups. CONCLUSION: Results in the control group showed more favorable outcomes in terms of anti-arrhythmic drug usage, electroshock application, and arrhythmia prevalence. This study showed advantages for the standard warm blood aortic root reperfusion technique in managing post-operative cardiac rhythm disturbances, in comparison with the trial group.

Humans

Development and validation of an LC-MS/MS method for the quantification of the KRASG12C inhibitor divarasib.

Divarasib is a newly developed covalent KRASG12C inhibitor, currently under clinical investigation in a phase 3 trial in patients with non-small cell lung cancer (NSCLC). At the moment, very limited pharmacokinetic data are publicly known. However, obtaining more insight into the pharmacokinetic properties of divarasib is important, since this may provide a better understanding of its efficacy and safety risks. Pre-clinical studies have been performed in mouse models to evaluate the effect of drug transporters and drug-metabolizing enzymes on the plasma exposure and tissue distribution of divarasib. Therefore, a reliable quantification method is required. To our knowledge, no bioanalytical assay of divarasib has been published yet. Therefore, in this study we developed and validated an assay to quantify divarasib in human plasma and in eight different mouse-related matrices, and partially in mouse plasma, using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The method was initially evaluated over a concentration range of 1-10,000&#xa0;nM. However, due to carry-over observed at 10,000&#xa0;nM, the validated calibration range was established at 1-2000&#xa0;nM, with matrix-dependent LLOQs of 1-10&#xa0;nM. Erlotinib was used as an internal standard and acetonitrile was utilized to perform protein precipitation as sample pretreatment. Divarasib demonstrated stability in human plasma and in mouse plasma and tissue homogenates under various experimental conditions. A pilot in vivo study showed the applicability of our validated LC-MS/MS method. Ongoing clinical trials may collect plasma samples, and this developed method enables quantification of divarasib in both mouse and human plasma samples.

Animals

Smart crutch tipsTM real-time feedback improves adherence to partial weight-bearing protocols following lower extremity fracture surgery: a pilot study.

PURPOSE: To evaluate the effectiveness of Smart Crutch Tips&#x2122; in promoting adherence to prescribed early partial weight-bearing (PWB) protocols and to assess patient experience with real-time weight-bearing feedback during home rehabilitation. METHODS: Twenty patients with lower extremity fractures prescribed partial weight-bearing (PWB) were randomized into two groups utilizing real-time feedback crutch tips (RFC). The Intervention group (n&#x2009;=&#x2009;10) used Smart Crutch Tips&#x2122; (ComeBack Mobility Inc., Kiev, Ukraine), which provided real-time feedback on weight-bearing compliance. The Control group (n&#x2009;=&#x2009;10) also used crutches equipped with Smart Crutch Tips&#x2122;, but notifications were disabled, allowing passive data collection without patient feedback. Weight-bearing compliance was defined as the percentage of steps within &#xb1;&#x2009;10% of the prescribed target. Secondary outcomes included patient satisfaction and device usability assessed using the System Usability Scale (SUS) throughout the home rehabilitation period. RESULTS: The Intervention group demonstrated significantly greater PWB compliance compared with the Control group (73.6% vs. 21.1%, p&#x2009;<&#x2009;0.01). The Intervention group reported a mean SUS score of 84.25, indicating excellent usability. No device-related complications or adverse events were observed. Patient satisfaction, assessed through video interviews, was high, with participants in the Intervention group expressing a strong willingness to recommend the device to others with similar injuries and rating it 10 out of 10. CONCLUSION: Smart Crutch Tips&#x2122; significantly improved adherence to prescribed partial weight-bearing protocols following lower extremity fracture surgery. The RFC device demonstrated high usability, excellent patient satisfaction, and no device-related complications during home rehabilitation throughout the study period.

Humans

Angiotensin II regulates anxiety and social-affective top-down and bottom-up attention control in a sex-dependent manner.

BACKGROUND: The renin-angiotensin system (RAS) has been increasingly recognized as potent modulator of cognitive and affective functions, with angiotensin II type 1 receptor (AT1R) antagonists emerging as repurposing candidate for anxiety and stress-related disorders. However, it remains unclear whether transient AT1R blockade modulates emotional attentional control and whether these effects are sex-dependent. METHODS: We conducted a preregistered, randomized, double-blind, placebo-controlled pharmacological eye-tracking study in 79 healthy adults (males and females) and determined effects of transient AT1R blockade via losartan (50&#xa0;mg) on emotional attention control using a validated anti-saccade paradigm with social (emotional faces) and non-social stimuli. Treatment effects on state anxiety and oculomotor responses were characterized using traditional metrics and a novel trial-history informed dynamic control framework. RESULTS: Losartan reduced state anxiety irrespective of sex but induced sexually dimorphic effects on attentional control. In females, losartan enhanced performance by reducing endpoint error without altering latency. Conversely, in males, losartan increased endpoint error and prolonged latency of the first correct saccade. Trial-history analyses revealed losartan reduced error probabilities following errors and repeat trials in both sexes. Yet, following correct trials, females receiving losartan maintained lower error probabilities, while males exhibited higher errors, potentially reflecting failure to disengage from effortful control. CONCLUSIONS: The RAS modulates anxiety and attentional control, the latter sex-dependently. AT1R blockade reconfigures attentional processing and adaptive control, suggesting sex-specific therapeutic potential in disorders characterized by excessive anxiety and attentional dysregulation. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov; https://clinicaltrials.gov/;NCT06329050.

Humans

Determination of 13 per- and polyfluoroalkyl substances in human plasma samples using LC-MS/MS: application to capillary microsamples.

Per- and polyfluoroalkyl substances (PFAS) are chemicals widely applied in industrial processes and highly persistent in the environment, whose extensive use has been linked to adverse health effects. Venous plasma is the conventional matrix for PFAS assessment in blood, and LC-MS/MS is the most used quantification technique. Despite the relevance of this topic, biomonitoring data on human exposure to PFAS in Brazil remain limited. This study validated an LC-MS/MS method for determination of 13 PFAS in human plasma. Blood samples were collected from volunteers by phlebotomy, followed by protein precipitation with acetonitrile containing 1% formic acid (v/v) and solid-phase extraction. Chromatographic separation was achieved on an Acquity UPLC HSS T3 column. The assay was linear over a calibration range of 0.2-20&#xa0;ng/mL. Intra- and inter-assay precision (CV%) were within the ranges of 2.06-12.0% and 0.25-10.7%, respectively. As for accuracy, results were 89.0-112.9%. Matrix effect ranged from -1.31 to 0.05%. Stability after four freeze/thaw cycles and under autosampler conditions were also confirmed for all analytes. The method was applied to 40 paired venous and capillary plasma samples. Both measures exhibited high correlation (r&#xa0;=&#xa0;0.926). PFOS was the only compound detected at concentrations &#x2265;0.2&#xa0;ng/mL (LLOQ) in all samples, with capillary plasma concentrations of 0.85-13.50&#xa0;ng/mL. In summary, the method showed good validation performance and demonstrated the suitability of capillary plasma samples as an alternative matrix for PFAS quantification.

Humans

Unravelling bioanalytical innovations, degradation processes, and impurity landscapes of VEGFR inhibitors.

From pre-formulation studies to clinical trials, VEGFR-targeted small-molecule tyrosine kinase inhibitors (TKIs) require rigorous analytical standards. Bioanalysis, stability-indicating studies, and impurity profiling are used to examine chromatographic advances for VEGFR-targeted TKIs like sunitinib, pazopanib, axitinib, sorafenib, cabozantinib, vandetanib, apatinib, lenvatinib, nintedanib, and regorafenib. An LC-MS/MS and UPLC-MS/MS routinely show sub ng/mL performance, as shown by LLOQs (0.2&#xa0;ng/mL) for sunitinib and axitinib, 1&#xa0;ng/mL for pazopanib, 5-7&#xa0;ng/mL for sorafenib, 0.5-1.5&#xa0;ng/mL for regorafenib metabolic products, and 0.1-0.5&#xa0;ng/mL for lenvatinib. These approaches are used for pharmacokinetics and therapeutic drug monitoring due to their good correlation coefficient of 0.1-10,000&#xa0;ng/mL, accuracy of 95%-108%, and precision of 15% RSD. UPLC-QTOF-MS/MS distinguishes degradants and metabolites during forced degradation studies, enabling structural elucidation following ICH M7 risk evaluation protocol. HPTLC/MLC offers fast, sensitive screenings, while RP-HPLC/DAD or HPLC-UV offer reliable, cost-effective routine quality-control solutions with LOD/LOQ in the &#x3bc;g/mL range and linearity of 10-240&#xa0;&#x3bc;g/mL. This review lists the structures and CAS numbers of ten VEGFR-2 TKI degradants and metabolites, as well as pharmacopeial impurities in SMILES forms. It will be useful for future method development and regulatory applications. To ensure VEGFR-targeted TKI quality, safety, and therapeutic efficacy, LC-MS/MS for trace quantification and HRMS for structure elucidation provide a robust, future-oriented framework. To improve VEGFR-targeted TKI quality, safety, and regulatory compliance, analytical development should focus on HRMS-based impurity characterization, AI-assisted degradation prediction, green chromatography, and harmonized bioanalytical validation.

Humans

Emerging techniques of CRISPR/Cas system in antiviral therapy and diagnostics: Applications, limitations, and translational perspectives.

The CRISPR/Cas (clustered regularly interspaced short palindromic repeats) system is a versatile technology for developing antiviral medicines and editing viral genomes in both diagnostics and vaccine synthesis. Emerging insights into class 2 effectors, such as Cas9, Cas12, and Cas13, which target viral DNA and RNA, have revolutionized vaccines against viruses such as HIV, HPV, HBV, and EBV. Innovative diagnostic techniques such as SHERLOCK, DETECTR, and FELUDA have demonstrated system's diversity and accuracy in detecting the virus markers, supporting clinical decision-making, indicating adaptability and precision of CRISPR. This review critically evaluates CRISPR's role in RNA editing, emphasizing its importance for functional genomics and development of recombinant vaccines. Translational challenges are critically discussed, including off-target effects, delivery limitations, and ethical issues, for which unique approaches such as high-fidelity Cas variants, non-viral delivery systems, and bioethical frameworks are evaluated to address these limitations. This review also covers other social implications, such as accessibility and biosecurity risks, associated with CRISPR technologies Collectively, these advances underscore the transformative potential of CRISPR technologies in shaping next-generation antiviral diagnostics and therapeutics.

CRISPR-Cas Systems

SBUF-SMUF: On the path to the optimum hemofiltration technique in pediatric cardiopulmonary bypass: A randomized clinical trial.

BACKGROUND: Hemofiltration during pediatric cardiopulmonary bypass (CPB) is essential to mitigate hemodilution, inflammatory responses, and postoperative complications. Conventional ultrafiltration (CUF) is widely practiced, but novel methods such as subzero balanced ultrafiltration combined with simple modified ultrafiltration (SBUF-SMUF) may offer superior outcomes. OBJECTIVE: To compare the clinical efficacy and safety of CUF versus SBUF-SMUF in pediatric patients undergoing open-heart surgery. METHODS: In this prospective randomized, outcome-assessor-blinded clinical trial, 80 pediatric patients with congenital heart disease were allocated to either CUF (n = 40) or SBUF-SMUF (n = 40) during CPB. Baseline demographics, intraoperative characteristics, fluid balance, blood product utilization, and postoperative outcomes were assessed. Statistical analysis was conducted using independent t-tests, Chi-square tests, and Fisher's exact tests. Statistical significance was defined as a two-tailed p-Value of less than 0.05. RESULTS: Demographic and preoperative variables were comparable between groups. Mean fluid balance was significantly positive in the CUF group (+192.1 &#xb1; 178.8 mL) but negative in the SBUF-SMUF group (-105.0 &#xb1; 78.9 mL, p < 0.001). The SBUF-SMUF group required significantly less intraoperative PRBC (141.7 &#xb1; 70.2 vs. 261.0 &#xb1; 68.8 mL, p < 0.001) and postoperative FFP transfusion (2% vs. 10%, p = 0.020). Post-bypass hematocrit levels were higher (31.2% vs. 27.3%, p = 0.001) and extubation occurred earlier in the SBUF-SMUF group (1.05 &#xb1; 1.03 vs. 2.27 &#xb1; 2.37 days, p = 0.006). No significant differences were observed in potassium levels or incidence of acute kidney injury. CONCLUSION: The SBUF-SMUF technique is safe, effective, and superior to CUF in optimizing fluid balance, reducing blood product utilization, and facilitating earlier extubation in pediatric cardiac surgery. No additional risk of oliguria or electrolyte imbalance was observed compared to CUF. Its simplicity and reproducibility support its consideration as a standard approach in pediatric CPB.

Humans

Wearable Sleep Monitoring in Pediatric Acute Lymphoblastic Leukemia: Associations With Subjective Sleep Ratings and Neurocognitive Functioning.

BACKGROUND: Sleep disturbances are associated with increased fatigue, reduced quality of life, and neurocognitive dysfunction and have emerged as a common complication among pediatric cancer survivors. Sleep disturbances are particularly concerning given their potential to exacerbate existing neurocognitive impacts of cancer treatments. This pilot study examined the feasibility and acceptability of a home-wearable EEG-based sleep device (Sleep ProfilerTM) for acute lymphoblastic leukemia (ALL) survivors as well as associations between specific sleep parameters and neurocognitive functioning. PROCEDURE: Children (ages 8-12; M = 10 years, SD = 1.6; N = 23) >6 months post-treatment for ALL were enrolled at clinical visits and wore the Sleep ProfilerTM for two consecutive nights at home, followed by neurocognitive testing of attention, inhibitory control, working memory, and processing speed. Parents completed subjective measures of child sleep, anxiety, depression, and acceptability. Feasibility reflected the percentage of children wearing the device at least one night and the percentage of nights with good EEG quality data. RESULTS: All participants wore the device both nights, with 84% meeting the threshold for good quality measurement. Few children met recommended quantity and quality sleep thresholds based on objective measurement, including 5 patients with elevated snoring levels; 43.5% of subjective ratings fell above the threshold for sleep disturbance. Greater sleep latency was associated with worse inhibitory control (r = -0.42, p = 0.046), and total sleep time was positively associated with inhibitory control and attention. CONCLUSIONS: Findings confirm the feasibility and acceptability of home EEG sleep monitoring in school-age survivors, and associations of sleep latency and snoring with reduced neurocognitive functioning may offer modifiable risk factors for aspects of neuropsychological dysfunction common in pediatric survivorship. CLINICAL TRIAL REGISTRATION: At the time this study was conducted, we were not required to register the study on ClinicalTrials.gov. It was a single-institution feasibility study without intervention, which was not considered a clinical trial.

Humans

E-cigarette product characteristics and packaging features and interest in e-cigarette use: Results from a randomized within-person trial nested in three prospective cohorts.

BACKGROUND: Product characteristics and packaging may be key targets for regulation to reduce e-cigarette use among youth, but existing data are limited. METHODS: Data are from an experimental study (2018-2020) nested within three prospective cohorts (age 14-26) in southern California (N&#x2009;=&#x2009;3565). Participants were shown five e-cigarette (e-liquid) packages in a random order that varied in flavor (sweet vs. tobacco), flavor name (descriptive ["blueberry cheesecake"] vs. concept ["smurf cake"] vs. none [number only]), and cartoon image on package (yes/no). For each stimuli, survey items assessed the following outcomes: product appeal (self-enjoyment, others' enjoyment; Likert scale [1-5]), susceptibility to use (use if friends offered, curiosity; 4 ordered responses [definitely not-definitely yes]), peer acceptability (definitely not-definitely yes), and perceived harm (definitely not-definitely yes). Mixed effects proportional odds models evaluated within-person effects of each factor (flavor, flavor name, cartoon) with each outcome. RESULTS: Participants reported greater appeal, susceptibility, and peer acceptability (OR range=3.7-16.9; ps<0.05), and lower perceived harm (OR=0.61; 95%CI=0.53, 0.70) for sweet (vs. tobacco-flavored) e-cigarettes; effects were progressively stronger for younger cohorts. The descriptive flavor name rated higher than the concept flavor (OR range=1.13-2.02; ps<0.05) or number only (OR range=1.18-1.69; ps<0.05) for appeal and susceptibility measures; no differences for concept vs. number were found. The cartoon image rated higher for appeal, curiosity, and peer acceptability (OR range=1.24-1.51; ps<0.05). CONCLUSIONS: Sweet flavors, descriptive flavor names, and cartoon images may increase the appeal of e-cigarettes among youth and young adults with no history of e-cigarette use, and are key targets for regulation.

Humans

Cost-Effectiveness of Electronic Patient-Reported Outcome Measure Interventions in Cancer: Systematic Review and Parameter Extraction for Economic Modeling.

BACKGROUND: Complex digital interventions that integrate electronic patient-reported outcome measures (ePROM) into clinical practice in cancer have the potential to improve quality of life, increase survival, and reduce health resource use and costs. Such systems can help patients with cancer self-manage chemotherapy symptoms, reduce clinicians' workloads through automated decision support, and resolve problems earlier. However, more research on the cost-effectiveness of ePROM monitoring is needed. OBJECTIVE: This paper comprises two complementary components: (1) a systematic literature review summarizing and evaluating the quantitative and qualitative evidence related to the cost-effectiveness of ePROM monitoring and (2) a health economic model parameter extraction. We also conducted supplementary targeted searches and scoping to provide context to our findings. METHODS: We searched Ovid (including MEDLINE and Embase), Scopus, and the International Health Technology Assessment Database for original English-language papers published on or before March 2025 using search strings that combined terms related to ePROMs, health economics, and cancer/oncology. We included papers reporting health economic-related outcomes for ePROM interventions designed for adult cancer populations and excluded screening tools and conference abstracts. RESULTS: We included 34 publications from 27 unique studies and identified and analyzed 26 ePROM-integrated interventions within these. Most (23/26) of the included interventions explicitly described some form of alert handling and automated decision support based on remote ePROM monitoring. Of the 34 publications, 5 presented full cost-effectiveness analysis results, of which 3 were highly uncertain and lacked clear differences in costs and health outcomes between ePROMs and standard care; conversely, 2 presented strong evidence of cost-effectiveness due to quality-of-life improvements, reduced hospitalizations, and potentially more autonomy in health-related travel (eg, ePROM-monitored patients can drive or walk to the hospital instead of using taxis or ambulances). A further 5 publications reported partial health economic results (eg, cost-consequence and budget impact), of which 1 detected no difference in strategies; in contrast, 4 reported lower health resource use and costs of ePROMs, mainly due to hospitalization reductions. Overall, 12 of the 27 studies included a qualitative component but mostly focused on user experience and design-related themes; only 2 of these addressed economic-specific themes (eg, changes in workflow and resource use due to ePROM implementation and integration), indicating some potential for time saving due to ePROM monitoring. CONCLUSIONS: Some ePROM-integrated interventions demonstrated cost-effectiveness in cancer care, but the evidence base remains limited. Where evidence does exist, cost-effectiveness appears driven by reduced hospitalization and improved quality of life. Qualitative research within the included studies rarely addressed economic questions. We provide a detailed parameter extraction for use in future economic modeling and recommend research priorities, including quantitative mapping of ePROM symptom data onto health resource use patterns, and qualitative work exploring how ePROM implementation affects clinical workloads and patient-perspective costs.

Humans

Predicting ACL injury risk in athletes: A systematic review of machine learning-based models.

BACKGROUND: Early ACL injury risk identification in athletes is essential. This systematic review examines machine learning (ML) models for predicting ACL injuries, evaluating their methodological quality, performance, and reliability. METHOD: A comprehensive electronic search was conducted across PubMed, Scopus, Web of Science, and IEEE Xplore databases, supplemented by Google Scholar for grey literature, covering articles published between January 1, 2015, and August 30, 2025. Eligible studies were appraised using the Prediction Model Study Risk of Bias Assessment Tool (PROBAST) for methodological quality and risk of bias, and the Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis (TRIPOD) guidelines for quality of evidence. RESULTS: Ten studies were included. PROBAST showed eight studies had moderate risk of bias and two low risk. TRIPOD found only two studies met quality criteria. ML models included logistic regression (n&#xa0;=&#xa0;5), support vector machines (n&#xa0;=&#xa0;4), k-nearest neighbor (n&#xa0;=&#xa0;3), decision trees (n&#xa0;=&#xa0;3), random forests (n&#xa0;=&#xa0;5), neural networks (n&#xa0;=&#xa0;2), linear discriminant analysis (n&#xa0;=&#xa0;1), and pre-trained CNNs (n&#xa0;=&#xa0;1). AUC ranged from 0.63 to 0.98. Accuracy (reported in six studies) ranged from 26% to 95%; however, these values should be interpreted with caution due to the absence of confidence intervals, lack of class imbalance handling, and limited external validation across studies. Tree-based ensemble methods such as random forest achieved competitive accuracy (74-86%), while SVM, a non-ensemble classifier, reported accuracy ranging from 71% to 95%; however, the highest values were obtained in studies with notably small sample sizes (n&#xa0;=&#xa0;12 to n&#xa0;=&#xa0;39), raising concerns about overfitting and generalizability. CONCLUSION: Current ML algorithms show promise for identifying athletes at high ACL injury risk and detecting relevant risk factors. Although study quality was generally satisfactory, future research should prioritize external validation and model interpretability to support clinical translation.

Humans

Probiotic-derived extracellular vesicles as food-based nanocarriers: Mechanisms, functional applications, and future perspectives in food systems.

Probiotic-derived extracellular vesicles (PDEVs) are a promising type of postbiotic nanoparticle derived by fermentation of probiotics, and have gained growing interest as a potential application in food science and nutrition. These are lipid bilayer vesicles of nanoscale, which are naturally released by probiotic cells and contain a wide variety of bioactive molecules, such as proteins, nucleic acids, and metabolites. Moreover, PDEVs are highly stable, biocompatible, and can be easily engineered to have surfaces with high functionality, which makes them good candidates in functional engineering. In contrast to traditional live probiotics, PDEVs overcome the difficulties of preserving microbial viability during processing and storage, thus providing superior safety, stability, and predictable biological performance. This is a systematic review of the various functions of PDEVs in food systems. We conclude on the processes through which PDEVs control intestinal barrier integrity, alter gut microbiota composition, and alter host immune responses, and their potential to enhance gut health when added to functional foods. In addition to their health-promoting effects, PDEVs have shown significant potential as natural antimicrobial agents to preserve food and as effective nanocarriers of hydrophobic bioactive compounds, including fucoxanthin, to improve their stability, bioavailability, and targeted delivery. Moreover, PDEVs can be used as new regulators of microbial fermentation. However, it should be noted that a lot of the evidence that is available is still preliminary and the effectiveness of these applications in real food-processing and storage conditions has not been fully proven. Although they have potential, there are a number of challenges that still hinder the widespread use of PDEVs in the food industry. These involve the creation of scalable and cost-effective production processes, batch-to-batch consistency, vesicle stability in a variety of food matrices, and regulatory and safety considerations. Other emerging engineering approaches, such as surface functionalization and cargo loading, are also discussed in this review and could further increase the specificity, functionality, and application versatility of PDEVs in food systems. Moving forward, the incorporation of PDEVs into the next generation functional foods, novel food preservation methods, and customized nutrition plans should be prioritized in future studies. Further developments in these fields can make PDEVs useful platforms at the interface of food microbiology, nanotechnology, and human health.

Probiotics

Temporal evolution of minimally invasive pediatric urolithiasis treatment over 30 years.

Urolithiasis in children has increased substantially over the past 30 years, and surgical management maintains an important role in treatment. Technological advances such as lasers and miniaturization have broadened treatment options, and researchers investigate the best indications for each procedure. The aim was to identify publication trends in the field and explore reasons why Extracorporeal Shockwave Lithotripsy is being gradually less applied in the treatment of pediatric urolithiasis. A Reverse Systematic Review of the literature was conducted regarding the surgical treatment of urolithiasis in children. Five databases were screened, gathering all articles from inception that were evaluated in systematic reviews. We examined 123 publications, 197 reports, and 15,878 procedures, consisting of the largest studied population in the field. There was an increasing number of publications, although in progressively less prestigious journals. The number of studies on miniaturized percutaneous techniques and flexible ureteroscopy has increased closely with the rise in popularity of these procedures worldwide, mainly driven by studies from Asia, Europe, and North America. A trend of self-renewed interest is fueled by technological innovation and has led to fewer publications on Extracorporeal Shockwave Lithotripsy over the years. This review highlights the fact that, despite positive results in recent studies, the low popularity of ESWL within the scientific community is driving a decline in the technique's indications. Moreover, based on the findings of this study, key research priorities include continued reporting of high-quality outcomes, and technological progress in ESWL would contribute meaningfully to the field.

Humans

Assessing the threat of Bacillus cereus: From toxin characterization to modern detection strategies.

Bacillus cereus is a spore-forming pathogen responsible for both diarrheal and emetic foodborne illnesses worldwide. Its significance in food safety has received growing attention. Recent advances, including the discovery of novel virulence factors and the development of emerging detection technologies, have provided new insights into its pathogenic mechanisms and surveillance strategies. This review critically examines the global burden of B. cereus infections, and molecular mechanisms of its major virulence factors, and the performance characteristics of current detection knowledge gaps such as the viable-but-non-culturable state and regulatory blind spots for emetic toxins, and discuss unresolved challenges in clinical management. By integrating epidemiological, microbiological, and technological perspectives with critical lens, this review aims to provide a valuable reference for future research and food safety practices.

Bacillus cereus

Selective monitoring of trace-level catechin and myricetin in herbal and aqueous matrices using magnetic MIP-DSPME: Optimization via design of experiments.

A novel dispersive solid-phase microextraction approach utilizing a magnetic molecularly imprinted polymer (MMIP) integrated with HPLC-UV detection was developed for the concurrent quantification of catechin and myricetin in herbal extracts and aqueous samples. The sorbent was engineered as a core-shell nanocomposite, consisting of a selective polymer layer deposited onto Fe3O4@SiO2-APTMS magnetic nanoparticles. Dual-template imprinting using catechin and myricetin generated complementary binding cavities within the polymer framework. Experimental variables influencing extraction were systematically screened and subsequently optimized. A Plackett-Burman design was first applied to identify the most influential factors, with pH and sorption time identified as the dominant variables. These parameters were subsequently fine-tuned using a central composite design, and the optimization process was completed in only 30 experimental runs. The sorption characteristics of the imprinted sorbent (MMIP) were compared with those of its non-imprinted counterpart (MNIP). The MMIP demonstrated markedly higher maximum binding capacities (Qmax), reaching 119.3&#xa0;mg&#xa0;g-1 for myricetin and 112.1&#xa0;mg&#xa0;g-1 for catechin, whereas the corresponding values for the MNIP were 32.55 and 32.08&#xa0;mg&#xa0;g-1, respectively. Moreover, the affinity constants (KL&#xa0;=&#xa0;0.760-0.950&#xa0;L&#xa0;mg-1) were approximately 2.3-fold higher for the MMIP, confirming its stronger and more selective interactions with the target analytes. The selectivity coefficients for the targeted flavonoids relative to structurally related compounds, including ferulic acid, p-coumaric acid, melatonin, and curcumin, exceeded 3.5 for the MMIP, whereas the corresponding values for the MNIP were close to 1.1, demonstrating the high molecular recognition capability of the imprinted sorbent. Method validation demonstrated limits of detection (LODs) of 0.33-0.59&#xa0;ng&#xa0;mL-1 and limits of quantification (LOQs) of 1.10-1.96&#xa0;ng&#xa0;mL-1, and excellent linearity over the concentration range of 5.0-5500&#xa0;ng&#xa0;mL-1 (R2&#xa0;>&#xa0;0.998). The method achieved recoveries of 93.96% to 105.69% with RSDs below 5.5%, while the preconcentration factors ranged from 209 to 229. Furthermore, the sorbent retained more than 95% of its extraction efficiency after four consecutive reuse cycles and more than 80% after six cycles, demonstrating excellent stability and reusability. The proposed method was successfully applied to the analysis of six medicinal plant extracts and water samples, showing negligible matrix interference and superior sensitivity, selectivity, and operational simplicity compared with conventional solid-phase extraction methods.

Flavonoids