Escherichia coli is a metabolically adaptable microorganism and secrets some metabolites including electroactive metabolites to maintain intracellular redox balance depending on environmental oxygen levels. To the best of our knowledge, this is the first preliminary report for electrochemical monitoring of electroactive metabolites secreted by E. coli supplied with glucose during the aerobic-to-anaerobic transition. The reduction current detected at the aerobically cultured E. coli-modified carbon felt electrode connected to Pt lead wire increased upon sequential addition of fumarate and glucose during the aerobic-to-anaerobic transition. Cyclic voltammetric data, along with inhibitor studies suggested that one of the electroactive compounds that most strongly contributed to the current response was protons probably originated from the metabolically-overflowed organic acids from E. coli. Moreover, it was found that E. coli supplied with glucose during the aerobic-to-anaerobic transition secreted NAD+ and NADH at the nanomolar levels in the electrochemical measurement solution.
Maternal opioid use disorder (OUD) has risen exponentially in the US, impacting pregnancy outcomes. This analysis describes and evaluates a secret shopper methodology for prenatal capacity and quality care research, addressing key considerations for study design. In recent years, this innovative methodology has gained popularity in research to obtain unbiased data on patient experiences in real-time. However, there is a lack of research on accessing prenatal care for pregnant patients with OUD. This analysis provides a comprehensive assessment of the secret shopper methodology's application in the prenatal care setting for patients with OUD. A trained group of racially and ethnically diverse callers followed a standardized script and used Google Voice numbers to call randomly selected prenatal care providers throughout Florida. The sample was obtained via geocoding providers, assessing the sampling frame for equal probability of provider selection, stratified randomized sampling in each of the 11 Agency for Health Care Administration regions, assigning an order of calls for providers with multiple locations, and blocked randomization of providers. The approach was pilot tested, and the protocol iteratively refined based on feedback loops from callers and a reflective Advisory Committee of parents with lived experience. Evaluation of this methodology was guided by key domains and constructs from the Consolidated Framework in Implementation Research. The methodology's relative advantage over traditional research methods, trialability, adaptability, cost-effectiveness, and telephonic approach allowed for a greater reach of physicians statewide, providing unique insights into healthcare access and quality. The study identified lessons learned during development and implementation, emphasizing the need for piloting, stakeholder support, and multidisciplinary collaboration to address unforeseen issues and ensure effective implementation. The methodology uncovered the challenges faced by pregnant individuals with OUD when seeking prenatal care and demonstrates the utility of secret shopper methods in assessing various facets of healthcare.
This study presents an enhanced approach for recovering the secret key of the standard classical transposition cryptosystem using a recently introduced metaheuristic, the coati optimization algorithm. To adapt the coati optimization algorithm for cryptanalysis, its core framework is specifically customized for the considered transposition cryptosystem. The performance of the tailored coati optimization algorithm is benchmarked against three established metaheuristics, namely genetic algorithm, cuckoo search and particle swarm optimization based on accuracy, effectiveness, and efficiency. Experimental results demonstrate that the proposed method performs competitively, often surpassing genetic algorithm, cuckoo search, and particle swarm optimization across all evaluation metrics. However, the current experimental evaluation is limited to English-language ciphertexts using English n-gram statistics; therefore, the applicability of the proposed framework to multilingual cryptanalysis remains a direction for future investigation.
Cervical screening in Australia is currently accessed through a healthcare provider, typically a general practitioner in primary care. We aimed to assess the real-world availability of and access to cervical screening services, including self-collection. Cross-sectional study was conducted using a secret shopper methodology with a standardized telephone script that emulated real-life calls. A random sample of Australian general practices, from each State/Territory (contacted November 2024-February 2025). Of the 310 general practices, 72 (23%) could not offer a cervical screening appointment for new patients. Among practices able to provide an appointment, 217 (89%) said self-collection was available. By jurisdiction, the proportion of practices reporting availability of cervical screening ranged from 72 to 83% but did not significantly differ. The proportion of clinics that offered the choice of self-collection differed significantly by State/Territory ( χ 7 2 =15·774, P = ·013), ranging from 60 to 100%. More regional clinics (94%) offered self-collection compared to metropolitan clinics (85%)(P = ·017). Practices located in the most disadvantaged socioeconomic quintile had a significantly higher proportion offering self-collection (95%) compared to those located in the most advantaged quintile (79%)(P = ·043). Out-of-pocket or gap fees were charged by 183 (75%) clinics (average: $AU50·73, range $AU15-$94·15). Our study highlighted that access to cervical screening may be constrained by limited appointments for new patients, out-of-pocket costs, and other factors. These barriers may disproportionately affect individuals facing structural and financial disadvantage. We found significant variability in availability of self-collection by location. Exploring flexible models, including mail-out, pharmacy supported, or community-led models, may improve accessibility and reduce burden on general practices.
PurposeTo provide a representative Australian sample of ADHD assessment information available to consumers prior to booking an appointment, psychologists, psychiatrists, and paediatricians (N = 736) were contacted through a secret shopper design. Assessment information included the types of measures, the number of measures, the use of multiple informants, and the number of sessions required for adult and child assessments.Major Findings56% of providers declined to provide information about assessment content before booking an appointment. Psychologists provided information at a higher rate than psychiatrists and paediatricians. The majority of providers did not indicate the use of multiple informants (76.8% of psychologists and 100% of psychiatrists for adult assessments; 53.2% of psychologists, 85.7% of psychiatrists, and 50% of paediatricians for child assessments).ConclusionsThese findings demonstrate a lack of readily available information to consumers prior to booking ADHD assessments, limiting the consumer's ability to anticipate if best-practice methods would be used.
FDA approval of the over-the-counter Opill® presents a significant opportunity to expand access to contraception in the United States. We aimed to assess the Opill's® availability, affordability, and accuracy of pharmacist provided information nationwide, hypothesising that pharmacies located in states with higher abortion restrictions and smaller populations would have less availability and more inaccurate counselling. Utilising secret shopper methodology, we called pharmacies representing 530 randomly selected cities based on a modified version of the Guttmacher abortion restriction metric which classified states into three categories. Pharmacies were equally distributed between cities with populations above and below 50,000. Pharmacists were asked about availability, cost, and differentiation from abortive medications. Data was analysed by restriction category and population size using Chi-square (or Fischer's exact) tests. The cohort included 513 pharmacies, with the distribution proportionate to the number of states in each abortion restriction category and evenly distributed by population size. Overall, the Opill® was available in 65% of pharmacies and 47% reported a cost of under $20 per month. There were no significant differences in availability or cost by abortion restriction category, however, pharmacies in areas with <50,000 people were less likely to have the Opill® available (56% vs 73%) and reported higher costs than pharmacies with ≥50,000 population size (both p < 0.01). This study found that two thirds of pharmacies had the Opill® available but access was significantly reduced in less populated areas; however, this did not seem to be affected by state level abortion restrictions.
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The James Webb Space Telescope (JWST) has discovered bright galaxies at high redshifts (z≈10-14) and various galaxy candidates extending to even higher redshifts (z≈15-30). Many astrophysical and beyond the Standard Model physics scenarios have been proposed to explain these observations. We investigate, for the first time, the implications of dark matter (DM) scattering with baryons (protons and electrons) in light of the JWST UV luminosity function (UVLF) observations. These interactions suppress structure formation on galactic scales, which may have an observable effect on the UVLF measurements at high redshifts. Using a recent galaxy formation model designed to explain high-redshift observations, we obtain strong upper limits on DM-baryon scattering cross sections and explore new regions of the parameter space. For DM-proton scattering with cross section ∝v^{-2} velocity dependence, we obtain the strongest limit for DM masses of ∼1-500  MeV. For other cases that we study (DM-proton scattering cross section ∝v^{0},v^{-4} and DM-electron scattering cross section ∝v^{0},v^{-2},v^{-4}), our limits are competitive with those obtained from other cosmological observables. Our Letter highlights the potential of JWST observations as a novel and powerful probe of nongravitational interactions of DM.
Liquid biopsy is emerging as a powerful approach for less invasive biomarker discovery, with extracellular vesicles (EVs) in cerebrospinal fluid (CSF) showing promise for the assessment of central nervous system (CNS) disorders without actual tissue biopsy and as a complement to imaging techniques. EVs carry molecular cargo such as proteins, nucleic acids, and lipids that mirror those at the tissue of origin, offering unique opportunities to quantify disease-related changes in biomarkers. Compared with plasma-derived EVs, those from CSF provide more direct insights into the CNS because of direct shedding of brain EVs to CSF and bypass of confounding factors involving entry to systemic circulation. Despite this potential, translation into clinical practice is limited by challenges such as low yields, purity concerns, and lack of standardized isolation protocols. Addressing these difficulties, alongside integrating multiomics approaches, will advance our understanding of EV molecular cargo and their functional roles in CNS diseases. Over time, CSF-derived EVs could become the new driver of precision medicine in neurology, offering biologic insight for both diagnostic and therapeutic applications. This perspective provides a critical evaluation of the current status of EV-based liquid biopsy in CSF and offers recommendations for future research and clinical translation of data from CSF-derived EVs, highlighting their potential to inform physiologically based pharmacokinetic (PBPK) models. This state-of-the-art article evaluates existing evidence and highlights key knowledge gaps.
The discovery of clathrin was a foundational event in membrane traffic research. Its identification as the major protein component of the coat that surrounds endocytic vesicles kickstarted the biochemical and molecular characterization of endocytosis. During this explosive period of cell biology, there was a parallel storyline involving clathrin which developed more slowly. It emerged that clathrin has an alternative function during mitosis, and that this function is unrelated to its membrane trafficking role. Clathrin forms part of a multiprotein complex that stabilizes microtubules of the mitotic spindle during the chromosome segregation events that occur during cell division. Due to this dual functionality, clathrin is sometimes referred to as a "moonlighting" protein. In this Perspective, we will take a look at this secret life of clathrin and examine how it carries out its mitotic function.
To uncover the principles behind the multifaceted topic of animal flight, we must incorporate perspectives on physics, physiology, ecology, and evolution, themes explored in the "Dinosaurs to Drones: Comparative Approaches to Understanding Flight" symposium. Yet these fields often remain siloed by differences in terminology and approaches. By contrasting evolution and engineering optimization, we highlight how differences between seemingly similar concepts can lead to misunderstandings, and how appreciation of those differences can be leveraged to reveal fundamental flight principles such as multifunctional constraints and adaptive versatility. These principles can then be integrated with conventional optimization methodology to both expand the design space for robust aerial systems and deepen insight into how biology achieves adaptable flight. Finally, drawing on the symposium's panel discussion on how to successfully execute interdisciplinary endeavors, we emphasize the importance of supervisory and institutional support for establishing interdisciplinary training, collaboration, and communication opportunities.
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Low-code platforms like OpenAI custom GPTs (cGPTs) promise easy development of specialized AI assistants for complex bioinformatics and clinical tasks, allowing researchers to integrate proprietary data into intuitive chatbot interfaces. However, these commercial frameworks operate as opaque "black boxes," fundamentally clashing with open-science values and principles of reproducibility. To audit their hidden configurations, we performed "jailbreak" (prompt injection) attacks. We found that all tested cGPTs were critically vulnerable, leading to the leakage of private system instructions, full knowledge base files, and proprietary API details. This systemic failure poses severe security and privacy risks, particularly when handling sensitive patient data, clinical notes, or proprietary basic science assets. While low-code tools lower the barrier to AI adoption, their commercial nature and security flaws warrant extreme caution, forcing biomedical researchers to weigh convenience against the non-negotiable standards of data integrity and security.
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Parkinson's disease (PD) is a chronic neurodegenerative disorder that leads to motor and non-motor challenges, significantly impacting the quality of life. Research highlights body's antioxidant systems role in mitigating PD. This study investigated neuroprotective capabilities of Tinospora sinensis stem extract (TSSE) in a rat model of PD induced by rotenone. PD was induced in rats by subcutaneous rotenone injections (2 mg/kg/day) for 35 days. TSSE was administered orally at 100, 200, and 400 mg/kg doses, with levodopa-carbidopa as the standard reference. Motor impairments were assessed through catalepsy, locomotor activity, and rotarod tests. Biochemical evaluations included oxidative stress markers, antioxidant enzymes (glutathione, superoxide dismutase, and catalase), and dopamine levels, and monoamino oxidase-B (MAO-B). Histopathological examination of brain assessed neuronal integrity. Rotenone administration led to significant motor impairments, increased oxidative stress, reduced dopamine levels, and neuronal damage. Treatment with TSSE resulted in notable, dose-dependent enhancements in motor abilities and restored antioxidant enzyme activities, while also reducing lipid peroxidation, as indicated by decreased malondialdehyde levels. Additionally, TSSE decreased MAO-B level and increased brain dopamine level and maintained neuronal structure. The TSSE 400 mg/kg exhibited neuroprotective effects comparable to those of standard. TSSE shows significant neuroprotective effects, likely by enhancing endogenous antioxidant defenses and restoring dopaminergic neurotransmission. These findings suggest, TSSE could serve as a complementary therapeutic approach that targets oxidative and neurodegenerative mechanisms in PD.
We introduce a privacy measure called statistic maximal leakage that quantifies how much a privacy mechanism leaks about a specific secret random variable, relative to the adversary's prior information about that secret, in the worst case over all possible priors. Statistic maximal leakage is an extension of the well-known maximal leakage framework. Unlike maximal leakage, which protects an arbitrary, unknown secret random variable, statistic maximal leakage is designed to protect a known function of a public random variable. We show that statistic maximal leakage satisfies composition and post-processing properties. Additionally, we show how to efficiently compute it in the special case of deterministic data release mechanisms. We analyze two important mechanisms under statistic maximal leakage: the quantization mechanism and randomized response. We show theoretically and empirically that the quantization mechanism achieves better privacy-utility tradeoffs in the settings we study. This framework may benefit data holders and privacy practitioners who release data containing known secrets by enabling them to assess leakage without specifying an exact prior and to better preserve data utility while protecting those secrets.
We present 'Burn After Reading' - an innovative data protection mechanism featuring self-destructive capability - and integrate it into the steganography model, thus establishing the Burn After Reading Steganography Model (BARStega), a new architectural paradigm for secret data steganography. The concept of 'Burn After Reading' was first introduced into steganography research, it can be characterized as a self-destructive steganography protocol in which the stego image becomes invalidated after the initial data extraction operation, thus preventing subsequent attempts at secret data extraction. Our BARStega model ensures persistent protection of preexisting secret data, even in scenarios where the receiver's model is stolen by adversary. Through systematic optimization of the Stable Diffusion architecture for steganography requirements, our BARStega model enables both high controllability and high visual quality in stego image generation. Experimental results demonstrate that the proposed BARStega effectively facilitates the functionality of 'Burn After Reading'. Moreover, the model demonstrates competitiveness in both the accuracy of secret data extraction and security.