The objective was to evaluate the influence of two tongue cleaning methods (copper tongue scraper and toothbrush) on morning halitosis in dental students. Thirteen dental students were included. After training, the first participant took the halimeter home and used it for 6 days. On the first three days, halitosis was measured immediately after the participant woke up in the morning. The night before each of these first three days, before going to sleep, the participant cleaned their mouth with dental floss and a soft-bristled toothbrush. The individual's same soft-bristled toothbrush was also used to brush his tongue. Only one halitosis measurement was taken per day and the value was recorded each day (toothbrush group). On the fourth, fifth and sixth day, the same process was carried out, but the night before measuring halitosis, a copper tongue scraper was used to clean the participants' tongue. Only one halitosis measurement was taken per day and the value was recorded each day (tongue scraper group). Subsequently, for each participant, the highest halitosis value of the first three days (toothbrush group) was chosen, as well as the highest halitosis value of the last three days (tongue scraper group). The Wilcoxon test was used to compare the two groups (P<0.05). The halitosis value (median) in the toothbrush group was significantly higher than that in the tongue scraper group. Only the tongue scraper group showed a clinically acceptable halitosis value (imperceptible odour). Therefore, the copper tongue scraper is more recommended for cleaning the tongue.
Lower Paleolithic human adaptations were facilitated by the Acheulian stone toolkit, composed of various implements. Flake scrapers, a ubiquitous component of Acheulian toolkits, have received comparatively little scholarly attention despite their widespread presence and long temporal span. This paper presents a technotypological and functional analysis of Late Acheulian scrapers from the Late Lower Paleolithic localities of Jaljulia, Israel, dated to 500-200 ka. Traditional Acheulian scraper production at the site was supplemented by a limited number of uncharacteristic large flake scrapers, a trajectory that subsequently diminished, as well as by recurrent scrapers shaped by stepped and scaled-stepped Quina-like retouch. Our observations indicate that scrapers with distinct working edge attributes were predominantly used for both scraping and cutting activities. The emergence of Quina-like retouch within a Late Acheulian context marks a significant development in the evolution of Paleolithic scrapers. Late Acheulian toolmakers produced Quina-like scrapers alongside other scraper types, preceding and coinciding with the broad adoption of the Quina method in the subsequent Acheulo-Yabrudian Cultural Complex. Our results challenge the notion of Acheulian technological stagnation, highlighting the capability of Homo erectus to implement innovations into predominantly traditional toolkits. We propose a possible Acheulian origin for other technologies and cultural markers considered post-Acheulian as well.
Scraper conveyor load prediction is crucial to realize the cooperative speed regulation of coal mining machine and scraper conveyor. In the synthesized mining face, due to the uncertainty of the coal fall, the load of the scraper conveyor fluctuates due to the change of the coal load, which shows a strong nonlinearity and non-smoothness, leading to the difficulty of prediction. To solve this problem, this paper proposes a BP neural network model combined with wavelet transform for scraper conveyor current prediction. By studying the mapping relationship between motor load and current based on the BP neural network algorithm, and taking the scraper conveyor current as the input condition, wavelet decomposition and data reconstruction of historical current data are carried out, and time series prediction is performed on the original data samples and reconstructed data samples, respectively. The simulation results show that the reconstructed BP neural network model using wavelet decomposition has higher prediction accuracy, in which the root mean square error is reduced by 13.26%, the average absolute error is reduced by 14.19%, and the percentage error is reduced by 17.43%. The model meets the accuracy requirements of scraper conveyor load prediction, and can provide theoretical basis for cooperative speed regulation of coal mining machine and scraper conveyor.
A growing body of archaeological data points towards distinct cultural innovations during Marine Isotopic Stage (MIS) 5 in Africa. At Bushman Rock Shelter in South Africa, we described previously a large corpus of end-scrapers that constitute a technological novelty in the context of MIS 5 developments. Here, we describe 25 bones with impressions collected from the same deposits. Middle Stone Age layers at the site represent a succession of distinct technological phases, but the bones with impressions are strictly associated with one of them only, characterised by the presence of end-scrapers. Our refined optically stimulated luminescence and U-series chronology, presented here, dates securely this technological association to 103 ± 3 ka. Amongst the bones with impressions, there is a marked preference for the diaphyses of large ungulate long bones. Scraping marks linked to periosteum removal and evidence of fresh breakage indicate the use of bones while still fresh. Macro- and microscopic characteristics of the used areas confirm that the bones were used during percussive activities. The orientation of the bone surface modifications indicates repeated, similar technological gestures. We propose that these bones with impressions are bone retouchers that were fully integrated into the production of the end-scrapers and that they document a clear technological imbrication between the processing of animal resources and the manufacture and use of stone tools. We argue that the use of bones in lithic retouching or resharpening activities represents a critical step in the technological process that led to the exploitation of bone as a versatile raw material by hunter-gatherers.
Predicting the original mass of a retouched scraper has long been a major goal in lithic analysis. It is commonly linked to lithic technological organization of past societies along with notions of stone tool general morphology, standardization through the reduction process, use life, and site occupation patterns. In order to obtain a prediction of original stone tool mass, previous studies have focused on attributes that would remain constant or unaltered through retouch episodes. However, these approaches have provided limited success for predictions and have also remained untested in the framework of successive resharpening episodes. In the research presented here, a set of experimentally knapped flint flakes were successively resharpened as scraper types. After each resharpening episode, four attributes were recorded (scraper mass, height of retouch, maximum thickness and the GIUR index). Four machine learning models were trained using these variables in order to estimate the mass of the flake prior to any retouch. A Random Forest model provided the best results with an [Formula: see text] value of 0.97 when predicting original flake mass, and a [Formula: see text] value of 0.84 when predicting percentage of mass lost by retouch. The Random Forest model has been integrated into an open source and free to use Shiny app. This allows for the wide spread implementation of a highly precise machine learning model for predicting initial mass of flake blanks successively retouched into scrapers.
To address walking errors such as rail-biting and derailment in large-span sludge scrapers, this study establishes a kinematic theoretical model to describe the geometric motion relationship between the scraper's wheels and rails. Based on this model, the constraint conditions for rail-biting and derailment are derived, including the critical deviation angle and the permissible wheel-rail clearance. To better match real engineering conditions, a Δ correction factor is introduced to account for chamfers, transition arcs, and structural deviations of the wheel-rail system.An experimental platform was built to validate the model, using high-precision laser ranging sensors and rainfall sensors to monitor wheel-rail distance variations under both normal and critical states. The results show that the Δ correction reduces the prediction error of the critical deviation angle by about 91%, confirming the model's reliability. This study clarifies the geometric mechanism of scraper walking errors and provides a theoretical basis for the synchronous control and safety optimization of large-span sludge scrapers.
With the ongoing integration of offshore wind power and marine aquaculture, increasing attention has been paid to the potential biological effects of continuous low-frequency noise generated during wind farm operations on surrounding fish species. In this study, juvenile black scrapers (Thamnaconus modestus), a demersal species with low auditory sensitivity, were exposed to 500 Hz noise at low, medium, and high intensities (root-mean-square (RMS) sound pressure levels (SPLrms): 95 ± 5, 115 ± 5, and 135 ± 5 dB re 1 μPa) for 14 days to investigate physiological responses and molecular regulatory mechanisms. Low-intensity noise primarily suppressed the expression of feeding and digestion genes (Ghrl, Prss1) and activated oxidative stress and neuroprotective pathways. Medium-intensity noise caused dysregulation of lipid metabolism genes (Gba1, Degs2), significantly elevated malondialdehyde (MDA) content, and downregulated the expression of key genes in the neutrophil extracellular trap formation pathway (Ncf1, Ncf2, Ncf4). High-intensity noise disrupted the expression of circadian clock genes (Bmal1, Per2) and upregulated cholesterol synthesis pathway genes (Sqle, Cyp51a1, Dhcr24). Collectively, long-term low-frequency noise exposure during operation induced dose-dependent physiological stress on juvenile T. modestus, affecting digestive function, redox balance, lipid metabolism, immune responses, and circadian rhythm regulation. These findings contribute to understanding the potential impacts of low-frequency noise from offshore wind farms on marine fish and suggest that low-frequency noise should be incorporated as a key assessment criterion in the siting of marine ranching and fishery resource conservation.
To understand the changes in gonadal sex differentiation, digestive enzyme activity, and growth-related hormone levels in the larval and juvenile black scraper, Thamnaconus modestus, continuous sampling was conducted from 0 to 91 days post-hatching (dph). 17β-estradiol (E2) and testosterone (T) levels, six digestive enzymes, as well as T3, T4, GH, and IGF-I were detected. The results showed that oogonia or spermatogonia was observed at 60 dph. During the sex differentiation to female or male, both E2 and T levels significantly increased (p < 0.05), suggesting that E2 and T may induce the sex differentiation to female or male in T. modestus, respectively. The amylase activity from 0 to 35 dph showed a slow upward trend, which may be due to the transition from endogenous to exogenous nutrition at this time. From 12 to 25 dph, alkaline protease activity significantly decreased (p < 0.05), while acid protease levels significantly increased (p < 0.05), suggesting that as organs in the digestive system continue to develop, acid protease plays an important role. T3 and T4 could already be detected at 0 dph, and the T4 content was always much higher than T3 throughout the stages, indicating that T4 may play more important roles than T3. Additionally, the changes in IGF-I and GH content followed a trend of an initial increase, a subsequent decrease, and then an increase, ultimately showing an overall upward trend. These results indicate that T4, IGF-I, and GH play crucial roles in growth and development in the juvenile fish. In conclusion, the results of this study provide useful information for growth, artificial reproduction, and sex regulation in T. modestus.
This study addresses the issue of miss seeding in spoon-chain potato seed-metering devices, which impacts planting efficiency and quality, by proposing a miss-seeding detection and compensation system based on an improved YOLOv5s model integrated with a preparatory seed scraper-belt compensation mechanism. The enhanced model incorporates the Convolutional Block Attention Module (CBAM) and Soft Non-Maximum Suppression (Soft-NMS), achieving a mean average precision (mAP) of 99.40% in complex field environments. The system combines visual recognition with mechanical compensation. Experimental results demonstrate that at operating speeds of 0.2-0.4 m/s, the original miss-seeding rate of 5.28%-9.40% is reduced to 0.70%-1.68%, with a reseeding success rate of 82.14%-86.67% and a preparatory seed reseeding success rate exceeding 96%. The study validates the system's efficiency and reliability under medium-low speeds, with slight performance degradation at higher speeds due to vibrations. This solution offers an intelligent upgrade path for traditional potato seed-metering devices and advances precision agriculture technologies.
The objective of this study was to evaluate the efficacy of scraping without endothelial keratoplasty technique using a novel cell scraper for treating corneal endothelial dysfunction and explore the adjuvant effects of a ROCK inhibitor (ROCKi). Human donor tissues (n = 3) were mounted on an artificial anterior chamber, and one-half of the corneal endothelium was scraped with a novel cell scraper. The tissues were then stained with hematoxylin and eosin (H&E) to assess cell removal. In parallel, central peeling (descemetorhexis) using sharp acute forceps (n = 8) and cell scraping using a novel cell scraper (n = 8) was compared with and without ROCKi to investigate the wound healing response. RT-PCR analysis to assess the endothelial-to-mesenchymal transition using ZEB1 , SNAI1/2 , VIM , and CDH1/2 genes was performed after storage. An ex vivo surgical setup using an artificial anterior chamber demonstrated the feasibility and efficacy of using the cell scraper. Superior wound healing (88%) was observed in the endothelial cell-scraping group compared with Descemet membrane peeling (22%) at day 16. Application of ROCKi expedited wound healing after endothelial scraping (97%) and peeling (40%) compared with their respective controls at day 16. ROCKi treatment promoted endothelial-to-mesenchymal transition; however, with enhanced wound healing after cell scraping, endothelial cells formed a monolayer on native Descemet membrane compared with the peeling method. Scraping without endothelial keratoplasty can be performed effectively using the cell scraper and offers a potential alternative to endothelial keratoplasty, which can be effective in treating bullous keratopathy with healthy peripheral endothelial cells. ROCKi enhances wound healing, supporting further clinical testing and potentially delaying corneal tissue implantation.
Aquatic insect larvae in high mountain streams reflect natural changes in water chemistry, making them effective bioindicators of ecosystem health. Changes in element accumulation in the bodies of larvae from the functional feeding groups scrapers and predators were monitored over a 5-year period (2019-2023). We aimed to evaluate long-term and seasonal trends in the accumulation of selected elements and to assess whether these patterns were linked to hydrological conditions or reflected post-disturbance recovery. Element concentrations were measured using ED-XRF spectrometry. Principal component analysis was used to identify accumulation patterns and their relationships with water flow rate and total dissolved solids (TDS). In scrapers, principal component (PC) 1 indicated general element accumulation, which varied significantly by year and season. PC2 showed increased in iron, copper, zinc, and lead with decreased in phosphorus and sulphur, with significant seasonal variation. PC3 linked an increase in iron and barium with higher flows and reduced chlorine and TDS, showing notable variation across years and seasons. In predators, PC1 also represented general element accumulation but involved fewer elements than scrapers. PC2 showed increased chromium and copper with higher flows and lower TDS, and PC3 indicated increased sulphur with higher flow and decreased zinc. Unlike scrapers, predators did not exhibit significant interannual variation, though seasonal variations were evident. These findings suggest that scrapers are more responsive to long-term environmental changes, while seasonal accumulation patterns in both groups are influenced by stream flow, food availability, and physiological changes during ontogeny.
Neonicotinoids are widely used in agriculture to manage insect pests; however, their application can harm the well-being of aquatic animals and non-target insects in surrounding ecosystems. While previous studies have identified relationships between neonicotinoid transport and soil chemistry in agricultural ecosystems, there is a lack of research exploring how the molecular properties of organic carbon in soils affect neonicotinoid mobility. In addition, there is even less research exploring the interconnected dynamics between neonicotinoid transport and nontarget biological endpoints, such as benthic macroinvertebrates. In this study, soil, stream sediment, and benthic macroinvertebrates were collected monthly across agricultural and naturalized land cover in Southern Ontario from April to October 2023 to quantify neonicotinoid levels in agricultural watersheds. Fourier transform ion cyclotron resonance mass spectrometry was used to characterize the molecular composition of water extractable organic matter in soil and sediment samples, and three neonicotinoids were detected using a triple quadrupole mass spectrometer. Thiamethoxam concentrations peaked early in the sampling period, reaching 6.27 ± 0.31 ng g-1 in April before steadily declining, coinciding with reductions in scrapers-grazer functional feeding groups. Conversely, thiamethoxam levels in stream sediments exhibited a delayed peak, rising to 6.82 ± 0.94 ng g-1 in later summer months, suggesting mobilization from soils in as little as three months after application. Overall, thiamethoxam emerged as the most frequently detected neonicotinoids in both soil and sediment samples and a significant positive correlation was observed between WEOM and thiamethoxam (Spearman ρ = 0.803, p = 0.022). Accumulated thiamethoxam is also likely transported by phoshrpus and sulphur-containing WEOM from soils to sediments, where thiamethoxam correlated with significant decreases in scraper-grazers population in stream sediments. Together, our results identify molecular signatures within the WEOM that can serve as indicators of enhanced thiamethoxam transport from soils to sediments and highlight the rapid effects of neonicotinoids on benthic macroinvertebrate communities.
Halitosis is a term that defines any unpleasant odour smell originating from the oral cavity and may have a local or systemic origin. This project aims to determine the effectiveness of treatment involving antimicrobial photodynamic therapy (aPDT) combined with treatment using probiotics at reducing halitosis. 92 individuals from 18 to 60 years of age with a diagnosis of halitosis (sulfide≥112 ppb, gas chromatography) will be selected. The participants will be randomly allocated to four groups (n=23). Group 1 (control): brushing, dental floss and tongue scraper; group 2: brushing, dental floss, tongue scraper and aPDT with blue Light Emitting Diode (LED) +annatto; group 3: brushing, dental floss, tongue scraper and aPDT with blue Light Emitting Diode (LED) +annatto and probiotic lozenges containing Streptococcus salivarius K12 (BLIS K12); and group 4: brushing, dental floss, tongue scraper and probiotic lozenges containing S. salivarius K12 (BLIS K12). Comparisons will be made of the respiratory analysis results before and immediately after the first treatment session, at the end of the 30-day treatment period and again 60 days after the treatment initiation. Microbiological analysis (counts of colony-forming units of viable bacteria from coated tongue) will be performed at the same time. The microbiome analysis will be conducted before treatment, 30 days after treatment completion and 60 days after treatment initiation, following DNA extraction. All groups will receive oral hygiene instructions as well as brushes, toothpaste and dental floss. Data normality will be checked using Shapiro-Wilk test. In the case of normality, analysis of variance is used for the comparisons. In the case of non-parametric data, Kruskal-Wallis test will be used. Wilcoxon test will be used to analyse the results of each treatment between two assessment times. This protocol has been approved by the Human Research Ethics Committee of Nove de Julho University (certificate number: 82830524.6.0000.5511; approval date: 2 October 2024). Participants will agree to take part in the study by signing an informed consent form. The findings will be published in a peer-reviewed journal. The collected data will be available in the OSF data repository. NCT06583720.
BackgroundWeb scraping-the automated extraction of data from websites-has become an essential technique for researchers seeking to collect large-scale data that would be impractical to gather manually. Surgeon-scientists increasingly encounter publicly available web data relevant to outcomes research, health services analysis, workforce studies, and policy work, yet technical guidance on implementing web scrapers remains limited in the surgical literature.MethodsThis tutorial provides a clinician-oriented technical guide to web scraping for surgical research. We present key concepts including static vs dynamic websites, CSS selectors, browser automation, rate limiting, and ethical considerations. A complete worked example demonstrates the full pipeline by scraping a surgical research group's publication page (https://www.onetomapanalytics.com) to build a structured bibliometric database.ResultsThe worked example successfully extracts structured publication data-including titles, author lists, abstracts, keywords, and PubMed links-from a JavaScript-rendered website, producing an analysis-ready data set. We demonstrate how this pipeline generalizes to other surgical research applications including hospital price transparency data, residency program characteristics, and quality metrics.ConclusionsWeb scraping is a powerful tool for surgeon-scientists when implemented with technical rigor and ethical responsibility. By anchoring the tutorial to a concrete surgical use case and providing a reusable code template, we equip surgical researchers with the foundational knowledge to design, implement, and adapt web scrapers for their own data collection projects.
Although price is critical in determining alcohol purchase and subsequent harms, researchers rarely have access to comprehensive alcohol price data. Web scraping is an advanced data collection technique that uses automated computer scripts to efficiently gather extensive website data. The aims of this paper are to demonstrate web scraping's capacity to generate alcohol policy relevant data, and to assess the method's consistency by comparing datasets collected by a commercial provider with those produced by a university-developed scraper. Price and product data from the entire online catalogues of major retailers representing the majority of the Australian market were scraped daily by the commercial provider since 2020, with data collected from all jurisdictions, and products sold by multiple retailers matched. A university-developed web scraper collected a single-day's catalogue data from the country's largest alcohol retailer to compare with the commercial dataset as a reliability cross-check. Of the 16,409 products identified in both the commercial and university databases, there was an excellent match on the product prices (intraclass correlation coefficient=0.997 [95 %CI: 0.9972-0.9973]). A visualisation from the three largest Australian retailers demonstrated how daily prices varied over a 12-month period, for example with more frequent price changes for Australia's largest retailer compared to the second and third, and across jurisdictions, such as some deeper discounting in Victoria. This study presented an independently cross-checked large-scale and longitudinal web scraping approach to collect alcohol price data, and demonstrated that the adapted data could aid understanding of the alcohol retail market. Web scraping is a feasible method to collect price data to support the development of evidence-based alcohol price policy.
To introduce a novel treatment for a secondary failed penetrating keratoplasty (PK), termed Descemet's Membrane Endothelial Keratoplasty with endothelial scraping and without descemetorhexis (DMEK-SWD), through the presentation of two clinical cases. In this prospective, single-center case series, two patients with previous PK for keratoconus developed endothelial decompensation, presenting with decreased visual acuity (Patient A: counting fingers; Patient B: 0.8 logMAR) and increased central corneal thickness (A: 735 μm; B: 653 μm). DMEK-SWD was performed using a 7.5-mm cell scraper through the temporal port to mechanically remove the host endothelium. A pre-stripped 7.5-mm DMEK graft was inserted using a standardized no-touch technique. Postoperative management included subconjunctival injections of gentamycin and dexamethasone. Graft attachment was maintained in both cases, although Patient B required single rebubbling procedure.Postoperative graft endothelial cell density (ECD), measured from confocal imaging (HRT3-RCM Cell Count), was 1,125 cells/mm2 at 12 months in Patient A and 1,544 cells/mm2 at 8 months in Patient B. At final follow-up (A: 18 months; B: 8 months), both patients showed improved best-corrected visual acuity (A: 0.2 logMAR; B: 0 logMAR) and reduced CCT (A: 496 μm; B: 505 μm). This pilot study demonstrates the feasibility of DMEK-SWD in treating failed PK, with a mean graft clearance time of 1.5 weeks for the two cases analyzed. The technique may represent a promising alternative to repeat full-thickness transplantation and supports further investigation in larger cohorts. Given the very small sample size and the incomplete availability of endothelial cell count data, these findings should be regarded as preliminary.
A recent TikTok trend of users reporting nasal size reduction after oral isotretinoin has conflated this acne medication as a nonsurgical rhinoplasty option, termed "Accutane rhinoplasty". We conducted a systematic review of studies reporting outcomes of rhinoplasty and oral isotretinoin and analyzed TikTok reels published under this emerging aesthetic trend. A comprehensive systematic literature search was conducted in December 2024 using the MEDLINE, Web of Science, and EMBASE databases following PRISMA guidelines. Studies reporting outcomes of rhinoplasty patients treated with oral isotretinoin were included. TikTok Scraper extracted details of English-language TikTok reels posted up to September 2024 under three hashtags: #accutanenosejob, #accutanenose, and #accutanenosejobcheck. Five articles met inclusion criteria. Studies included a median of 24 patients, with isotretinoin administered postoperatively in all studies and preoperatively in two studies. Two of three prospective studies reported positive findings, including lower frequency of facial acne, reduced facial skin thickness, and higher patient satisfaction. Retrospective studies reported mixed findings, including improved nasal skin appearance, increased rhinoplasty complications, and isotretinoin side effects. TikTok hashtags have 68.5 million views, and 100 reels were included for review. Self-reported physicians represented 10% (10/100) of reels and self-reported patients reporting nasal size reduction after isotretinoin represented 90% (90/100) of reels. Current evidence on isotretinoin use in rhinoplasty patients is limited, with small sample sizes and mixed findings. While some studies suggest potential benefits in patients with thick nasal skin or severe acne, the long-term effects and safety profile remain unclear. The popularity of "Accutane rhinoplasty" on TikTok contrasts with the scarcity of rigorous clinical data, underscoring the need for further high-quality studies and greater clinician engagement in online discussions. Therapeutic study. This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
Environments are becoming increasingly more variable, as a function of climate change. As this occurs, species may be exposed to conditions outside their preferred range. Such variability in the environment can influence community abundance as individual species respond either similarly (synchronous dynamics) or differently (asynchronous dynamics) to each other. These fluctuations in abundances are important for understanding the impact of environmental variability on species temporal fluctuations in aquatic macroinvertebrates. This group of organisms is species-rich and highly sensitive to environmental fluctuations. We analyzed 18 stream macroinvertebrate communities sampled by the National Ecological Observatory Network between 2014 and 2022 to understand how community synchrony is related to stream temperature variability, discharge variability, and species turnover. We then quantified individual species contributions to community synchrony. These contributions were aggregated by functional feeding group to understand how resource acquisition strategies influenced species contributions. Species with higher contributions are often more synchronous with many other species. Here, community synchrony was expected to be negatively related to increasing environmental variability and turnover. Opposite our expectation, temperature variability, turnover, and discharge variability were unrelated to community synchrony. Contributions to community synchrony significantly varied among functional feeding groups. Scrapers had the highest proportion of taxa with significant positive contributions, followed by filterers. Shredders had the lowest proportion of species contributing to synchrony. Scrapers and shredders were significantly less synchronous than other functional feeding groups. This suggests that functional feeding group may explain patterns of community synchrony. Using a standardized, long-term dataset, we demonstrated how temperature variability, turnover, and functional feeding groups relate to community synchrony. While identifying the drivers of community synchrony remains challenging, integrating functional groupings provides an approach to identify species that drive community dynamics.
Invisible watermarking has long been a cornerstone for copyright protection due to its imperceptibility and forensic traceability. However, traditional watermarking remains a passive defense that fails to preclude unauthorized AI-driven analysis, such as the automated categorization and indexing of private media by illicit scrapers. To address this, we propose invisible and robust adversarial watermarking (IRAW), a unified framework that transitions image protection from passive traceability to proactive defense. By leveraging the discrete cosine transform (DCT) domain, IRAW ensures native compatibility with the JPEG compression protocols prevalent on mainstream social media platforms. The framework treats watermark embedding and adversarial perturbation generation as a synergistic optimization task. Specifically, an evolutionary optimization mechanism based on the integration of basin hopping (BH) with crossover and adaptive mutation operators is employed to navigate the search space and identify optimal perturbation patterns. To further enhance security, we implement a cross-domain defense architecture featuring dual spatial-domain encryption for host images and watermarks, combined with frequency-domain coordinate obfuscation. This mechanism not only bolsters cryptographic strength but also increases the structural complexity of perturbations, assisting the BH algorithm in escaping local optima to improve perturbation success rates. Experimental results demonstrate that IRAW generates high-fidelity adversarial examples with exceptional robustness against common image operations, such as JPEG compression and noise, while enabling reliable watermark recovery for forensic provenance. These findings establish IRAW as an effective and industrially compatible mechanism for modern digital image protection.
This study aimed to examine the number of FDA-approved cancer pharmacotherapies and analyse pivotal study characteristics over time, including sample sizes. We developed a web scraper to collate a cohort of FDA-approved cancer pharmacotherapies from 1953 until 31 December 2024. For each pharmacotherapy, details of pivotal studies leading to approval were recorded, including protocol and final sample size, study design, therapy type, and quality assessment using Cochrane Risk of Bias tools. We used regression analyses and discretization to identify trends in sample size. Type I error was set at 0.05.(Study protocol pre-registration: https://doi.org/10.17605/OSF.IO/KVA23). We identified 255 pharmacotherapies, supported by 306 pivotal studies; 125 (49%) were targeted pharmacotherapies, 61 (24%) chemotherapies, 47 (18%) immunotherapies, 21 (8%) hormonal therapies, and 1 (0.4%) other. The median sample size was 290 (IQR = 427); sample sizes increased in the 1990s (median = 407) and remained stable thereafter. Stratified analysis demonstrated smaller sample sizes for phase 1 and 2 studies before 1980, with no change in phase 3 studies. For 165 studies reporting protocol sample sizes, studies from 2020-2024 (median = 147.5) were smaller than those from 2010-2019 (median = 320). The increase in sample sizes during the 1990s may reflect new policies and legislation. Subsequent stability in sample size could be due to modern trial designs (eg, basket/umbrella studies, surrogate endpoints) that require smaller sample sizes. The recent decrease in protocol sample sizes may herald a similar decline for future studies but requires post-market surveillance to verify credibility.