Search Results (20)

Purpose: Adjuvant trastuzumab therapy has improved outcomes in HER2-positive breast cancer, but the impact of the timing of its initiation remains unclear. This study evaluates the effect of time to adjuvant trastuzumab-based therapy (TTAT) after surgery on survival in HER2-positive breast cancer. Methods: In this retrospective study, HER2-positive breast cancer patients treated with surgery followed by adjuvant trastuzumab without prior neoadjuvant therapy were analyzed. Patients were grouped by TTAT ≤ 42 days or >42 days post-surgery. Key endpoints included overall survival (OS), disease-free survival (DFS), and distant metastasis-free survival (DMFS), evaluated through Kaplan–Meier and Cox regression analyses. Results: Patients with TTAT greater than 42 days had significantly worse OS, DFS, and DMFS (p = 0.036, p = 0.045, and p = 0.048, respectively, log-rank test) than those initiating trastuzumab within 42 days. On multivariate analysis, delays beyond 42 days were associated with a significantly increased risk of recurrence and mortality, showing reduced DFS (HR 2.52; p = 0.027) and OS (HR 4.48; p = 0.004). These findings indicate that even moderate delays in trastuzumab initiation can adversely affect survival. Conclusions: Delaying trastuzumab initiation beyond 42 days post-surgery negatively impacts survival in HER2-positive breast cancer, emphasizing the need for timely treatment. These results support clinical guidelines advocating prompt initiation of adjuvant therapy to improve long-term outcomes for HER2-positive patients. Full article

Developing solutions to reduce traffic accidents requires experimentation and much data. However, due to confidentiality issues, not all datasets used in previous research are publicly available, and those that are available may be insufficient for research. Building datasets with real data is costly. Given this reality, this paper proposes a procedure to generate synthetic data sequences of driving events using the Time series GAN (TimeGAN) and Real-world time series (RTSGAN) frameworks. First, a 15-feature driving event dataset is constructed with real data, which forms the basis for generating datasets using the two mentioned frameworks. The generated datasets are evaluated using the qualitative metrics PCA and T-SNE, as well as the discriminative and predictive score quantitative metrics defined in TimeGAN. The generated synthetic data are then used in an unsupervised algorithm to identify clusters representing vehicle crash risk levels. Next, the generated data are used in a supervised classification algorithm to predict risk level categories. Comparison results between the data generated by TimeGAN and RTSGAN show that the data generated by RTSGAN achieve better scores than the the data generated with TimeGAN. On the other hand, we demonstrate that the use of datasets trained with synthetic data to train a supervised classification model for predicting the level of accident risk can obtain accuracy comparable to that of models that use datasets with only real data in their training, proving the usefulness of the generated data. Full article

Background: Chronic progressive external ophthalmoplegia (CPEO) belongs to the group of mitochondrial encephalomyopathies. Anaesthesia for patients with CPEO may be associated with an increased risk due to known drug effects on mitochondrial metabolism. Therefore, the aim of this analysis was to evaluate anaesthesiological concepts in patients with CPEO requiring ophthalmic surgery. Methods: This is a retrospective, monocentric cohort analysis of eleven patients with CPEO undergoing ophthalmic surgery either with general anaesthesia or local anaesthesia in a German university hospital from January 2012 to February 2022. Results: A total of twelve ophthalmic surgery procedures were performed in eleven adult patients with CPEO. Six patients underwent surgery after receiving local anaesthesia (LA cohort). Five patients underwent six surgical procedures under general anaesthesia (GA cohort). In five cases within the GA cohort, propofol and remifentanil were used for the maintenance of anaesthesia. In one case, balanced anaesthesia with desflurane and remifentanil was used. The median duration of general anaesthesia was 37.5 min (range, 25–65 min). Patients stayed in the recovery room for a median of 48.5 min (range, 35–70 min). All patients were discharged on the first postoperative day. No relevant complications occurred in either the LA or GA cohort. Conclusion: Both local and general anaesthesia are feasible concepts for patients with CPEO undergoing ophthalmic surgery. Propofol, at least with a short duration (less than one hour) of use, appears to be a feasible hypnotic drug in CPEO patients. Full article

The problems with current driving datasets are their exclusivity to autonomous driving applications and their limited diversity in terms of sources of information and number of attributes. Thus, this paper presents a novel driving dataset that contains information from several heterogeneous sources and targets road traffic safety applications. We used an acquisition module based on software and hardware to collect information from a vehicle scanner and a health monitor. This module also consumes information from a weather web service and databases on traffic accidents and road geometric characteristics. For the acquisition sessions, drivers of different ages and genders drove vehicles on two routes at different day hours in different weather conditions. POLIDriving contains around 18 h of driving data, more than 61k observations, and 32 attributes. Unlike the other related datasets that include information on vehicle and road conditions, POLIDriving also includes information on the driver, weather conditions, traffic accidents, and road geometric characteristics. The dataset was tested in learning models to predict the risk levels of suffering a traffic accident. Hence, we built two learning models: Gradient Boosting Machine (GBM) and Multilayer Perceptron (MLP). GBM reached an accuracy value of 95.6%, and MLP reached an accuracy of 98.6%. Undoubtedly, POLIDriving will contribute greatly to the research on traffic accident prevention by providing a novel, numerous, and diverse driving dataset. Full article

Wastewater-based epidemiology (WBE) has emerged as a key method for the continuous monitoring of COVID-19 prevalence including circulating SARS-CoV-2 lineages. WBE addresses the limitations of traditional clinical COVID-19 surveillance such as clinical test availability, fluctuating testing rates, and increased reliance on rapid antigen tests. Our study in Perth, Western Australia found a significant positive correlation between SARS-CoV-2 concentrations in wastewater and clinical PCR positivity rates (rs = 0.772; p < 0.001) over an 18-month period that included four successive COVID-19 waves. A strong positive correlation was apparent between the proportions of SARS-CoV-2 lineages in wastewater and clinical cases within the same region (rs = 0.728, p < 0.001), including earlier detection of Omicron and recombinant lineages in wastewater before clinical case confirmation. The successful integration of WBE with healthcare data underscores its critical role in enhancing public health decision-making and pandemic management. This approach not only demonstrates the value of WBE in current global health surveillance efforts but also highlights the potential of WBE to address future public health challenges, as a comprehensive disease monitoring and response approach. Full article

Anacondas, genus Eunectes, are a group of aquatic snakes with a wide distribution in South America. The taxonomic status of several species has been uncertain and/or controversial. Using genetic data from four recognized anaconda species across nine countries, this study investigates the phylogenetic relationships within the genus Eunectes. A key finding was the identification of two distinct clades within Eunectes murinus, revealing two species as cryptic yet genetically deeply divergent. This has led to the recognition of the Northern Green Anaconda as a separate species (Eunectes akayima sp. nov), distinct from its southern counterpart (E. murinus), the Southern Green Anaconda. Additionally, our data challenge the current understanding of Yellow Anaconda species by proposing the unification of Eunectes deschauenseei and Eunectes beniensis into a single species with Eunectes notaeus. This reclassification is based on comprehensive genetic and phylogeographic analyses, suggesting closer relationships than previously recognized and the realization that our understanding of their geographic ranges is insufficient to justify its use as a separation criterion. We also present a phylogeographic hypothesis that traces the Miocene diversification of anacondas in western South America. Beyond its academic significance, this study has vital implications for the conservation of these iconic reptile species, highlighting our lack of knowledge about the diversity of the South American fauna and the need for revised strategies to conserve the newly identified and reclassified species. Full article

With the rising prevalence of obesity, non-alcoholic fatty liver disease (NAFLD) now affects 20–25% of the global population. NAFLD, a progressive condition associated with oxidative stress, can result in cirrhosis and liver cancer in 10% and 3% of patients suffering NAFLD, respectively. Therapeutic options are currently limited, emphasizing the need for novel treatments. In this study, we examined the potential of activating the transcription factor NRF2, a crucial player in combating oxidative stress, as an innovative approach to treating NAFLD. Utilizing a CRISPR/Cas9-engineered human HEK293T cell line, we were able to monitor the expression of heme oxygenase-1 (HMOX1), an NRF2 target, using a Nanoluc luciferase tag. Our model was validated using a known NRF2 activator, after which we screened 1200 FDA-approved drugs, unearthing six compounds (Disulfiram, Thiostrepton, Auranofin, Thimerosal, Halofantrine, and Vorinostat) that enhanced NRF2 activity and antioxidant response. These compounds demonstrated protective effects against oxidative stress induced by hydrogen peroxide and lipid droplets accumulation in vitro with hepatoma HUH-7 cells. Our study underscores the utility of CRISPR/Cas9 tagging with Nanoluc luciferase in identifying potential NRF2 activators, paving the way for potential NAFLD therapeutics. Full article

The objective of this study is to explore and compare the mechanical response of AlCrSiN coatings deposited on two different substrates, namely, WC-Co and cBN. Nano-indentation was used to measure the hardness and elastic modulus of the coatings, and micro-indentation was used for observing the contact damage under Hertzian contact with monotonic and cyclic (fatigue) loads. Microscratch and contact damage tests were also used to evaluate the strength of adhesion between the AlCrSiN coatings and the two substrates under progressive and constant loads, respectively. The surface damages induced via different mechanical tests were observed using scanning electron microscopy (SEM). A focused ion beam (FIB) was used to produce a cross-section of the coating–substrate system in order to further detect the mode and extent of failure that was induced. The results show that the AlCrSiN coating deposited on the WC-Co substrate performed better in regard to adhesion strength and contact damage response than the same coating deposited on the cBN substrate; this is attributed to the lower plasticity of the cBN substrate as well as its less powerful adhesion to the coating. Full article

Phishing is a type of cyber-attack that aims to deceive users, usually using fraudulent web pages that appear legitimate. Currently, one of the most-common ways to detect these phishing pages according to their content is by entering words non-sequentially into Deep Learning (DL) algorithms, i.e., regardless of the order in which they have entered the algorithms. However, this approach causes the intrinsic richness of the relationship between words to be lost. In the field of cyber-security, the innovation of this study is to propose a model that detects phishing attacks based on the text of suspicious web pages and not on URL addresses, using Natural Language Processing (NLP) and DL algorithms. We used the Keras Embedding Layer with Global Vectors for Word Representation (GloVe) to exploit the web page content’s semantic and syntactic features. We first performed an analysis using NLP and Word Embedding, and then, these data were introduced into a DL algorithm. In addition, to assess which DL algorithm works best, we evaluated four alternative algorithms: Long Short-Term Memory (LSTM), Bidirectional LSTM (BiLSTM), Gated Recurrent Unit (GRU), and Bidirectional GRU (BiGRU). As a result, it can be concluded that the proposed model is promising because the mean accuracy achieved by each of the four DL algorithms was at least 96.7%, while the best performer was BiGRU with 97.39%. Full article

The emergence of novel potentially pandemic pathogens necessitates the rapid manufacture and deployment of effective, stable, and locally manufacturable vaccines on a global scale. In this study, the ability of the Escherichia coli expression system to produce the receptor binding domain (RBD) of the SARS-CoV-2 spike protein was evaluated. The RBD of the original Wuhan-Hu1 variant and of the Alpha and Beta variants of concern (VoC) were expressed in E. coli, and their biochemical and immunological profiles were compared to RBD produced in mammalian cells. The E. coli-produced RBD variants recapitulated the structural character of mammalian-expressed RBD and bound to human angiotensin converting enzyme (ACE2) receptor and a panel of neutralizing SARS-CoV-2 monoclonal antibodies. A pilot vaccination in mice with bacterial RBDs formulated with a novel liposomal adjuvant, Army Liposomal Formulation containing QS21 (ALFQ), induced polyclonal antibodies that inhibited RBD association to ACE2 in vitro and potently neutralized homologous and heterologous SARS-CoV-2 pseudoviruses. Although all vaccines induced neutralization of the non-vaccine Delta variant, only the Beta RBD vaccine produced in E. coli and mammalian cells effectively neutralized the Omicron BA.1 pseudovirus. These outcomes warrant further exploration of E. coli as an expression platform for non-glycosylated, soluble immunogens for future rapid response to emerging pandemic pathogens. Full article

Next generation concentrated solar power (CSP) plants promise a higher operating temperature and better efficiency. However, new issues related to the corrosion against protection of the construction alloys need to be solved. In this work, two different duplex stainless steels grades, namely 2205 (DS2205) and 2507 (DS2507), were evaluated for their compatibility with the eutectic molten salt mixture of Li₂CO₃-K₂CO₃-Na₂CO₃ at 500 °C in air for thermal energy storage applications. Corrosion tests combined with complementary microscopy, microanalysis and mechanical techniques were employed to study the oxide scales formed on the surface of the duplex steels. The corrosion tests evidenced that the attack morphology in both duplex steels was a uniform oxidative process without localized corrosion. DS2507 presented a better corrosion resistance than DS2205, due to the formation of thinner, compact and continuous oxide layers with higher compositional content in Cr, Ni and Mo than DS2205. The oxide scales of DS2507 showed more remarkable mechanical integrity and adhesion to the metallic substrate. Full article

A preterm infant with central hypoventilation was diagnosed with multifocal neuroblastoma. Congenital anomalies of the autonomic nervous system in association with neuroblastoma are commonly associated with germline mutations in PHOX2B. Further, the ALK gene is frequently mutated in both familial and sporadic neuroblastoma. Sanger sequencing of ALK and PHOX2B, SNP microarray of three tumor samples and whole genome sequencing of tumor and blood were performed. Genetic testing revealed a germline ALK F1174I mutation that was present in all tumor samples as well as in normal tissue samples from the patient. Neither of the patient’s parents presented the ALK variant. Array profiling of the three tumor samples showed that two of them had only numerical aberrations, whereas one sample displayed segmental alterations, including a gain at chromosome 2p, resulting in two copies of the ALK-mutated allele. Whole genome sequencing confirmed the presence of the ALK variant and did not detect any aberrations in the coding or promotor region of PHOX2B. This study is to our knowledge the first to report a de novoALK F1174I germline mutation. This may not only predispose to congenital multifocal neuroblastoma but may also contribute to the respiratory dysfunction seen in this patient. Full article

The purpose of this study was to evaluate mechanisms behind the intestinal permeability of minoxidil, with special emphasis on paracellular transport, and elucidate the suitability of minoxidil to be a reference drug for Biopharmaceutics Classification System (BCS). The permeability of minoxidil (vs. metoprolol) was evaluated in-silico, in-vitro using both the PAMPA assay and across Caco-2 cell monolayers, as well as in-vivo in rats throughout the entire intestine. The permeability was studied in conditions that represent the different segments of the small intestine: upper jejunum (pH 6.5), mid small intestine (pH 7.0), distal ileum (pH 7.5), and colon (pH 6.5). Since we aimed to investigate the paracellular transport of minoxidil, we have also examined its permeability in the presence of quercetin (250 µM), which closes the tight junctions, and sodium decanoate (10 mM), which opens the tight junctions. While metoprolol demonstrated segmental-dependent rat and PAMPA permeability, with higher permeability in higher pH regions, the permeability of minoxidil was pH-independent. Minoxidil PAMPA permeability was significantly lower than its rat permeability, indicating a potential significant role of the paracellular route. In rat intestinal perfusion studies, and across Caco-2 monolayers, tight junction modifiers significantly affected minoxidil permeability; while the presence of quercetin caused decreased permeability, the presence of sodium decanoate caused an increase in minoxidil permeability. In accordance with these in-vitro and in-vivo results, in-silico simulations indicated that approximatelly 15% of minoxidil dose is absorbed paracellularly, mainly in the proximal parts of the intestine. The results of this study indicate that paracellular transport plays a significant role in the intestinal permeability of minoxidil following oral administration. Since this permeation route may lead to higher variability in comparison to transcellular, these findings diminish the suitability of minoxidil to serve as the low/high BSC permeability class benchmark. Full article

Quinoa is a crop originating in the Andes but grown more widely and with the genetic potential for significant further expansion. Due to the phenotypic plasticity of quinoa, varieties need to be assessed across years and multiple locations. To improve comparability among field trials across the globe and to facilitate collaborations, components of the trials need to be kept consistent, including the type and methods of data collected. Here, an internationally open-access framework for phenotyping a wide range of quinoa features is proposed to facilitate the systematic agronomic, physiological and genetic characterization of quinoa for crop adaptation and improvement. Mature plant phenotyping is a central aspect of this paper, including detailed descriptions and the provision of phenotyping cards to facilitate consistency in data collection. High-throughput methods for multi-temporal phenotyping based on remote sensing technologies are described. Tools for higher-throughput post-harvest phenotyping of seeds are presented. A guideline for approaching quinoa field trials including the collection of environmental data and designing layouts with statistical robustness is suggested. To move towards developing resources for quinoa in line with major cereal crops, a database was created. The Quinoa Germinate Platform will serve as a central repository of data for quinoa researchers globally. Full article

Studies show conflicting results on whether exercise interventions to improve outcomes for women with breast cancer are cost-effective. We modelled the long-term cost-effectiveness of the Exercise for Health intervention compared with usual care. A lifetime Markov cohort model for women with early breast cancer was constructed taking a societal perspective. Data were obtained from trial, epidemiological, quality of life, and healthcare cost reports. Outcomes were calculated from 5000 Monte Carlo simulations, and one-way and probabilistic sensitivity analyses. Over the cohort’s remaining life, the incremental cost for the exercise versus usual care groups were $7409 and quality-adjusted life years (QALYs) gained were 0.35 resulting in an incremental cost per QALY ratio of AU$21,247 (95% Uncertainty Interval (UI): Dominant, AU$31,398). The likelihood that the exercise intervention was cost-effective at acceptable levels was 93.0%. The incremental cost per life year gained was AU$8894 (95% UI Dominant, AU$11,769) with a 99.4% probability of being cost effective. Findings were most sensitive to the probability of recurrence in the exercise and usual care groups, followed by the costs of out-of-pocket expenses and the model starting age. This exercise intervention for women after early-stage breast cancer is cost-effective and would be a sound investment of healthcare resources. Full article