Dairy farming dates to the early Neolithic era in Europe, Middle East, Asia, and Africa. Over time, the industry has evolved from small ranches and farmhouses milk processing units to large, intensive dairy farms and big, high-tech processing units. Despite the industry’s contribution to the economy and food production, multiple studies have tainted cattle farming as a main contributor to climate change. This study explores literature in dairy farming and sustainable development goals (SDGs) to identify current scholarly developments since the formulation and adoption of SDGs in 2015 and themes for future research. This paper argues that dairy animals are not the source of sustainability shortfalls as depicted by multiple scholarly articles, but human processes associated with dairy farming. Data was analyzed using R package, Excel, NVIVO, and VoS Viewer. A review of literature shows that dairy farming and its contribution to sustainability has gained more intensive scientific interest since 2015. Moreover, livestock management, feed production and management, stakeholder’s management, logistics and supply chain management, and waste management are the sources of environmental adversities associated with dairy farming. Notably, these are human processes developed from commercialization of dairy farming and involve multiple stakeholders across the supply chain. While solutions are embedded within these processes, innovation emerges as a key driver of sustainability and source of opportunities to strengthen sustainability in dairy farming sector and achieve the sustainable development goals.

As a precious natural resource, forests are being destroyed. In previous studies, there is a lack of interactive assessment of its distribution that comprehensively considers multiple external disturbances. This paper takes the Barcelona Metropolitan Region as an example. Based on remote sensing, it analyzes the development process of the forest from 2006 to 2018 through multiple landscape indicators, and OLS models were established to analyze variables that have direct and indirect effects on forest distribution. In addition, the ecological structure of the forest was analyzed based on NDVI. It was found that the forest area is the largest but has been decreasing, becoming more complex in distribution structure. Much of the forest was converted to agricultural land and grassland. The green quality of forests was increasing, and the broad-leaved forest, the second largest area, contributes the most. NDVI is the most important positively correlated variable, and daytime surface temperature is an important inverse factor related to NDVI. In addition, NDBI is also a negative condition that inhibits forest development. In conclusion: The BMR forest area is decreasing and becoming more fragmented. NDVI and daytime LST are the two most significant factors. Climate warming may lead to worse forest development.

The movement of liquid droplets on the energy gradient surface has attracted extensive attention. Inspired by biological features in nature, such as the periodic spindle-shaped nodes in spider silks and conical-like barbs of cacti, the structure-property-function relationship of multifunctional gradient surfaces. In this study, a series of specific patterns are fabricated by 3D printing technology, followed by modification via the atmospheric pressure plasma treatment and liquid phase chemical deposition, resulting in enhancing the ability of water droplets of 5μL to travel 18.47mm on a horizontal plane and 22.75mm against gravity up to 20° tilting angle. Additionally, analysis techniques have been employed including contact angle analyzer, ESCA and laser confocal microscope to evaluate the sample performance. This work could further be applied to many applications related to microfluidic devices, drug delivery and water/fog collection.

Carotenoids are common and diverse organic compounds with various functional roles in ani-mals. Except for certain aphids, mites, and gall midges, all animals acquire necessary carotenoids only through their diet. The House fly (Musca domestica) is a cosmopolitan pest insect that populates diverse habitats. Its larvae feed on organic substrates that may vary in carotenoid composition according to their specific content. We hypothesized that the carotenoid composition in the adult House fly’s body would reflect its composition in the larval feed. We reared house fly larvae on substrates that differed in carotenoid composition and characterized the carotenoid composition of the emerging adults. Our results indicate that the carotenoid composition of adult House flies is related to the carotenoid composition in its natal substrate, but does not directly reflect it. We suggest that these findings may be developed to identify sources of House fly in-festations. We also recommend that care should be taken when considering the rearing substrates of House fly larvae used for animal feed.

Short video addiction refers to a psychological dependency on short video applications, characterized by an intense attachment and an inability to control usage, leading to typical addiction symptoms. While its definition bears similarities to substance addiction, significant differences also exist. According to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), published in 2013, short video addiction has not yet been officially classified as an addiction disorder. To facilitate more in-depth and standardized research on short video addiction, it is essential to synthesize and organize existing studies on its theoretical foundations and mechanisms.

The spread of fake news poses a serious threat to public trust and informed decision-making. The emergence of AI-generated fake news exacerbates this issue, as it can be produced more rapidly and convincingly than human-generated content. Addressing this issue, our paper introduces a robust approach to detect AI-generated fake news that is applicable across major disinformation domains: Politics and Elections, Health and Medicine, Science and Technology, and Entertainment and Celebrities. Our models differentiate between AI-generated and human-generated news articles while assessing their truthfulness. Utilizing large language models such as ChatGPT, we curated datasets spanning both AI and human generated fake and genuine news. Following extensive data preprocessing and the application of diverse feature extraction techniques, our models were trained using multiple machine learning algorithms. Our results show the feasibility of accurately identifying AI-generated fake news, thereby adding a significant layer of defense in combating misinformation across various sectors. In addition, we have explored the potential utility of transferable machine learning models trained on data from one domain (e.g., politics), when tested on another domain (e.g., health).

The Eurasian grapevine (Vitis vinifera L.) is the most widely grown horticultural crop in the world and is important for the economy of many countries. In the wine production chain, grape varieties play an important role as they directly influence the authenticity and classification of the product. Identifying the different grape varieties is therefore fundamental for quality control and inspection activities, as well as for regulating production. Currently, ampelography and molecular analysis are the main approaches to identifying grape varieties. However, both methods have limitations. Ampelography is subjective and prone to errors and is experiencing enormous difficulties as ampelographers are increasingly scarce. On the other hand, molecular analyses are very demanding in terms of cost and time. In this scenario, Deep Learning (DL) and Machine Learning (ML) methods have emerged as a classification alternative to deal with the scarcity of ampelographs and avoid molecular analyses. In this study, the most recent and current methods for identifying grapevine varieties using DL classification-based approaches are presented through a systematic literature review. The classification pipeline of the 31 studies found in the literature was described, highlighting its pros and cons. Most of the studies used DL-based models trained with leaf images acquired in a controlled environment at a maximum distance of 1.2 metres to classify grape varieties. In addition, there is a large gap between practical applications and the datasets used: a great lack of varieties, limited data acquired in the field and a lack of tests on plants under adverse conditions. Potential directions for improving this area of research were also presented.

Residential segregation refers to the phenomenon where people of different socioeconomic backgrounds live in spatially separated areas. It is essential to ensure equitable access to urban amenities for all residents in pursuit of the normative values in urban planning. To achieve this planning goal, the disparity in accessibility to urban amenities needs to be appropriately diagnosed. Private apartments and public rental apartments are representative types of residences where residential segregation is likely to occur in the context of South Korea, since these two types show considerable differences in the education, income, and occupations. The objective of this study is to develop an analysis framework for diagnosing the difference in accessibility to urban amenities between the two residential types, and to empirically demonstrate their utility in the planning process. The empirical analysis conducted on Seoul revealed that not only were there significant local variations in accessibility between the two segregated residential areas, but the overall differences across the entire area were also pronounced. The proposed framework is useful in supporting decision-making processes for locating new public facilities or identifying regional priorities for guiding the placement of private amenities, with the aim of mitigating differences between segregated residential areas.

Smart City has emerged as the mainstream paradigm for urban governance innovation, sustainable development, and strategy upgrades, which is drawing attention from scholars worldwide. However, current frameworks for Smart City assessment remain incomplete and simplistic. In is paper, 30 national or provincial capitals in China were selected and we designed a tri-dimensional SPI model—Social, Physical, and Information Space—for smart city spatial development assessment. Utilizing methods such as entropy weighting, coupled coordination degree models, and the Dagum Gini coefficient, this study assesses the spatial development and coupled coordination of 30 cities from 2011 to 2019. Finally, by means of BP neural networks, the study examines the contribution of each indicator to the spatial coupled coordination. The results indicated that with a narrowing disparity in development speeds among different regions, the spatial coupled coordination development level of smart capitals in China has steadily increased, presenting a pattern of staggered distribution. Moreover, the IS subsystem plays the most significant role in coupled coordination. The significance of this research lies in its tri-dimensional spatial perspective of the spatial development and coupled coordination differences of the Smart City, providing evidence-based support for the regional layout and optimization in China.

Introduction: Atrial fibrillation (AF) is a common cardiac arrhythmia whose prevalence rises with age and is linked to increased morbidity and mortality due to the risk of thromboembolism. Management typically involves anticoagulation and rhythm control, but the treatment of elderly patients with multiple comorbidities requires careful consideration of drug side effects and interactions. Cibenzoline, a Vaughan-Williams class IA antiarrhythmic, is effective against AF but has risks of toxicity, especially in older people and those with renal impairment, due to its renal excretion and prolonged half-life in these populations. Discussion: This paper presents a case of an 80-year-old woman with paroxysmal AF who suffered cardiac arrest due to cibenzoline toxicity despite receiving standard adjusted dosages. The patient's cibenzoline blood concentration was significantly higher than the therapeutic range, leading to cardiotoxicity, which was exacerbated by drug interactions with bisoprolol and edoxaban, both metabolized by the CYP3A4 enzyme. Venoarterial extracorporeal membrane oxygenation (V-A ECMO) and intra-aortic balloon pump (IABP) successfully managed the cardiac arrest. This case emphasizes the unpredictable pharmacokinetics of cibenzoline in elderly patients with renal impairment and the need for vigilant therapeutic drug monitoring to avoid adverse events. Conclusions: Cibenzoline can pose a significant risk of severe toxicity in elderly patients with renal impairment, and drug interactions may potentiate this risk. The paper underscores the importance of careful dose adjustment and monitoring of drug levels in this population. In cases of cibenzoline-induced cardiac arrest, V-A ECMO and IABP are effective treatment modalities. The case study serves as a critical reminder for clinicians to remain vigilant for drug-induced complications and to apply aggressive supportive treatments when necessary.

Pavement crack detection is one of the key links in highway pavement maintenance management. In the current road crack detection, the network model easily ignores the shallow geometric features of cracks and cannot extract the key feature information of cracks. Aiming at the above problems, an EC-YOLOX network model is proposed. The CFPN is constructed to cross-fuse different scale features to solve the feature scale invariance. In the strengthen feature extraction layer, ECANet is fused to enhance the ability to pay attention to key information. The WEIoU loss function is proposed, which assigns different penalty terms to the target box in the vertical and horizontal directions. In terms of data, geometric distortion constraint correction is performed on the single-point perspective pavement image. The experimental data show that the accuracy of EC-YOLOX on the self-built data set reaches 76.34% [email protected], which is 4.45% higher than that of YOLOX. The loss curve of EC-YOLOX is smoother than that of YOLOX, and the minimum training loss value is 2.136, which is 0.648 lower than the minimum loss value 2.784 of YOLOX. Many experiments have verified the effectiveness of EC-YOLOX in improving the detection effect in pavement crack detection.

The Food and Drug Administration’s 2011 Process Validation Guidance and International Council for Harmonization Quality Guidelines recommend continued process verification (CPV) as a mandatory requirement for pharmaceutical, biopharmaceutical, and other regulated industries. As a part of product life cycle management, after process characterization in stage 1 and process qualification and validation in stage-2, CPV is performed as stage-3 validation during commercial manufacturing. CPV ensures that the process continues to remain within a validated state. CPV requires the collection and analysis of data related to critical quality attributes, critical material attributes, and critical process parameters on a minimum basis. Data is then used to elucidate process control regarding the capability to meet predefined specifications and stability via statistical process control tools. In statistical process control, control charts and Nelson rules are commonly used throughout the industry to monitor and trend data to ensure that a process remains in control. In the control chart, the mean value is taken as the center line, and 3σ limits are placed on either side of the center line. In CPV, manufactured lots are summarized, trended, and discussed at a cross-functional level at pre-defined intervals (either weekly, bi-weekly, or even monthly) based on the batch run rate. A cross-functional team assesses details regarding 1) violation frequency, 2) statistical strength of the signal, 3) violation magnitude and its impact on process or quality, and 4) any potential root causes for out-of-expectation or out-of-trend signals. The cross-functional team must analyze whether any signal identified by the control chart is reliable and must determine whether corrective action should be taken and justify the decision in the CPV meeting minutes based on statistical strength and reliability of the signal. However, basic control charts are susceptible to false alarms and nuisance alarms. Therefore, it is imperative to understand the assumptions behind control charts and the inherent false alarm rates for different Nelson rules. In this article, the authors have detailed the assumptions behind the usage of control charts, the rate of false alarms for different Nelson rules, the impact of skewness and kurtosis of a data distribution on the false alarm rate, and methods for optimizing control chart design by reducing false alarm rates and nuisance signals.

Grain quality, cooking quality and nutritional quality traits are some of the major attributes that enhance uptake and utilisation of improved cowpea varieties. Therefore, there is need for a better understanding of the genetic variation and inter-relationships among these quality traits in cowpea to integrate them in cowpea breeding programs. The study was conducted to determine genetic variability among 306 cowpea genotypes for grain quality, cooking quality and nutritional quality traits and to understand the interrelationships among these traits for exploitation in breeding programs. The results showed highly significant differences (P

To assure the opacity, an optimal problem is to retain the occurring events sequences as many as possible. Contrary to such problem, the other optimal problem is to preserve the minimal occurring events sequences. In the paper, based on the choosing cost, an optimal opacity-enforcing model is presented to minimize the sum of discount choosing cost, which is not only to preserve the opacity, but also to retain the secret to the maximum. To solve the model, two scenarios on opacity are considered. For the two scenarios, some algorithms are presented to achieve the optimal solution for the model by using the method of dynamic programming. And then, the solutions produced by the algorithms are proved correctly by theoretical proof. Finally, some illustrations for the algorithms are given.

Oilseed plants of the Brassicaceae plant family are cultivated for food, feed and industrial purposes on large-scale in Europe. This review gives an overview of current market-oriented applications of new genomic techniques (NGTs) in relevant Brassicaceae oilseed crops based on a literature survey. In this respect, changes in oil quality, yield, growth and resistance to biotic and abiotic stress are goals in oilseed rape (B. napus) and camelina (C. sativa). Environmental risk assessment scenarios are developed for specific NGT applications in Brassicaceae oilseed crops with either a changed oil composition or with fitness related traits. In case of a changed oil composition an increase or decrease of polyunsaturated fatty acids (PUFA) demonstrates risks for health and survival of pollinators. In case of fitness related traits other risks were identified, i. e. an increased risk of spread and persistence of NGT plants. Furthermore, there are indications for potential disturbance of interactions with the environment, involving signalling pathways and reaction to stress conditions. It is shown that for a comprehensive risk assessment the technological potential of NGTs, the plants’ biology and the scale of releases have to be considered in combination. Therefore, the release of NGT plants into the environment for agricultural purposes will require risk assessment and monitoring of single traits as well as of combinatorial and long-term cumulative effects. In addition, risk management should develop concepts and measures to control and potentially restrict the scale of releases. This is especially relevant for NGT Brassicaceae in Europe which is a centre of diversity of this plant family.

Background. The Stanford Health Assessment Questionnaire-Disability Index (HAQ) is widely used to measure functional ability in persons with Rheumatoid Arthritis (RA). The instrument was developed with limited involvement from persons with RA, and their perception of the instrument has not been studied in depth. The aim of this study was to explore how persons with RA experience the use of the HAQ in care. Methods. Forty persons with RA were purposefully recruited to participate in semi-structured interviews. The interviews were then analyzed qualitatively using thematic analysis. Results. The participants questioned the relevance of the HAQ but nevertheless experienced that the instrument had a profound effect on their understanding of health and how care is delivered. The analysis resulted in three themes: Problems with individual items, meaning of the summative score, and effects on care and health perceptions. Conclusions. To make the HAQ relevant to persons with RA, it needs to be revised or to include an option to select items most meaningful to the respondent. To ensure relevance, the HAQ update should preferably be co-created by researchers, clinicians and persons with RA.

Urban rail transit hub platform is the most important area for passenger flow distribution. In order to calculate passenger flow volume in platform and evaluate platform service level during rush hours, this paper presents a method for modeling and simulation of passenger flow distribution in platform. Passenger flow distribution model (PFDM) is proposed based on the basic analysis and the superposition principle of passenger flow. Simulation design for PFDM is proposed by Anylogic, which contains simulation process and simulation model. Experiment results show that PFDM and simulation design are effective and accordant with the reality scenario, and the simulation precision is comparatively ideal. This research could provide a beneficial reference for train scheduling and operation management under the viewpoint of traffic safety and service level.

Recycling waste products is an environmental-friendly activity that can bring benefits to accompany, saving manufacturing costs and improving economic efficiency. For the beer industry, recycling bottles can reduce manufacturing costs and reduce the industry's carbon footprint. This paper presents a model for a multi-objective collection-distribution center location and allocation problem in a closed loop supply chain for the beer industry, in which the objective is to minimize total costs and transportation pollution. Uncertainties in the form of randomness and fuzziness are jointly handled in this paper to ensure a more practical problem solution, for which returned bottle sand unusable bottles are considered fuzzy random variables. A heuristic algorithm based on priority-based global-local-neighbor particle swarm optimization (pb-glnPSO) is applied to ensure reliable solutions for this NP-hard problem. A case study on a beer operation company is conducted to illustrate the application of the proposed model and demonstrate the priority-based global-local-neighbor particle swarm optimization.

One of the most important agrotechnical factors that influence the growth conditions of crops is plant density. Alterations in habitat conditions result in the emergence of phytophagous organisms, whose development is closely associated with host plants. The objective of this study was to assess the abundance and species composition of thrips (Thysanoptera) collected in soybean plants of different varieties cultivated under different plant arrangements (row spacing, number of seeds sown differed). The research was conducted at two locations in southwestern Poland between 2015 and 2018. The herbivores that inhabit plants were caught using an entomological net. The experiments were carried out using the complete randomised block design, with four replications. Regardless of location and treatment, thrips were the most numerous group of pests. Thrips tabaci and T. fuscipes were the dominant species within the collected material. A total of 24 species of thrips were identified and their dietary specialisation was determined. The assemblages of studied insects were also analysed due to the density of the plants and the stage of development. The increase in the sowing density of soybean (90 seeds per m2) resulted in a greater total number of thrips compared to a lower sowing density (50 seeds per m2). The number of thrips significantly increased during the flowering period and shortly after the flowering time, which made them a significant threat to the plants. Therefore, it is crucial to develop innovative pest management strategies tailored to effectively grow soybean to mitigate potential pest-related challenges.

Few studies have explored the gender wage gap among farmworkers, and there is a notable absence of research on how farm wages impact household welfare differently based on gender. This study aims to fill this gap by examining how farm wages affect gender disparities in household welfare among farmworkers in Nigeria. Using survey data from 720 farmworkers, we investigated gender-based differences in household welfare. Our approach combined parametric methods (Blinder-Oaxaca decomposition) to assess gender gaps in household welfare and non-parametric techniques (Propensity Score Matching, PSM) to estimate the effects of farm wages. The analysis reveals that female farmworkers experience significantly lower per capita food consumption expenditure (₦11,486.51 less) compared to their male counterparts. These disparities partly stem from differences in socioeconomic factors, job characteristics, and enterprise attributes between male and female farmworkers. The study underscores the role of farm wages in mitigating gender gaps in household welfare, demonstrating that farm wages have increased per capita food consumption expenditure for female farmworkers by ₦6,640.698. This finding highlights the potential of wage increases to enhance livelihoods, underscoring the importance of equitable wage policies in farming. Furthermore, our findings emphasize that the impact of farm wages on welfare varies with household characteristics, suggesting the need for targeted interventions tailored to enhance identified household attributes. Addressing these factors could effectively reduce gender inequalities in farm work and contribute to overall welfare improvements.

Placental protein 13 (PP13) exhibits a plasma concentration that increases gradually during normal gestation, a process disrupted in preeclampsia, characterized by elevated vascular resistance, re-duced utero-placental blood flow and intrauterine growth restriction. This study investigated PP13’s role in vascular tone regulation and its molecular mechanisms. Uterine and subcutaneous arteries isolated from both pregnant and non-pregnant women were precontracted with the thromboxane analogue U46619, and exposed to PP13 using pressurized myography. The molecular mechanisms were further investigated using specific inhibitors for ni-tric oxide synthase (L-NAME+LNNA at 10-4 M) and guanylate cyclase (ODQ at 10-5 M). Results showed PP13 induced vasodilation in uterine arteries but not in subcutaneous arteries. Ad-ditionally, PP13 counteract U46619-induced vasoconstriction, which is particularly pronounced in pregnancy. Further investigation revealed that PP13's mechanism of action is dependent on activa-tion of the Nitric oxide-cGMP pathway. This study provides novel insights into the vasomodulatory effects of PP13 on human uterine ar-teries, underscoring its potential role in regulating utero-placental blood flow. These findings suggest PP13 may be a promising candidate for improving utero-placental blood flow in condi-tions such as preeclampsia. Further research and clinical studies are warranted to validate PP13's efficacy and safety as a therapeutic agent for managing preeclampsia.

The high prevalence of human papillomavirus (HPV) infection in oropharyngeal squamous cell carcinoma (OPSCC) is well-established, with p16 expression being a strong predictor. HPV-related tumors exhibit unique mechanisms targeting p16 and p53 proteins. However, re-search on HPV prevalence and the combined predictive value of p16 and p53 expression in head and neck cutaneous squamous cell carcinomas (HNCSCC), especially in Asian populations, is limited. This retrospective study surveyed 62 HNCSCC patients (2011–2020), excluding those with facial warts or other skin cancers. All patients underwent wide excision and biopsy. Immuno-histochemical staining for HPV, p16, and p53 yielded both positive and negative results. The relevance of each marker was investigated by categorizing the tumor locations into high-risk (Area H) and mid-risk (Area M) zones based on recurrence frequency. Of the 62 patients, 20 (32.26%) were male, with an average age of 82.27 years (26–103). Area H included 19 cases (30.65%), with the eyelid and lip being the most common sites (five cases, 8.06%). Area M in-cluded 43 cases (69.35%), with the cheek being the most common site (29 cases, 46.77%). p16 ex-pression was positive in 24 patients (38.71%), p53 expression in 42 patients (72.58%), and HPV in five patients (8.06%). No significant association was found between p16 expression and HPV presence (p > 0.99), with a positive predictive value of 8.33%. This indicates that p16, a surrogate marker of HPV in OPSCC, is not a reliable marker for HPV in HNCSCC. This study enhances our understanding of the relationship between HPV, p53, and p16 in HNCSCC in Asian populations and offers valuable insights for further research.

Yaba monkey tumor virus (YMTV) and Tanapox virus (TPV) are members of the Yatapoxvirus genus and can infect humans and other primates. Despite the threat posed by yatapoxviruses, the factors determining their host range are poorly understood. In this study, we analyzed the ability of YMTV and TPV orthologs of vaccinia virus K3 (called 012 in YMTV and TPV), which share 75% amino acid identity with one another, to inhibit PKR from 15 different primate species. We first used a luciferase-based reporter, and found that YMTV and TPV K3 orthologs inhibited PKR in a species-specific manner and showed distinct PKR inhibition profiles. TPV 012 inhibited PKR from 11 primates, including human, substantially better than YMTV 012. In contrast, both K3 orthologs inhibited the other four primate PKRs comparably well. Using YMTV 012 and TPV 012 hybrids, we mapped the region responsible for the differential PKR inhibition to the C- terminus of the K3 orthologs. Next, we generated chimeric vaccinia virus strains to investigate whether TPV K3 and YMTV K3 orthologs could rescue replication of a vaccinia virus strain that lacks PKR inhibitors K3L and E3L. Virus replication in primate-derived cells generally correlated with the patterns observed in the luciferase-based assay. Together, these observations demonstrate that yatapoxvirus K3 orthologs have distinct PKR inhibition profiles and inhibit PKR in a species-specific manner, which may contribute to the differential susceptibility of primate species to yatapoxvirus infections.

Natural risks encompass a range of disasters and dangers, requiring comprehensive management through assessments, anticipations, and advanced alert systems. Our specific focus is on landslides in challenging terrains. The evaluation of landslide risks employs sophisticated multicriteria models, such as the weighted sum approach, integrating qualitative parameters. Despite the challenges of the rugged terrain in Northern Algeria, it paradoxically hosts a dense population attracted by valuable hydro-agricultural resources. Our research is dedicated to studying landslide risks in these areas, particularly in the Mila region, with the aim of constructing a statistical model integrating considerations of both danger and vulnerability. This complex process identifies threats and their determining factors, including geomorphology and socio-economic conditions. The result is a valuable tool for effective risk management, strengthening safety and resilience against natural disasters. By understanding the intricate interplay of geological, environmental, and social elements, our research can contribute to the development of targeted interventions, fostering a more resilient community in the face of natural adversities.

Background: Mental capacity is a fundamental aspect that enables patients to fully par-ticipate in various healthcare procedures. To assist healthcare professionals (HCPs) in assessing patients' capacity, especially in the mental health field, several standardized tools have been developed. These tools include the MacArthur Competence Assessment Tool for Treatment (MacCAT-T), the MacArthur Competence Assessment Tool for Clinical Research (MacCAT-CR), and the Competence Assessment Tool for Psychiatric Advance Directives (CAT-PAD). The core dimensions explored by these tools include Understanding, Appreciation, Reasoning, and Expression of a choice. Objective: This meta-analysis aimed to investigate potential differences in deci-sion-making capacity within the healthcare context among groups of patients with bi-polar disorder (BD) and schizophrenia spectrum disorder (SSD). Methods: A systematic search was conducted on Medline/Pubmed, and Scopus. Addi-tionally, Google Scholar was manually inspected, and a manual search of emerging re-views and reference lists of the retrieved papers was performed. Eligible studies were specifically cross-sectional, utilizing standardized assessment tools, and involving pa-tients diagnosed with BD and SSD. Data from the studies were independently extracted and pooled using random-effect models. Hedges g was used as a measure for outcomes. Results: Six studies were identified, with three studies using the MacCAT-CR, two studies the MacCAT-T, and one the CAT-PAD. The participants included 189 individuals with BD and 324 individuals with SSD. The meta-analysis revealed that patients with BD performed slightly better, and the difference was statistically significant, compared to patients with SSD, particularly in the domain of Appreciation (ES=0.23, 95% CI: 0.01 to 0.04, p=0.037). There was no statistically significant difference between the two groups for Understanding (ES=0.09, 95% CI: - 0.10 to 0.27, p=0.352), Reasoning (ES=0.18, 95% CI: - 0.12 to 0.47, p=0.074), and Expression of a choice (ES = 0.23, 95% CI: - 0.01 to 0.48, p=0.60). In the sensitivity analysis, furthermore, when considering only studies involving patients in symptomatic remission, the difference for Appreciation also resulted in non-significant (ES=0.21, 95% CI: -0.04 to 0.46, p=0.102). (ES=0.21, 95% CI: -0.04 to 0.46, p=0.102). Conclusions: These findings indicate that there are no significant differences between patients with BD and SSD during remission phases, while differences are minimal during acute phases. The usefulness of standardized assessment of capacity at any stage of the illness should be considered, both for diagnostic-therapeutic phases and for research and advance directives. Further studies are necessary to understand the reasons for the overlap in capacity between the two diagnostic categories compared in this study.

In this work, two plasmonic structures with two different periodic nanostructures (nanodisk and nanostrip arrays) separated from the gold layer by an ultrathin dielectric Al2O3 layer are proposed, and their optical properties are simulated as 3-dimensional models using COMSOL Multiphysics software tool. The optical responses, such as the amplification of the electric field and the scattering, absorption and extinction cross sections of the two structures, are investigated and compared. The results show that both structures show strong field enhancement in their gap layer, and the structure with the periodic array of metal nanodisks shows stronger field enhancement and larger absorption, extinction, and scattering cross sections in its dipole resonance wavelength, which is defined as a bright plasmonic mode. In addition, some weaker resonant modes are observed for both structures and the reason for their generation is dis-cussed. The analysis of different possible modes in such structures is crucial for their application in various fields.

Objective: to retrospectively evaluate the incidence rate (IR) of echocardiographic signs suspected for pulmonary hypertension (PH) in Systemic sclerosis (SSc) patients after the introduction of a combination therapy with bosentan and sildenafil for treatment or prevention of digital ulcers. Methods: patients attending the Scleroderma Unit of the Universital Hospital of Careggi from July 2010 to July 2023 were enrolled. Patients older than 18 years old, with an history of digital ulcers, treated with bosentan and sildenafil in combination for at least 12 months were included. Patients with a diagnosis of PH preceding the introduction of the therapy were excluded. Demographical data, disease duration, laboratoristic and instrumental data (pulmonary function tests, echocardiographic estimation of pulmonary artery pressure (PAPs) and ultrasonographic value of renal resistive index) were collected. The IR of echocardiographic signs suspected for pulmonary hypertension and their 95% confidence interval were calculated in events/1000 patients-years.Results: forty-seven patients were enrolled; mean disease duration was 12,14 years (SD 5,87). Mean duration of the combination treatment was 78.33 (SD 41.37) months and total at-risk time was 3525 months. Two patients (4,2%) presented echocardiographic signs of PH (sPAP 50 mmHg and 40 mmHg); the IR was calculated to be 6.8/1000 patients-years (95% CI 6,02-7,7). In one of the 2 patients RHC excluded PAH, while the other patient refused to undergo to RHC and PAH could not be confirmed/excluded. A stability of PFTs and echocardiografic PAPs was observed during the observation time. Conclusions: the results of this retrospective study suggest that combination therapy with endothelin receptor antagonist and Phosphodiesterase-5 (PDE5) inhibitors could help in preventing PAH in SSc; prospective case-control studies on larger population are needed to improve knowledge in this field.

Critically ill patients treated in the intensive care unit (ICU) can present many abdominal conditions that need a prompt diagnosis and timely treatment because of their general frailty. Clinical evaluation and diagnostic tools like ultrasound or CT scan are not reliable or feasible in these patients. Bedside laparoscopy (BSL) is a minimally invasive procedure that allows surgeons to assess the abdominal cavity directly in the ICU, thus avoiding unnecessary exploratory laparotomy or incidence related to intra-hospital transfer. We conducted a review of the literature to summarize the state-of-the-art of BSL. Medline, The Cochrane Central Register of Controlled Trials (CENTRAL), and Scopus databases were utilized to identify all relevant publications. Indications, contraindications, technical aspects, and outcomes are discussed. The procedure is safe, feasible, and effective. When other diagnostic tools fail to diagnose or exclude an intra-abdominal condition in ICU patients, BSL should be preferred over exploratory laparotomy.

The global usage of veterinary antibiotics is significant. These antibiotics can be released into the aquatic environment and exert toxic effects on non-target organisms. To explore the physiological effects of tetracycline antibiotics on aquatic life, the growth characteristics of and toxin release from the cyanobacterium Microcystis aeruginosa (M. aeruginosa) were studied. Results showed that the toxicity order of the three target antibiotics was TC (tetracycline) > CTC (chlortetracycline hydrochloride) > OTC (oxytetracycline) in terms of inhibition occurrence time and the EC₁₀ and EC₂₅ values. Further, the target antibiotics regulated the production of MC-LR (microcystin-LR) to different degrees. CTC destroyed the M. aeruginosa cells and resulted in a decreased MC-LR release but stimulated the ability to synthesise MC-LR. OTC had a relatively weaker toxicity compared with CTC, while TC was the most toxic among the three antibiotics. Therefore, TC is friendly to the aquatic environment because it simultaneously reduced the intracellular and extracellular MC-LR content. These results aid our understanding of the effects of tetracycline antibiotics on Microcystis aeruginosa, which is important for environmental evaluation and protection. These results are also helpful for guiding the application of veterinary antibiotics in agricultural settings.

Lily tepals have a short lifespan. Once the tepals senesce, the ornamental value of the flower is lost. Some cultivars have attractive purple ovaries and fruits which greatly enhance the ornamental value of Asiatic hybrid lilies. However, little is known about the molecular mechanisms of anthocyanin biosynthesis in Asiatic hybrid lily ovaries. To investigate the transcriptional network that governs purple ovary coloration in Asiatic hybrid lilies, we obtained transcriptome data from green ovaries (S1) and purple ovaries (S2) of Asiatic ‘Tiny Padhye’. Comparative transcriptome analysis revealed 4228 differentially expressed genes. Differential expression analysis revealed that nine unigenes including four CHS genes, one CHI gene, one F3H gene, one F3′H gene, one DFR gene, and one UFGT gene were significantly up-regulated in purple ovaries. One MYB gene, LhMYB12-Lat, was identified as a key transcription factor determining the distribution of anthocyanins in Asiatic hybrid lily ovaries. Further qPCR results showed unigenes related to anthocyanin biosynthesis were highly expressed in purple ovaries of Asiatic ‘Tiny Padhye’ at stages 2 and 3, while they showed an extremely low level of expression in ovaries of Asiatic ‘Yellow Pixels’ during all developmental stages. In addition, shading treatment significantly decreased pigment accumulation by suppressing the expression of several unigenes related to anthocyanin biosynthesis in ovaries of Asiatic ‘Tiny Padhye’. These results could further our understanding of the molecular mechanisms of anthocyanin biosynthesis in Asiatic hybrid lily ovaries.

Exposure to malachite green (MG) may pose great health risks to humans, thus it is of prime importance to develop fast and robust methods to quantitatively screen the presence malachite green in environment. Herein application of extractive electrospray ionization mass spectrometry (EESI-MS) has been extended to the trace detection of MG within lake water and aquiculture water, due to the intensive use of MG as biocide in fisheries. This method has the advantage of obviating offline liquid-liquid extraction or tedious matrix separation prior to the measurement of malachite green in native aqueous medium. The experimental results indicate that the extrapolated detection limit for MG was ~3.8 ug L-1 (S/N=3) in lake water samples and ~ 0.5 ug L-1 in ultrapure water under optimized experimental conditions. The signal intensity of MG showed good linearity over the concentration range of 10–5000 ug L-1. Measurement of practical water samples fortified with MG at 0.01 and 0.1 mg L-1 gave a good validation of the established calibration curve. The average recoveries of malachite green in lake water and Carassius carassius fish farm effluent water were 114.9% (6.6% RSD) and 85.4% (9.2% RSD), respectively. Overall, the established EESI-MS/MS method has been demonstrated suitable for sensitive and rapid (<2 min per sample) quantitative detection of malachite green in various aqueous media, indicating its potential for online real-time monitoring of real life samples.

This paper is aimed at studying the temporal evolution of the surface displacements occurred over the past few years in the ocean-reclaimed platforms of the Shanghai megacity (China), which are mainly ascribable to consolidation processes of large dredger fills and alluvial deposits. With respect to previous analyses carried out over the same area, this work provides a joint multi-platform differential interferometry synthetic aperture radar (DInSAR) analysis, based on the application of the advanced Small BAseline Subset (SBAS) algorithm. This led us to retrieve long-term deformation time-series that are helpful for a better understanding of the on-going deformation phenomena. To this aim, we have exploited two sequences of SAR data collected by the ASAR/ENVISAT and by the COSMO-SkyMed (CSK) sensors, respectively, spanning the whole time period from 2007 to 2016. Unfortunately, the large time gap (of about three years) existing between the available ASAR/ENVISAT and CSK datasets gave rise to additional difficulties for their combination. Nevertheless, this problem has been faced by benefiting from the knowledge of a time-dependent model describing the temporal evolution of the expected deformations affecting the Shanghai ocean-reclaimed platforms.

Mutations in p53 and KRAS are seen in most cases of colon cancer. The impact of these mutations on signaling pathways related to cancer growth has been studied in depth, but relatively less is known on their effects on amino acid transporters in cancer cells. This represents a significant knowledge gap because amino acid nutrition in cancer cells profoundly influences macropinocytosis and ferroptosis, two processes with opposing effects on tumor growth. Here we used isogenic colon cancer cell lines to investigate the effects of p53 loss and KRAS activation on two amino acid transporters relevant to macropinocytosis (SLC38A5) and ferroptosis (SLC7A11). Our studies show that the predominant effect of p53 loss is to induce SLC7A11 with resultant potentiation of antioxidant machinery and protection of cancer cells from ferroptosis whereas KRAS activation induces not only SLC7A11 but also SLC38A5, thus offering protection from ferroptosis as well as improving amino acid nutrition in cancer cells via accelerated macropinocytosis. Niclosamide, an FDA-approved anti-helminthic, blocks the functions of SLC7A11 and SLC38A5, thus inducing ferroptosis and suppressing macropinocytosis with resultant effective reversal of tumor-promoting actions of oncogenic mutations in p53 and KRAS. These findings underscore the potential of this drug in colon cancer treatment.

Selecting road networks in cartographic generalization has consistently posed formidable challenges, driving research towards the application of intelligent models. Despite previous efforts, the accuracy and connectivity preservation in these studies, particularly when dealing with road types of similar sample sizes, still warrant improvement. To address these shortcomings, we introduce a Heterogeneous Graph Attention Network (HAN) for road selection, where feature masking method is initially utilized to assess the significance of road features. Concentrating on the most relevant features, two meta-paths are introduced within the HAN framework: one for aggregating features of the same road type within the first-order neighborhood, emphasizing local connectivity, and another extending this aggregation to the second-order neighborhood, capturing a broader spatial context. For a comprehensive evaluation, we introduce a set of metrics considering both quantitative and qualitative aspects of the road network. Compared to traditional neural networks, our HAN model demonstrates superior accuracy and F1-score, particularly for road types with comparable samples. Additionally, it enhances the overall connectivity of the selected network. In summary, our HAN-based method provides an advanced solution for road network selection, surpassing previous approaches in terms of accuracy and connectivity preservation.

Banana wilt caused by Fusarium oxysporum f. sp. cubense tropical race 4 (Foc TR4) is a devastating fungal disease. Biocontrol strategies owned immense potential in inhibiting the spread of Foc TR4. Here, thirty actinobacteria were isolated from soils and screened for their antagonistic activity against Foc TR4. Strain SCA4-21T exhibited broad-spectrum antifungal activity against nine phytopathogenic fungi including Foc TR4. The strain was identified as the genus Streptomyces according to phenotypic characteristics and 16S rRNA gene phylogenetic analysis. Multi-locus sequence analysis based on five house-keeping gene alleles (atpD, gyrB, recA, rpoB, and trpB) revealed that strain SCA4-21T clustered into S. hygroscopicus subsp. hygroscopicus NBRC 13472T with 100% of bootstrap value. Average nucleotide identity and dDDH were 98.49% and 44.30% above the threshold of novel species. Hence, strain SCA 4-21T represented a novel species within the genus Streptomyces, named as Streptomyces luomodiensis sp. nov.. The type strain is SCA4-21T (=GDMCC4.340T= JCM36555T). By the CAZymes analysis, 348 carbohydrate-active enzymes were detected, including 15 chitinases and 8 β-1,3-glucanases. The fermentation broth of strain SCA4-21T showed high activities of chitinase and β-1,3-glucanase, contributing to the antifungal activity. Our results showed an innovative potential biocontrol agent for managing plant fungal diseases, specifically banana fusarium wilt.

Chronic kidney disease patients treated by hemodialysis present a high cardio-vascular morbidity and mortality. There is an imperative need for novel biomarkers in identifying and to offer possible therapeutically intervention in these patients. We performed a prospective observational cohort study on 77 patients in the period October 2021 – October 2023. We measured serum plasma levels of Interleukin 1-Beta, Galectin 3, human suppression of tumorigenicity factor 2, bone morphogenetic protein 2 and fibroblastic growth factor 23 at the inclusion. We evaluated the correlations of these biomarkers with cardiac function and structure evaluated by echocardiography. Mean age was 61.02 (±11.81) years, 45 (56.2%) males and with a dialysis vintage of 4.95 (2.4-7.8) years. Median ejection fraction was 51 (43-54 %) and more than two thirds of the patients presented valvular calcifications. Overall mortality was 22%. Interleukin 1-Beta correlated positively with ejection fraction and global longitudinal strain and negatively with left atrium diameter and left ventricle tele systolic diameter. Galectin 3 values negatively correlated with aortic valve fibrosis and mitral valve calcifications and human suppression tumorigenity factor 2 negatively correlated with mitral valve calcifications. Some of these novel biomarkers could be used to better asses the cardio-vascular disease in patients on maintenance hemodialysis.

Background: The effect of velamentous cord insertion (VCI) on perinatal outcomes in twin pregnancies is unclear due to conflicting findings. This retrospective study aimed to examine VCI prevalence and related risk factors in twin pregnancies and its association with adverse perinatal outcomes. Methods: Women with twin pregnancies who delivered between January 2012 and December 2021 in a single tertiary hospital were included. The participants were divided into dichorionic (DC) and monochorionic diamniotic (MCDA) groups, and their maternal and fetal characteristics and VCI rates were compared. Logistic regression models were used to identify risk factors for VCI and VCI-related perinatal outcomes. Results: Among the 694 twin pregnancies included in this study, the VCI rate was significantly higher in MCDA than in DC twins. Body mass index and MCDA twins were significant risk factors for VCI, whereas assisted reproductive technology pregnancy was a significant protective factor against VCI. In DC twins, VCI did not affect perinatal outcomes. Conclusion: In MCDA twins, VCI was a significant risk factor for fetal growth restriction, twin-to-twin transfusion syndrome, and preterm birth at

Antibiotic resistance is a global health problem. The human gut microbiome is implicated in the dynamics of antibiotic resistance acquisition and transmission, with the gut microbiota thought to play a crucial role. This study aimed to determine the potential influence of human gut bacteria microbiota on the gut resistome and the relationship between gut background microbiota and Escherichia coli resistome. The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines was used to systematically review studies that characterised gut microbiota and resistome using metagenomic analysis and/or those that reported gut E. coli resistome in healthy individuals. Changes in the diversity and abundance of bacterial gut microbiota and the resistome across different groups and the microbiota composition of the gut harbouring antibiotic-resistant E. coli were summarised. Findings suggest that lower bacterial microbiota diversity is likely associated with an increased abundance of the overall gut resistome. Age-related differences were observed, with younger infants exhibiting lower microbiota diversity and higher ARG abundance compared to older infants and adults. Studies that reported correlation revealed positive correlations between the compositional relative abundance of Proteobacteria and ARGs abundance, mainly driven by members within the Enterobacteriaceae family, particularly E. coli. This study also revealed that human gut microbiome studies that investigate gut resistome using metagenomic sequencing approaches in apparently healthy individuals are at least uncommon.

Three-dimensional (3D) geological modeling technology offers intricate geological information services and technical support for the research of urban geological conditions and their evolutionary mechanisms. It further facilitates the analysis of environmental geological problems, encompassing their distinguishing features and genetic mechanisms. The precision of such three-dimensional models is predominantly influenced by the caliber of modeling data, the chosen modeling methodologies, and the intricacy of the modeled geological objects. This research, exemplified by the three-dimensional geological structure modeling of the Wuhan metropolitan development area, aims to explore a comprehensive three-dimensional modeling framework for urban geology, particularly in scenarios with large-scale and complex geological conditions. This study holds significant technical value in enhancing the application of 3D geological modeling, as well as practical importance for urban geological investigations and research.

This study explores the role of inflammation and oxidative stress, hallmarks of COVID-19, in accelerating cellular biological aging. We investigated early molecular markers—DNA methylation age (DNAmAge) and telomere length (TL)—in blood leukocytes, nasal cells (NC), and induced sputum (IS) one-year post-infection in pauci- and asymptomatic healthcare workers (HCWs) infected during the first pandemic wave (February-May 2020), compared to COPD patients, model for "aged lung". Data by questionnaires, Work Ability Index (WAI), blood analyses, autonomic cardiac balance assessments, heart rate variability (HRV), and pulmonary function tests were collected. Elevated leukocyte DNAmAge significantly correlated with advancing age, male gender, daytime work, and an aged phenotype characterized by chronic diseases, elevated LDL and glycemia levels, medications affecting HRV, and declines in lung function, WAI, lymphocyte count, hemoglobin levels, and HRV (p&lt;0.05). Increasing age, LDL levels, job positions involving intensive patient contact, and higher leukocyte counts collectively contributed to shortened leukocyte TL (p&lt;0.05). Notably, HCWs exhibited accelerated biological aging in IS cells compared to both blood leukocytes (p≤0.05) and NC (p&lt;0.001), and were biologically older than COPD patients (p&lt;0.05). These findings suggest the need for monitoring aging in pauci- and asymptomatic COVID-19 survivors, who represent the majority of the general population.

Enhancement of orthodontic tooth movement (OTM) through local administration of biofunctional molecules has become increasingly significant, particularly for adult patients seeking aesthetic and functional improvements. This comprehensive systematic review analyzes the efficacy of various biofunctional molecules in modulating OTM, focusing on the method of administration and its feasibility, especially considering the potential for topical application. A search across multiple databases yielded 36 original articles of experimental human and animal OTM models, which examined biofunctional molecules capable of interfering with the biochemical reactions that cause tooth movement during orthodontic therapy, accelerating the OTM rate through their influence on the bone metabolism (Calcitriol, Prostaglandins, Recombinant human Relaxin, RANKL and RANKL expression plasmid, growth factors, PTH, osteocalcin, vitamin C and E, biocompatible reduced graphene oxide, exogenous thyroxine, sclerostin protein, a specific EP4 agonist (ONO-AE1-329), carrageenan and herbal extracts). The results indicated a variable efficacy in accelerating OTM, with Calcitriol, Prostaglandins (PGE1 and PGE2), RANKL, growth factors and PTH, among others, showing promising outcomes. PGE1, PGE2 and Calcitriol experiments had statistically significant outcomes in both human and animal studies, and, while other molecules underwent only animal testing, they could be validated in the future for human use. Notably, only one of the animal studies explored topical administration, which also suggests a future research direction. This review concluded that while certain biofunctional molecules demonstrated potential for OTM enhancement, the evidence is not definitive. The development of suitable topical formulations for human use could offer a patient-friendly alternative to injections, emphasizing comfort and cost-effectiveness. Future research should focus on overcoming current methodological limitations and advancing translational research to confirm these biomolecules' efficacy and safety in clinical orthodontic practice.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising chemotherapeutic agent because of its selective apoptotic action on cancer cells. However, resistance to TRAIL-induced apoptosis remains a challenge in many cancers. The gintonin-enriched Panax ginseng extract fraction (GEF) has diverse pharmacological benefits. We explored the combined efficacy of GEF and TRAIL in inducing apoptosis in human renal cell carcinoma (RCC) cells. The effect of GEF treatment on viability, clonogenic potential, wound healing, and TRAIL-induced apoptotic signaling of RCC cells was studied in vitro. Our investigation revealed that GEF pre-treatment sensitized RCC cells to TRAIL-induced apoptosis, as evidenced by DNA fragmentation and cell proliferation, colony formation, and migration inhibition. This sensitization was linked to the upregulation of death receptors 4 and 5 and alterations in apoptotic protein expression; notably, decreased expression of Mu-2-related death-inducing gene, a novel anti-apoptotic protein. Our findings underscore the necessity of caspase activation for GEF/TRAIL-induced apoptosis using the pan-caspase inhibitor Z-VAD-FMK. It demonstrates that GEF sensitizes human RCC cells to TRAIL-induced apoptosis by upregulating DR4/5 and modulating apoptotic protein expression. These findings suggest a promising strategy for overcoming TRAIL resistance in cancer therapy and highlight the potential of GEF as a valuable adjunct to TRAIL-based treatments.

Hyperspectral imaging, a rapidly evolving technique, furnishes exhaustive information on Earth's surface reflectance over an extensive spectrum of wavelengths. We have developed a more precise method for analyzing spectral data by meticulously selecting plant leaf pixels and employing a relative reference approach. This enhanced technique correlates camera pixel values with light intensity, bypassing the need for complex equations and thereby providing clearer insights into vegetation vitality. The findings of this study not only enhance the precision of hyperspectral imaging but also bolster our capability for ecological monitoring and understanding environmental health. A novel algorithm based on the red-edge slope was established to classify images, exploiting the spectral reflectance data gleaned from the hyperspectral Liquid Crystal Tunable Filter (LCTF) camera. Compared with conventional SVM and K-means algorithms, our novel algorithm demonstrated commendable performance, achieving an overall accuracy of 90% with a Kappa Coefficient of 0.86. This comparison highlights the novel algorithm's relative strength and potential for large-scale satellite and drone imagery analysis applications. The advancements facilitated by this research are instrumental in ecological assessments, conservation efforts, and resource management strategies, signaling a leap forward in the era of environmental monitoring and analysis.

Dearth of information on extent of genetic variability in cassava limits the genetic improvement of cassava in Sierra Leone. This study aimed at assessing the genetic variability and relationships within 103 cassava genotypes using agro-morphological and culinary markers. A field trial was conducted in the School of Agriculture and Food Sciences research site. The experiment was laid in an augmented randomized block design. Morphological classification based on qualitative and quantitative traits categorized the germplasm into three different groups. A total of ten principal components (PCs) in the qualitative and six PCs in the quantitative trait sets accounted for 66.74% and 67.27% of the total genetic variation, respectively. Traits with significantly strong and positive correlations included presence of fruit (PFRT) and presence of seed (PSE)(r = 0.86***),root yield per plant (RYPP) and number of storage root (NSR) (r = 0.76***), RYPP and number of commercial root (NCR) (r = 0.68***), length of leaf lobe (LLL) and width of leaf lobe (WLL) (r = 0.66***),and between NSR and NCR (0.84***). Cooking time, cooking percentage, texture, mealiness, taste and aroma varied widely among the accessions. Findings established that the cassava germplasm possess useful genetic variability that could be exploited through selection for short term release programme, genetic conservation of valuable germplasm and genetic improvement of the crop.

Weight loss solutions are on the rise, and there is growing interest in natural alternatives to the pharmaceuticals in the market, which are not devoid of relevant side effects. To this end, the objective of the current study is to assess the effects of a botanical-based blend comprised of lemon verbena and hibiscus extracts in weight management, body fat, appetite, lipid, and glucose profiles, in an overweight population, for 90 days. As a result, the volunteers presented significant weight loss in absence of diet, which coincided with decreased body fat. Body fat was assessed by anthropometry, electrical bioimpedance and DEXA scan. Cholesterol levels were also significantly decreased. Satiety assessment revealed that the product contributed to increased feeling of fullness and satisfaction after a meal, compared to the placebo group, which could contribute to the weight loss observed. Blood glucose and blood pressure levels remained unchanged, which was expected as the volunteers were normoglycemic and their blood pressure was in the healthy range. In conclusion, daily supplementation of a botanical-based blend contributes to weight loss in overweight individuals, in absence of diet, while not affecting other parameters that are in the healthy range. This product could be a candidate alternative or add-on to other weight loss products, as part of a healthy lifestyle.

The aim of the present trial was to evaluate the growth performance of buffalo calves fed diets characterized by different forage/concentrate ratio with or without the Saccharomyces Cerevisiae supplementation (CBS 493.94, Yea-Sacc®). Twenty-four male buffalo calves (mean age 145.1 ± 16.1 days; mean weight 108.0 ± 18.7) were assigned randomly to 4 groups, homogeneous for age, fed four different diets: diet 1 F:C ratio 50:50; diet 2 F:C ratio 30:70; diet 3 F:C ratio 50:50 + Yea-Sacc® and diet 4 F:C ratio 30:70 + Yea-Sacc®. Buffalo calves were individually weighted before the start of the experiment and the data were used as a covariate, monthly until the end of the trial. Dry matter intake (DMI), daily weight gain (DWG) and feed conversion ratio (FCR) were calculated. The differences in diets’ composition significantly (p

Background: The purpuse was to investigate the influence induced by magnesium chloride (MgCl2) and zinc gluconate (ZnG) supplementation on liver and kidney injuries experimentally-induced with acetaminophen (AAPh) and potentiated by ciprofloxacin addition in rats. Material and methods: The experiment was performed on 5 animals groups: group 1 – control, treated for 6 weeks with normal saline, 1mL/kg; group 2 – AAPh, treated for 6 weeks with AAPh, 100 mg/ kg/day; group 3 – AAPh+C, treated AAPh 100 mg/kg/ day for 6 weeks and ciprofloxacin, 50mg /kg/day, only in the last 14 days of the experiment; group 4 – AAPh+C+Mg, with the same treatment as group 3, but, and in the last 14 days, MgCl2 10 mg/ kg/day was added; group 5 – AAPh+C+Zn, with the same treatment as group 3, but, and in the last 14 days, zinc gluconate (ZnG),10 mg/kg/day was added. All administrations were performed by oral gavage. At the end of the experiment, the animals were sacrificed and blood samples were collected for biochemistry examinations. Results: Treatment with AAPh for 6 weeks determined an alteration of the liver function (increases in alanine aminotransferase, aspartate aminotransferase, lactic dehydrogenase and, and gamma-glutamyl transferase) and of renal function (increases in serum urea and creatinine) (P < 0.001 group 2 vs. group 1 for all mentioned parameters). Also, the antioxidant defense capacity was impaired in group 2 vs. group 1 (superoxide dismutase and glutathione peroxidase activity decreased in group 2 vs. group 1, 0.001 < P < 0.01, respectively 0.01 < P < 0.05). The addition of ciprofloxacin, 50 mg/kg/day during the last 14 days resulted in further increases in alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, urea and creatinine (0.01 < P < 0.05, group 3 vs. group 2). MgCl2 provided a slight protection against liver enzymes increase and a more pronounced protection against the increase in serum urea and creatinine (0.001 < P < 0.01 group 4 vs. group 3). MgCl2 provided a slight protection against the decrease in superoxide dismutase (0.01 < P < 0.05 group 4 vs. group 3), but not against decrease of glutathione peroxidase. The improvement of mentioned parameters could also be seen in case of ZnG, to a higher extent especially in the case of alanine aminotransferase and lactic dehydrogenase (0.01 < P < 0.05 group 5 vs. group 4). Conclusions: This study represents a furthermore proof for beneficial effect of magnesium and zinc salts against toxicity induced by different agents, including antibacterials added to the analgesic and antipyretic acetaminophen; the protection is proven on the liver and kidney’s function; the antioxidant profile improvement has a key role, especially in case of zinc gluconate.

Spodoptera frugiperda (J.E. Smith) is a global agricultural pest that poses a threat to crop production, characterized by its refractory polyphagous nature that makes it difficult to control and may lead to damage to woody plants. However, research on its adaptability to woody plants remains limited. This study compares the feeding adaptations (survival rate, pupation time, pupation rate, weight, length, and feeding volume), protective enzyme activities, and feeding preferences of S. frugiperda on leaves of six economically significant tree species (Areca catechu, Aquilaria sinensis, Cocos nucifera, Camellia oleifera, Dalbergia odorifera and Hevea brasiliensis) and maize as a control treatment. The results indicate that A. sinensis as the most vulnerable trees in high risk, H. brasiliensis and C. nucifera presented varying degrees of susceptibility, A. catechu, C. oleifera, and D. odorifera were unsuitability for S. frugiperda. In conclusion, this report extensively explores the feeding effects of S. frugiperda on six economically important tree species, and provides insights into the feeding preferences on these plants, thereby informing the potential threat posed by S. frugiperda to economically vital trees.

A four-step synthesis of bifunctional, noncovalent organocatalysts based on the chiral (1R,2R)-cyclohexane-1,2-diamine scaffold containing a 1,2-benzenediamine H-bond donor was developed. Nucleophilic aromatic substitution of the 2-fluoronitrobenzene derivative with the commercial (1R,2R)-cyclohexane-1,2-diamine was followed by selective alkylation of the primary amino group, reduction of the aromatic nitro group and final derivatization of the primary aromatic amino group, i.e. acylation, sulfonation, reductive alkylation and arylation, leading to the four subtypes of organocatalysts. All new compounds were fully characterized. The prepared organocatalysts (32 examples) were tested in the Michael addition of acetylacetone to trans-β-nitrostyrene, yielding the addition product with incomplete conversions (up to 93%) and enantioselectivities of up to 41% ee.

This paper presents a novel approach to power management techniques in energy storage system (ESS) interoperability with the energy power system (EPS) by inserting a SCADA controlled directional protection relay for improving the mode switching sequence. According with latest European standards, all necessary measures for re-synchronization and reconnection for health work of the system must be taken. The proposed approach intends to improve the “interface” between storage systems and electric power grid by using a directional relay which provides interoperability improvement by automatic recognizing and differentiating the switching sequence of the mode of operation from the fault mode. Simulated results from a small scale electrical generating system are provided. The results demonstrate that the proposed power management solution is technically ideal to achieve high quality energy while retaining the stability of the power grid network. The interoperability of PHS systems integrated with the electric power grid usually leads to perturbations in terms of frequency of the generated voltage, and for improving it we designed an automatic treating and re-connecting software module. This work regards the importance of producing electricity from green and renewable energy sources, while retaining the stability and reliability of the power grid. ESS systems are widely used to help balancing of intermittent forms of load demand on the electrical power grid at specific key moments. In this article, the pumped hydro storage (PHS) technologies are proposed as an economical way to utilize smoothly the off-peak energy or surplus energy, by pumping water to a reservoir at a higher level. During peak load periods, the stored water is discharged through the reversible pump-turbine to generate electricity to meet the peak demand controlled by designed SCADA application.

Genome-wide association studies (GWAS) have successfully revealed numerous susceptibility loci for obesity. PREDATORR study (2014) shows that in Romania, 34,6% of adults aged 20-79 y/o are overweight, 31,4% are obese with a high risk of cardiometabolic complications, a number that puts almost 67% of Romania's population in the abnormal weight group. Our study aims to investigate the current staus of genetic foundation in metabolic disease associated with obesity, applied to a pilot group of patients specifically examining the impact of known polymorphisms and their haplotype of six food intake-regulating genes: leptin (LEP), leptin receptor (LEP-R), serotonin receptor (5HTR2A), ghrelin (GHRL), neuropeptide Y (NPY) and fat-mass and obesity-associated (FTO) with the following polymorphisms: LEP A-2548G, LEPR A-223G, 5HTR2A G-1439A, GHRL G-72T, NPY T-29063C, FTO A-T and body mass index (BMI). A notable link between the LEP-2548 rs7799039 gene's AG genotype and the risk of obesity was observed, particularly pronounced in males aged 40-49, with an approximately sevenfold increased likelihood of obesity. The 5HTR2A rs6311 AA genotype was associated with a higher BMI, not statistically significant. The FTO rs9939609 gene's AA genotype emerged as a significant predictor of obesity risk. Besides these significant findings, no substantial associations were observed with the LEPR, 5HTR2A, GHRL and NPY genes. Haplotype association analysis showed a suggestive indication of GRGMLA (rs7799039, rs1137101, rs6311, rs696217, rs16139, rs9939609 sequence) haplotype with susceptibility effect towards obesity predisposition. Linkage disequilibrium (LD) analysis showed statistically significant associations between LEP and LEPR gene (p = 1e-04), LEP and GHRL gene (p = 0.0047), GHRL and FTO gene (p=0.03). The outcomes of this study, to our knowledge, one of the very few on the Romanian population, aimed to be a starting point for further research on the targeted interventional strategies to reduce cardiometabolic risks.

In order to investigate the size distributions and seasonal variations of carbonaceous aerosols (OC and EC), the carbonaceous species were collected and then analyzed by using a 9-stage Anderson-type aerosol sampler and DRI Model 2001A Thermal/Optical Carbon Analyzer on the typical industrial city Nanjing in Yangtze River Delta, China in the summer, autumn and winter of 2013 and spring of 2014. OC, EC, SOC and POC exhibited obvious seasonal variations, with the highest level in winter (39.1±14.0, 5.7±2.1, 23.6±11.7 and 14.1±5.7 μg•m^-3) and the lowest level in summer (20.6±6.7, 3.3±2.0, 12.2±3.8 and 8.4±4.1 μg•m^-3), and were mainly centralized in PM_1.1 in four seasons. The concentrations of OC in PM_1.1 varied in the order of winter > autumn > spring > summer, while EC ranked in the order of autumn > winter > summer > spring. In the PM_1.1-2.1 and PM_2.1-10, the concentrations of OC and EC decreased in the sequence of winter > spring > autumn > summer. The size spectra of OC, EC and SOC had bimodal distributions in four seasons, except for EC with four peaks in summer. The size spectra of POC varied greatly with seasons, exhibiting bimodal distribution in winter, trimodal distribution in spring and summer, and four peaks in autumn. The OC/EC ratios were 7.0, 6.3, 7.6 and 6.9 in spring, summer, autumn and winter, respectively, which demonstrated the abundance of secondary organic aerosols in Nanjing. The sources of carbonaceous aerosol varied significantly with seasons, and were dominated by vehicle exhaust, coal and biomass burning in PM_2.1, and dominant by dust, coal and biomass burning in PM_2.1-10.

Abstract: Qatar and other Gulf States have a diverse range of marine vegetation that is adapted to the stressful environmental conditions of seawater. The industrial wastewater produced by oil and gas activities adds further detrimental conditions for marine aquatic photosynthetic organ-isms on the Qatari coastlines. Thus, these organisms experience severe stress from both seawater and industrial wastewater. This review discusses the biodiversity in seawater around Qatar, as well as remediation methods and metabolic pathways to reduce the negative impacts of heavy metals and petroleum hydrocarbons produced during these activities. These methods include phyto-stabilization phyto-accumulation, phyto-volatilization, and phyto-degradation. Phy-to-degradation in particular is discussed in detail, including metabolic pathways such as alkane and aromatic-compound degradation pathways. The role of microorganisms that are adjacent to or associated with these aquatic marine organisms is discussed, including rhizosphere biodeg-radation. In this type of biodegradation, exudates are released by plant roots and supply nutrients to microorganisms in the rhizosphere, which enhances their ability to degrade organic pollutants. Special attention is paid to mangrove forests and their roles in remediating shores polluted by industrial wastewater. Seagrasses (Halodule uninervis, Halophila ovalis, and Thalassia hemprichii) and seaweeds (Chlorophyta, Phaeophyta, and Rhodophyta) around the peninsula of Qatar are also discussed.

Yttria stabilized zirconia (Y-TZP) ceramics with drastically reduced yttria content have been introduced by different manufacturers aiming at improving the damage tolerance of ceramic components. In this study an alumina doped 1.5Y-TZP was axially pressed, pressureless sintered in air at 1250–1400 °C for 2 h and characterized with respect to mechanical properties, microstructure and phase composition. The material exhibits a combination of high strength of 1000 MPa and a high toughness of 8.5–10 MPa√m. The measured fracture toughness is, however, extremely depending on measurement protocol. Direct crack length measurements overestimate toughness due to trapping effects. The initially purely tetragonal material has a high transformability of &gt; 80 %, the transformation behavior is predominantly dilatoric, measured R-curve related toughness increments are in good agreement with transformation toughness increments derived from XRD data.

In the extended malfatti problem, the numbers of circles in the triangle are triangle numbers, because the tangency properties among the internal circles and 3 sides of the triangle have special type of structure. That is, the corner circle tangent to two sides of the triangle and two boundary circles, the boundary circles tangent to one side of the triangle and 4 other circles, and the inner circles always tangent to 6 other circles. The circles we find in extended general Malfatti’s problem has the property that the smallest radius and the largest radius for the circle has big difference. In this paper, we proposed algorithms to solve the problem that the tangency properties among circles and sides of triangle is not fixed, so that the number of circles in the triangle is not necessary a triangle numbers. The purpose of this change is try to find the radii of the circles in the triangle is within a small range.

The Range–Doppler (R-D) model is extensively employed for the geometric processing of Synthetic Aperture Radar (SAR) images. Refining the sensor motion state and imaging parameters is the most common method for achieving high-precision geometric processing using the R-D model, comprising a process that involves numerous parameters and complex computations. In this study, we introduce a novel approach to improve the positioning accuracy of the R-D model, implementing a low-order polynomial to compensate for the original imaging errors without altering the initial positioning parameters. We also design low-order polynomial compensation models with different parameters. The models are evaluated on various SAR images from different platforms and bands, including spaceborne TerraSAR-X and GF3-C images, manned airborne SAR-X images, and unmanned aerial vehicle-mounted miniSAR-Ku images. Furthermore, image positioning experiments involving the use of different polynomial compensation models and various numbers and distributions of Ground Control Points (GCPs) are conducted. The experimental results demonstrate that geometric processing accuracy comparable to that of the classical rigorous positioning method can be achieved even when applying only an affine transformation model to the images. Compared to classical refinement models, however, the proposed image-compensated R-D model is much simpler and easy to implement. Thus, this study provides a convenient, robust, and widely applicable method for the geometric positioning processing of SAR images, offering a potential approach for the joint-positioning processing of multi-source SAR images.

Peanut hulls (PH) are an edible food waste that is an underutilized food source for human consumption. While edible and palatable, they are mainly diverted to livestock feed or building materials. Here, we describe existing literature on human food valorization of PHs and propose methods to optimize recapturing nutrients (e.g. protein, fiber, polyphenols) lost by treating PHs as waste. Incorporated into common foods, PHs can be processed into functional ingredients to improve nutrient-density and the corresponding positive health outcomes associated with increases in plant foods. PH valorization can also address additional priorities of the UN Sustainable Development Goals using a Food Systems Approach (FSA) including food waste, increasing economic opportunities for farmers, and increasing the availability of healthy shelf-stable foodstuffs to address food security. Recent advances in sustainable food processing technologies can be utilized to safely incorporate peanut hulls into human food streams. We propose future applications that could make meaningful impacts to food availability and the nutritional composition of common foods. While the limited literature on this topic spans several decades, no global operations exist to incorporate peanut hulls and most publications precede the technological ‘green revolution’. The approaches outlined in this review may help bolster commercialization of this underutilized and nutritious food potentially improving opportunities for multiple global stakeholders.

Parents play an important role in shaping the eating habits of their children through: appropriate selection of food products, snacking between meals and appropriate exposure to information from television advertisements, the press or the Internet. The level of parents' knowledge about proper nutrition and substances added to food is therefore crucial in promoting appropriate dietary choices in children and adolescents in order to prevent diet-related diseases. Objectives: Assessment of the consumption of snack foods by children and adolescents according to the surveyed parents and analysis of parents' knowledge about additional substances in food. Methods: The study was conducted among 129 parents of students from selected primary schools. The research tool was an original survey questionnaire consisting of 24 questions. Survey interviews were conducted with parents during meetings at schools. Statistical analysis was performed using the Pearson ch2 test, the significance level was set to p&lt;0.05. Results: Parents most often indicated sweets, confectionery products and sweetened drinks (25%) and vegetables or fruit (21%) as the form of snack for their children. 46% of children and adolescents drank sweetened drinks at least once a day. Parents had an average level of knowledge about food additives. Significant correlations were found between the level of knowledge of parents of school-age children about food additives and their level of education. Parents' knowledge and education did not significantly influence the level of snack consumption by their children. Children's eating behavior should be considered unsatisfactory. Conclusions: Research has shown the need for parents to be educated about food additives and to pay more attention to reading food labels so that they can reliably prepare their children to make the right food choices. Measures should be implemented to improve the eating habits of children and adolescents.

The demonstration of compliance of rolling stock against disturbance limits for railway signaling, and in particular track circuits, is subject to a large deal of variability, caused by the diverse values of the electrical parameters of the railway line and resulting transfer functions, as well as operating conditions of rolling stock during tests. Instrumental uncertainty is evaluated with a Type B approach and shown to be much less than the experimental variability. Repeated test runs in acceleration, coasting, cruising, braking conditions are considered, deriving both max-hold (spread) and sample dispersion curves compared to the respective mean values (Type A approach to the evaluation of uncertainty). The major source of variability affecting a significant portion of the spectrum is caused by the superposed oscillations of the onboard LC filter, for which different choices of the transformation window duration are discussed. The test runs and the acquired data covered overall 1 day of tests along about 300 km of the Italian 3 kV DC railway network.

Yttria stabilized zirconia materials are frequently used in mechanical engineering and biomedical applications. Demanding loading conditions require materials combining a high level of strength and fracture toughness. A ready to press alumina doped 2 mol% yttria stabilized zirconia powder was shaped by axial pressing and sintering in air at 1250 - 1500 °C for 2 h. The best combination of strength and toughness value of 7.8 MPa√m. Materials sintered in the middle of the chosen temperature range combine fully density, high transformability and small grain size. Toughness measurements by direct crack length measurements delivered unrealistically high fracture toughness values.

This study presents a groundbreaking approach in the field of gaming AI, focusing on the classic game” Pacman” through the lens of DRL integrated with advanced optimization techniques. The core of the research involves adapting DRL models for” Pacman”, utilizing the ESO for hyper- parameter tuning. These novel adaptations significantly enhance the AI agent’s performance, demonstrating a remarkable improvement in adaptability, responsiveness, and efficiency within the game environment. A pivotal aspect of this research is the innovative integration of metaheuristic optimization techniques into the DRL framework, a first in the domain of Atari gaming AI. This integration has proven essential in fine-tuning the DRL models, leading to a more effective and dynamic gaming experience. The study thoroughly evaluates and compares the performance of these algorithms, providing empirical support for their effectiveness and setting a new benchmark in AI-driven game development. The implications of this research extend beyond gaming AI, opening up possibilities for future exploration in several directions. Expanding DRL models to other complex gaming environments, continuous algorithmic enhancements, real-time learning adaptations, and applying these principles to robotics and autonomous vehicles are examples. The research also emphasizes ethical and responsible AI use in gaming to address fairness and addiction issues.

Despite the growing capabilities of large language models, concerns exist about the biases they develop. In this paper, we propose a novel, automated mechanism for debiasing through specified dataset augmentation in the lens of bias producers that can be useful in a variety of industries, especially ones that are “restricted” and have limited data. We consider that bias can occur due to intrinsic model architecture and dataset quality. The two aspects are evaluated using two different metrics we created. We show that our dataset augmentation algorithm reduces bias as measured by our metrics.

It has been empirically observed that the upper tail of the firm size distribution follows either the Pareto distribution or the Zipf distribution, with both patterns being explained by Gibrat’s law (Gabaix, 1999). This article analyzed firm revenue data from China, spanning from 2005 to 2013, to examine the whole range of the firm size distribution. Our empirical analysis revealed that firm revenue data over these years is well fitted by a three-parameter generalized Pareto distribution, with the fitted parameters indicating a dichotomy: The size distribution of large-sized firms, namely the upper tail, is asymptotically characterized by a Pareto distribution or a Zipf distribution, whereas the size distribution of smaller and medium-sized firms is approximated by an exponential distribution. This finding suggests that Gibrat’s law should be extended to account for the emergence of a generalized Pareto distribution.

A PLS-based quality prediction method is proposed for batch processes using two-dimensional extended windows. To realize the adoption of information in the direction of sampling time and batch, a new definition region of support (ROS), k-i-back-extended region of support (KIBROS), is proposed to establish the extended window, which including the data of the previous sampling times in the same batch, the data of the same sampling time in the historical batches, the data of the previous sampling times in the historical batches and the data of the later sampling times in the historical batches. According to these regions of support, extended windows are established, and different models are proposed based on the extended windows for batch processes quality prediction. Further, using a typical batch process as an example, the injection molding process, the proposed quality prediction method is experimentally verified, proving that the proposed methods have higher prediction accuracy than the traditional method and the prediction stability is also improved.

This work presents an innovative application of optimal control theory to the strategic scheduling of battery storage in the day-ahead electricity market, with a focus on enhancing profitability while factoring in battery degradation. The study incorporates in the optimisation framework the cost of battery capacity degradation, the effects of capacity degradation and internal resistance degradation into dynamics. We employ a continuous-time representation of the dynamics, in contrast with many other studies that use a discrete-time approximation with rather coarse intervals. We adopt an equivalent circuit model coupled with empirical degradation parameters to simulate a battery cell’s behaviour and degradation mechanisms with good support from experimental data. Utilising direct collocation methods with mesh refinement allows for precise numerical solutions to the complex, nonlinear dynamics involved. Through a detailed case study of Belgium’s day-ahead electricity market, we determine the optimal charging and discharging schedules under varying objectives: maximizing net revenues, profits considering capacity degradation, and profits considering both capacity degradation and internal resistance increase due to degradation. The results demonstrate the viability of our approach and underscore the significance of integrating degradation costs into the market strategy for battery operators, alongside its effects on the battery’s dynamic behaviour. Our methodology extends previous work by offering a more comprehensive model that empirically captures the intricacies of battery degradation, including a fine and adaptive time domain representation, focusing on the day-ahead market, and utilising accurate direct methods for optimal control. The paper concludes with insights into the potential of optimal control applications in energy markets and suggestions for future research avenues.

Detection of subsurface archaeological remains using a range of remote sensing methods, poses several challenges until today. Recent studies regarding the detection of archaeological proxies like those of cropmarks highlight the complexity of the phenomenon. In this work we present three different methods, and associated indices, for identifying stressed reflectance signatures indicating buried archaeological remains, based on a dataset of measured ground spectroradiometric reflectance. Several spectral profiles between the visible and near infrared part of the spectrum, were taken over a controlled environment in Cyprus during the 2011-2012 and are re-used in this study. The first two (spectral) methods are based on a suitable analysis of the spectral signatures in (1) the visible part of the spectrum, and in particular in the neighborhood of 570 nm, and (2) the red edge-near infrared part of the spectrum, in the neighborhood of 730 nm. Machine learning (decision trees) allows for the deduction of suitable wavelengths to focus on, in order to formulate the proposed indices and the associated classification criteria (decision boundaries) that can enhance the detection probability of stressed vegetation. Noise in the signal is taken into account by simulating reflectance signatures perturbed by white noise. Applying decision tree classification on the ensemble of simulations and basic statistical analysis we refine the formulation of the indices and criteria for the noisy signatures. The success rate of the proposed methods is over 90%. The third method rests on the estimation of vegetation/canopy reflectance parameters through inversion of the physical-based PROSAIL reflectance model and the associated classification through machine learning methods. The obtained results provide further insights into the formation of stress vegetation that occurred due to the presence of shallow buried archaeological remains, which are well aligned with physical-based models and existing empirical knowledge. To the best of the authors' knowledge, this is the first study demonstrating the usefulness of radiative transfer models such as PROSAIL for understanding the formation of cropmarks. Similar studies can support future research directions towards the development of regional remote sensing methods and algorithms if systematic observations are adequately dispersed in space and time.

Dynamic systems which underly controlled systems are expected to increase in complexity as robots, devices, and connected networks become more intelligent. While classical stable systems converge to a stable point (a sink), another type of stability is to consider a stable path rather than a single point. Such stable paths can be made of saddles which draw in trajectories from certain regions, and then push the trajectory toward the next saddle point. These are chains of saddles are called stable heteroclinic channels (SHCs), and can be used in robotic control to represent time sequences. While we have previously shown that each saddle is visualizable as a trajectory waypoint in phase space, how to increase the fidelity of the trajectory was unclear. In this paper, we hypothesized that the waypoints can be individually modified to locally vary fidelity. Specifically, we expected that increasing the saddle value (ratio of saddle eigenvalues) causes the trajectory to slow to more closely approach a particular saddle. Combined with other parameters that control speed and magnitude, a system expressed with an SHC can be modified locally, point by point, without disrupting the rest of the path, supporting their use in motion primitives. However, even more complex trajectory shape modifications are possible. While some combinations can enable a trajectory to better reach into corners, other combinations can rotate, distort and round the trajectory in the region of a corner. In our example, modifying select saddle values produced a 32% decrease in the trajectory error of a complex trajectory produced using this system. This is an effect not visible in previous 1D studies, that can lead to different learnable and tunable representations of dynamic systems.

Driving factors of smart city construction are exploratively studied by grounded theory method based on text sources from journal papers in SCI and CSSCI databases. Initial scale of driving factors about smart city construction is obtained on the basis of above analyses. This paper modifies measuring items of the initial scale with a small sample pretest and reliability test, then forms final items by exploratory factor analysis. According to the above scale, questionnaires are designed to obtain empirical data, and confirmatory factor analysis is used to verify further validity and reliability of the scale. The results show that driving factors of smart city construction include three main dimensions: problem-oriented factors, business- or technology-driven factors and endogenous development requirements.

This paper investigates an Energy Neutral System using Micro Energy Harvesters for a Health Monitoring Wireless Sensor Node (HM-WSN). We have implemented HM-WSN consisting of a solar cell energy harvester, a Power Management Unit (PMU) and the ucontroller, sensor and transmitter acting as load. A battery extender and a switching logic circuit for sensor node is designed to evaluate the efficiency of the proposed system. The HM-WSN senses body temperature with improvement in lifetime of coincell. The HM-WSN is built using commercially available off the shelf (COTS components and consumes 47.2uW for data being updated every 134s. It can be operated for approximately 1.32 years only on a coincell. Furthermore, the HM-WSN can be operated with solar energy at 200lux, achieving 96.36 years with a combination of a coincell with an additional capacitor of 2.2mF. It attains 4.07 years to 16.87 years lifetime with the load capacitor varying from 1mF to 1.5mF at 350lux lighting condition. With the same ambient condition and a 2mF load capacitor, HM-WSN attains complete energy autonomy.

Background: Acute kidney disease (AKD) is a known risk factor for increased mortality and evolution towards chronic kidney disease (CKD) in adults. The data regarding children are scarce. The purpose of our study is to explore the risk factor for AKD and impact of AKD following an acute kidney injury (AKI) episode in children on mortality and new-onset CKD. Methods: We retrospectively evaluated 736 children with ages between 2 and 18 years old with AKI admitted in a tertiary care hospital from the west Romania over a 9 years period. Results: AKD incidence following AKI was 17%. Patients that developed AKD were older, with higher baseline serum creatinine values, urea, C reactive protein and lower proteins, haemoglobin and sodium. They were more often exposed to sepsis, critical illness and nephrotoxic medications and presented certain susceptibilities like CKD, neoplasia, anemia, heart failure, arterial hypertension, stem cell transplant and female gender. AKI causes that increased the risk of AKD were intrinsic ones. AKD increased the overall mortality by three times. The factors that independently increased the risk of evolution towards CKD were AKD, acute tubular necrosis and higher baseline serum creatinine values. Conclusions: AKD is an independent risk factor for mortality and new-onset CKD in children.

Cancer-specific monoclonal antibodies (CasMabs) that recognize cancer-specific antigens with in vivo antitumor efficacy are innovative therapeutic strategies for minimizing the adverse effects. We previously established a cancer-specific anti-human epidermal growth factor receptor 2 (HER2)monoclonal antibody (mAb), H₂Mab-250/H₂CasMab-2. In flow cytometry and immunohistochemistry, H₂Mab-250 reacted with HER2-positive breast cancer cells but did not show the reactivity to normal epithelial cells. In contrast, a clinically approved anti-HER2 mAb, trastuzumab, strongly recognizes both breast cancer and normal epithelial cells in flow cytometry. The human IgG₁ version of H₂Mab-250 (H₂Mab-250-hG₁) possesses compatible in vivo antitumor effects against breast cancer xenografts with trastuzumab despite the lower affinity and effector activation than trastuzumab in vitro. This study compared the antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cellular cytotoxicity (CDC) between H₂Mab-250-hG₁ and trastuzumab. Both H₂Mab-250-hG₁ and trastuzumab showed ADCC activity against CHO/HER2 and breast cancer cell lines (BT-474 and SK-BR-3) in the presence of human natural killer cells. Some tendency was observed that trastuzumab showed a more significant ADCC effect compared to H₂Mab-250-hG₁. Importantly, H₂Mab-250-hG₁ exhibited superior CDC activity in these cells compared to trastuzumab. Similar results were obtained in mouse IgG_2a types of both H₂Mab-250 and trastuzumab. These results suggest the different contributions of ADCC and CDC activities to the antitumor effects of H₂Mab-250-hG₁ and trastuzumab and indicate the future direction for the clinical development of H₂Mab-250-hG₁ against HER2-positive tumors.

Epithelial ovarian cancer significantly contributes to cancer-related mortality in women, often recurring post-treatment with chemotherapy resistance. Dietary interventions have demonstrated influence on cancer progression; for instance, caloric restriction has exhibited tumor growth reduction and enhanced survival in animal cancer models. This study aims to calculate a transcriptomic signature based on caloric-restriction for ovarian cancer patients and explore its correlation with disease progression. We identified proteins modulated by fasting, intermittent fasting or caloric restriction in human females. Based on their gene expression, we calculated a Non-Fasting Genomic Signature score for ovarian cancer samples from the TCGA database. We examined the association between this genomic profile and clinical characteristics. The non-fasting signature, comprising eight genes, demonstrated higher prevalence in primary ovarian tumors compared to normal tissue. Patients with elevated signature expression exhibited reduced overall survival and increased lymphatic invasion. The mesenchymal subtype, associated with chemotherapy resistance, displayed the highest signature expression. Multivariate analysis suggested the non-fasting genomic signature as a potential independent prognostic factor. Ovarian cancer tumors expressing a “non-fasting” transcriptional profile correlate with poorer outcomes, emphasizing the potential impact of caloric restriction on improving patient survival and treatment response. Further investigations, including clinical trials, are warranted to validate these findings.

Background/Objectives: Laryngeal squamous cell carcinoma (LSCC) is the most prevalent form, accounting for nearly 95% of laryngeal cancer. This study evaluates the effectiveness of chemotherapy and radiation therapy combined for treating LSCC, along with exploring miR-449a as a potential biomarker for predicting treatment response and prognosis in LSCC patients. Patients and Methods: The study had 81 patients with advanced laryngeal cancer and 50 healthy controls. Chemotherapy was given for two cycles, followed by an evaluation of the response. Disease progression cases had surgical resection and radiation therapy. Positive responders had radiation therapy after a third cycle. The study also assessed miR-449a expression levels in tumor tissue, normal tissue, and serum samples from control subjects. Results: 31% achieved a complete response, and 49% showed a partial response. 31% of complete response participants maintained laryngeal integrity and vocal function. After radiation therapy, 74% of 65 patients responded completely and preserved laryngeal functions. Lower MiR-449a levels found in LSCC tissues and serum samples were correlated with aggressive tumor behavior, poor prognostic markers, and decreased survival. Conversely, elevated levels were seen in treatment responders. Conclusions: Combined chemo and radiotherapy preserve vocal function and improve outcomes in LSCC. MiR-449a is a promising indicator for diagnosis and treatment efficacy in LSCC.

The PAX8/PPARγ rearrangement, producing the PAX8–PPARγ fusion protein (PPFP), is thought to play an essential role in the oncogenesis of thyroid follicular tumors. To identify PPFP-targeted drug candidates and establish an early standard of care for thyroid tumors, we performed ensemble docking-based compound screening. Specifically, we investigated which pocket structure should be adopted to search for a promising ligand compound for the PPFP; the position of the ligand binding pocket on the PPARγ side of the PPFP is common to that of PPARγ; however, the shape is slightly different between them due to environmental factors. We developed a method for selecting a PPFP structure with a relevant pocket and high prediction accuracy for ligand binding. This method was validated using PPARγ, whose structure and activity values are known for many compounds. Then, we performed docking calculations to PPFP for 97 drug or drug-like compounds with a thiazolidine backbone, which is one of the characteristics of ligands that bind well to PPARγ, registered in the DrugBank database. Furthermore, the binding affinities of promising ligand candidates were estimated more reliably using the molecular mechanics-Poisson–Boltzmann surface area method. Thus, we propose promising drug candidates for the PPFP with a thiazolidine backbone.

Recently, immunotherapy has arisen as a novel treatment approach for patients with colorectal cancer (CRC), but the effectiveness of immunotherapy varies in these patients. We hypothesized that immune checkpoint molecules (ICMs), which are the targets of immunotherapy, are often exhibit concomitantly. Our objective was to investigate the patterns of ICM expression in patients with CRC and the differences in ICM expression based on the microsatellite instability status. Immunohistochemical expression of programmed cell death protein 1 (PD-1), programmed cell death ligand 1 (PD-L1), T cell immunoglobulin and mucin-domain containing-3 (TIM-3), and lymphocyte-activation gene 3 (LAG-3) in the tumor center and periphery was assessed in patients with non-metastatic colorectal cancer. We enrolled 83 patients with CRC: 40 with microsatellite stable (MSS) and 43 with microsatellite instability-high (MSI-H). PD-L1 was more frequently expressed in the tumor center in patients with MSI-H than that in patients with MSS (18 [41.9 %] vs. 3 [7.5 %], respectively; P &lt; 0.001), and the same trend was observed for TIM-3 expression (30 [69.8 %] vs. 19 [47.5 %], respectively; P = 0.047). Concomitant expression of two or more ICMs was more frequently observed than no expression or expression of a single molecule in both MSS and MSI-H groups; 34 (79.7 %) patients with MSI-H and 23 (57.5 %) with MSS showed ICM expression at the tumor center, whereas 34 (79.7 %) patients with MSI-H and 22 (55 %) with MSS showed expression at the tumor periphery. Patients with the genetic characteristics of MSI-H showed higher expression levels of ICMs than that in patients with MSS, and predominantly, two or more ICMs were concurrently expressed. Our findings highlight the potential efficacy of the dual-blockade approach in immunotherapy, particularly in patients with MSI-H CRC.

Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) is a rare and aggressive hematologic cancer originating from the malignant transformation of plasmacytoid dendritic cell precursors. This malignancy progresses rapidly, with frequent relapses and a poor overall survival rate, underscoring the urgent need for effective treatments. However, diagnosing and treating BPDCN have historically been challenging due to its rarity and the lack of standardized approaches. Recognizing BPDCN as a distinct disease entity is recent, and standardized treatment protocols are yet to be established. Traditionally, conventional chemotherapy and stem cell transplantation have been the primary methods for treating BPDCN patients. Advances in immunophenotyping and molecular profiling have identified potential therapeutic targets, leading to a shift towards CD123-targeted immunotherapies in both clinical and research settings. Ongoing developments with SL-401, IMGN632, CD123 Chimeric Antigen Receptors (CAR) T-cells, and Bispecific Antibodies (BsAb) show promising advancements. However, the therapeutic effectiveness of CD123-targeting treatments needs improvement through innovative approaches and combining treatments with other anti-leukemic drugs. Exploring combinations, such as CD123-targeted immunotherapies with azacitidine and venetoclax, is suggested to enhance antineoplastic responses and improve survival rates in BPDCN patients. In conclusion, this multifaceted approach offers hope for more effective and tailored therapeutic interventions against this challenging hematologic malignancy

The concept and policies of multiple early cancer detection (MCED) have gained significant attention from governments worldwide in recent years. In the era of burgeoning artificial intelligence (AI) technology, the integration of MCED with AI has become a prevailing trend, giving rise to a plethora of MCED AI products. However, due to the heterogeneity of both the detection targets and the AI technologies, the overall diversity of MCED AI products remains considerable. The types of detection targets encompass protein biomarkers, cell-free DNA, or combinations of these biomarkers. In the development of AI models, different model training approaches are employed, including datasets of case-control researches or real-world cancer screening datasets. Various validation techniques, such as cross-validation, location-wise validation, and time-wise validation are used. All of the factors show significant impacts on the predictive efficacy of MCED AIs. After the completion of AI model development, deploying the MCED AIs in clinical practice presents numerous challenges, including presenting the predictive reports, identifying the potential locations and types of tumor, and addressing cancer-related information such as clinical follow-up and treatment. This study reviews several mature MCED AI products currently available in the market, detecting their composing factors from serum biomarkers detection, MCED AIs training/validation, and the clinical application. The review illuminates the challenges encountered by existing MCED AI products across these stages, offering insights into the continued development and obstacles within the field of MCED AI.

Abstract Background: Small Cajal body-specific RNAs (scaRNAs) are a specific subset of small nucleolar RNAs (snoRNAs) that have recently been emerged as pivotal contributors in diverse physiological and pathological processes. However, their defined roles in carcinogenesis remain largely elusive. This study aims to explore the potential function and mechanism of SCARNA12 in bladder cancer (BLCA) and to provide a theoretical basis for further investigations into the biological functionalities of scaRNAs. Materials and Methods: TCGA, GEO and GTEx data sets were used to analyze the expression of SCARNA12 and its clinicopathological significance in BLCA. Quantitative real-time PCR (qPCR) and in situ hybridization were applied to validate the expression of SCARNA12 in both BLCA cell lines and tissues. RNA sequencing (RNA-seq) combined with bioinformatics analyses were conducted to reveal the changes of gene expression patterns and functional pathways in BLCA patients with different expression of SCARNA12 and T24 cell lines upon SCARNA12 knockdown. Single-cell mass cytometry (CyTOF) was then used to evaluate the tumor-related cell cluster affected by SCARNA12. Moreover, SCARNA12 was stably knocked down in T24 and UMUC3 cell lines by lentivirus-mediated CRISPR/Cas9 approach. The biological effects of SCARNA12 on the proliferation, clonogenic, migration, invasion, cell apoptosis, cell cycle and tumor growth were assessed by in vitro MTT, colony formation, wound healing, transwell, flow cytometry assays and in vivo nude mice xenograft models, respectively. Finally, chromatin isolation by RNA purification (ChIRP) experiment were further conducted to delineate the potential mechanisms of SCARNA12 in BLCA. Results: The expression of SCARNA12 was significantly up-regulated in both BLCA tissues and cell lines. RNA-seq data elucidated that SCARAN12 may play a potential role in cell adhesion and extracellular matrix (ECM) related signaling pathways. CyTOF results further showed that an ECM-related cell cluster with vimentin+, CD13+, CD44+, CD47+ was enriched in BLCA patients with high SCARNA12 expression. Additionally, SCARNA12 knockdown significantly inhibited the proliferation, colony formation, migration, and invasion abilities in T24 and UMUC3 cell lines. SCARNA12 knockdown prompted cell arrest in the G0/G1 and G2/M phase, and promoted the apoptosis in T24 and UMUC3 cell lines. Furthermore, SCARNA12 knockdown could suppress the in vivo tumor growth in nude mice. ChIRP experiment further suggested that SCARNA12 may combine transcription factors H2AFZ to modulate transcription program and then affect BLCA progression. Conclusion: Our study is the first to propose aberrant alteration of SCARNA12 and elucidate its potential oncogenic roles in BLCA via the modulation of ECM signaling. The interaction of SCARNA12 with the transcriptional factor H2AFZ emerges as a key contributor to the carcinogenesis and progression of BLCA. These findings suggest SCARNA12 may serve as a diagnostic biomarker and potential therapeutic target for the treatment of BLCA.

Precision cancer medicine primarily aims to identify individual patient genomic variations and exploit vulnerabilities in cancer cells to select suitable patients for specific drugs. These genomic features are commonly determined by gene sequencing prior to therapy, to identify individuals who would be most responsive. This precision approach in cancer therapeutics remains a powerful tool that benefits a smaller pool of patients, sparing others from unnecessary treatments. A limitation of this approach is that proteins, not genes, are the ultimate effectors of biological functions, and therefore the targets of therapeutics. An additional dimension in precision medicine that considers an individual’s cytokine response to cancer therapeutics is proposed. Cytokine responses to therapy are multifactorial and vary among individuals. Thus, precision is dictated by the nature and magnitude of cytokine responses in the tumor microenvironment exposed to therapy. This review highlights cytokine responses as modules for precision medicine in cancer therapy, including potential challenges. For solid tumors, both detectability of cytokines in tissue fluids and their being amenable to routine sensitive analyses could address the difficulty of specimen collection for diagnosis and monitoring. Therefore, in precision cancer medicine, cytokines offer rational targets that can be utilized to enhance the efficacy of cancer therapy.

Aberrant estrogen receptor (ER) signaling is a major driver of breast tumor growth and progression. Sigma 2 receptor has long been implicated in breast carcinogenesis based on pharmacological studies, but its molecular identity had been elusive until TMEM97 was identified as the receptor. Herein we report that TMEM97/sigma 2 receptor is highly expressed in ER positive breast tumors and its expression is strongly correlated with ER and progesterone receptor (PR) but not with HER2 status. High expression levels of TMEM97 are associated with reduced overall survival of patients. Breast cancer cells with increased expression of TMEM97 had growth advantage over the control cells under both nutrition limiting and sufficient conditions, while knockdown of TMEM97 expression reduced tumor cell proliferations. When compared to their vector control cells, MCF7 and T47D cells with increased TMEM97 expression presented increased resistance to tamoxifen treatment and also grew better under estrogen depleted conditions. TMEM97/sigma 2 receptor enhanced ERα transcriptional activities and increased the level of transactivated ERα, especially the nuclear soluble and chromatin bounded ERα. Increased TMEM97 also stimulated mTOR/S6K1 signaling pathways in MCF7 and T47D cells. The increased level of active, phosphorylated ERα, and the enhanced resistance to tamoxifen treatment with increased TMEM97 could be blocked by an mTOR inhibitor. Knockdown of TMEM97 expression reduced ERα and mTOR/S6K1 signaling activities, rendering the cells with increased sensitivity to tamoxifen. The observations suggest that TMEM97/sigma 2 receptor is a novel regulator of ERα activities in breast tumor cell growth.

Background: Lung cancer is still the most lethal malignancy in the world from the report of Cancer Statistics in 2021. Platinum-based chemotherapy combined immunotherapy is the first-line treatment in lung cancer patients. However, the 5-year survival rate always affected by the adverse reaction and drug resistance caused by platinum-based chemotherapy. DNA damage and repair system is one of the important mechanisms which can affect the response to chemotherapy and clinical outcome in lung cancer patients. Objective: The objective of this study is to find the relationship between the polymorphisms of DNA repair genes with the prognosis in platinum-based chemotherapy in lung cancer patients. Patients and Methods: We performed genotyping in 17 single nucleotide polymorphisms (SNPs) of Excision Repair Cross-Complementation group (ERCC) genes and X-ray Repair Cross-Complementing (XRCC) genes of 345 lung cancer patients by Sequenom MassARRAY. We used Cox proportional hazard models, state and plink to analyze the associations between SNPs and the prognosis of lung cancer patients. Results: We found that the ERCC5 rs873601 was associated with the overall survival time in lung cancer patients treat by platinum-based chemotherapy (p=0.031*). We also discovered that the polymorphisms in rs873601 was significantly associated with the prognosis in age more than 55 years, Small Cell Lung Cancer (SCLC) and smoking patients, Long Intergenic Non-protein Coding RNA (PNKY) rs2444933 in age less than 55 years, SCLC, metastasis and stage III/IV/ED patients, Short Tau Inversion Recovery (STIR1) rs3740051 in SCLC and metastasis patients, PNKY rs1869641 in SCLC patients, XRCC5 rs1051685 in non-metastasis patients, respectively. Conclusion: The ERCC5 rs873601(G>A) maybe a valuable biomarker for predicting the prognosis in lung cancer patients treated with platinum-based chemotherapy. Statements and Declarations: The authors declare that they have no conflict of interest.

Apigenin (API) possesses excellent antitumor properties, but its limited water solubility and low bioavailability restrict its therapeutic impact. Thus, a suitable delivery systems is needed to overcome these limitations and improve the therapeutic efficiency. Poly (lactic-co-glycolic acid) (PLGA) is a copolymer extensively utilized in drug delivery. Hyaluronic acid (HA) is a major extracellular matrix and can specifically bind with CD44 on colon cancer cells. Chitosan (CS) can serve as an intermediate binding with HA and PLGA. Herein, we aimed to perpare receptor-selective HA-coated PLGA nanoparticles (NPs) for colon cancer with high expression of CD44. Firstly, API was encapsulated in PLGA to obtain PLGA-API-NPs, which were then sequentially combined with CS and HA to form HA-coated PLGA NPs. HA coated PLGA NPs had a stronger sustained-release capability. Cellular uptake of HA coated PLGA NPs was enhanced in HT-29 cells with high expression of CD44. HA-PLGA-DiR-NPs can target specificity towards the HT-29 ectopic tumor model. Overall, HA coated PLGA NPs was an effectively drug deliver platform for API in treatment of colon cancer with high expression of CD44.

CXCL14 is one of the most evolutionarily conserved members of the chemokine family and is constitutionally expressed in multiple organs, suggesting that it is involved in the homeostasis maintenance of the system. CXCL14 is highly expressed in colon epithelial cells and shows obvious gene silencing in clinical colon cancer samples, suggesting that its silencing is related to the immune escape of cancer cells. In this paper, we analyzed the expression profiles of multiple human clinical colon cancer datasets and mouse colon cancer models to reveal the variation trend of CXCL14 expression during colitis, colon polyps, primary colon cancer, and liver metastases. The relationship between CXCL14 gene silencing and promoter hypermethylation was revealed through the colorectal carcinoma methylation database. The results suggest that CXCL14 is a tumor suppressor gene in colorectal carcinoma, which is activated first and then silenced during the process of tumor occurrence and deterioration. Promoter hypermethylation is the main cause of CXCL14 silencing. The methylation level of CXCL14 is correlated with the anatomic site of tumor occurrence and positively correlated with patient age, and associated with prognosis. Reversing the hypermethylation of CXCL14 may be an epigenetic therapy for colon cancer.

Breast cancer (BC) is the second leading cause of death in the United States in women. 1 in 8 women in their lifetime has a risk of developing breast cancer. With advances in omics technology, more data is available for diagnosis, treatment, and prognosis. The help of Machine Learning algorithms, a subdomain of Artificial Intelligence, would allow for a better clinical support tool. Machine Learning could be the key to answering a complex problem in BC. The methodology of this research question involves collecting and finding data such as RNA-Seq datasets, selecting and training appropriate machine learning algorithms, and evaluating the performance of the algorithms in predicting BC prognosis. Also, the study explores and tries to identify the most relevant genes and pathways through feature selection extraction and dimensionality reduction techniques. After applying feature extraction, the top 10 genes were extracted using the Univariate Feature Selection (UFS) method, precisely the SelectKBest technique. After employing different machine learning algorithms, such as Networks, Random Forest, Linear SVM, Logistic Regression, and Quadratic Discriminant Analysis (QDA), we found QDA was the best model in classifying the RNA-seq dataset with a 96% accuracy rate and 94% ROC AUC. This study suggests that AK2 and CD68 have a positive correlation with each other, and it could potentially be a biomarker and therapeutic target for BC.

Helicobacter pylori (H. pylori) is known to play a significant role in the development of peptic ulcer diseases and gastric cancer. Previous studies have reported the existence of polymorphism in the ureC gene of H. pylori. However, the relationship between genetic sequence variations in ureC and the pathogenesis of peptic ulcer diseases remains unclear. We aimed to investigate the associations between ureC sequence variations and the development of gastric ulcer and gastric cancer. PCR amplification and DNA sequencing to analyze ureC sequences, and conducted phylogenetic analysis using MEGA X software. Samples from Taiwanese patients with gastric ulcer and gastric cancer were included in this study. PCR was used to amplify the ureC gene from these samples, followed by DNA sequencing. The obtained sequences were then subjected to phylogenetic analysis using MEGA X software. In addition, ureC sequences from different geographical regions, including China and other countries, were included in the analysis for comparison. Analysis of the ureC se-quences from Taiwanese samples revealed that 6 out of 7 gastric ulcer samples clustered together in one group, while the sequences from 7 out of 8 gastric cancer samples were distributed across other groups. Phylogenetic analysis incorporating ureC sequences from different geographical regions showed that Taiwanese ureC sequences could be divided into two distinct groups, although the bootstrap values supporting this separation were low. Notably, the ureC sequences from China formed a distinct group with a high bootstrap value, separate from sequences from all other countries. There are two genotypes of ureC sequences present in Taiwanese samples, with one genotype showing a closer association with gastric cancer. Additionally, the ureC sequences from China appear to be unique and separate from those obtained from other countries, indicating the presence of genetic diversity in ureC sequences among H. pylori strains from different regions, potentially contributing to differences in disease outcomes. Further research is needed to elucidate the specific mechanisms by which ureC sequence variations may influence the pathogenesis of peptic ulcer diseases and gastric cancer.

Bromodomain-containing protein 4 (BRD4) is an intracellular protein that regulates expression of various cellular functions. This study investigated whether BRD4 inhibition can alter the immunomodulatory and antitumor effects of radiation therapy (RT). A murine breast cancer cell line was implanted into BALB/c mice. The dual-tumor model was used to evaluate the abscopal effects of RT. A total of 24 Gy was delivered and BRD4 inhibitor was injected intravenously. Tumor size was measured and in vivo imaging was performed to evaluate tumor growth. Flow cytometry and immunohistochemistry were performed to examine immunologic changes upon treatment. The combination of BRD4 inhibitor and RT significantly suppressed tumor growth compared to RT alone. BRD4 inhibitor reduced the size of the unirradiated tumor indicating that it may induce systemic immune responses. Expression of HIF-1α and PD-L1 in tumor was significantly downregulated by the BRD4 inhibitor. Proportion of M1 tumor-associated macrophages (TAMs) increased, and proportion of M2 TAMs decreased upon BRD4 inhibition. BRD4 inhibitor expanded CD4+ and CD8+ T cell populations and reduced the population of monocytic myeloid-derived suppressor cells (M-MDSCs). RT-induced splenic M-MDSCs decreased upon addition of BRD4 inhibitor. Therefore, addition of BRD4 inhibition significantly enhanced the systemic antitumor responses of local RT.

The identification of cancer predisposition syndromes (CPSs) plays a crucial role in understanding the etiology of pediatric cancers. CPSs are genetic mutations that increase the risk of developing cancer at an earlier age compared to the risk for the general population. This article aims to provide a comprehensive analysis of three unique cases involving pediatric patients with CPS who were diagnosed with multiple simultaneous or metachronous cancers. The first case involves a child with embryonal rhabdomyosarcoma, nephroblastoma, glioma, and subsequent medulloblastoma. Genetic analysis identified two pathogenic variants in the BRCA2 gene. The second case involves a child with alveolar rhabdomyosarcoma, Xanthogranuloma Juvenile, gliomas, and subsequent JMML/MDS/MPS. A pathogenic variant in the NF1 gene was identified. The third case involves a child with pleuropulmonary blastoma and pediatric cystic nephroma/nefroblastoma in whom a pathogenic variant in the DICER1 gene was identified. Multiple simultaneous and metachronous cancers in pediatric patients with CPSs are a rare but significant phenomenon. Comprehensive analysis and genetic testing play crucial roles in understanding the underlying mechanisms and guiding treatment strategies for these unique cases. Early detection and targeted interventions are crucial for improving outcomes in these individuals.

Major limitations in the effective treatment of neurological cancer include systemic cytotoxicity of chemotherapy, inaccessibility, and inoperability. The capability to successfully target a drug to the tumor site(s), without incurring serious side effects, especially in the case of aggressive tumors, such as glioblastoma and neuroblastoma, would represent a significant breakthrough in therapy. Orthotopic systems, capable of storing and releasing proteins over a prolonged period at the site of a tumor, utilising nanoparticles, liposomes, and hydrogels have been proposed. One candidate for drug delivery is Micro-Fragmented Adipose Tissue (MFAT). Obtained easily from the patient by abdominal subcutaneous liposuction (autologous), and with a high content of Mesenchymal Stem Cells (MSC), mechanically derived nanofat is a natural tissue graft with a structural scaffold organization. It has a well preserved stromal vascular fraction, and a prolonged capacity to secrete anti-tumorigenic concentrations of pre-absorbed chemotherapeutics within extracellular vesicles. This review discusses current evidence supporting the potential of drug modified MFAT for the treatment of neurological cancer with respect to recent preclinical and in vitro studies. Possible limitations and future perspectives are considered.

Lung cancer is the leading cause of cancer death worldwide, with non-small cell lung cancer (NSCLC) making up 80% of cases. Some genetic factors leading to NSCLC development include genetic mutations and PD-L1 expression. PD-L1 proteins are targeted in an NSCLC treatment called targeted gene therapy. However, this treatment is effective in a low percentage of patients. This study aimed to create machine learning models to use features like the number of mutations and the level of PD-L1 proteins in cancer cells, along with others, to predict whether a patient will receive clinical benefit from gene therapy treatment. This was done by downloading and merging datasets from cbioportal.org to create a sample size for the model. Features with high correlations to clinical benefit were identified. Three machine-learning models were created using these features to predict clinical benefits in patients, and each model’s accuracy was evaluated. All three models were accurate between 55-85%, with two of the models averaging an accuracy around 75%. Doctors can use these models to more accurately predict whether gene therapy treatment is likely to work in a patient before prescribing it to them.

The quality of life (QOL) is an important indicator of human satisfaction and wellbeing. QOL is significantly and persistently affected for patients after a cancer diagnosis. Despite some evidence suggesting that psycho-oncologic interventions can provide lasting benefits, the inclusion of such interventions in cancer therapy is not universal. This article overviews known approaches to the evaluation of QOL in cancer patients and various interventions for improving patients’ outcomes with a focus on the Eastern European regional and specific Romanian context. With a mortality rate above and cancer care performance below the EU average and unequally distributed, Roma-nia urgently needs a national coordination program which is discussed in our review highlighting the main psychological tools needed for the assessment and its challenges towards implementing the program. In the end, we suggest some directions for future development of the psycho-oncologic approach in the context of social, policy and unexpected financial challenges the nation provides

The approval of monoclonal antibodies against programmed death-ligand 1 (PD-L1) and programmed cell death protein (PD1), has changed the landscape of cancer treatment. To date, many Immune Checkpoint Inhibitors (ICIs) have been approved by the FDA for the treatment of metastatic cancer as well as locally recurrent advanced cancer. However, immune-related adverse events (irAEs) of ICIs highlight the need for biomarker analysis with strong predictive value. Liquid biopsy is an important tool for clinical oncologists to monitor cancer patients and administer or change appropriate therapy. CTCs frequently express PD-L1 and this constitutes a clinically useful and non-invasive method to assess PD-L1 status in real time. This review summarizes all the latest findings about the clinical significance of CTC for the management of cancer patients during administration of immunotherapy and mainly focuses on the assessment of PD-L1 expression in CTCs.

The Epidermal Growth Factor Receptor (EGFR) overexpression or its mutation mediates the sustaining proliferative signaling in cancers. Human EGFR-targeting monoclonal antibody (mAb) therapy such as cetuximab has been approved for clinical use in patients with colorectal cancers and head and neck squamous cell carcinomas. A reliable preclinical mouse model is essential to further develop the mAb therapy against EGFR. However, a mAb against mouse EGFR (mEGFR) for flow cytometry has not been established. In this study, we developed a specific and sensitive mAb for mEGFR using the Cell-Based Immunization and Screening (CBIS) method. The established anti-mEGFR mAb, EMab-300 (rat IgG1, kappa) reacted with mEGFR-overexpressed Chinese hamster ovary-K1 (CHO/mEGFR) and endogenously mEGFR-expressed cell lines, including NMuMG (a mouse mammary gland epithelial cell) and Lewis lung carcinoma cells by flow cytometry. The kinetic analysis using flow cytometry indicated that the dissociation constant (KD) of EMab-300 for CHO/mEGFR and NMuMG was 4.3 × 10−8 M and 1.9 × 10−8 M, respectively. These results indicated that EMab-300 applies to the detection of mEGFR by flow cytometry, and is expected in the use of preclinical study.

Colorectal cancer remains one of the most commonly diagnosed cancers. Advanced rectal cancer patients receive neoadjuvant radiochemotherapy as well as surgery and suffer under reduced health-related quality of life due to various side effects. We were interested in the role of the COVID-19 pandemic and how it affected those patients’ quality of life. A total of 489 advanced rectal cancer patients from the University Hospital Erlangen in Germany were surveyed between May 2010 and March 2022 and asked to fill out the EORTC QLQ-C30 and QLQ-CR38 questionnaire over eight different time points: in the beginning, during and after radiochemotherapy, right before surgery and in yearly intervals after surgery for up to four years. Answers were converted to scores to compare the COVID-19 period to the time before March 2020 focusing on the follow-ups, the developments over time – including by sex and age - and the influence of the TNM cT-stage. Overall, a trend of impaired functional and symptom scores was found across all surveys with few significances (body image -10.6 percentage points (pp) after one year; defecation problems +13.5 pp, insomnia +10.2 pp and weight loss +9.8 pp after three years; defecation problems +11.3 pp after four years). cT4-stage patients lost significantly more weight than their cT1-3-stage counterparts (+10.7 to 13.7 pp). Further studies should be conducted to find possible causes and develop countermeasures for future major infectious diseases.

We explored the outcomes of germline BRCA1/2 pathogenic/likely pathogenic variants (PVs/LPVs) in the endocrine-sensitive disease treated with first line standard of care cyclin-dependent kinase 4/6 (CDK4/6) inhibitors. Three studies retrospectively showed a reduction in overall survival (OS) and progression free survival (PFS) in gBRCA1/2m patients compared to both germinal BRCA1/2 wild type (gBRCA1/2wt) and to the untested population. Regarding the efficacy of PI3K inhibitors, there are no subgroup or biomarker analyses in which germinal BRCA status was explored. However, the biological interactions between the PIK3CA/AKT/mTOR pathway and BRCA1/2 at a molecular level could help us to understand the activity of these drugs when used to treat BC in BRCA1/2 PVs/LPVs carriers. The efficacy of trastuzumab deruxtecan (T-DXd), an antibody-drug conjugate (ADC) targeting HER2 for HER2-low and HER2-positive (HER2+) BC, has been increasingly described. Unfortunately, data on T-DXd in HER2+ or HER2-low metastatic BC harboring germinal BRCA1/2 PVs/LPVs is lacking. Including germinal BRCA1/2 status in the subgroup analysis of the registration trials of this ADC would be of great interest, especially in the phase III trial DESTINY-breast04. This trial enrolled patients with HER2-negative (HER2-) and both HR+ and HR- metastatic disease, which can now be categorized as HER2-low. The HER2-low subgroup includes tumors that were previously classified as triple negative, so it is highly likely that some women were germline BRCA1/2 PVs/LPVs carriers and this data was not reported. Germline BRCA1/2 status will be available for a higher number of individuals with BC in the near future and data on the prognostic and predictive role of these PVs/LPVs is needed in order to choose the best treatment options.

Currently, skin cancer is the most commonly diagnosed form of cancer in humans and is one of the leading causes of death in patients with cancer. Biopsy methods are an invasive research method and are not always available for primary diagnosis. Imaging methods have low accuracy and depend on the experience of the dermatologist. Artificial intelligence technologies can match and surpass visual analysis methods in accuracy, but they have the risk of a false negative response when a malignant pigmented lesion can be recognized as benign. One possible way to improve accuracy and reduce the risk of false negatives is to analyze heterogeneous data, combine different preprocessing methods, and use modified loss functions to eliminate the negative impact of unbalanced dermatological data. The paper proposes a multimodal neural network system with a modified cross-entropy loss function that is sensitive to unbalanced heterogeneous dermatological data. The accuracy of recognition in 10 diagnostically significant categories for the proposed system was 85.19%. The novelty of the proposed system lies in the use of cross-entropy loss when training the modified function with the help of weight coefficients. The introduction of weighting factors has reduced the number of false negative forecasts, as well as improved accuracy by 1.02-4.03 percentage points compared to the original multimodal systems. The introduction of the proposed multimodal system as an auxiliary diagnostic tool can reduce the consumption of financial and labor resources involved in the medical industry, as well as increase the chance of early detection of skin cancer.

Hypoxia, a condition of low oxygenation frequently found in triple-negative breast tumors (TNBC), promotes extracellular vesicle (EV) secretion and favors cell invasion, a complex process in which cell morphology is altered, dynamic focal adhesion spots are created, and ECM is re-modeled. Here, we investigated the invasive properties triggered by TNBC-derived hypoxic small EV (SEVh) in vitro in cells cultured under hypoxic and normoxic conditions, using pheno-typical and proteomic approaches. SEVh characterization demonstrated increased protein abundance and diversity over normoxic SEV (SEVn), with enrichment in pro-invasive pathways. In normoxic cells, SEVh promotes invasive behavior through pro-migratory morphology, in-vadopodia development, ECM degradation and matrix metalloprotease (MMP) secretion. Pro-teome profiling of normoxic cells exposed to SEVh determined enrichment in metabolic processes and cell cycle, modulating cell health to escape apoptotic pathways. In hypoxia, SEVh was re-sponsible for proteolytic and catabolic pathway inducement, interfering with integrin availabil-ity and gelatinase expression. Overall, our results demonstrate the importance of hypoxic signal-ing via SEV in tumors for the early establishment of metastasis.

Cancer invasion through basement membranes represents the initial step of tumor dissemination and metastasis. However, little is known about how human cancer cells breach basement membranes. Here, we used a 3-dimensional in vitro invasion model consisting of cancer spheroids encapsulated by a basement membrane and embedded in 3D collagen gels to visualize the early events of cancer invasion by confocal microscopy and live-cell imaging. Human breast cancer cells generated large numbers of basement membrane perforations, or holes, of varying sizes that expanded over time during cell invasion. We used a wide variety of small molecule inhibitors to probe the mechanisms of basement membrane perforation and hole expansion. Protease inhibitor treatment (BB94), led to a 63% decrease in perforation size. After myosin II inhibition (blebbistatin), basement membrane perforation area decreased by only 15%. These treatments produced correspondingly decreased cellular breaching events. Interestingly, inhibition of actin polymerization dramatically decreased basement membrane perforation by 80% and blocked invasion. Our findings suggest that human cancer cells can primarily use proteolysis and actin polymerization to perforate the BM and to expand perforations for basement membrane breaching, with a relatively small contribution from myosin II contractility.

Breast cancer (BC) is a heterogeneous disease representing a substantial economic burden. In order to develop policies that successfully decrease this burden, the factors affecting costs need to be fully understood. Evidence suggests that early detection in Stage I has a lower cost than late detection. We aim to provide conservative estimates of BC's stage-wise medical costs from German healthcare and the payer's perspective. To this end, we conducted a literature review of articles evaluating stage-wise costs of BC in Germany through PubMed, Web of Science, and Econ Lit databases supplemented by Google Scholar. We developed a decision tree model to estimate BC related medical costs in Germany using available treatment and cost information. The review generated seven studies; none estimated the stage-wise costs of BC. The studies were classified into two groups: (1) case scenarios (five studies) and two studies based on administrative data. The first sickness funds data study (Gruber, Stock, et al. 2012) used 1999 information to approach BC attributable cost; their results suggest a range between €3,929 and €11,787 depending on age. The second study (Kreis, Plöthner, et al. 2020) used 2011-2014 data and suggested an initial phase incremental cost of €21,499, an intermediate phase cost of €2,620, and a terminal phase cost of €34,513 per incident case. Our decision tree model based BC stage-wise cost estimates were €21,523 for Stage I, €25,679 for Stage II, €30,156 for Stage III, €42,086 for Stage IV. Alternatively, the modeled cost estimates are €20,284 for the initial phase of care, €851 for the intermediate phase of care, and €34,963 for the terminal phase of care. Our estimates for phases of care are consistent with recent German estimates provided by Kreis and Plöthner et al. Furthermore, the data collected by sickness funds are collected primarily for reimbursement purposes, where the German ICD-10 classification system defines a cancer diagnosis. As a result, claims data lack the clinical information necessary to understand stage-wise BC costs. Our model-based estimates fill the gap and inform future economic evaluations of BC interventions.

Therapeutic efficacy of retroviral replicating vector (RRV)-mediated prodrug activator gene therapy has been demonstrated in a variety of tumor models, but clinical investigation of this approach has so far been restricted to glioma and gastrointestinal malignancies. In the present study, we evaluated replication kinetics, transduction efficiency, and therapeutic efficacy of RRV in experimental models of lung cancer. RRV delivering GFP as a reporter gene showed rapid viral replication in a panel of lung cancer cells in vitro, as well as robust intratumoral replication and high levels of tumor transduction in subcutaneous and orthotopic pleural dissemination models of lung cancer in vivo. Toca 511 (vocimagene amiretrorepvec), a clinical-stage RRV encoding optimized yeast cytosine deaminase (yCD) which converts the prodrug 5-fluorocytosine (5-FC) to the active drug 5-fluorouracil (5-FU), showed potent cytotoxicity in lung cancer cells upon exposure to 5-FC prodrug. In vivo, Toca 511 achieved significant tumor growth inhibition following 5-FC treatment in subcutaneous and orthotopic pleural dissemination models of lung cancer in both immunodeficient and immunocompetent hosts, resulting in significantly increased overall survival. This study demonstrates that RRV can serve as highly efficient vehicles for gene delivery to lung cancer, and indicates the translational potential of RRV-mediated prodrug activator gene therapy with Toca 511/5-FC as a novel therapeutic strategy for pulmonary malignancies.

This study aimed to determine the feasibility of the development of an over-the-counter (OTC) screening model using machine learning for breast cancer screening in the Asian women population. Data were retrospectively collected from women who came to the Hospital Universiti Sains Malaysia, Malaysia. Five screening models were developed based on machine learning methods; random forest, artificial neural network (ANN), support vector machine (SVM), elastic-net logistic regression and extreme gradient boosting (XGBoost). Features used for the development of the screening models were limited to information from the patients’ registration form. The model performance was assessed across the dense and non-dense groups. SVM had the best sensitivity while elastic-net logistic regression had the best specificity. In terms of precision, both random forest elastic-net logistic regression had the best performance, while, in terms of PR-AUC, XGBoost had the best performance. Additionally, SVM had a more balanced performance in terms of sensitivity and specificity across the mammographic density groups. The three most important features were age at examination, weight and number of children. In conclusion, OTC models developed from machine learning methods can improve the prognostic process of breast cancer in Asian women.