Previously, we analyzed 316 herbal extracts to evaluate their potential nematocidal properties in Caenorhabditis elegans. In this study, our attention was directed towards Torenia sp., resulting in reduced survival and heightened larval arrest/lethality, alongside a noticeable decrease in DAPI-stained bivalent structures and disrupted meiotic progression, thus disrupting developmental processes. Notably, Torenia sp. extracts activated a DNA damage checkpoint response via the ATM/ATR and CHK-1 pathways, hindering germline development. LC–MS analysis revealed 13 compounds in the Torenia sp. extracts, including flavonoids, terpenoids, tanshinones, an analog of resveratrol, iridoids, carotenoids, fatty acids, and alkaloids. Of these, 10 are known for their antitumor activity, suggesting the potential of Torenia species beyond traditional gardening, extending into pharmaceutical and therapeutic applications. Full article

Metformin, a widely used first-line anti-diabetic therapy for the treatment of type-2 diabetes, has been shown to lower hyperglycemia levels in the blood by enhancing insulin actions. For several decades this drug has been used globally to successfully control hyperglycemia. Lactic acidosis has been shown to be a major adverse effect of metformin in some type-2 diabetic patients, but several studies suggest that it is a typically well-tolerated and safe drug in most patients. Further, recent studies also indicate its potential to reduce the symptoms associated with various inflammatory complications and infectious diseases including coronavirus disease 2019 (COVID-19). These studies suggest that besides diabetes, metformin could be used as an adjuvant drug to control inflammatory and infectious diseases. In this article, we discuss the current understanding of the role of the anti-diabetic drug metformin in the prevention of various inflammatory complications and infectious diseases in both diabetics and non-diabetics. Full article

(1) Background: Infections caused by multidrug-resistant (MDR) bacteria represent one of the major global public health problems of the 21st century. Beta-lactam antibacterial agents are commonly used to treat infections due to Gram-negative pathogens. New β-lactam/β-lactamase inhibitor combinations are urgently needed. Combining relebactam (REL) with imipenem (IMI) and cilastatin (CS) can restore its activity against many imipenem-nonsusceptible Gram-negative pathogens. (2) Methods: we performed a systematic review of the studies reporting on the use of in vivo REAL/IPM/CS. (3) Results: A total of eight studies were included in this review. The primary diagnosis was as follows: complicated urinary tract infection (n = 234), complicated intra-abdominal infections (n = 220), hospital-acquired pneumonia (n = 276), and ventilator-associated pneumonia (n = 157). Patients with normal renal function received REL/IPM/CS (250 mg/500 mg/500 mg). The most frequently reported AEs occurring in patients treated with imipenem/cilastatin plus REL/IPM/CS were nausea (11.5%), diarrhea (9.8%), vomiting (9.8%), and infusion site disorders (4.0%). Treatment outcomes in these high-risk patients receiving REL/IPM/CS were generally favorable. A total of 70.6% of patients treated with REL/IPM/CS reported a favorable clinical response at follow-up. (4) Conclusions: this review indicates that REL/IPM/CS is active against important MDR Gram-negative organisms. Full article

Chemotherapeutic drugs are indispensable in cancer treatment, but their effectiveness is often lessened because of non-selective toxicity to healthy tissues, which triggers inflammatory pathways that are harmful to vital organs. In addition, tumors’ resistance to drugs causes failures in treatment. Chlorogenic acid (5-caffeoylquinic acid, CGA), found in plants and vegetables, is promising in anticancer mechanisms. In vitro and animal studies have indicated that CGA can overcome resistance to conventional chemotherapeutics and alleviate chemotherapy-induced toxicity by scavenging free radicals effectively. This review is a summary of current information about CGA, including its natural sources, biosynthesis, metabolism, toxicology, role in combatting chemoresistance, and protective effects against chemotherapy-induced toxicity. It also emphasizes the potential of CGA as a pharmacological adjuvant in cancer treatment with drugs such as 5-fluorouracil, cisplatin, oxaliplatin, doxorubicin, regorafenib, and radiotherapy. By analyzing more than 140 papers from PubMed, Google Scholar, and SciFinder, we hope to find the therapeutic potential of CGA in improving cancer therapy. Full article

(1) Background: Crohn’s disease (CD) and right-sided colorectal-carcinoma (CRC) are two common indications for right colectomies. Many studies have tried to identify risk factors associated with post-operative complications for both CD and CRC. However, data directly comparing the outcomes of the two are sparse. This study aims to compare the 30-day post-operative outcome after a right colectomy for CD versus CRC. Its secondary aim is to identify the factors associated with these outcomes for each group. (2) Methods: A retrospective cohort study of 123 patients who underwent a right colectomy for CD or CRC in a single institution between March 2011 and March 2016. (3) Results: There were no significant differences between the groups when comparing the overall complication rate, the median Clavien–Dindo score, reoperation rates and the length of hospitalization. The leak rate was higher in the Crohn’s group (13.95% (6/43) vs. 3.75% (3/80)), p = 0.049), although the stoma rate was the same (4/43 9.5%; 7/80 9.9%). (4) Conclusions: This study has shown that post-operative complication rate is similar for right colectomy in CD and CRC. However, Crohn’s disease patients did have a higher leak rate. Full article

Background: The effectiveness and reliability of diagnostic tests that detect DNA sequences largely hinge on the quality of the used primers and probes. This importance is especially evident when considering the specific sample being analyzed, as it affects the molecular background and potential for cross-reactivity, ultimately determining the test’s performance. Methods: Predicting primers based on the consensus sequence of the target has multiple advantages, including high specificity, diagnostic reliability, broad applicability, and long-term validity. Automated curation of the input sequences ensures high-quality primers and probes. Results: Here, we present a use case for developing a set of consensus primers and probes to identify antibiotic resistance and virulence genes in Staphylococcus (S.) aureus using the ConsensusPrime pipeline. Extensive qPCR experiments with several S. aureus strains confirm the exceptional quality of the primers designed using the pipeline. Conclusions: By improving the quality of the input sequences and using the consensus sequence as a basis, the ConsensusPrime pipeline pipeline ensures high-quality primers and probes, which should be the basis of molecular assays. Full article

This study examined the efficacy of an optimized DeepLabCut (DLC) model in motion capture, with a particular focus on the sit-to-stand (STS) movement, which is crucial for assessing the functional capacity in elderly and postoperative patients. This research uniquely compared the performance of this optimized DLC model, which was trained using ’filtered’ estimates from the widely used OpenPose (OP) model, thereby emphasizing computational effectiveness, motion-tracking precision, and enhanced stability in data capture. Utilizing a combination of smartphone-captured videos and specifically curated datasets, our methodological approach included data preparation, keypoint annotation, and extensive model training, with an emphasis on the flow of the optimized model. The findings demonstrate the superiority of the optimized DLC model in various aspects. It exhibited not only higher computational efficiency, with reduced processing times, but also greater precision and consistency in motion tracking thanks to the stability brought about by the meticulous selection of the OP data. This precision is vital for developing accurate biomechanical models for clinical interventions. Moreover, this study revealed that the optimized DLC maintained higher average confidence levels across datasets, indicating more reliable and accurate detection capabilities compared with standalone OP. The clinical relevance of these findings is profound. The optimized DLC model’s efficiency and enhanced point estimation stability make it an invaluable tool in rehabilitation monitoring and patient assessments, potentially streamlining clinical workflows. This study suggests future research directions, including integrating the optimized DLC model with virtual reality environments for enhanced patient engagement and leveraging its improved data quality for predictive analytics in healthcare. Overall, the optimized DLC model emerged as a transformative tool for biomechanical analysis and physical rehabilitation, promising to enhance the quality of patient care and healthcare delivery efficiency. Full article

Families’ education investment in their children is crucial for fostering and accumulating human capital among rural children in China. This study examines the impact of the Poverty Alleviation Relocation Program (PARP) on household education investment using panel data from a large-scale survey conducted in 16 counties across 8 provinces over three waves. Employing a staggered difference-in-differences (DID) method, we find a significant increase in average education investment per student in households following the PARP’s implementation, supported by multiple robustness tests. Mechanism analysis reveals that the increase is primarily driven by a higher household income and lower medical expenses among relocated families. Heterogeneity analysis shows notable variations based on relocation attributes and household characteristics, with stronger effects particularly observed for dispersed relocation, scattered resettlement, and household heads with over 6 years of education or in good health. The impact is sustained and strengthens with longer durations of relocation. Our findings offer valuable insights for enhancing rural household education investment. Full article

Metaphylactic antibiotic use in feeder cattle is a common practice to control respiratory disease. Antimicrobial stewardship is important to ensure continued efficacy and to protect animal welfare. The objective of this study is to identify characteristics of cohorts of cattle that had not received metaphylaxis that would have benefited economically from the use of metaphylaxis. Cohorts (n = 12,785; 2,206,338 head) from 13 feedlots that did not receive metaphylaxis were modeled using an economic model to estimate net returns for three metaphylactic options. Logistic regression models with covariates for entry weight, sex, average daily weight gain, number of animals per cohort, and days on feed, with feedlot as a random effect, were used to determine the model-adjusted probability of cohorts benefiting economically from metaphylaxis. Most (72%) cohorts in this data set that had not received metaphylaxis at arrival would not economically benefit from metaphylaxis. Sex, entry weight category, number of cattle in the cohort, and average daily weight gain were associated with the likelihood of benefitting economically from metaphylaxis. The results illustrated that cattle cohort demographics influenced the probability that cohorts would benefit economically from metaphylaxis and the type of metaphylaxis utilized, and integrating this information has the potential to influence the metaphylaxis decision. Full article

Pleural mesothelioma (PM), linked to asbestos-induced inflammation, carries a poor prognosis. Therapy ranges from therapy limitation to aggressive multimodality treatment. Given the uncertainty about treatment benefits for patients, this study aimed to assess the role of Ki67 as a prognostic and predictive parameter in PM. Ki67 was measured in the specimens of 70 PM patients (17 female, 53 male) from two centers and correlated to overall survival (OS) and therapy outcome. The median OS was 16.1 months. The level of Ki67 expression was divided into low (≤15%) and high (>15%). A low value of Ki67 expression was associated with a longer OS (Ki67 ≤ 15%: 31.2 (95% CI 6.5–55.8) months vs. Ki67 > 15%: 11.1 (95% CI 7.7–14.6) months, p = 0.012). The 5-year survival represents 22% in the low Ki67 expression group, in contrast to 5% in the high Ki67 expression group. We found a significant interaction term of Ki67 with multimodality treatment (p = 0.031) translating to an OS of 48.1 months in the low expression Ki67 group compared to 24.3 months in the high Ki67 expression group when receiving surgery within multimodality therapy. Therefore, Ki67 stands out as a validated prognostic and, most importantly, novel predictive biomarker for treatment benefits, particularly regarding surgery within multimodality therapy. Full article

Artificial Intelligence (AI) and Machine Learning (ML) approaches that could learn from large data sources have been identified as useful tools to support clinicians in their decisional process; AI and ML implementations have had a rapid acceleration during the recent COVID-19 pandemic. However, many ML classifiers are “black box” to the final user, since their underlying reasoning process is often obscure. Additionally, the performance of such models suffers from poor generalization ability in the presence of dataset shifts. Here, we present a comparison between an explainable-by-design (“white box”) model (Bayesian Network (BN)) versus a black box model (Random Forest), both studied with the aim of supporting clinicians of Policlinico San Matteo University Hospital in Pavia (Italy) during the triage of COVID-19 patients. Our aim is to evaluate whether the BN predictive performances are comparable with those of a widely used but less explainable ML model such as Random Forest and to test the generalization ability of the ML models across different waves of the pandemic. Full article

A simple higher-order model (HOM) is presented in this study for the bending analysis of an intact or delaminated composite and sandwich beam. This model adopts the concept of sub-laminates to simulate multilayered structures, and each sub-laminate takes cubic variation for axial displacement and linear variation for transverse displacement through the thickness. A sub-laminate possesses displacement components at its surfaces (bottom and top) that provide a straightforward way to improve the accuracy of prediction by stacking several sub-laminates. Thus, analysts will have the flexibility to balance the computational cost and the accuracy by selecting an appropriate sub-lamination scheme. The proposed model was implemented by developing a C⁰ beam element that has only displacement unknowns. The model was used to solve numerical examples of composite and sandwich beams to demonstrate its performance. Full article

In early childhood, children are extremely susceptible to the acquisition of habits and the establishment of health-promoting habits. Therefore, the patterns, routines, and rules transmitted and expected by the adults surrounding the child are of paramount importance and can correlate with the level of their health literacy. Our cross-sectional, quantitative, exploratory study aimed to examine the relationships between parental health literacy and preschool children’s health-related habits, using simple, non-random sampling (n = 598). In addition to the sociodemographic characteristics, the measuring tool we compiled included the standardized European Health Literacy Survey Questionnaire (HLS-EU-Q16), as well as a set of questions containing 30 statements suitable for exploring children’s habit systems. The health literacy of the parents involved in our study proved to be more favorable than that of the general population. Regarding children’s habit systems, we found significant differences in several areas by age group (p < 0.05) and gender (p < 0.05). The levels of parental health literacy (0.003 ≤ p ≤ 0.048) and parents’ education (p < 0.05) show a correlation with the children’s health-related habit systems: the indicators of children with parents who have a higher level of health literacy and a higher level of education are more favorable in terms of established habits. In the long term, the formation of health-promoting habits may facilitate the internalization of favorable health behavior motives for the future, contributing to the establishment of positive physical, mental, and social health in adulthood. Full article

Background: Intravenously administered indocyanine green (ICG) accumulates in lung tumors, facilitating their detection via a fluorescence spectrum measurement. This method aids in identifying tumor locations that are invisible to the naked eye. We aim to determine the optimal ICG dose and administration method for accurate tumor identification during lung resection surgeries, utilizing a novel ICG fluorescence spectroscopy system for precise tumor localization. Materials and Methods: ICG should be dissolved in the provided solution or distilled water and administered intravenously approximately 24 h before surgery, beginning with an initial dose of 0.5 mg/kg. If the tumor detection rate is insufficient, the dose may be gradually increased to a maximum of 5.0 mg/kg to determine the optimal dosage for effective tumor detection. This fluorescence spectroscopy during surgery may reveal additional lesions that remain undetected in preoperative assessments. The primary endpoint includes the correct diagnostic rate of tumor localization. The secondary endpoints include the measurement of the intraoperative ICG fluorescence spectral intensity in lung tumors, the assessment of the operability and safety of intraperitoneal ICG administrations, the measurement of the ICG fluorescence spectral intensity in surgical specimens, the comparison of the spectral intensity in lung tissues during collapse and expansion, the correlation between ICG camera images and fluorescence spectral intensity, and the comparison of fluorescence analysis results with histopathological findings. The trial has been registered in the jRCT Clinical Trials Registry under the code jRCTs011230037. Results and Conclusions: This trial aims to establish an effective methodology for localizing and diagnosing malignant lung tumors, thereby potentially improving surgical outcomes and refining treatment protocols. Full article

Influenza vaccination is an important public health measure that can reduce disease burden, especially among older persons (those aged 65 and over) who have weaker immune systems. Evidence suggests enhanced vaccines, including adjuvanted quadrivalent vaccines (aQIV), may be particularly effective in this group. This study reports the results of a systematic review of the cost-effectiveness of aQIV in this population. The review was undertaken and reported in accordance with good practice guidelines. Medline and EMBASE were searched from 2013 to the present. Pre-selected eligibility criteria were employed and quality assessment undertaken using the Consensus Health Economic Criteria (CHEC-extended) checklist and Consolidated Health Economic Evaluation Reporting Standard (CHEERS) 2022 checklists. A total of 124 records were returned, with 10 full text papers retained. All were modelling studies and exhibited heterogeneity in approach, perspective, and parameter estimation. Nine papers reported cost-effectiveness ranging from EUR 6694/QALY to EUR 20,000/QALY in evaluations employing a payer perspective and from EUR 3936/QALY to EUR 17,200/QALY in those using a societal perspective. Results remained robust to a range of sensitivity analyses. One paper that reported contrary findings adopted a distinct modelling approach. It is reasonable to conclude that there is a broad consensus as to the cost-effectiveness of aQIV in this population group. Full article

Augustine’s sermons on the Psalms of Ascent, part of the Enarrationes in Psalmos, are a unique entry in the venerable tradition of those writings that aim to help us ascend to a higher reality. These sermons transform the ascent genre by giving, in the place of the Platonic account of ascent, a Christian ascent narrative with a Trinitarian structure. Not just the individual ascends, but the community that is the church, the body of Christ, also ascends. The ascent is up to God, the Idipsum or the Selfsame, the ultimate reality, confessed by the church as God the Father, God the Son, and God the Holy Spirit. Through the grace of the Incarnation, God the Son enables us to ascend, making himself the way of ascent from the humility we must imitate at the beginning of the ascent all the way up to Heaven, where he retains his identity as Idipsum. Meanwhile, the Holy Spirit works in the ascending church to convert our hearts to the love of God and neighbor. I review the Platonic ascent tradition in Plato’s Republic and Plotinus’ Enneads; overview ascent in some of Augustine’s earlier writings; introduce the narrative setting of the sermons on the Psalms of Ascent; and analyze the Trinitarian structure of their ascent narrative. I close with some reflections on the difference between a preached Trinitarianism that encourages ascent and a more academic effort to understand God such as we find in Augustine’s de Trinitate. Full article

The COVID-19 pandemic had a profound impact on food systems. Despite disrupting conventional markets—such as grocery stores—farmers that focused on short supply chains found new market opportunities. As consumers increasingly became concerned with the safety of in-person shopping, some turned to purchasing directly from farmers and markets that carried products marketed as local, organic, and/or sustainable. With these changes in mind, I ask how consumer perceptions of local food systems (LFSs) changed in the two years after COVID-19. If consumers are more aware of local markets, farmers might reorient production to focus on local supply chains and sustainable production methods. To evaluate consumer perceptions, I use survey responses from residents in five communities in the US South in 2019 and 2022. Using a treatment effects model with propensity score matching, I show that residents became more aware of most local market channels, such as specialty retail stores and Community Supported Agriculture (CSA). Some residents were also more likely to have a positive perception of markets that provide fresh vegetables to low-income residents. Finally, residents wanted more investment into markets that make fresh, local products more available, such as community-owned groceries and CSA. Full article

This research investigates the potential of utilizing recycled concrete aggregate (RCA) and recycled sand (RS), derived from crushed concrete cubes, as sustainable alternatives in construction materials. The study comprehensively evaluates the properties of RCA and RS, focusing on workability, impact resistance, abrasion resistance, and compressive strength to determine their viability as substitute construction materials. A notable finding is RS’s enhanced fire and heat resistance when used as a fine aggregate in mortar blends, mixed with cement and Sinicon PP in a 3:1 ratio. The experimental analysis included thorough assessments of uniformity, durability, and curing time, alongside Scanning Electron Microscopy (SEM) for structural examination. Results show that RCA has an Aggregate Impact Value (AIV) of 5.76% and a Los Angeles Abrasion Value (LAA) of 21.78%, demonstrating excellent strength of the recycled aggregates. The mortar mix was also prepared using recycled sand, cement, and Sinicon PP, and its stability was confirmed through soundness tests, which resulted in a 0.53 mm expansion and a satisfactory consistency level of 44%. Ultrasonic pulse velocity (UPV) tests also indicated high-quality concrete formation using RCA and RS. SEM imaging corroborated this by revealing a bond between the cement paste and the aggregates. Incorporating RS and RCA in concrete mixtures impressively yielded a compressive strength of 26.22 N/mm² in M20-grade concrete. The study concludes that using RCA and RS waste materials in the construction sector underlines that sustainable practices can be integrated without compromising material quality. This approach aligns with sustainable development goals and fosters a more environmentally friendly construction industry. Full article

The Cornus mas L. fruit is well known for having a high presence of bioactive substances that include phenolic compounds, anthocyanins, vitamins, flavonoids, carotenoids, and ursolic acid. The health-promoting effects of those substances are mainly associated with their antimicrobial, anti-inflammatory, and antioxidant properties. In this study, we investigated the role of Cornus mas L. fruit ethanolic extract on the cell vitality of a model eukaryotic organism, the yeast Schizosaccharomyces pombe. The effect of Cornus mas L. fruit ethanolic extract on cell viability was determined by analyses of cell growth and cell doubling time during exposure to the extract. To determine the ability of Cornus mas L. to reduce or induce oxidative stress, quantification of intracellular reactive oxygen species and malondialdehyde levels was performed. Additionally, the enzyme activity of superoxide dismutase and catalase was evaluated together with the determination of changes in the expression of genes related to oxidative stress response. The data suggest a dose-dependent cytotoxic effect of the Cornus mas L. fruit ethanol extract, as a higher concentration (2%) led to increased oxidative stress and reduced cell viability of S. pombe cells, while a lower concentration (0.5%) showed only a subtle effect on the analyzed parameters. This study provides a new perspective on the possible antimicrobial or medicinal properties of Cornus mas L. fruit ethanol extract due to its ability to induce oxidative stress in the cell. Full article

Considering that land use and land cover (LULC) change is one of the most important challenges to biodiversity today, we used Copernicus products to analyze LULC changes at the level of the “Nordul Gorjului de Vest” Natura 2000 site (Romania) from 1990 to 2018. The interpretation of the impact of these changes on areas with very high potential for three regulating ecosystem services (ESs) (local climate regulation, regulation of waste, and water purification) was performed. Forest habitats are the major LULC class category in the “Nordul Gorjului de Vest” Natura 2000 site, with broad-leaved forest as the dominant forest class. In terms of areas lost or gained by the different LULC classes for each analyzed time interval, most transformations took place in the period 2000–2006, changes which were also reflected in the overall study period (1990–2018). During this time frame, the conversion of transitional forest shrubs into broad-leaved forest, which is the second largest transition in terms of absolute area changed, led, in terms of contribution rates, to an increase in the areas with very high potential for two of the three analyzed ESs. The conversion of transitional woodland shrub into broad-leaved forest was conductive only to synergy for all the pairwise interactions between the three ESs. Full article

Offshore wind farms on the east offshore of Korea to produce multi-GW power from floating wind platforms are being planned. The objectives of the present study are to develop a new TLP-type floating wind platform with a 15 MW turbine for the planned site and to confirm the feasibility of the TLP design under extreme typhoon environments. The concept design of the 15 MW TLP floating platform was completed for installation at a water depth of 137 m. The platform was vertically moored with highly pretensioned wire rope tendons. The platform and tendons were designed to withstand extreme conditions for up to 50 years. Additionally, a platform with an integrated turbine was designed to be wet-towable from the quayside without dedicated vessels to minimize the pre-service cost and risk. An extreme response analysis was conducted to evaluate the platform motion, acceleration, airgap and tendon tension for wave variation, intact and damaged condition of the tendon, environment heading change, and water level variation. The platform design results were validated using the design criteria from the industry standards and recommendations, and the design was verified to comply with the design requirements for the planned sites. Full article

Inflammatory bowel disease (IBD) represents a heterogenous and complex group of idiopathic chronic inflammatory conditions affecting the gastrointestinal tract and other extraintestinal systems with rising global incidences. The interplay of genetic predisposition and environmental factors contributes to its pathogenesis. Among the key cytokines implicated in IBD molecular alterations, IL-33 stands out for its multifaceted roles in both pathogenesis and repair mechanisms. IL-33, known for its action in initiating immune responses, is closely associated with Th2 immunity and is considered a potent inflammatory factor with dual functions, acting both as a pro-inflammatory cytokine and a transcriptional regulator. Primarily expressed by non-hematopoietic cells in the gastrointestinal tract, IL-33 interacts with its receptor, ST2, to modulate immune responses. In IBD, dysregulated IL-33 expression exacerbates mucosal inflammation, compromising barrier integrity and promoting tissue damage and fibrosis. Additionally, IL-33 plays a complex role in IBD-related colorectal cancer (CRC), affecting tumor progression and angiogenesis. This review summarizes the multifaceted roles of IL-33 in gastrointestinal health and disease, emphasizing its significance in the pathogenesis of IBD and CRC. Moreover, we thought it of interest to provide new insights into potential therapeutic avenues targeting IL-33 signaling for the management of these debilitating conditions. Full article