Floral nectar is a key reward in Leguminosae despite the exceptional diversity of flowers in this family. The paper aims to summarize the available data on structure, ontogeny, regulation, and possible evolution of the leguminous floral nectaries. To date, detailed characterization of ultrastructure and mode of secretion is available only for a few representative of the family whereas the majority remains understudied from this perspective. In most cases, regardless of flower symmetry, nectaries are localized between stamens and a carpel. The nectar is usually exuded from modified stomata although the exact mode of secretion by specialized parenchyma may differ between taxa. The leguminous floral nectaries often have certain features of monosymmetry with preferentially abaxial development. Nectaries were independently lost in several lineages, and equally recurrent is the emergence of substitutive, i.e. evolutionary innovative, nectar-producing structures. Floral nectaries possess a certain degree of evolutionary inertia, i.e. they remain stable even in lineages in which flower morphology underwent significant changes compared with an ancestral plan, such as shifts in merism, symmetry, organ number and alike. Due to their evolutionary stability, floral nectaries are rarely used in taxonomy of Leguminosae.

Litsea martabanica root's antioxidant and AChE activity showed promise as a pesticide detoxification agent in our previous study. In addition to roots, its leaves can help mitigate pesticide exposure, although there is limited scientific evidence supporting their efficacy. However, the use of roots in many countries, such as Thailand, could contribute to environmental degradation, as highland communities traditionally cut down whole trees to obtain them. This study aims to evaluate the antioxidant activity and anti-pesticide potential of water extracts from L. martabanica leaves instead of its roots through in vitro and in vivo investigations. The findings showed that L. martabanica water extracts and fractions demonstrated varied antioxidant activity. The water extract, obtained using traditional extraction methods, was chosen for in vivo experiments. Rats received the extract followed by chlorpyrifos exposure for 16 days. Results indicated reduced acetylcholinesterase activity in chlorpyrifos-exposed rats, while treatment with leaf extract led to increased activity, suggesting its potential as a detoxifying agent. Histopathological examination revealed no liver cell necrosis and showed liver cell regeneration, indicating potential protection against free radical-induced liver damage without affecting rat liver weight or biochemical profiles. Utilizing L. martabanica leaves for healthcare purposes holds promise without negative environmental impact.

The effect of salinity on seed germination/emergence in narrow-leaved ash (Fraxinus angustifolia) was studied both under field and laboratory conditions, in order to detect critical values to NaCl exposure. Research Highlights: Novel statistical methods in germination ecology has been applied (i) to determine the effects of chilling length and salinity (up to 150 mM NaCl) on Fraxinus angustifolia subsp. oxycarpa seed emergence, and (ii) to estimate threshold limits treating germination response to salinity as a biomarker. Background and Objectives: Salinity cut values at germination stage had relevant interest for conservation and restoration aims of Mediterranean floodplain forests in coastal areas subjected to salt spray exposure and/or saline water introgression. Results: Salinity linearly decreased germination/emergence both in the field and laboratory tests. Absence of germination was observed at 70 mM NaCl in the field and at 150 mM NaCl for 4-week (but not for 24-week) chilling. At 50 mM NaCl germination percentage was 50% (or 80%) of control for 4-week (or 24- week) chilling. Critical values for salinity were estimated between freshwater and 50 (75) mM NaCl for 4-week (24-week) chilling by Bayesian analysis. After 7-week freshwater recovery, critical cut-off values included all tested salinity levels up to 150 mM NaCl, indicating a marked resumption of seedling emergence. Conclusions: Fraxinus angustifolia is able to germinate at low salinity and to tolerate temporarily moderate salinity conditions for about two months. Prolonged chilling widened salinity tolerance.

A field study was conducted at the Eastern Mediterranean Agricultural Research Institute, Adana, Turkey, during the 2022/23 cropping seasons to examine the impact of Mepiquat chloride dosage applied at different intervals to optimize growth, yield characteristics enhancement and improve fiber quality attributes of cotton. The study employed a split-split plot design with three replications. The results revealed that differences among treatments were not statistically significant for most parameters investigated. The observed discrepancies indicated that all treatments tested in 2012 delayed cotton development, whereas in 2023, they led to premium fibers. In 2023, the fiber percentage was highest in the control treatment, and in 2022, it was highest at 400 mL·ha-1. Across all years, the Selin variety exhibited the highest fiber percentage when Mepiquat chloride was applied at the bolling stage. The shoot-root ratio was highest at 400 mL·ha-1 during harvest in 2022 and at 0 mL·ha-1 during the reproductive stage in 2023. Overall, the results demonstrated that the application of Mepiquat chloride altered the physiological characteristics of the cotton plants, leading to bottom-up effects on cotton performance. This implies that the effectiveness of Mepiquat chloride in cotton production to alleviate drought stress is influenced by weather-related conditions.

This paper explores indigenous perspectives on the understanding and management of cultural heritage within the Mapungubwe and Makgabeng Cultural landscapes in South Africa. State-based management system paid little attention to indigeneity resulting in contested interpretation of the archaeological past. This by-passing of indigenous input is a product of colonial and apartheid policies that glorified Western practices at the expense of black African heritage stakeholders. World heritage mechanisms are also skewed in favor of modern practice which is overly designed to be sensitive to tangible aspects of the past than the intangible elements that make up much of indigenous African heritage. We used the archaeology of Mapungubwe and Makgabeng Cultural landscapes as a test case for the impact of indigenous voices on heritage, but the results have wider applicability. We employed semi-structured interviews and focus group discussions to gather qualitative data that we calibrated with our lived experiences as products of Tsonga-speakers from this broader landscape. The results expose that indigenous people use physical manifestation of sites, ethnographic inquiry, names, oral history, spirit mediums, landscape memory, genealogy, and praise poetry to identify, interpret, evaluate, and manage their cultural heritage. Additionally, indigenous perspectives which rely on collective memory, ritual practices, and indigenous knowledge systems have huge potential for enriching our understanding of the archaeological heritage. We propose a more inclusive archaeology and heritage management practice that involve indigenous groups in the identification, interpretation, grading, and presentation of the African past.

Despite global efforts to improve vaccination coverage, the number of zero dose and under immunized children has increased in the African continent, particularly in Nigeria where more than 2.3 million unvaccinated children currently reside, making it the country with highest number of unvaccinated children on the African continent. It is thus imperative to identity barriers and facilitators of immunization in Nigeria with a view to formulate and design targeted interventions that can effectively bridge the immunization gap in Nigeria. In this review, we systematically mapped and summarized existing literature and data on key barriers to vaccine uptake, and facilitators influencing immunization practices in Nigeria. The electronic databases were systematically searched and articles that reported determinants of routine immunization uptake in Nigeria from inception of the databases up till October 2023 were included. The eligible articles were evaluated using a set of pre-defined criteria and the extracted data were analysed and visualized. This scoping review identified barriers spanning logistical, socio-economic, cultural, and healthcare system-related aspects, highlighting the need for a multi-pronged approach to address these challenges. While considerable progress has been made over the years, persistent barriers like distance between area of residence of caregivers and immunization centers, vaccine shortages, poor interpersonal relationship between healthcare workers and caregivers and cultural/religious influences persist. Lastly, collaborative efforts among stakeholders and communities remain paramount in ensuring improved routine immunization coverage across the Nigeria’s diverse socio-cultural landscape.

In our study, we assessed the effects of verbenone, the most widely studied bark beetle aggregation inhibitor, on saproxylic beetles of a Mediterranean pine forest in Tuscany. Verbenone pouches were devised in the laboratory and then applied to Ips sexdentatus pheromone traps so that catches could be compared to those of traps with just the bait. The trial was carried out in spring-summer 2023, collecting insect catches every two weeks. A total of 9440 beetles were collected, belonging to 32 different families and 57 species. About 80% of captures were bark beetles, mainly Orthotomicus erosus. Beetle predators accounted for about 17% of the captures, with a total of 12 species. Some of these predator species had never been studied yet in relation to verbenone effects, like other saproxylic beetles recorded in this study. A significant reduction of captures was recorded for some beetles (e.g. I. sexdentatus and O. erosus), for other species no differences emerged, and in some cases captures increased significantly when verbenone was present in the traps (i.e.. Hylurgus ligniperda, Corticeus pini, Aulonium ruficorne). The diversity of caught saproxylic beetles increased significantly in verbenone traps, highlighting possible implications of the use of verbenone when managing bark beetle outbreaks.

A phase 1-2, prospective, multicenter, randomized, open-label clinical trial (Code RPCEC00000382, https://rpcec.sld.cu/trials/RPCEC00000382-En/), with parallel groups, involving 1161 participants was designed to assess safety and immunogenicity of two Cuban COVID-19 vaccines (Mambisa and Abdala) in boosting COVID-19 immunity of convalescent adults after receiving one dose of either vaccine. The main safety outcome was severe vaccination adverse events occurring in <5% of vaccinees. Main immunogenicity success endpoints were ≥4-fold anti-RBD IgG seroconversion or ≥20% increase in ACE2-RBD inhibitory antibodies in >55% of vaccinees in Phase 1 and >70% in Phase 2. Neutralizing antibody titers against SARS-CoV-2 variants were evaluated. Both vaccines were safe; no deaths or severe adverse events occurred. Mild intensity adverse events were the most frequent (>73%); headache predominated for both vaccines. Phase 1 responders were 83.3% (p = 0.0018) for Abdala. Mambisa showed similar results. Phase 2 responders were 88.6% for Abdala (p <0.0001) and 74.2% for Mambisa (p = 0.0412). In both phases, anti-RBD IgG titers, inhibition percentages and neutralizing antibody titers increased significantly after the booster dose. Both vaccines were safe and their immunogenicity surpassed the study endpoints.

In Mexico there is a deficit in the production of pine resin, because it depends on natural forests. Therefore, it is necessary to select provenances and phenotypes of potential species such as P. oocarpa. The objective was to determine the difference between provenances and the variation of resin components and quality, as well as the effect of geographic and climatic factors. Resin from five provenances was collected from southern Mexico. The percentage of rosin, turpentine and water was obtained, as well as the acidity and saponification index. P. oocarpa resin had 80.94 % rosin, 7.7 % turpentine and 11.49 % water. The saponification and acidity index was 125.47 and 117.49 mg KOH.g_1, respectively. All variables showed differences (p≤ 0.0001) between provenances. The provenance contributed between 6.44 and 11.71 % to the total variance, the error contributed between 88.29 and 93.56 %. Geographic and climatic variables only had an effect on the percentage of turpentine; the correlation was negative with altitude and longitude, but positive with temperature and precipitation. The results allow defining seed collection sites for resin plantations and orienting the selection for a P. oocarpa improvement program.

Clinical trials, by contributing to the development of diagnostics and to the search for modern, more effective, and safer therapies, have become one of the most important elements of the healthcare system. The aim of this study was to assess Poles' knowledge and beliefs about clinical trials. Methods: The survey was conducted among Poles aged 18 and over with the help of external company, Ariadna, which is an independent research panel. The questionnaire contained 22 questions, of which 13 questions concerned beliefs and attitudes towards clinical trials. Results: One thousand and seventy-nine participants took part in the study (N = 1079). The mean age of respondents was 44.96 years (SD = 16.30). Slightly more women (N = 568, 52.6%) than men (N = 511, 47.4%) took part in the study. Among the respondents, 86.5% (N = 933) were aware of clinical trials. The main sources of information about clinical trials were the media (53.8%) including the Internet (N= 355, 32.9%), TV (N = 175, 16.2%), press (N = 30, 2.8%) and radio (N = 21, 1.9%). 43.2% (N = 466) of respondents reported little knowledge of clinical trials, while more than three quarters (N = 805, 75.2%) said they would like to learn more about clinical trials. Most respondents (N = 879, 81.4%) agreed with the statement that participation in a clinical trial is completely voluntary, and more than half (N = 580, 53.7%) agreed with the statement that hospitals participating in clinical trials provide better healthcare. The statement that the results of clinical trials are made available to the public was disagreed with by 37.2% (N = 402) of participants. Only 30.3% (N = 327) of participants agreed that clinical trials should be conducted with children. Conclusions: Poles rate their knowledge of clinical trials as low and would like to learn more. To reach the largest possible group of Polish patients, parallel educational activities on multiple levels may have the best effect. Poles' knowledge of clinical trials is mainly based on commercial sources. Further studies in different groups, i.e., clinical trial patients and investigators, are needed.

Pragmatic trials aim to assess intervention efficacy in usual patient care settings, contrasting with explanatory trials conducted under controlled conditions. In aging research, pragmatic trials are important designs for obtaining real-world evidence in elderly populations, which are often underrepresented in trials. In this review, we discuss statistical considerations from a frequentist approach for the design and analysis of pragmatic trials. When choosing the dependent variable, it is essential to use an outcome that is highly relevant to usual medical care while also providing sufficient statistical power. Besides traditionally used binary outcomes, ordinal outcomes can provide pragmatic answers with gains in statistical power. Cluster randomization requires careful consideration of sample size calculation and analysis methods, especially regarding missing data and outcome variables. Mixed effects models and generalized estimating equations (GEEs) are recommended for analysis to account for center effects, with tools available for sample size estimation. Multi-arm studies pose challenges in sample size calculation, requiring adjustment for design effects and consideration of multiple comparison correction methods. Secondary analyses are common but require caution due to the risk of reduced statistical power and false-discovery rates. Safety data collection methods should balance pragmatism and data quality. Overall, understanding statistical considerations is crucial for designing rigorous pragmatic trials that evaluate interventions in elderly populations under real-world conditions. In conclusion, this review focuses on various statistical topics of interest to those designing a pragmatic clinical trial, with consideration of aspects of relevance in the aging research field.

Non-coding RNAs, specifically microRNAs (miRNAs), exhibit altered expression and contribute significantly to the pathological processes observed in numerous diseases, encompassing various types of human cancers. Recent discoveries regarding miRNAs underscore their crucial roles in tumor pathogenesis and their responses to diverse therapeutic interventions. miRNAs are a subset of non-coding RNAs that regulate the expression of a multitude of genes post-transcriptionally and thus are potential diagnostic, prognostic, and predictive biomarkers and have also emerged as potential therapeutics. Because miRNAs are involved in the post-transcriptional regulation of their target mRNAs via repressing gene expression, defects in the miRNA biogenesis pathway and miRNA expression perturb the expression of a multitude of oncogenic or tumor-suppressive target genes that are involved in the pathogenesis of various cancers. As such, numerous miRNAs have been identified to be downregulated or upregulated in many types of cancers functioning as either oncomiRs or oncosuppressor miRs. Moreover, dysregulation of miRNA biogenesis pathways can also change miRNA expression and function in cancer. Profiling deregulated miRNAs in many cancer types has been shown to correlate with disease diagnosis, indicate optimal treatment options, and predict response to a specific therapy. Specific miRNA signatures can track all stages of disease including many cancer types and hold potential as biomarkers and therapeutic targets as well as therapeutics as miRNA mimics and inhibitors (antagomirs). As such, identifying specific miRNAs and mRNAs they regulate in many types of cancer along with downstream pathways can be used as potential therapeutic targets. Because a single miRNA can regulate a pool of targets involved in similar cellular processes and pathways, thereby amplifying the cellular response, this potentially makes miRNAs powerful therapeutics to restore cell functions that are altered as part of a disease phenotype. However, because a single miRNA regulates multiple gene expressions their cellular effects are numerous leading to potential off-target effects. Besides their intended targeting issues, there is a need to reduce the immunogenic reactions and determine the minimal dosing to achieve the desired effect while minimizing side effects. As such, a careful risk evaluation of miRNA therapeutics is needed to minimize off-target effects and to avoid overdosing of miRNA drugs. Furthermore, a limited understanding and validation of the specific roles of miRNAs limits their clinical application. In addition, there are many challenges concerning the delivery, sensitivity, specificity, toxicity, and applicability of the potential utility of miRNAs as therapeutic targets or therapeutics. Thus, future work will warrant if miRNAs can be used as cancer biomarkers as well as therapeutics for clinical application.

The aim of the present study was to assess the efficacy of All Cosmos Industries (ACI) bio-organic and bio-chemical fertilizers and ACI N-Fixer (N-Bio Booster) on the paddy yields based on the field trial plots at Langkat, Medan, Indonesia. This application of ACI bio-organic fertilizer (NPK 5/5/5) and ACI bio-chemical (NPK 15/15/15) fertilizer and ACI N-Fixer tests were conducted at the paddy farm at Langkat from May-October 2018. This study employed a factorial randomized complete block design which consisted of two factors, namely: Factor I with four types of fertilizers while Factor II consisted of two paddy varieties (Inpari 30 and Inpari 32). Overall, the filled grains in the ACI treatments are significantly (P< 0.05) higher than those in the control treatments that used Normal Chemical Compound NPK. Overall, total weight per meter² (368-617g) in ACI treatments are also significantly (P< 0.05) higher than those (319-371g) in the control treatments. At harvesting time at 105 days after transplanting, significantly higher (P< 0.05) colony counts (13-15 x 10⁶ CFU/mL) (for ACI treatments), than those (8 x 10⁶ CFU/mL) in the controls positively indicated higher total yields of paddy grains per hectare. It was found that the application of ACI bio-organic and bio-chemical fertilizers and ACI N-Fixer can improve paddy yields of the two rice varieties, between 16.4-38.2% (up to 5.75 MT/ha), in the field trial plots at Langkat. These commercial fertilizers play an imperative role in refining the soil fertility and thereby can increase the yield of rice production. Therefore, it is highly recommended that ACI bio-organic and ACI bio-chemical fertilizers and ACI N-Fixer (N-Bio Booster) can be employed to increase the paddy yield in this region.

Amidst worsening climate change, drought stress imperils global agriculture, jeopardizing crop yields and food security, necessitating urgent exploration of sustainable methods like biopriming, harnessing beneficial microorganisms to bolster plant resilience. Recent research has revealed diverse biological compounds with versatile applications produced by Schizophyllum commune, rendering this fungus as a promising contender for biopriming applications. For the first time this study aimed to investigate,the potential of S. commune exo- (EPSH) and intra-PSH (IPSH), isolated from two strains: Italian (ITA) and Serbian (SRB) under submerged cultivation, in enhancing the resilience of Pisum sativum L. seeds through biopriming technique. Testing of seed quality of bioprimed, hydroprimed, and unprimed seeds was done using a germination test, under optimal and drought conditions. In optimal conditions, the IPSH SRB increased germination energy by 5.50% compared to the control, while the highest percentage of germination (94.70%) was shown after biopriming with PSH isolated from the ITA strain. Additionally, all assessed treatments resulted in a boost in seedling growth and biomass accumulation, where the ITA strain demonstrated greater effectiveness in optimal conditions, whereas the SRB strain showed superiority in drought conditions. The drought tolerance indices increased significantly in response to all examined treatments during the drought, with EPSH ITA (23.00%) and EPSH SRB (24.00%) demonstrating the greatest effects. Results demonstrate a significant positive influence of fungal PSH, indicating their potential as biopriming agents and offers insights into novel strategies for agricultural resilience in the face of changing environmental conditions.

Lipids have not traditionally been considered likely candidates for catalyzing reactions in biological systems. However, there is significant evidence that aggregates of amphiphilic compounds are capable of catalyzing reactions in synthetic organic chemistry. Here we demonstrate the potential for the hydrophobic region of a lipid bilayer to provide an environment suitable for catalysis by means of a lipozyme, or lipid aggregate capable of speeding up a chemical reaction. By bringing organic molecules into the non-polar or hydrophobic region of a lipid bilayer, reactions can be catalyzed by collections of small, nonpolar or amphiphilic molecules. We demonstrate this concept by the ester hydrolysis of calcein-AM to produce a fluorescent product, which is a widely used assay for esterase activity in cells. The reaction was first carried out in a two phase octanol-water system with the organic phase containing the cationic amphiphiles cetyltrimethylammonium bromide (CTAB) or octadecylamine. The octanol was then replaced with DOPC added to the water in the form of vesicles, where the reaction was also found to be carried out. The reaction was monitored using quantitative fluorescence which revealed catalytic turnover numbers on a scale of 10−4s−1 for each system, which is comparable to some slow enzymes. The reaction product was characterized by 1H-NMR measurements which were consistent with ester hydrolysis. The implications of thinking about lipid aggregates as catalytic entities are discussed in the context of biochemistry, pharmacology and synthetic biology.

This article describes rationales and limitations for making inferences based on data from randomized controlled trials (RCTs). We argue that obtaining a representative random sample from a patient population is impossible for a clinical trial because patients are accrued sequentially over time and thus comprise a convenience sample, subject only to protocol entry criteria. Consequently, the trial’s sample is unlikely to represent a definable patient population. We use causal diagrams to illustrate the difference between random allocation of interventions within a clinical trial sample and true simple or stratified random sampling, as done in surveys. We argue that group-specific statistics, such as a median survival time estimate for a treatment arm in an RCT, have limited meaning as estimates of larger patient population parameters. In contrast, random allocation between interventions facilitates comparative causal inferences about between-treatment effects, such as hazard ratios or differences between probabilities of response. Comparative inferences also require the assumption of transportability from a clinical trial’s convenience sample to a targeted patient population. We focus on the consequences and limitations of randomization procedures in order to clarify the distinctions between pairs of complementary concepts of fundamental importance to data science and RCT interpretation. These include internal and external validity, generalizability and transportability, uncertainty and variability, representativeness and inclusiveness, blocking and stratification, relevance and robustness, forward and reverse causal inference, intention to treat and per protocol analyses, and potential outcomes and counterfactuals.

Background: Despite advances in the treatment of hepatocellular carcinoma (HCC) over the last few decades, treatment opportunities for patients with HCC remain limited. HCC is the most common form of liver cancer, accounting for approximately 90% of all cases worldwide. Moreover, apart from the current pharmacological interventions, hepatic resection and liver transplantation are the mainstay curative approaches for patients with HCC. Methods: This systematic review included phase I, II, III, and IV clinical trials (CTs) and randomized controlled trials (RCTs) on current treatments for patients with HCC in an Asian population (2013–2023). A total of 427 articles were screened, and 184 non-duplicate publications were identified. After screening titles and abstracts, 96 publications were excluded, and another 28 were excluded after full-text screening. The remaining 60 eligible RCTs/CTs were finally included. Results: Sixty clinical trials fulfilled our inclusion criteria and screened 36 drugs as monotherapy or combination therapy for HCC. Most studies used sorafenib alone or in combination with any of the treatment regimens. Lenvatinib or atezolizumab with bevacizumab was used for HCC after initial sorafenib treatment. Eighteen studies compared the efficacy of sorafenib with that of other drugs, including lenvatinib, cabozantinib, tepotinib, tigatuzumab, linifanib, erlotinib, resminostat, brivanib, tislelizumab, selumetinib, and refametinib. Conclusion: This study provides comprehensive insights into effective treatment interventions for HCC in Asian populations. The overall assessment indicated that sorafenib alone or in combination with atezolizumab and bevacizumab has been the first treatment choice in the past decade to achieve better outcomes in patients with HCC in an Asian population

Lifestyle interventions can prevent type 2 diabetes (T2DM). However, some in-dividuals do not experience anticipated improvements despite weight loss. Bi-omarkers to identify such individuals at early stages are lacking. IGF-1 and IGFBP-1 were shown to predict T2DM onset in prediabetes. We assessed if these markers also predict the success of lifestyle interventions, thereby possibly guid-ing personalized strategies. We analyzed fasting serum levels of IGF-1, IGFBP-1 and IGFBP-2 in relation to changes in metabolic and anthropometric parameters, including intrahepatic li-pids (IHL) and visceral adipose tissue (VAT) volume measured by MRI, in 345 high-risk prediabetic participants (54% female; aged 36-80 years). Participants were enrolled in three randomized dietary intervention trials and assessed both at baseline and one year post-intervention. Statistical analyses were performed using IBM SPSS Statistics (version 28), significance set at p

African trypanosomes are an early branch in eukaryotic evolution and developed a unique endomembrane system as an adaptation to their parasitic life style. The key virulence mechanism of many pathogens is successful immune evasion to enable survival within the host, which is a feature requiring both genetic events and membrane transport in African trypanosomes. Intracellular trafficking not only plays a role in immune evasion, but also in homeostasis of intracellular and extracellular compartments and interactions with the environment. Significantly, historical and recent work has unravelled some of the connections between these processes and highlighted how immune evasion mechanisms associated with adaptations in membrane trafficking may have, paradoxically, provided specific sensitivity to drugs. Here we explore these advances in understanding the membrane composition of the trypanosome plasma membrane and organelles and provide a perspective for how transport could be exploited for therapeutic purpose.

Micro plasma devices (MPD) with power gains are of interest in applications involving operations in the presence of ionizing radiations, in propulsion, in control, amplification of high power electromagnetic waves, and in metamaterials for energy management. Here we review and discuss MPDs with an emphasis on new architectures that have evolved during the past 7 years. Devices with programmable impact ionization rates and programmable boundaries are developed to control the plasma ignition voltage and current to achieve power gain. Plasma devices with 1-10 μm gaps are shown to operate in the sub-Paschen regime in atmospheric pressures where ion-assisted field emission results in a breakdown voltage that linearly depends on the gap distance in contrast to the exponential dependence dictated by the Paschen curve. Small gap devices offer higher operation frequencies at low operation voltages with applications in metamaterial skins for energy management and in harsh environment inside nuclear reactors and in space. In addition to analog plasma devices, logic gates, digital circuits, and distributed amplifiers are also discussed.

In order to harness the potential of mobile technologies to enhance the quality of clinical research, it is critical to first understand how to engage patients and research sites when planning and conducting mobile clinical trials. The Clinical Trials Transformation Initiative has developed the first comprehensive, evidence-based set of recommendations for incorporating patient and site perspectives in mobile clinical trials, which can aid in engaging stakeholders, addressing site challenges, and maximizing value for participants.

Railway has been used as one of the most crucial means of transportation in public mobility and economic development. For efficiently operating railways, the electrification system in railway infrastructure, which supplies electric power to trains, is essential facilities for stable train operation. Due to its important role, the electrification system needs to be rigorously and regularly inspected and managed. This paper presents a supervised learning method to classify Mobile Laser Scanning (MLS) data into ten target classes representing overhead wires, movable brackets and poles, which are recognized key objects in the electrification system. In general, the layout of railway electrification system shows a strong regularity of spatial relations among object classes. The proposed classifier is developed based on Conditional Random Field (CRF), which characterizes not only labeling homogeneity at short range, but also the layout compatibility between different object classes at long range in the probabilistic graphical model. This multi-range CRF model consists of a unary term and three pairwise contextual terms. In order to gain computational efficiency, MLS point clouds is converted into a set of line segments where the labeling process is applied. Support Vector Machine (SVM) is used as a local classifier considering only node features for producing the unary potentials of CRF model. As the short-range pairwise contextual term, Potts model is applied to enforce a local smoothness in short-range graph. While, long-range pairwise potentials are designed to enhance spatial regularities of both horizontal and vertical layouts among railway objects. We formulate two long-range pairwise potentials as the log posterior probability obtained by Naïve Bayes classifier. The directional layout compatibilities are characterized in probability look-up tables which represent co-occurrence rate of spatial relations in horizontal and vertical directions. The likelihood function is formulated by multivariate Gaussian distributions. In the proposed multi-range CRF model, the weight parameters to balance four sub-terms are estimated by applying the Stochastic Gradient Descent (SGD). The results show that the proposed multi-range CRF can effectively classify detailed railway elements, representing the average recall of 97.66% and the average precision of 97.07% for all classes.

In this project, four of fibers Bragg gratings were fabricated by injecting different volumes of liquids (star line Glass Mechanix optical adhesive material, olive oil diluted with ethanol) into the hollow core fiber. The amplitude splitting interferometric technique with a high resolution specially designed translation stage was used for the fabrication process. The fabrication was done using ultraviolet laser operated at wavelength 405nm. The fabricated Bragg length of the four fibers is equal to 3.8 cm. The results presented fiber Bragg grating (FBG) with successful fabrication at 653.3 nm Bragg reflected wavelength.

As the number of end-of-life vehicles continues to grow, the field of separation technology for broken copper and aluminium parts of end-of-life vehicles has emerged as a significant area of research. As a key technology for the separation of non-magnetic non-ferrous metals, such as copper and aluminium, eddy current separation can achieve efficient separation of non-magnetic non-ferrous metals according to their differing conductivity and density. Nevertheless, further research is required in the separation of large-scale broken copper and aluminium parts of end-of-life vehicles. This paper presents a novel magnetic roller model comprising circumferential and axial periodic arrangements of permanent magnets. A single permanent magnet was constructed as an equivalent current model, and the magnetic scalar potential equations were solved using simulation tools. This allowed the distribution of the magnetic field outside the magnetic roller to be studied. The results demonstrate that the novel permanent magnet array magnetic roller can enhance the magnetic field intensity and action distance of the external magnetic field, which is more conducive to the separation of large-scale broken copper and aluminium parts of scrap cars. The findings of this research provide a theoretical foundation for the separation of scrap car broken copper and aluminium parts.

Conventional fertilization practices can lead to many ecological problems, such as nutrient imbalance, soil acidity, and reduced soil fertility in natural rubber plantations. To address these challenges, a field investigation was strategically carried out to substitute inorganic fertilizer with organic fertilizers consisted of six treatments, i.e., no fertilization (CK), inorganic fertilizer (NPK), 25 % replacement of inorganic through organic (25%M), 50 % replacement of inorganic through organic (50%M), 75 % replacement of inorganic through organic (75%M), and 100% organic fertilizer (100%M). The soil physicochemical properties (SOC, TN, AN, C:N, pH, NH4+-N, and NO3--N) and carbon and nitrogen converting enzymes (BG, NAG, and LAP) were all determined. The partial substitution of inorganic fertilizers with organic fertilizers (i.e., 75%M at surface soil layer) showed higher SOC (14.52 g.kg-1), TN (1.06 g.kg-1), AN (20.07 mg.kg-1), C:N (14.63), NH4+-N (10.63 mgkg-1), and NO3--N(11.06 mg.kg-1) than NPK and CK. Such increase in physicochemical properties in partial replacement of inorganic with organic fertilizers plots resulted from higher carbon and nitrogen enzymes activities (BG (143.17 nmol.g-1.h-1), NAG (153.96 nmol.g-1.h-1), and LAP (153.48 nmol.g-1.h-1)) compared to NPK and CK, and further the person correlation and RDA analysis confirmed a significant positive correlation between SOC, AN, and soil enzymes. This study presents a new strategy for assessing the impact of partially replacing inorganic fertilizers with organic fertilizers in rubber plantations, mainly by modifying the soil nutrient composition in tropical regions.

Minirhizotron tubes were installed to monitor root growth dynamics of mature Shiraz grapevines in a rootstock trial established in the hot climate Riverina region of New South Wales, Australia. The vertical root distribution and seasonal root growth dynamics of Shiraz on own-roots and Shiraz grafted on the rootstocks Ramsey, 140 Ruggeri and Schwarzmann was studied for five seasons across a seven-year period to a depth of 60 cm. New root production was significantly influenced by genotype, soil depth, season, growth stage and year. Soil moisture and soil tem-perature were monitored at 10, 30 and 60 cm in the last two seasons. Soil moisture at 30 cm and soil temperature at all three depths were significant predictors of root growth. New root numbers were significantly higher in 140 Ruggeri than the other rootstocks. To the depth studied, 140 Ruggeri roots were evenly distributed from the topsoil down, whereas the majority of roots of Schwarzmann and Shiraz were located at intermediate depths in the 10-40 cm ad 20-40 cm zones respectively, while Ramsey roots were found at 20 cm or below. Depending on genotype, root growth occurred across several phenological stages but tended to peak at flowering. In some years we observed root growth in early and late winter at rates exceeding that of autumn, and this was associated with warmer temperatures during this period. Overall, seasonal rooting dynamics were responsive to abiotic factors but dominated by genotype.

A low cost, scalable and robust process has been proposed as innovative method for coating solar mirrors with a self-cleaning, transparent in the full solar range and versatile material based on auxetic aluminium nitrides, previously obtained on the laboratory scale. This work presents the scaling-up of fabrication process from laboratory to prototypal scale and pre-liminary results of outdoor self-cleaning solar mirror prototypes testing in the demonstrative CSP plant ENEASHIP located in Casaccia (Rome) ENEA research centre. Prototypes 50x40cm have shown stability in external conditions: no degradation occurs during the test campaign. Their washing restores the initial reflectance affected by soiling and the self-cleaning performance allows the utilization of a reduced quantity of water for cleaning operations with respect to uncoated glass of back surface mirrors. A similar self-cleaning AlN coating could be utilized on other solar components affected by soiling, such as glass envelopes of heat collecting elements, PV panels and everywhere are required self-cleaning performance combined to optical ones.

Meat serves as a vital component of the human diet, offering a rich source of protein and essential trace elements. China stands as both a significant producer and consumer of meat on a global scale, leading the world in terms of total meat production and consumption. As the standard of living within the country continues to rise, there is a growing emphasis on the nutritional value and safety of meat consumption. The tenderness of meat is a critical factor influencing its overall quality. Traditionally, tenderness has been assessed through shear force testing, a method that is inherently destructive, inefficient, and results in considerable sample wastage. In light of these drawbacks, non-destructive testing techniques have emerged as a preferred alternative, promising greater accuracy, efficiency, and convenience without compromising the integrity of the samples. This paper delves into the application of five advanced non-destructive testing technologies in the realm of meat tenderness assessment. These include near-infrared spectroscopy, hyperspectral imaging, Raman spectroscopy, airflow optical fusion detection, and nuclear magnetic resonance detection. Each technology is scrutinized for its respective strengths and limitations, providing a comprehensive overview of their current utility and potential for future development. Moreover, the integration of these techniques with the latest advancements in artificial intelligence (AI) technology is explored. The fusion of AI with non-destructive testing offers a promising avenue for the development of more sophisticated, rapid, and intelligent systems for meat tenderness evaluation. This integration is anticipated to significantly enhance the efficiency and accuracy of quality assessment in the meat industry, ensuring a higher standard of safety and nutritional value for consumers. The paper concludes with a set of technical recommendations aimed at guiding the future direction of non-destructive, AI-enhanced meat tenderness detection, thereby contributing to the ongoing improvement of the meat industry in China and beyond.

We develop an action principle for producing a single fluid, two-constituent system with dissipation in general relativity. The two constituents in the model are particles and entropy. The particle flux creation rate is taken to be zero, while the entropy creation rate is non-zero. Building on previous work, it is demonstrated that a new term (the proper time derivative of the matter space ``metric'') is required in the Lagrangian in order to produce terms typically associated with bulk and shear viscosity. Equations of motion, entropy creation rate, and energy-momentum-stress tensor are derived. Using an Onsager approach of identifying thermodynamic ``forces'' and ``fluxes'' a model is produced which delivers the same entropy creation rate as the standard, relativistic Navier-Stokes equations. This result is then contrasted with a model generated in the spirit of the action principle, which takes as its starting point a specific Lagrangian and then produces the equations of motion, entropy creation rate, and energy-momentum-stress tensor. Unlike the equations derived from Onsager reasoning, where the analogs of the bulk and shear viscosity coefficients are prescribed ``externally'', we find that the form of the coefficients in the second example are a direct result of the specified Lagrangian. Furthermore, the coefficients are shown to satisfy evolution equations along the fluid worldline; also a product of the specific Lagrangian.

The growing interest in benchtop NMR systems is visible in a vast number of applications in science and industry. Low-field nuclear magnetic resonance (LF-NMR) became an instant in technologies that productions are dependent on the reliable structure identification, grade and purity control, chemical process inspection or reaction monitoring. Beyond the benefits of being cost-, space-, maintenance- and user friendly, insufficient sensitivity and low signal resolution are the main drawbacks, due to which the low-field NMR (LF-NMR) in the fields of organic chemistry and synthesis remains limited to solely academic teaching purposes. Herein, we discuss the possibilities of LF-NMR for the needs of organic chemistry and synthesis on a set of compounds 1-4 achieved as the products of student’s laboratory course and organic derivatives 5-8 that are from our research interests. Chemical structure determination of all compounds 1-8 presented herein was performed using the benchtop-type NMR instrument operating at 60 MHz (Pulsar Oxford Ltd.). Structure of novel compounds 5-7 prepared under the aims of our research was characterized by combined 1H/19LF-NMR and compared with an appropriate high-field NMR data from Bruker Ascend Instrument (400 MHz). Finally, possibilities of the low-field NMR as an analytical tool for the research purposes in the fields of organic chemistry and synthesis are documented on a set of 1H and 2D 1H-1H COSY for azomethine 8.

Western countries are experiencing an increasing aging population, resulting in heightened disability and mobility issues. This trend is expected to escalate in the coming decades. Therefore, ensuring adequate accessibility in collective residential housing –where individuals spend much of their daily lives– is of paramount importance. This paper presents a case study focused on the accessibility of building entrances in collective residential housing in Southeast Spain, specifically in the Region of Murcia. In this region, 9.8% of the population has disabilities, and 15.75% were over 64 years old in 2020. The study began by compiling the relevant national and regional accessibility regulations for existing buildings. Subsequently, extensive fieldwork was conducted, analyzing 150 collective residential housing buildings. Based on this analysis, a set of recommendations to enhance accessibility was formulated for buildings not complying with the regulations. The results are presented and discussed in detail. The most frequent recommendation was the construction of accessible ramps, identified as the primary solution in over 40% of cases, either alone or in conjunction with other measures. In 54% of the cases, multiple interventions were necessary to achieve effective accessibility adaptation. The findings of this study could inform the development of public policies aimed at improving accessibility conditions in urban areas.

To address the issue of reduced orbit estimation accuracy resulting from discrepancies between in-orbit measured geomagnetic field values and IGRF model values in autonomous orbit estimation of microsatellites based on geomagnetic field measurements, this study introduces an adaptive cubature H-infinity filtering algorithm. Firstly, it presents the low-altitude orbital dynamics model and geomagnetic field measurement model for microsatellites. Subsequently, within the adaptive cubature H-infinity filtering algorithm, a spherical simplex rule and a second-order Gaussian-Legendre quadrature criterion are employed to compute the spherical surface integral and radial integral. Additionally, a spherical simplex-radial quadrature rule is proposed to enhance the approximation accuracy of nonlinear Gaussian weighted integrals. Furthermore, by integrating extended H-infinity filtering based on game theory with the cubature quadrature rule, an inverse proportional relationship between constraint level and filtering innovation is established. This allows for adaptive adjustment of the constraint level to enhance robustness against model errors. Finally, through semi-physical simulation experiments, it is demonstrated that compared with traditional algorithms, the proposed algorithm improves autonomous orbit estimation position accuracy of microsatellites by 7.49%, while also enhancing velocity accuracy by 3.1%, thus validating its effectiveness.

Silver ion (Ag+) are recognized for their potent antibacterial properties; however, their utilization in food preservation is restricted by factors such as inadequate stability, a transient antibacterial impact, and the potential for human absorption. Hydrogel-based antibacterial agents are capable of exerting their antibacterial effects by establishing appropriate microenvironments, which facilitate the efficient delivery of antimicrobial molecules to the contaminated regions of food. In previous studies, we observed that chitosan (CS) and silver nitrate (AgNO3) were able to reduce Ag+ to silver nanoparticles (AgNPs) with enhanced antibacterial properties. This not only significantly extended the stability of the antibacterial agent but also demonstrated exceptional inhibitory capabilities against pathogenic bacteria, including common grape contaminants such as P. expansum, A. niger, and B. cinerea. Utilizing ultrasound-induced complexation technology, this study has successfully synthesized a chitosan-silver (CS-AgNPs) hydrogel. The efficacy of this hydrogel against the pathogenic fungus responsible for jujube black spot disease has been thoroughly investigated. The morphology structures of CS-AgNPs hydrogels were characterized by TEM, FTIR and UV-vis. The results indicated that AgNPs ranging from 80 to 110 nm were uniformly dispersed within the gel matrix and remained stable for extended periods at room temperature. In vitro antibacterial assays and fractional inhibitory concentration index (FICI) studies revealed that the pronounced antibacterial efficacy of the CS-AgNPs hydrogel was primarily attributed to the additive antibacterial effect of CS and AgNPs. These insights underscore the significant potential of CS-AgNPs hydrogels in combating fungal diseases of jujube, offering innovative strategies and materials for the management of agricultural pathogens.

The state detection of power cable is very important to ensure the reliability of power supply. Traditional sensors are mostly based on electric field detection, the operation is complex, and its efficiency needs to be improved. This paper optimizes the design and development of the magnetic field detection sensor for AC power cables. Firstly, through the establishment of the magnetic field sensor model, it is determined that permalloy is the material of the magnetic core, the optimal aspect ratio of the magnetic core is 20, and the ratio of coil length to core length is 0.3. Secondly, the coil simulation model is established, and it is determined that the optimal number of turns of the coil is 11000 turns, the diameter of the enamelled copper wire is 0.08mm, and the equivalent magnetic field noise of the sensor is 0.06pT. Finally, the amplifying circuit based on negative magnetic flux feedback is designed and the sensor is assembled, and the experimental circuit is built for sensitivity test. the results show that the sensitivity of the magnetic field sensor is 327.6mV/μT. The sensor designed in this paper has the advantages of small size, high sensitivity, easy to carry and high reliability.

Introduction: Cervical cancer is the fourth most common cancer in women globally and the most common cancer in Tanzania, resulting in about 9772 new cases and 6695 deaths each year. Research has shown an association between low levels of risk perception and knowledge of the prevention, risks, signs, etiology, and treatment of cervical cancer and low screening uptake, as contributing to high rates of cervical cancer-related mortality. However, there is scant literature on the perspectives of a wider group of stakeholders (e.g., policymakers, healthcare providers (HCPs), and women at risk), especially those living in rural and semi-rural settings. Methods: We adapted Risso-Gill and colleagues’ framework for a Health Systems Appraisal (HSA), to identify HCPs' perspective of the extent to which health system requirements for effective cervical cancer screening, prevention, and control are in place in Tanzania. We adapted interview topic guides for cervical cancer screening using the HSA framework approach. Study participants (69 in total) were interviewed between 2014-2018 –participants included key stakeholders, HCPs, and women at risk for cervical cancer. The data was analyzed using reflexive thematic analysis methodology. Results: Seven themes emerged from our analysis of semi-structured interviews and focus groups: 1) knowledge of cervical cancer risk and the role of screening and preventive care/services (e.g., prevention, risks, signs, etiology, and treatment), 2) training and knowledge of HCPs, 3) knowledge of cervical cancer screening among women at risk, 4) beliefs about cervical cancer screening, 5) role of traditional medicine, 6) risk factors, and 7) symptoms and signs. Conclusion: It is evident that there is a low level of knowledge of cervical cancer risk and the role of screening and preventive services among stakeholders, HCPs, and women living in rural and semi-rural locations in Tanzania. There is a critical need to implement more initiatives and programs to increase the uptake of screening and related services and allow women to make more informed decisions on their health.

Delivering effective messages is critical to creating a more sustainable and resilient culture. The explosion of social media has enhanced information access but has often reinforced and polar-ized pre-existing viewpoints and norms. In contrast, digital signs are an “in your face in your space” technology that has the potential to deliver common content to a diverse local audience. Environmental Dashboard (ED) is a communications platform and set of content applications that combines information on current environmental conditions, real-time resource consumption, positive actions being taken by community members, and a community calendar. We conducted a longitudinal study to assess whether ED content delivered via digital signs in public locations would result in desirable psychological changes within a community. Participants completed surveys in six designated signage locations prior to installation (N = 174) and following two years of continuous exposure (N = 133). We observed: increases in pro-environmental social norms among people of color (a demographic emphasized); enhanced awareness of and sense of connection with the local community and ecology; increased self-reported electricity conservation; and increased perception of youth engagement (another demographic emphasized). Changes were mediated by exposure to digital signage. These findings support the hypothesis that content delivered through digital signs can strengthen pro-environmental and pro-social culture within communities.

As of the end of 2022, despite the disruptions caused by the COVID-19 pandemic, the global HIV epidemic persists, with 39 million individuals living with the virus and 1.3 million new infections reported in that year. Opportunistic infections associated with AIDS claimed the lives of over 630,000 people in 2022, contributing to a cumulative death toll exceeding 40.4 million since the disease's emergence in 1981. Although advances in HIV diagnosis and antiretroviral therapy have transformed the disease into a manageable chronic condition, issues like drug resistance, low compliance, and high treatment costs persist. Until a vaccine becomes available, a comprehensive approach involving prevention and therapy is essential, particularly for high-risk populations. Research shows that prevention strategies are more cost-effective than treatment. The development of antiretroviral drugs has also spurred the creation of antivirals for other infections. The emergence of COVID-19 vaccines has opened new avenues for HIV vaccine development, as lessons from vaccine platform technologies like mRNA, viral vectors, and protein subunits can be applied to HIV. This review explores the most promising prophylactic and therapeutic HIV vaccine trials, emphasizing the need for a multi-pronged approach combining vaccines with non-vaccine strategies. Though significant progress is anticipated, the road to a viable HIV vaccine remains long, especially for high-risk populations, such as medical workers, blood transfusion recipients, and drug users. The combinatorial approach, capitalizing on various aspects of immunity, may hold the key to defeating HIV in the future.

In order to reduce the silique shattering loss of rapeseed mechanical harvesting process, based on the state of force on the silique during rapeseed harvesting reel branch, Ningza 1810, Zhenyou 8 and Fengyou 306 were used as research objects, and the experimental research on the factors affecting rapeseed siliques shattering was carried out using the swing impact method. The experimental analysis showed that: rapeseed varieties, silique moisture content, silique growth position, collision material, impact speed, force position and other factors had significant effects on silique shattering. The impact velocity was less than 1.5m·s-1, the difference on the effect of each factor on pod-shattering was not significant, it was not easy to shatter when the moisture content of rapeseed silique was higher. The impact resistance of the front side of rapeseed was 2 to 4 times that of the bonding surface of rapeseed petals, the shattering rate of the top rapeseed silique was twice that of the bottom siliques, when siliques were supported, they were more likely to shatter under external forces than when they were unsupported. The experimental study of the mechanical properties of rapeseed siliques was carried out using the impending fracture method, the experimental analyses showed that the support position and force position of the silique, the loading speed and the growth position of the silique had a significant effect on the mechanical properties of the silique. The maximum cracking force was higher and bending strength was stronger when the body of the silique was supported, which the range of the maximum cracking force were 3.05N to 4.16N, and the bending strength range were 8.48 MPa to 11.57 MPa. The maximum cracking force and bending strength of the silique was stronger when the front side of the silique petal was pressurized than when the bonding surface of the petal was pressurized. Based on Pearson's correlation and grey correlation analysis, the morphological characteristics of rapeseed siliques were ranked in order of their influence on the performance of siliques in terms of the angle between silique and stalk, stalk diameter, petal thickness, beak length, silique thickness, silique width and silique length. This study can be used as a reference for the design and optimization of the rapeseed harvesting reel branch mechanism and the selection of machine harvestable rapeseed varieties.

A nutritional approach could be a promising strategy to prevent or slow the progression of neurodegenerative diseases such as Parkinson’s and Alzheimer’s disease, since there is no effective therapy for these diseases so far. The beneficial effects of omega-3 fatty acids are now well established by a plethora of studies through their involvement in multiple biochemical functions, including synthesis of antinflammatory mediators, cell membrane fluidity, intracellular signalling and gene expression. This systematic review will consider epidemiological studies and clinical trials that assessed the impact of supplementation or dietary intake of omega-3 polyunsaturated fatty acids on neurodegenerative diseases such as Parkinson’s and Alzheimer’s diseases. Indeed, treatment with omega-3 fatty acids, being safe and well tolerated, represent a valuable and biologically plausible tool in the management of neurodegenerative diseases in their early stages.

Clinical trials are research studies performed on people that are aimed at evaluating a medical, surgical, or behavioural intervention. It is a primary way that researchers find out if a new treatment, like a new drug or diet, or medical device is safe and effective in people. In this paper blockchain technology is embedded in a digital twin aiming to improve the quality of clinical trials through the boost of data integrity among the quality-related activities, and to promote participants' safety. First, a blockchain-embedded quality-enabled digital twin is proposed and the interactions among the enablers and peers are highlighted. Then, a prototype of the proposed system is developed, and the data of a pilot trial is used to justify the applicability of the system. The results showed that the proposed system is efficient, and hence it is feasible to adopt into a clinical trial. With the successful development of the proposed system, it is promising to provide effective data integration and knowledge management for improving participant safety.

Cardiovascular diseases (CVDs) remain the leading cause of mortality. Traditional approaches to diagnosing and treating CVDs often involve interpretation, which can lead to errors. The emergence of Artificial Intelligence (AI) and Machine Learning aids the management of CVDs. AI examines amounts of data and identifies patterns offering solutions for disease detection, risk prediction, and patient care. The American Heart Association's 2023 Scientific Sessions (AHA23) showcased studies that highlight AIs potential to revolutionize cardiac healthcare. This article presents a review of these cutting-edge studies exploring how AI is applied in health, the outcomes of these applications, and their implications for clinical practice. The insights gained from this review will contribute to the discussion on AI's role in healthcare and its capacity to enhance outcomes.

Deep underground laboratories offer advantages for conducting high-precision observations of weak geophysical signals, benefitting from a low background noise level. It is both valuable and feasible to enhance strong, noisy ground electromagnetic (EM) field data using synchronously recorded underground EM signals, which typically exhibit a high signal-to-noise ratio. In this study, we propose an EM field reconstruction method employing a Long Short-Term Memory (LSTM) recurrent neural network with referenced deep underground EM observations. Initially, a deep learning model was developed to capture the time-varying features of underground multi-component EM fields using the LSTM recurrent neural network. Subsequently, this model was applied to process synchronously observed strong, noisy data from other conventional observation systems, such as those at surface, to achieve noise suppression through signal reconstructions. Both theoretical analysis and practical observational data suggest that the proposed method effectively suppresses noise and reconstructs clean EM signals. This method is efficient and time-saving, representing an effective approach to fully utilizing the advantages of deep underground observation data. Furthermore, this method could be extended to the processing and analysis of other geophysical data.

The carbonyl iron particles were dispersed in a polychloroprene rubber (CR) matrix under an external magnetic field for practical application as microwave absorption composites film. The film prepared under external magnetic field with a thickness of only 0.54 mm showed least reflection loss of -15.98 dB and the reflection loss value less than -10.0 dB over the frequency range of 11.4~14.8 GHz. In comparison with the microwave absorption properties of calculation by transmission line theory based on the tested relative complex permittivity and permeability and film prepared by general route without external magnetic field, the film made with external magnetic field exhibited more excellent microwave absorption properties, strongly depending on the increment of anisotropy and rearrangement of magnetic particles. The results indicated the composite film made under external magnetic field have excellent microwave absorption properties, which suggest that the composites thin film could be used as a thinner and lighter microwave absorber.

The teaching of mathematics at the Faculty of Military Technology of the University of Defense in the first two years of the five-year Military master’s degree is divided into the teaching of students in four specializations: Military Technologies – Mechanical, Military Technologies – Electrical, Military Geography and Cartography, and Cybersecurity. The article discusses the previous five-year experience in teaching the subjects Mathematics I, Mathematics II, Mathematics III, and Graph theory for the specialization in Cybersecurity, that the author of the paper gained while teaching, as a guarantor of these four subjects. The article provides an overview of the topics that are covered, typical exam assignments, and an evaluation of the results of the semester exams in the five years since the accreditation of the Cybersecurity specialization was granted.

This study aimed to develop a state-of-the-art method for assessing chemical risks. The method combined desk research findings and the authors' practical knowledge to identify the major shortcomings in performing risk assessments at the workplace. Data were collected from nine SMEs across three sectors: agriculture, laboratory research, and conservation and restoration laboratories. The results of the discussions with the workers and on-site observations were used to develop the method to assess chemical risks. The method uses numerical factors to account for the level of conformity and the duration of exposure to support an estimation of the probability of an incident. The developed method was designed to enhance risk assessment practices and tackle common issues encountered by enterprises, including SMEs.

The coronavirus disease 2019 (COVID-19) pandemic has caused considerable global disruption to clinical practice. This article will review the impact that the pandemic has had on oncology clinical trials. It will assess the effect of the COVID-19 situation on the initial presentation and investigation of patients with suspected cancer. It will also discuss the impact of the pandemic on the subsequent management of cancer patients and how clinical trial approval, recruitment and conduct were affected during the pandemic. An intriguing aspect of the pandemic is that clinical trials investigating treatments for COVID-19 and vaccinations against the causative virus, SARS-CoV-2, have been approved and conducted at unprecedented speed. In light of this, this re-view will also discuss the potential that this enhanced regulatory environment could have on the running of oncology clinical trials in the future.

Faced with increasing climate challenges, this pioneering study introduces groundbreaking approaches to ensure the resilience of potato crops in east-central Poland. Our research aimed to develop an innovative, cost-effective system tailored to the diverse local conditions of this region. Conducted between 2018 and 2020, the study analyzed integrated and organic production systems across different soil types and potato varieties. The experiment was conducted using a randomized block design with three replications in two locations. Integrated practices, enhanced by mineral fertilization and chemical protection, notably delayed the onset of late blight by 16 days and extended the critical infection period by 17% compared to their organic counterparts. Remarkably, the integrated systems resulted in a 49% increase in total production and a 52% increase in commercial yields, demonstrating their effectiveness in enhancing crop resilience. Different potato varieties exhibit varied responses to cultivation systems, influencing both yield and disease resistance. Further investigation into these varietal responses can help optimize cultivation practices, leading to improved efficiency and sustainability in potato farming. Location and soil conditions have a significant impact on potato yield and the spread of potato blight. Further research into specific soil properties and the adaptation of varieties to local conditions can contribute to increased productivity and stability in potato production. This study not only paves the way towards sustainable agriculture but also highlights the crucial role of soil diversity in shaping resilient farming practices.

There is currently no unified explanation for the origin of Earth's magnetic field, planetary magnetic fields, stellar magnetic fields, and neutron star magnetic fields, and most importantly, none of these theories have been experimentally verified. This paper is based on a new unified theory of mechanics and its derived applications, which may provide a better explanation for the origin of magnetic fields in celestial bodies and can be experimentally tested to better answer the observed phenomena: (1) the greater the mass of the celestial body, the stronger the magnetic field; (2) the faster the rotation speed of the celestial body, the stronger the magnetic field; (3) the higher the density of the celestial body, the stronger the magnetic field produced.

It is extremely fascinating and astonishing that the gravitational field on the surface of a neutron star is with a relativistic mass density of 2.65*10¹⁶~5.87*10¹⁸kgm^-3 which can be larger than the mass density of the neutron star (~10¹⁷kgm^-3).Therefore, it is the author’s first intuitional imagining that this field could directly convert into mass. In so strong a gravitational field, electron and proton could be produced directly from graviton–photon collision. The gravitational field exists in everywhere in our universe. No vacuum that the region of a space is “empty” does exist. A particle is clearly always being acted on by the gravitational field. The quantum vacuum fluctuation and vacuum polarization need be re-understood with the interaction between photon and gravitational field. Therefore, the gravitational field is naturally one of the foundations of modern physics.

Immune checkpoint inhibitors (ICIs) are a class of drug that produces durable and sustained anti-tumour responses in a wide variety of malignancies. The exponential rise in their use has been mirrored by a rise in immune-related adverse events (irAEs). Knowledge of such toxicities, as well as effective management algorithms for these toxicities, is essential to optimize clinical efficacy and safety. Currently, the guidelines for management of the irAEs are based largely on retrospective studies and case series. In this article, we review the current landscape of clinical trials investigating the management of irAEs with an aim to develop standardized, randomized controlled trial-based management algorithms for ICI-related toxicities.

Despite the recent approval of novel immunotherapies, as immunomodulatory drug, proteasome inhibitors and anti-CD38 monoclonal antibodies, Multiple Myeloma (MM) remains incurable and the acquisition of triple-refractoriness leads to really dismal outcomes, in even earlier lines of therapy. More recently, innovative therapeutic strategies targeting B cell maturation antigen (BCMA), highly expressed on the plasma cell surface, are drawing different future landscapes in terms of effectiveness and outcomes. Belantamab Mafodotin, a first-in-class anti-BCMA antibody drug conjugates, demonstrated good efficacy and safety profile in triple-refractory patients in the phase 2 DREAMM-2 trial and it was approved for the treatment of MM triple-exposed patients with >4 prior lines of therapy. Here, starting from Belantamab Mafodotin clinical trials also exploring combination studies and different schedules in order to improve its efficacy and toxicity, we focused on real life experiences all over the world, which have confirmed clinical trial data and encourage further Belantamab Mafodotin investigations

Photonic sensors are innovative devices that leverage the principles of light-matter interaction to enable precise and efficient detection of various physical parameters. These sensors operate by exploiting the interaction between photons, the fundamental particles of light, and matter. The light propagates through an optical waveguide, and a portion of the electromagnetic field extends beyond the waveguide surface, forming the evanescent field. This evanescent field interacts with the surrounding medium, allowing for highly sensitive detection of changes in the refractive index or properties of nearby substances. The underlying concept involves the modulation of light properties, such as intensity, wavelength, or phase, when it interacts with a target substance or undergoes changes in the surrounding environment. The advancements in photonic sensor technology have paved the way for enhanced sensitivity, selectivity, and miniaturization, making them invaluable tools in diverse industries. The ability to harness light-matter interactions for sensing purposes not only facilitates highly sensitive measurements but also allows for non-intrusive and remote monitoring, contributing to the evolution of smart and connected systems. In this overview, the material platforms and waveguide structures are explored that can make highly sensitive photonic devices applied to gas and biosensing applications.

The aim of this review was to provide an update on the potential of cell therapies to restore or replace damaged and/or lost cells in retinal degenerative and optic nerve diseases, describing the available cell sources and the challenges involved in such treatments when these techniques are applied in real clinical practice. Sources include human fetal retinal stem cells, allogenic cadaveric human cells, adult hippocampal neural stem cells, human CNS stem cells, ciliary pigmented epithelial cells, limbal stem cells, retinal progenitor cells (RPCs), human pluripotent stem cells (PSCs) (including both human embryonic stem cells (ESCs) and human induced pluripotent stem cells (iPSCs)) and mesenchymal stem cells (MSCs). Of these, RPCs, PSCs and MSCs have already entered early-stage clinical trials since they can all differentiate into RPE, photoreceptors or ganglion cells, and have demonstrated safety, while showing some indicators of efficacy. Stem/progenitor cell therapies for retinal diseases still have some drawbacks, such as the inhibition of proliferation and/or differentiation in vitro (with the exception of RPE) and the limited long-term survival and functioning of grafts in vivo. Some other issues remain to be solved concerning the clinical translation of cell-based therapy, including (1) the ability to enrich for specific retinal subtypes; (2) cell survival; (3) cell delivery, which may need to incorporate a scaffold to induce correct cell polarization, which increases the size of the retinotomy in surgery and, therefore, the chance of severe complications; (4) the need to induce retinal detachment to perform the subretinal placement of the transplanted cell; and (5) the evaluation of the risk of tumor formation caused by the undifferentiated stem cells and prolific progenitor cells. Despite these challenges, stem/progenitor cells represent the most promising strategy for retinal and optic nerve disease treatment in the near future, and therapeutics assisted by gene techniques, neuroprotective compounds and artificial devices can be applied to fulfil clinical needs.

It is shown that the relationship between gravity and quantum physics can be described in terms of the symmetry break of space due to elementary constituents, dubbed as “darks”, which constitute a universal energetic background field that extends from the cosmological level down to the nuclear level. It requires (a) the awareness of the polarisable second elementary dipole moment of a recently discovered third Dirac particle type, next to the electron-type and the Majorana-type, and (b) the awareness that Einstein’s Lambda is not a constant of nature, but, instead, a covariant integration constant with a value that depends on the scope of the cosmological system under consideration, such as solar systems and galaxies, eventually showing up as the Cosmological Constant at the level of the universe. The relationship has been made explicit by relating two major gravitational constants quantaties (the gravitational constant and Milgrom’s acceleration constant) with a single nuclear quantity (the rest mass of the pion derived from the Higgs boson value).

Modern medicine adopted four presumptions when it evolved from ancient experienced-based mind-body medicine. To understand its failure in finding cures for chronic diseases, we examined four presumptions, and found that statistical population of health properties does not exist for most research purposes, mathematical models are misused to model intensive properties, synthetic drugs are inherently more dangerous than nature-made medicines under their respective application conditions, and reductionist treatments are inferior and inherently dangerous. We found that clinical trials are valid only for research where treatment effect is much stronger than the total effects of all interfering or co-causal factors or errors introduced by misused mathematical models can be tolerated. In all other situations, clinical trials introduce excessive errors and fail to detect treatment effects, or produce biased, incorrect or wrong results. We further found that chronic diseases are manifestation of small departures in multiple process attributes in distinctive personal biological pathways networks, that modern medicine lacks required accuracy for accurately characterizing chronic diseases, and that reductionist treatments are good at controlling symptoms and safe for short term uses. For all stated reasons, as long as modern medicine continues relying on the flawed presumptions, it can never find predictable cures for chronic diseases. By implication, predictable cures to chronic diseases are adjustments to lifestyle, dietary, emotional, and environmental factors to slowly correct departures in process attributes responsible for chronic diseases.

We asked whether the level of peripheral fatigue would differ when three consecutive exercise trials were completed to task failure, and whether there would be delayed recovery in maximal voluntary contraction (MVC) force, neuromuscular activation and peripheral fatigue following task failure. Ten trained sport students performed three consecutive knee extension isometric trials (T1, T2, T3) to task failure without breaks between trials. T1 and T2 consisted of repeated 5-s contractions followed by 5-s rest. In T1, contractions were performed at a target force at 60% pre-exercise MVC. In T2, all contractions were MVCs, and task failure occurred at 50% MVC. T3 was a sustained MVC performed until force fell below 15% MVC. Evoked force responses to supramaximal electrical femoral nerve stimulation were recorded to assess peripheral fatigue. Electromyography signals were normalized to M-wave amplitude to assess neuromuscular activation. Lower levels of evoked peak forces were observed at T3 compared to T2 and T1. Within 5 s of task failure in T3, MVC force and neuromuscular activation recovered substantially without any recovery in evoked peak force. Neuromuscular activation 5-10 s after T3 was unchanged from pre-exercise values, but evoked peak forces were substantially reduced. These results challenge the existence of a critical peripheral fatigue threshold that reduces neuromuscular activation. Since neuromuscular activation changed independently of any change in evoked peak force, immediate recovery in force production after exercise is due to increased central recruitment and not to peripheral mechanisms.

Utilizing ecological engineering to manage pests by enhancing the biological control function of natural predators through the selection of high-efficiency bank plants and the establishment of bank plant systems within agricultural ecosystems is an optimal strategy. While bank plant systems have found widespread use in greenhouse crop cultivation, their application in rice fields remains limited. This study aimed to assess the efficacy of Leersia sayanuka as a bank plant for controlling planthoppers and to explore the potential of sesame as a complementary plant to enhance the effectiveness of the bank plant system through field trials. The findings revealed that planting a strip of L. sayanuka, at least 50 cm wide and extending over 1 m in length, had a notable impact on planthopper control in paddy fields. Moreover, the incorporation of Sesamum indicum, a nectar plant, into the bank plant system consisting of L. sayanuka, Nilaparvata muiri, and Anagrus nilaparvatae, led to a significant increase in the population of Anagrus spp. in rice fields. This increase was accompanied by a rise in the egg parasitism rate targeting rice planthoppers, resulting in a marked improvement in overall rice planthopper control in paddy fields. Thus, the combined system demonstrated efficiency as an effective bank plant system for managing rice planthoppers.

Aiming at the APF algorithm in the collision-free path planning and LQR algorithm tracking process, there are problems such as unreachable target points, local optimization, low safety coefficient of autonomous lane change collision avoidance tracking control and poor stability, this paper proposes an optimized APF method, which solves the defects of the traditional artificial potential field method by adding the distance adjustment factor, the safety distance protection model and the sub-target virtual potential field, and at the same time generates the autonomous driving car collision-free path. The path tracking control system is designed based on feed-forward control and DLQR controller, in which the vehicle dynamics state space model is used as the basis, the model is linearized and discretized, and the corresponding constraint variables are set to minimize the control command objective cost function under the constraints, and the objective of the DLQR controller.The objective is to accurately determine the steering angle in order to achieve path tracking and eliminate the lateral error between the reference path and the actual path caused by external interference.Finally, the simulink model and CarSim parameter configuration joint simulation platform are built, and different obstacle scenarios and different speeds are selected for collision-free path planning and tracking motion simulation research and analysis, which verifies the accuracy and practicability of the algorithm, and shows more obvious advantages in obstacle avoidance ability, path smoothing degree, and collision avoidance safety stability. The ideas proposed in this paper are expected to be further extended and popularized to actual path planning problems, which has important practical significance and engineering value.

Mpox, formerly known as Monkeypox, is a rare viral disease initially discovered in Africa in 1958. Since its first identification, several outbreaks have occurred in various African nations. Recently, the global community has witnessed a resurgence in the number of Mpox cases reported worldwide, prompting the World Health Organization (WHO) to declare the ongoing multi-country outbreak a public health emergency in July 2022. This study reports on the first cases of Mpox detected in Khartoum State, Sudan, outlining the epidemiology, preparedness, and public health response to this new challenge. A total of 55 suspected cases were identified, with two confirmed cases. The clinical manifestations observed in these cases align with the classic skin rash typical of Mpox, presenting alongside symptoms like fever, headache, and joint pain. The findings underscore the need for heightened surveillance, early detection, and timely intervention to prevent the domestic spread of Mpox and its potential impact on public health. Continued global efforts are needed to support effective screening, diagnostic, and control measures, ultimately enhancing preparedness and response in the face of this emerging disease.

With the progression of AI, embedding advanced AI technologies into small robotics and mobile devices has become essential, driving research towards lightweighting AI models. Our study enhances the EPINET depth estimation model for light field images, aiming for compactness and faster inference while preserving accuracy. We conducted two-step experiments aimed at enhancing inference efficiency: Initially, by adjusting input streams and convolution layers, we simplified the CNN model, achieving faster inference times at the cost of reduced accuracy. To address this reduction in accuracy, we then applied knowledge distillation, allowing the simplified model to learn from the original model’s more complex patterns. In our quantitative experiments using two error metrics, MSE (Mean Squared Error) and BadPix, we identified optimal knowledge positions and evaluated the required complexity for the student model. As a result, our method improved MSE by 21% and BadPix by 14% compared to training without it. Furthermore, the student model achieved an inference speed 13% faster than the teacher model and surpassed its accuracy by 10% in MSE. Additionally, we demonstrated that repeatedly applying our approach could further enhance both model compactness and accuracy.

The increasing cancer burden is a major health concern in Arab countries with variations in cancer profiles. Given the limited oncology research output and scarce data on cancer trial participation in the Arab region, this study explored the therapeutic cancer trial landscape in Arab countries over the past 20 years. A bibliometric analysis of the PubMed database was conducted on primary publications of therapeutic trials with a participating Arab center. Arab countries participated in 320 published cancer-related therapeutic trials (2000‒2021). There was a consistent increase in the number of trials, sample size, multiregional site participation, and number of randomized trials. However, most trials were small, did not receive external funding, and included a single Arab site. Compared with Arab-only trials, trials with joint non-Arab sites were larger (p = .003) and more likely to be externally funded (p < .001). Citation numbers and journal impact factors were higher in trial publications with joint non-Arab authorship than those without (p < .001, for both). Despite improving conduct and publication records of oncology trials with Arab centers, cancer trial participation remains limited in Arab countries. Concerted efforts are required to encourage sponsorship and international collaboration in this region.

Clinical trials for Alzheimer’s disease (AD) face multiple challenges, such as the high screen failure rate and even allocation of heterogeneous participants. Artificial intelligence (AI), which has become a potent tool of modern science with the expansion in the volume, variety, and velocity of biological data, offers promising potential to address these issues in AD clinical trials. In this review, we introduce the current status of AD clinical trials and topic of machine learning. Then, a comprehensive review is focused on the potential applications of AI in the steps of AD clinical trials, including the prediction of AD biomarkers and differential diagnosis of AD in the prescreen during eligibility assessment and the likelihood stratification of patients who will progress to AD dementia and fast cognitive decline group from the slow decline group in randomization. Finally, this review provides challenges, developments and the future outlook on the integration of AI into AD clinical trials.

Background: There is ongoing debate regarding the usefulness of laparoscopic pancreaticoduodenectomy. This study aimed to analyze all the randomized control trials published including the most recent one. Material and methods: The study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and MOOSE guidelines. Heterogeneity was measured using Q tests and I2. The random-effects models were used to summarise the relative risks, odds ratios, and mean differences as appropriate.Results:4 RCTs were included consisting of 818 patients. 411 patients were in the laparoscopic group and 407 in the open pancreaticoduodenectomy group. Weighted baseline patient characteristics were similar except more patients with pancreatic adenocarcinoma and more males were there in the open pancreaticoduodenectomy group. There was no difference in-hospital stay,90 days complications rate, 90 days mortality, R1 resection, postoperative pancreatic fistula, delayed gastric emptying, post pancreatectomy hemorrhage, bile leak between the two groups. Operative time was more in the laparoscopic group. Blood loss [mean difference -132.12 ml (-172.60,-91.65)] and surgical site infection [Risk ratio 0.41 ( 0.17-1.0)] were significantly lesser in laparoscopic group.Conclusion:There was no benefit in-hospital stay or clinical outcomes after laparoscopic pancreaticoduodenectomy. Blood loss and surgical site infection were lesser in laparoscopic pancreaticoduodenectomy.

COVID-19 is causing major turmoil around the globe, and the clinical trial industry is likely to face unprecedented challenges to health and business sectors. In an effort to find a suitable treatment and prevention options for COVID-19, several COVID-19 clinical trials are being planned and initiated, while a large number of clinical trials for non- COVID-19 indications are suffering delays. With over more than 1000 trials being disrupted and more trials being added to this category daily, there is a direct impact on trial site activation and patient enrolment. This analysis deals with the specific impacts of the COVID-19 pandemic on the clinical trial and pharmaceutical industry. The objective of this study is to provide an updated information of the disrupted clinical trials and its impact on various therapeutic areas and different drugs. Among the severely affected clinical trials, oncology and CNS trials are the hardest hit therapy areas.This article will certainly emphasize the need for advanced and innovative approaches to maintain the health of the clinical trial ecosystem by continuing the existing trials and the start of the new studies. We have to take and follow necessary actions to guarantee that the initiatives will not be locked during the COVID-19 pandemic, both for the treatment of patients and for the researchers to conduct decision-relevant clinical trials.

Sepsis is a life-threatening syndrome triggered by infection and accompanied by high mortality, with antimicrobial resistances (AMRs) further escalating clinical challenges. Rapid and reliable detection of causative pathogens and AMRs are key factors for fast and appropriate treatment, in order to improve outcome in septic patients. However, current sepsis diagnostics based on blood culture is limited by low sensitivity and specificity while current molecular approaches fail to enter clinical routine. Therefore, we developed a Suppression PCR-based selective enrichment sequencing approach (SUPSETS), providing a molecular method combining multiplex suppression PCR with Nanopore sequencing to identify most common sepsis-causative pathogens and AMRs using plasma cell-free DNA. Applying only 1 mL of plasma, we target eight pathogens across three kingdoms and ten AMRs in a proof-of-concept study. SUPSETS was successfully tested on first ten clinical samples and revealed comparable results to clinical metagenomics while clearly outperforming blood culture. Several clinically relevant AMRs could be detected additionally. Furthermore, SUPSETS provided first pathogen and AMR-specific sequencing reads within minutes of starting sequencing, thereby potentially decreasing time to results to 11 - 13 hours and suggesting diagnostic potential in sepsis.

It is well known that the photon trajectories follow a curved path in a gravitational field. We explore here the gravitational bending of electric field lines. It seems that the electric field lines of a charge, supported in a gravitational field, follow exactly the trajectories of photons emitted isotropically from a source situated at the charge location. From a detailed examination of the electrostatic field of a charge accelerated uniformly in the instantaneous rest frame, exploiting the strong principle of equivalence, one can determine the bending of the electric field lines of a charge in a gravitational field. The fraction of electric field lines crossing a surface, stationary above or below the charge in the gravitational field, is shown to be exactly similar to the fraction of photon trajectories, emitted from a source placed at the charge location, intersecting that surface. On the other hand, for a freely falling charge in the gravitational field there is no such bending of electric field lines. The field lines continue to extend in radial straight lines from the instantaneous 'present' position of the charge, as do the trajectories of photons streaming away from the instantaneous position of a freely falling source in the gravitational field. The electric field configuration of a freely falling charge in the gravitational field is shown to be exactly the same as that of a charge moving uniformly in an inertial frame with velocity equal to the instantaneous ``present'' velocity of the freely falling charge.

Background:Fontan completion is the last stage of univentricular repair, which drains the inferior vena cava against gravity to a higher-pressure pulmonary arterial circulation. The passivity and anti-gravity nature of this circulation render a failing Fontan, not an uncommon encounter, twenty years ago, Rodefeld and colleagues, decided to explore the feasibility of vascular pumps to support the passive nature of Fontan circulation, and since then, trials are still ongoing, and we aimed through this review to wrap up the results of these trials. Methods:A literature review has been conducted, to identify any in vivo or in vitro trial of a Fontan assist device. Several outcome parameters determined whether the trial will be included or not in this review, including, the flow rate of a pump if applicable, the number of compressions per minute if a compression device has been used, the resultant flow rate, the inferior and superior vena cava pressures, associated with each setting of the respective device, and any evidence of hemolysis or clotting within the circuit. Results:A total of ten trials have been included, with 23 different settings. Three designs have been identified, out of which two fall within the pump design, namely the connecting chamber and the intravascular pump designs; only one trial explored the possible use of a compression device. The commonest design encountered in in-vivo trials was the intravascular pump (67%). No reports of significant hemolysis or thrombosis were found. An increasing flow rate beyond 5L/min was associated with a negative outcome in the connecting chamber design, increasing upstream pressure in the SVC, while intravascular pumps did not display this limitation. Conclusion:Univentricular heart patients are a relatively small population, with very extensive needs, despite twenty years of trials, no study has yet concluded the optimal design or settings for a Fontan assist device. In this review, we identified that the intravascular pump remains the most practical design, due to its easy mode of insertion, and that it is not faced with the limitation or risk of increasing upstream resistance. There is still a long way to conclude its use as other designs such as compression devices have not yet been fully studied.

The manipulation of participant allocation in randomized controlled trials to achieve equal groups sizes may introduce allocation bias potentially leading to larger treatment effect estimates. This study aimed to estimate the proportion of nursing trials that have precisely equal group sizes and examine if there was an association with trial outcome. Data were extracted from a sample of 148 randomized controlled trials published in nursing science journals in 2017. One hundred trials (68%) had precisely equal group sizes. Respectively, a positive outcome was reported in 70% and 58% of trials with equal/unequal groups. Trials from Asia were more likely to have equal group sizes than those from the rest of the world. Most trials reported a sample size calculation (n=105, 71%). In a third of trials (n=36, 34%), the number of participants recruited precisely matched the requirement of the sample size calculation; this was significantly more common in studies with equal group sizes. The high number of nursing trials with equal groups may suggest nurses con-ducting clinical trials are manipulating participant allocation to ensure equal group size increasing the risk of bias.

Glioblastoma (GBM) is the most lethal form of brain tumor, characterized by rapid growth and surrounding tissue invasion. The current standard treatment is surgery followed by radiotherapy, and concurrent chemotherapy, typically with temozolomide. Although extensive research has been performed over the past years to develop an effective therapeutic strategy for the treatment of GBM, efforts have not provided major improvements in the overall survival of patients with GBM. Thus, new therapeutic approaches are urgently needed. A major challenge in the development of therapies for central nervous system (CNS) disorders is overcoming the blood–brain barrier (BBB). In this context, the intranasal (IN) route of drug administration has been proposed as a non-invasive alternative route to directly targeting the CNS. In fact, this route of drug administration may bypass the blood-brain barrier and reduce systemic side effects. Recently, formulations have been developed to further enhance nose-to-brain transport, mainly with the use of nano-sized and nanostructured drug delivery systems. The focus of this review will be on the strategies developed to deliver a number of anticancer compounds for the treatment of GBM using the nasal administration. In particular, the specific properties of nanomedicines proposed for the nose-to-brain delivery will be critically evaluated. The number of preclinical and clinical data reviewed support the idea that nasal delivery of anticancer drugs might represent a breakthrough advancement in the fight against GBM.

Event-related potentials (ERPs) are estimated by averaging time-locked single trial electroencephalography (EEG) signals in response to specific events or stimuli. Classifying ERPs accurately is a challenge because (a) single trials have poor signal-to-noise-ratios (SNRs) and (b) it is difficult to collect large single trial ensembles to generate high SNR ERPs for classifier training and testing. The m-subsample averaging (m-SA) strategy which generates small-sample ERPs by repeated averaging of a small number of single trials drawn without replacement, has been proposed as a solution to the two problems. An ERP formed by averaging m single trials is referred to as an m-ERP where m is referred to as the averaging parameter. In this study, we conduct thorough analyses of m-SA and focus on issues not addressed in previous studies to better understand the beneficial properties of m-SA and to further support its application for ERP classification. Specifically, we (a) analyze the improvement in SNR as a function of m using the mean-root-mean-square SNR and visual analyses of m-ERP plots with confidence intervals, (b) analyze the improvement in interclass separation as a function of m, (c) determine how the SNR and interclass separation analyses can help to select the averaging parameter m, (d) determine the number of distinct m-ERPs that can be drawn from a single-trial ensemble, and (e) determine several probabilities related to the generation of distinct m-ERPs. Furthermore, an extensive set of experiments are designed to analyze the performance of support vector machine and convolution neural network classifiers employing m-SA with various combinations of the averaging parameters used for generating the training and test sets. The results confirm that ERPs can be classified accurately using small subsample averaging. Most importantly, it is concluded that m-SA can be deployed in practice to accurately classify ERPs in brain activity research and in clinical applications without having to collect a prohibitively large number of single trials.

The emergence of new type of viral pneumonia cases in China, on December 31, 2019; identified as the cause of human coronavirus, labeled as "COVID-19," took a heavy toll of death and reported cases of infected people all over the world, with the potential to spread widely and rapidly, achieved worldwide prominence but arose without the procurement guidance. There is an immediate need for active intervention and fast drug discovery against the 2019-nCoV outbreak. Herein, the study provides numerous candidates of drugs (either alone or integrated with another drugs) which could prove to be effective against 2019-nCoV, are under different stages of clinical trials. This review will offer rapid identification of a number of repurposable drugs and potential drug combinations targeting 2019-nCoV and preferentially allow the international research community to evaluate the findings, to validate the efficacy of the proposed drugs in prospective trials and to lead potential clinical practices.

The bipartite entanglement is comprehensively investigated in the mononuclear molecular complex (Et3NH)[Ni(hfac)2L], where HL denotes 2-(2-hydroxy-3-methoxy-5-nitrophenyl)-4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazol-3-oxide-1-oxyl and hfacH stands for hexafluoroacetylacetone. From the magnetic point of view, the molecular compound (Et3NH)[Ni(hfac)2L] consists of an exchange-coupled spin-1 Ni2+ magnetic ion and a spin-12 nitronyl-nitroxide radical substituted nitrophenol. The nickel-radical molecular complex affords an experimental realization of a mixed spin-(12, 1) Heisenberg dimer with a strong antiferromagnetic exchange coupling J/kB= 505 K and two distinct g-factors gRad=2.005 and gNi=2.275. By adopting this set of magnetic parameters we demonstrate that the Zeeman splitting of a quantum ferrimagnetic ground-state doublet due to a weak magnetic field may substantially reinforce the strength of bipartite entanglement at low temperatures. The molecular compound (Et3NH)[Ni(hfac)2L] maintains sufficiently strong thermal entanglement even at room temperature, vanishing only above 546 K. Specifically, the thermal entanglement in the nickel-radical molecular complex retains approximately 40% of the maximum value corresponding to perfectly entangled Bell states at room temperature, which implies that this magnetic compound provides suitable platform of a molecular qubit with potential implications for room-temperature quantum computation and quantum information processing.

The West Pomeranian Anti-Crisis Package was an effective tool of the Voivodeship Executive Board of West Pomeranian self-government, which was used to combat and counteract and counteract the social and economic effects of the COVID-19 pandemic. The Anti-Crisis Package was prepared with a view to undertaking systemic, but also point-based measures in order to save and protect regional health care, entrepreneurs, the labour market, but also to use the existing social capital of non-governmental organizations involved in measures reducing the effects of the COVID-19 pandemic. The West Pomeranian Anti-Crisis Package, as evidenced not only by the financial outlays incurred, but also by the outcome of implementing measures achieved in 2020 and their continuation in 2021.

Euglena gracilis is an alga of great biotechnological interest and extensive metabolic capacity, able to make high levels of bioactive compounds, such as polyunsaturated fatty acids, vitamins and β-glucan. Previous work has shown that Euglena expresses a wide range of carbohydrate-active enzymes, suggesting an unexpectedly high capacity for the synthesis of complex carbohydrates for a single-celled organism. Here, we present an analysis of some of the carbohydrates synthesised by Euglena gracilis. Analysis of the sugar nucleotide pool showed that there are the substrates necessary for synthesis of complex polysaccharides, including the unusual sugar galactofuranose. Lectin- and antibody-based profiling of whole cells and extracted carbohydrates revealed a complex galactan, xylan and aminosugar based surface. Protein N-glycan profiling, however, indicated that just simple high mannose-type glycans are present and that they are partially modified with putative aminoethylphosphonate moieties. Together, these data indicate that Euglena possesses a complex glycan surface, unrelated to plant cell walls, while its protein glycosylation is simple. Taken together, these findings suggest that Euglena gracilis may lend itself to the production of pharmaceutical glycoproteins.

Approximately 6% of adults worldwide suffer from peripheral artery disease (PAD) primarily caused by atherosclerosis of lower limb arteries. Despite optimal medicine and revascularization, many PAD patients remain symptomatic and progress to critical limb ischemia (CLI) and risk major amputation. Delivery of pro-angiogenic factors as proteins or DNA, stem or progenitor cells confers vascular regeneration and functional recovery in animal models of CLI, but the effects are not well replicated in patients and no pro-angiogenic biopharmacological procedures are approved in the US. The reasons are unclear, but animal models that do not represent clinical PAD/CLI are implicated. Consequently, it is unclear whether the obstacles to clinical success lie in the toxic biochemical milieu of human CLI, or in procedures that were optimized by inappropriate models. The question is significant because the former case requires abandonment of current strategies, while the latter encourages continued optimization. These issues are discussed in the context of relevant preclinical and clinical data, and it is concluded that preclinical mouse models that include age and atherosclerosis as the only comorbidities that are consistently present and active in clinical trial patients are essential to predict clinical success. Of the reviewed materials, no biopharmacological procedure that failed in clinical trials had been tested in animal models that included advanced age and atherosclerosis relevant to PAD/CLI.

Probiotics have been widely used in gastroenteritis due to acute and chronic illnesses. However, evidence supporting the effectiveness of probiotics in different health conditions are inconclusive and conflicting. The aim of the study was to review existing literature on the effects of probiotics in gastroenteritis among adults. Only original articles on clinical trials that demonstrated the effects of probiotics in adults with gastroenteritis were used for this analysis. Multiple databases such as PubMed, Google Scholar, MEDLINE and Scopus databases were searched for the data. The study followed standard procedures for data extraction using PRISMA flow chart. A quality appraisal of the selected studies was conducted using CADIMA. Finally, a meta-analysis was conducted. Thirty-five articles met the selection criteria; of them, probiotics were found effective in the treatment and/or prevention of chronic inflammatory bowel disease (IBD) including ulcerative colitis and Crohn’s disease in 17 (49%), and the treatment of pouchitis in 4 (11.4%), antibiotic-induced diarrhea in 3 (8.6%), Helicobacter pylori infection in 2 (5.7%) and diverticulitis in 1 (2.9%), while the remaining 7 (20%) were ineffective and 1 study results were inconclusive. Meta-analysis, on the contrary, didn’t demonstrate any significant protective effects of probiotics. Having a τ² value of zero and I² of 6%, the studies were homogeneous and had minimum variances. Further studies are suggested to evaluate the beneficial effects of probiotics in IBDs and other chronic bowel diseases.

Indirect calorimetry (IC) is a widely used method to study animal energy metabolism by measuring gas exchange. The accuracy of IC depends on detecting variations in signals reflecting the metabolic response, which can be challenging due to measurement noise and external factors. In this study, we propose a methodology to validate IC systems, including an easy-to-use spreadsheet for data computing, to verify accuracy and detect whole-system leaks. We conducted a re-covery test using a simulation of CO2 dynamics in MS Excel and injecting a known CO2 concentration into four respirometry chambers. The clearance rate of CO2 was observed and compared to the expected clearance rate from the simulation. The results from the recovery test in our system show that the proposed methodology is accurate and precise. The proposed methodology and recovery test can be used to standardize the validation of IC systems, providing accurate measurements of animal energy metabolism in different environmental conditions and energy utilization from feeds.

A formulation of nonequilibrium thermo field dynamics has been performed using the nonequilibrium statistical operator method by D.N. Zubarev. Generalized transfer equations for a consistent description of kinetics and hydrodynamics of the dense quantum-field system with strongly coupled states are derived.

Due to its time effective, joint friendly and highly customizable character whole-body-electromyostimulation (WB-EMS) is regarded as a feasible solution for a large variety of training issues particularly in the area of non-athletic application. To identify gaps in research and summarize prevalent evidence we conducted an evidence map on outcomes addressed by WB-EMS trials in middle-aged to older, non-athletic adults. Based on a comprehensive systematic search in five databases and two study registers according to PRISMA, 54 projects published in 80 articles were included. More than 90% of the studies reported outcomes related to the physical fitness or function domain. Body composition parameters were addressed by two thirds of the projects. Health-related outcomes addressed by WB-EMS included cancer/neoplasm (n=7), endocrine regulation (n=8), glucose metabolism (15), nervous system diseases (n=2), cardiovascular system diseases (n=22), non-specific chronic low back pain (n=4), osteopenia (n=5) and diseases of the renal system (n=12). Outcomes related to inflammation were addressed 18 times. Of importance, no studies reported clinically relevant adverse effects related to the WB-EMS intervention. In summary, while considerable evidence on outcomes related to fitness/function and body composition is prevalent, evidence gaps of WB-EMS research were particular evident for diseases of the nervous and cerebrovascular system.

This paper investigates the influence of magnetic field for a two dimensional deformations on a two temperature problem at the free surface of a semi-infinite semiconducting medium under the effect of mechanical force during a photothermal theory and the effect of hydrostatic initial stress on the medium. The Harmonic Wave Method (Normal Mode Analysis) has been used to obtain the equations of elastic waves, heat conduction equation, quasi-static electric field, carrier density, two temperature coefficient, ratios, and constitutive relationships for the thermo-magnetic-electric medium. The effects of several parameters as thermoelastic and thermoelectric coupling parameters and two temperature parameter of this force on the displacement component, force stress, carrier density and temperature distribution has been depicted graphically.

In view of the problem that the output thrust of solenoid actuator is affected by various factors and is difficult to calculate in actual working conditions, this paper proposes a semi-analytical model constructed by magnetic field subdomain method with internal and external boundary conditions in cylindrical coordinate system for calculation, and the general solution equations of magnetic vector potential for each subdomain are derived and solved by MATLAB. Taking a push-pull electromagnet as an example, the finite element simulation and experimental comparative analysis are carried out. The correctness and applicable conditions of the subdomain method are illustrated by comparing the gradient plot of magnetic vector potential, inductance curve and electromagnetic force. By calculating the output thrust after considering the core gravity, spring force and electromagnetic force, it is shown that this method has the advantage of computational flexibility compared with the finite element method, and it is easier to write special algorithms according to various working conditions to calculate the important parameters in engineering applications.

The Clinical Trials Transformation Initiative (CTTI) Investigator Qualification Project addresses the need for a more efficient and effective means of identifying qualified clinical investigators and delegates. Selection of investigators and delegates who are qualified by training and experience to conduct clinical trials is essential to safeguarding protections for study participants and ensuring data quality and integrity. Sponsors generally document investigator qualification through training on the principles of good clinical practice (GCP), as defined by the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH), adopted by regulatory authorities in the US, Japan and the European Union. Although these GCP principles provide an important foundation for promoting the conduct of quality clinical trials, the industry standard “one-size-fits-all” GCP training may not fully prepare investigators and delegates for conducting quality clinical trials. Routine GCP training alone may not be sufficient to prepare an inexperienced member of a site team, while repeating such training is unlikely to enhance the qualifications of an experienced researcher. The CTTI project team used findings from qualitative research activities, as well as input from an expert meeting with multiple stakeholders, to identify gaps and redundancies in the current training of investigators and their delegates and recommend practical, action-based solutions. CTTI provides recommendations on how to implement a more efficient and effective means of qualification for investigators and delegates, determine whether a site team is a good fit for a particular protocol, and improve the quality of clinical trial conduct.

Whole-body electromyostimulation (WB-EMS) can be considered as a time-efficient, joint-friendly and highly customizable training technology that attracts a wide range of users. The present evidence map aimed to provide an overview of different non-athletic cohorts addressed by WB-EMS research. Based on a comprehensive systematic search according to PRISMA, eighty-six eligible longitudinal trials were identified that correspond with our eligibility criteria. In summary, WB-EMS research sufficiently covers all adult age categories in males and females. Most cohorts addressed (58%) were predominately or exclusively overweight/obese and in about 60% of them, diseases or conditions were inclusion criteria for the trials. Cohorts specifically addressed by WB-EMS trials suffer from cancer/neoplasm (n=7), obesity (n=6), diabetes mellitus (n=5), the metabolic syndrome (n=2), nervous system diseases (n=2), chronic heart failure (n=4), stroke (n=1), peripheral arterial diseases (n=2), knee arthrosis (n=1), sarcopenia (n=3), chronic unspecific low back pain (n=4), and osteopenia (n=3). Chronic kidney disease was an eligibility criterion in five WB-EMS trials. Finally, three studies included only critically ill patients, two further studies considered frailty as an inclusion criterion. Of importance, no adverse effects of the WB-EMS intervention were reported. In summary, evidence gaps of WB-EMS research were particular evident for cohorts with diseases of the nervous and cerebrovascular system.

Highly-doped graphene samples show the conductance reduced and the shot-noise power enhanced compared to standard ballistic systems in two-dimensional electron gas. These features can be understood within a model assuming incoherent scattering of Dirac electrons between two interfaces separating the sample and the leads. Here we find, by adopting the above-mentioned model for the edge-free (Corbino) geometry and by means of the computer simulation of quantum transport, that another graphene-specific feature should be observable when the current flow through a doped disk is blocked by high magnetic field. In case the conductance drops to zero, the Fano factor approaches the value of $F\approx{}0.56$, with a very weak dependence on the disk radii ratio. The role of finite source-drain voltages and the system behavior upon tuning the electrostatic potential barrier from a rectangular to parabolic shape are also discussed.

Wide-field (WF) retinal imaging is becoming a standard diagnostic tool for diseases involving the retinal periphery. Technological progress elicited the advent of wide-field optical coherence tomography (WF-OCT) and WF-OCT angiography (WF-OCTA) examinations. This review presents the results of studies that analyzed the implementation of these procedures in clinical practice and refers to them as traditional and ultra-wide-field fluorescein angiography (UWF-FA). The PUBMED search was performed using the terms WF-OCT OR WF-OCTA OR UWF-FA AND the specific clinical entity, including diabetic retinopathy (DR), retinal vein occlusion (RVO), Coats disease, peripheral retinal telangiectasia, peripheral retinal degeneration, lattice degeneration, and posterior vitreous detachment. The analysis only included the studies in which the analyzed field of view for the OCT or OCTA exam was larger than 55 degrees. The evaluation of the extracted studies indicates that WF imaging with OCT and OCTA provides substantial information on retinal disorders involving the retinal periphery. Vascular diseases, such as DR or RVO, can be reliably evaluated using WF-OCTA with results superior to standard-field fluorescein angiography. Nevertheless, UWF-FA provides a larger field of view and still has advantages over WF-OCTA concerning the evaluation of areas of non-perfusion and peripheral neovascularization. Detailed information on the vascular morphology of peripheral changes should be obtained via WF-OCTA, not angiographic examinations. WF-OCT can serve as a valuable tool for the detection and evaluation of vitreoretinal traction, posterior vitreous detachment, and peripheral retinal degeneration, and guide therapeutic decisions on a patient’s eligibility for surgical procedures.

Objectives: The aim of our current study was to analyze whether the use of important measures of methodological quality and reporting of randomized clinical trials published in the field of cardiovascular disease research have changed over time. Further aim was to investigate whether there was an improvement over time in the ability of these trials to provide a good estimate of the true intervention effect. Methods We conducted two searches in the Cochrane Central Register of Controlled Trials (CENTAL) database to identify cardiovascular clinical research trials published in either 2012 or 2017. Randomized clinical trials (RCTs) trials in cardiovascular disease research with adult participants were eligible to be included. We randomly selected 250 RCTs for both publication year 2012 and 2017. Trial characteristics, data on measures of methodological quality and reporting were extracted and risk of bias for each trial was assessed. Results As compared to 2012 in 2017 there were significant improvements in the reporting of the presence of a data monitoring committee (42.0% in 2017 compared to 34.4% in 2012), and a positive tendency of registering cardiovascular disease research RCTs in clinical trial registries (83.6% in 2017 compared to 72.0% in 2012). On the other hand, we also observed that significantly fewer RCTs reported sample size calculation (60.4% in 2017 compared to 98.4% in 2012) in 2017 as compared to 2012. RCTs in 2017 were more likely to have low overall risk of bias ( RoB ) than in 2012 (29.2% in 2017compared to 21.2% in 2012). Conclusion: As compared to 2012 in 2017 there were significant improvement in some, but not all the important measures of methodological quality. Although more trials in the field of cardiovascular disease research had a lower overall RoB in 2017, the improvement over time was not consistently perceived in all RoB domains.

It is currently recognized that an injudicious strategy in the last decades has been not only focusing of research typically on caries in children, but also the narrow focusing on fluoride, because despite sufficient availability of fluoride in water and oral healthcare products, caries levels escalate steadily as people get older and caries remain a main public health issue to be settled. In the last two decades the scientific community intensified efforts of exploring other products for caries prevention, herbal products being one of these approaches. Because preliminary evidence indicated that clinical trials for caries prevention with herbal products are heterogeneous in design, quality and products evaluated, we performed a scoping review intended to explore the main characteristics of such clinical trials. From an initial collection of 1986 unique papers from different literature databases, 56 articles satisfied the inclusion and exclusion criteria. The species investigated, dosage forms, study designs, duration of intervention, controls, endpoints, quality of reporting and risk of bias are discussed. 85.71% of the trials reviewed here reported positive results but given the methodological flaws and biases affecting them, it is difficult to conclude on the efficacy of those products based on the studies published thus far.

Despite all scientific efforts and many protracted and expensive clinical trials, no new drug has been approved by FDA for treatment of Alzheimer disease (AD) since 2003. Indeed, more than 200 investigational programs have failed or have been abandoned in the last decade. The most probable explanations for failures of disease-modifying treatments (DMTs) for AD may include late initiation of treatments during the course of AD development, inappropriate drug dosages, erroneous selection of treatment targets, and mainly an inadequate understanding of the complex pathophysiology of AD, which may necessitate combination treatments rather than monotherapy. Clinical trials’ methodological issues have also been criticized. Current drug-development research for AD is aimed to overcome these drawbacks. Preclinical and prodromal AD populations, as well as traditionally investigated populations representing all the clinical stages of AD, are included in recent trials. Systematic use of biomarkers in staging preclinical and prodromal AD and of a single primary outcome in trials of prodromal AD are regularly integrated. The application of amyloid, tau, and neurodegeneration biomarkers, including new biomarkers—such as Tau positron emission tomography, neurofilament light chain (blood and CSF biomarker of axonal degeneration) and neurogranin (CSF biomarker of synaptic functioning)—to clinical trials allows more precise staging of AD. Additionally, use of the Bayesian statistics, modifiable clinical trial designs, and clinical trial simulators enrich the trial methodology. Besides, combination therapy regimens are currently assessed in clinical trials. The abovementioned diagnostic and statistical advances, which have been recently integrated in clinical trials, are consequential to the recent failures of studies of disease-modifying treatments. Their experiential rather than theoretical origins may better equip potentially successful drug-development strategies.

The substitution of chemical fertilizers by organic manure plays a critical role in sustainable crop production. Nevertheless, organic amendments promote the global warming potential (GWP) in rice paddies due to increased methane (CH4) emissions. Increasing evidence shows that lime application can reduce CH4 emissions from acidic paddy soils, while it is still not clear whether liming can reduce the GWP in rice fields under organic manure substitution. A two-year field experiment was conducted to investigate the impacts of pig manure substitution and lime application on grain yield, CH4 and nitrous oxide (N2O) emissions in a subtropical double-cropped rice field in China. The experiment consisted of three treatments: chemical fertilization (CF, 100% N from urea), 50% of chemical N substituted by pig manure (1/2N + M), and the 1/2N + M treatment plus lime amendment (1/2N + M + L). On average, 1/2N + M reduced rice yield by 5.65% compared to CF, while lime application had no effect on rice yield. Mean cumulative CH4 emissions were 218.8% higher in 1/2N + M than in CF, whereas 1/2N + M + L reduced CH4 emissions by 36.6% compared to 1/2N + M. Neither pig manure substitution nor lime application affected N2O emissions. Consequently, 1/2N + M increased the GWP and greenhouse gas intensity (GHGI) by 214.6% and 228.3%, respectively, compared to CF. In contrast, 1/2N + M + L reduced the GWP and GHGI by 36.4% and 36.5% compared to 1/2N + M. Lime application can mitigate CH4 emissions and GWP induced by pig manure amendment in double-cropped rice fields.

Any photon, regardless of its origin, carries the same optical field profile. This feature and the quantum Rayleigh emissions generate temporally discrete groups of several photons in a resonant cavity incorporating one single quantum dot. A periodic stream of single photons is distorted by high-finesse optical cavities and the quantum Rayleigh spontaneous emission in a beam splitter. Groups of photons emerge from interferometric filters because of multiple internal reflections.

About half of the world's population is at risk of dengue infection. Epidemics of dengue fever caused an increased risk of morbidity and mortality in recent years, which led to the exploration of vaccines as a preventive measure. This systematic review and meta-analysis aimed to evaluate the efficacy, immune response, and safety of dengue vaccines in children by analyzing clinical trials. The review followed standard procedures for data extraction using PRISMA guidelines, and searching multiple databases including PubMed, CINAHL, Medline, Health Source, Science Direct, and Academic Search Premiere. Eligible studies involved children (0-17 years). Cochrane Collaboration criteria were used for quality assessment, with thematic data synthesis and meta-analysis. Among 38 selected studies, dengue vaccines showed varying efficacy against all four serotypes. CYD-TDV (Dengvaxia®), and Tekade (TAK-003) vaccines demonstrated strong protection against severe dengue, but their long-term efficacy varied. Vaccines triggered satisfactory immune responses, notably in those previously exposed to dengue. Safety profiles were mostly favorable, noting mild adverse events post-vaccination. Meta-analysis supported vaccine efficacy and immune response, but safety concerns warrant further exploration. In conclusion, dengue vaccines demonstrated promising efficacy and immune response, particularly against severe manifestations.

Based upon Maxwell's equations, it has long been established that oscillating electromagnetic (EM) fields incident upon a metal surface decay exponentially inside the conductor, leading to a virtual EM vacuum at sufficient depths. Magnetic resonance imaging (MRI) utilizes radiofrequency (r.f.) EM fields to produce images. Here we present the first visualization of a virtual EM vacuum inside a bulk metal strip by MRI, amongst several novel findings. We uncover unexpected MRI intensity patterns arising from two orthogonal pairs of faces of a metal strip, and derive formulae for their intensity ratios, revealing differing effective elemental volumes (voxels) underneath these faces. Further, we furnish chemical shift imaging (CSI) results that discriminate different faces (surfaces) of a metal block according to their distinct nuclear magnetic resonance (NMR) chemical shifts, which holds much promise for monitoring surface chemical reactions noninvasively. Bulk metals are ubiquitous, and MRI is a premier noninvasive diagnostic tool. Combining the two, the emerging field of bulk metal MRI can be expected to grow in importance. The fundamental nature of results presented here may impact bulk metal MRI and CSI across many fields.

Efficient commencement of clinical trials is pivotal for their successful execution. The purpose of this study was to determine and examine the factors that contribute to trial start-up delays. The study assessed 20 clinical trials' start-up stages in order to identify relevant variables. Results showed that trials with an emphasis on devices, trials that did not outsource, trials that utilized less auxiliary services, and trials that employed interventional designs had quicker start-up times than observational studies. Furthermore, approval times were substantially shortened by using a centralized Institutional Review Board (IRB) rather than a local IRB. Furthermore, compared to studies that successfully enrolled subjects, those who failed to do so required more time to complete contracts and budgets and secure IRB clearance. This study underscores the diverse impact of clinical trial features on start-up timelines. Understanding these factors is crucial for optimizing the initiation process of clinical trials.

Childhood overweight and obesity is a worldwide public health issue. Our objective was to describe planned, ongoing and completed randomized controlled trials (RCTs) designed for the prevention of obesity in early childhood. Two databases (World Health Organization International Clinical Trials Registry Platform, ClinicalTrials.gov) were searched to identify RCTs with the primary aim of preventing childhood obesity and at least one outcome related to child weight. Interventions needed to start in the first two years of childhood or earlier, continue for at least 6 months postnatally, include a component related to lifestyle or behaviors, and have a follow up time of at least 2 years. We identified 29 unique RCTs, implemented since 2008, with most being undertaken in high income countries. Interventions ranged from advice on diet, activity, sleep, emotion regulation and parenting education through individual home visits, clinic-based consultations or group education sessions. Eleven trials have published data on child weight related outcomes to date, though most were not sufficiently powered to detect significant effects. Many trials detected improvements in practices such as breastfeeding, screen time and physical activity in the intervention groups compared to the control groups. Further follow-up of ongoing trials is needed to assess longer-term effects.

There is a growing public health need for effective preventive interventions against dengue, and a safe, effective and affordable dengue vaccine against the four serotypes would be a significant achievement for disease prevention and control. Two tetravalent dengue vaccines, Dengvaxia (Sanofi Pasteur) and DENVax (Takeda Pharmaceutical Company), have now completed phase 3 clinical trials. While Dengvaxia resulted in serious adverse events and is restricted to individuals with prior dengue infections, DENVax has shown, at first glance, some encouraging results. Using the available data for the TAK 003 trial, we estimate, via the Bayesian approach, vaccine efficacy (VE) of the post-vaccination surveillance periods. Although better measurement over long time was expected for the second part of the post-vaccination surveillance, variation in serotype-specific efficacy needs careful consideration. Besides observing that individual serostatus prior to vaccination is determinant of DENVax vaccine efficacy, we also compare the VE estimations for 12 and 18 months and we observe that the efficacy is decreasing over time. The comparison of efficacies over time is informative and very important, bring up the discussion of the role of temporary cross-immunity in dengue vaccine trials and the impact of serostatus prior to vaccination in the context of dengue fever epidemiology.

The emergence of CDK4/6 inhibitors, such as palbociclib, ribociclib, and abemaciclib, has revolutionized the treatment landscape for hormone receptor-positive breast cancer. These agents have demonstrated significant clinical benefits in terms of both progression-free survival and overall survival. However, resistance to CDK4/6 inhibitors remains a challenge, limiting their long-term efficacy. Understanding the complex mechanisms driving resistance is crucial for the development of novel therapeutic strategies and improvement of patient outcomes. Translational research efforts, such as preclinical models and biomarker studies, offer valuable insight into resistance mechanisms and may guide the identification of novel combination therapies. This review paper aims to outline the reported mechanisms underlying CDK4/6 inhibitor resistance, drawing insights from both clinical data and translational research in order to help direct the future of treatment for hormone receptor positive metastatic breast cancer.

Coronavirus disease (COVID-19) is the current global public health threat with no specific, effective, and approved treatment available till date. The outbreak of COVID-19 has led the world into an unimagined and uncertain situation by disrupting the economies, claiming human lives, and leaving many into secondary mental health problems. As per the latest WHO report, approximately 8.2 million people are infected, and nearly 0.44 million lives are lost to COVID. The infection has spread to over 200 countries and territories around the world. The world is in search of efficient diagnostics and therapeutics, including vaccines, biologics and drugs. With the rapid increase in rates of infection and time constraints, drug repurposing seems to be a potential and viable option to find the promising anti-COVID therapeutics. In the wake of a rapid increase in the number of clinical trials involving drugs for repurposing, we aim to provide information on the safety concerns related to the drugs currently investigated in trials. This review also highlights the possible mechanisms of actions, adverse drug reactions, and contraindications of the drugs under repurposing evaluation.

The global pandemic of SARS-CoV-2, the causative viral pathogen of COVID-19, has driven the biomedical community to action – to uncover and develop anti-viral interventions. One potential therapeutic approach currently being evaluated in numerous clinical trials is the agent remdesivir, which has endured a long and winding developmental path. Remdesivir is a nucleotide analog prodrug that perturbs viral replication, originally evaluated in clinical trials to thwart the Ebola outbreak in 2014. Subsequent evaluation by numerous virology laboratories demonstrated the ability of remdesivir to inhibit coronavirus replication, including SARS-CoV-2. Here, we provide an overview of its mechanism of action, discovery, and the current studies exploring its clinical effectiveness.

Abstract Background: Cluster randomized controlled trials are increasingly becoming popular in public health research interventions and health services research in primary health care design and use in low and middle-income countries. However, the majority of researchers in these trials did not account correctly for the effect of confounders and clustering in the design and analysis stages. Objectives: This article aimed to review the main implications of implementing a cluster randomized controlled trials design in public health research and emphasize the practical application of proper analytical methods and the performance of different statistical models. Methods: The practical application of various analytical methods is validated via the utilization of experimental data from a public health research case study. This article also demonstrated the performance of hierarchical models and made comparisons in terms of empirically precise effect size estimates. Results: Three hierarchical statistical models were provided with highly varied effect sizes during the analysis of the intervention effect on outcome, such as model 1 (AOR: 14.32; 95% CI: 3.75–54.68), model 2 (ARR: 3.52; 95% CI: 2.16–5.77), and model 3 (ARR: 4.79; 95% CI: 2.69–5.52).Conclusion: Inaccurate results and potentially misleading conclusions can arise from improper cluster randomized controlled trial designs and analyses. This article has shown that real-world data can be adjusted for the effects of confounders and clustering, and we advocate for the routine use of suitable design and analytical methods. This article concludes that researchers should be careful when selecting hierarchical models to analyze cluster randomized controlled trials.

A two-year field experiment (2022–2023) was carried out to investigate the impact of different sowing periods (spring and winter) and nitrogen levels (0, 30, 60 kg/ha) on the phytoextraction potential of flax. The study site is characterized by high concentrations of heavy metals (Cd, Ni, Cu, Pb, Zn) and belongs to the Mediterranean climate type. Flax (var. Calista) was sown in the spring of 2022 and in the winter of 2023, following a split plot experimental design with three rep-lications, and applying low-input practices. Results showed that spring-sown flax produced short-er but thicker plants with significantly higher biomass (5.27 tn ha-1) when treated with 30 kg ha-1 N compared to winter-sown (2.30 tn ha-1) when treated with 60 kg ha-1 N. The concentration of contaminants in the aerial biomass varied according to metal type and sowing period. The higher biomass production in spring resulted in a higher quantity of heavy metals being removed from the soil, making flax a promising crop for phytoextraction purposes, especially in soils contami-nated with multiple heavy metals.