Background: Ice formation on power transmission lines presents significant risks, including structural damage and power outages. Traditional methods for detecting ice on these lines have limitations, particularly in challenging environmental conditions. This study aims to enhance ice detection accuracy by introducing a novel image segmentation and edge detection methodology using improved multi-scale Retinex and advanced morphological operations. Method: The proposed method integrates multi-stage image processing techniques, including image enhancement, grayscale conversion, thresholding, segmentation, object isolation, and edge detection. High-resolution binocular cameras were used to capture images of ice formations on transmission lines. The effectiveness of the method was assessed through a series of metrics, including accuracy, sensitivity, specificity, and precision, and compared with existing methodologies. Results: The proposed method demonstrated superior performance in both ice detection and thickness measurement. The method effectively identified and isolated ice formations under various conditions with an average accuracy of 98.35%, sensitivity of 91.63%, specificity of 99.42%, and precision of 96.03%. Additionally, the analysis of ice thickness measurements further highlighted the method’s accuracy, with a notably low root mean squared error (RMSE) of 1.20 mm and mean absolute error (MAE) of 1.10 mm, along with a strong R-squared value of 0.95. These statistical metrics show that the proposed method not only outperforms previous methods in consistency and alignment with manual measurements but also stands out as the most reliable option for tasks requiring precise measurements, offering significant advancements in accuracy and reliability over existing methodologies. Conclusions: The enhanced image segmentation and edge detection approach provides a more accurate and reliable method for monitoring ice formations on power transmission lines.

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.

Timber-concrete composite (TCC) systems join the positive aspects of engineered wood products (good seismic behaviour, low thermal conductivity, environmental sustainability, good behaviour under fire if appropriately designed) with those of concrete (high thermal inertia, durability, excellent fire resistance). TCC facades are typically composed by an internal insulated timber-frame wall and an external concrete slab, separated by a ventilated air cavity. However, there is very limited knowledge concerning the performance of TCC facades, especially for what concerns their thermal behaviour. The present paper deals with the development and optimisation of a 2D CFD model for the analysis of TCC ventilated façades thermal behaviour. The model is calibrated and validated against the experimental data collected during the annual monitoring of a real TCC ventilated envelope in the north of Italy. Also, a new solver algorithm is developed to significantly speed up the simulation. The final model can be used for the time-efficient analysis and optimisation of the thermal performance of TCC ventilated facades, as well as other ventilated facades with external massive cladding, avoiding the expensive and time-consuming construction of mock-ups, or the use of comparably slow (conventional) CFD solvers that are less suitable for optimization studies.

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.

(1) Background: The rapid development of information technology has changed the traditional concept of space, gradually shifting the "container space" to the "relational space" . The constraints of geographical spatial elements are diminishing, and the theory of virtual agglomeration is gaining attention. (2) Methods: In this study, we constructed an evaluation system for virtual agglomeration, comprising four primary indicators: virtual infrastructure level, virtual output level, virtual input level, and virtual service level. The TOPSIS method was used to calculate the virtual agglomeration level for each province, and the DEA-Malmquist method was employed to measure provincial total factor productivity (TFP) in China. Using panel data from 30 provincial regions in China from 2013 to 2021, we examined the mechanism and impact path of virtual agglomeration on TFP. (3) Result: There is an inverted U-shaped relationship between virtual agglomeration and TFP in China. The overall development level of virtual agglomeration is relatively low, within the range where the marginal effect of virtual agglomeration on TFP is positive but diminishing, indicating significant potential for further development. The impact of virtual agglomeration on TFP is stronger in the Yangtze River Economic Belt compared to non-Yangtze River areas, and the highest stable point of TFP is higher in central provinces than in eastern and western provinces. (4) Conclusions: This study provides a theoretical basis and practical reference for improving the level of virtual agglomeration.

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.

To date, the percentage composition of the lung microbiome in bronchopulmonary cancer has not been summarized. Existing studies on identifying the lung microbiome in bronchopulmonary cancer through 16S rRNA sequencing have shown variable results regarding the abundance of bacterial taxa. Objectives: To identify the predominant bacteria in the lung microbiome of bronchopulmonary cancer from samples collected through bronchoalveolar lavage and to assess their potential role in the diagnosis of bronchopulmonary cancers. Data Sources: A systematic review of English articles using MEDLINE, Embase, and Web of Science. Search terms included lung microbiome, lung cancer, bronchoalveolar lavage. Study Selection: Randomized clinical trials that investigated the lung microbiome in bronchopulmonary cancer with samples collected via bronchoalveolar lavage. Data Extraction: Independent extraction of articles using predefined data fields, including study quality indicators. Data Synthesis: Nine studies met the inclusion criteria, focusing on those that utilized a percentage expression of the microbiome at the phylum or genus level. There was noted heterogeneity between studies, both in terms of phylum and genus, with a relatively constant percentage of the Firmicutes phylum and the genera Streptococcus and Veillonella being mentioned. Significant differences were also observed regarding the inclusion criteria for study participants, the method of sample collection, and data processing. Conclusions: To date, there is no consistent percentage pattern at the phylum or genus level in bronchopulmonary cancer, with the predominance of a phylum or genus varying across different patient cohorts, resulting in non-overlapping outcomes.

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.

Clinical trials are essential in the development of new medical treatments, offering crucial data on their safety and effectiveness. This study provides a comprehensive analysis of clinical trials registered on ClinicalTrials.gov, examining trends, challenges, and innovations that have shaped the field over the past century. Data were extracted on July 15, 2024, and analyzed to identify patterns in trial design, sponsorship, participant demographics, and geographical distribution. The analysis reveals a significant increase in clinical trial registrations, peaking in 2021, driven by the COVID-19 pandemic. Most trials focus on cancer, reflecting its global burden, and are predominantly interventional, with randomized controlled trials (RCTs) being the most common study design. However, challenges persist, including underrepresentation of certain demographics, limited global distribution, and insufficient reporting of trial results. Additionally, the underrepresentation of pediatric, elderly, and minority populations in trials limits the generalizability of findings. The analysis underscores the need for more inclusive and globally distributed research to address disparities in health outcomes.

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.

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.

The interest in virtual fencing, as opposed to traditional physical barriers, has increased since it makes it easier to move the boundaries of animal enclosures for agricultural and rewilding purposes. Despite this, the implementation of virtual fence systems, such as the Nofence© system, requires large financial investments. The necessity of individual collars also makes it more difficult to implement this system on a larger scale. If a herd of cattle tend to maintain cohesive social groups around dominant individuals, it might be possible to use fewer collars thereby making the system more cost efficient. This study investigates the pattern in spatial distribution in a herd of 17 Angus cows on Fanø in Denmark with GPS locations, using a Nofence© system. The aim of this paper is to determine how individuals position themselves in a herd, spatially, and identify a pattern in ranks. The method used in this study examines the distances between an individual to the rest of the herd mates using nearest neighbour and distribution plots. Contrary to the expectations, this study did not show a distinct pattern in herd distribution. While some tendencies in spatial distribution patterns were observed, only a low concordance could be found (W=0.15,p=3.02e−16). Therefore, interactions among individuals should be considered in future studies, rather than only investigating the herd as one unit. A cumulative curves of the ranks estimated over the entire periods allowed however a rough estimation of the hierarchy and allowed the identification of the highest ranked cows. Therefore it might be possible to use fewer collars if the high ranked cows are discovered, but the estimation of the hierarchy will require a period of observation overall several days as the hierarchical positions are fluctuating too much from days to days. Therefore the cumulative rank curves seems to be a valid solution.

This research presents the creation of a Virtual Reality experience for the Balzi Rossi museum, commemorating the centenary of Prince Albert I Grimaldi's archaeological work at the site. The project, a collaboration between the University of Genoa's 3D Lab Factory, Eurodrone, and the Balzi Rossi archaeological museum, aims to preserve and convey the site's heritage through advanced VR technology. Initially employing Unreal Engine 4, the team used photogrammetry for 3D reconstruction of the "Caviglione" and "Florestano" caves, notable for their ancient rock engravings. This first VR model, despite hardware limitations, provided an interactive exploration of the site. The subsequent development phase utilized Unreal Engine 5, incorporating Nanite technology for enhanced visual fidelity. This advancement resulted in a more detailed and immersive VR experience, presenting the Balzi Rossi cliff across different historical periods, including the Würm glaciation. Key to this phase was optimizing the VR experience for performance, focusing on stable frame rates and minimizing motion sickness, and integrating a multi-lingual interface for broader accessibility. Since November 2023, the VR setup at the Balzi Rossi Museum has been an educational and interactive feature, enabling visitors to explore the site's history virtually. This research demonstrates the potential of VR in cultural heritage preservation and education, providing a foundation for future technological improvements in the field.

The combination of encryption and digital watermarking technologies is a trend to achieve full lifecycle data protection. Recently, reversible data hiding in encrypted domain (RDHED) has greatly aroused the interests of many scholars. But the fixed order of first encryption and then watermarking makes this kind of algorithms unsuitable to many applications. Commutative encryption and watermarking (CEW) technology realizes the flexible combination of encryption and watermarking, and suits more applications. However, most existing CEW schemes for vector maps are not reversible and unsuitable to high precision maps. To solve this problem, here we propose a commutative encryption and reversible watermarking (CERW) algorithm for vector maps based on virtual coordinates which are uniformly distributed on the number axis. The CERW algorithm consists of virtual interval step based encryption scheme and coordinate difference based reversible watermarking scheme. In the encryption scheme, the map coordinates are moved randomly by multiples of virtual interval step defined as distance between two adjacent virtual coordinates. In the reversible watermarking scheme, difference expansion (DE) technique is used to embed the watermark bit into the coordinate difference computed based on the relative position of a map coordinate in a virtual interval. Since the relative position of a map coordinate in a virtual interval keeps unchanged during the coordinate scrambling encryption process, the watermarking operation and the encryption operation don’t interfere with each other and the commutativity between encryption and watermarking achieves. Results show that: proposed method has high security, high capacity and good invisibility. In addition, the algorithm is not only applicable to polyline and polygon vector data, but also can be applied to sparsely distributed point data which the traditional DE watermarking algorithm often fails to watermark.

(1) Background: Multi-year research into the synergistic effect of cyclophosphamide and complex composite double-stranded DNA preparation (DNAmix) has made it possible to develop the novel Karanahan technology for treating malignant tumors, which is based on the eradication of cancer stem cells; (2) Methods: Pilot clinical trials for Karanahan technology were conducted in 12 patients with advanced stage IV breast cancer; (3) Results: The findings indicate that the analyzed treatment regimen ensures a local positive therapeutic response, significantly increases patient survival time, and activates the adaptive antitumor immune response. Adjustment of the basic regimen of Karanahan technology has been developed, which consists of increasing the dose of the DNAmix complex composite double stranded DNA preparation and its lymphotropic administration to the main lymph depots simultaneously with intratumoral injection; (4) Conclusions: Karanahan technology has a promising therapeutic potential in the treatment of inoperable stage IV breast cancer.

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.

In this paper, a method is developed for presenting a novel virtual torque sensor based on precise model and position measurements avoids the need of traditional strain gauges and amplifiers. More specifically, the harmonic drive compliance model and the Gaussian process regression (GPR) technique are used together to achieve virtual torque sensor measurement. While the harmonic drive compliance model provides the analytic part, the Gaussian process regression method is used to reconstruct the unmolded part based on motor-side and link-side joint angles as well as motor current. After an automatic offline calibration, the method allows for a lean online implementation. The virtual torque sensor measurement is compared with measurements of a commercial torque sensor, and the results have attested the effectiveness of the proposed method.

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

Introduction: The aim is to investigate the possibility of altering the delusional perceptions of psychotic patients by exposing them to a cognitively flexible virtual environment. A flexible vir-tual reality (VR) environment could challenge and enhance the ability to adapt to changing situa-tions and generate novel solutions to core psychotic symptoms. Materials and methods: A systematic review was conducted using different combinations of keywords in different databases. This study was conducted using the PRISMA statement. Results: There is a growing literature on the use of VR to manipulate and normalise perceptual distortions in psychosis. Over the last decade, the number of published studies on VR in mental health has increased 14-fold. Conclusions: A cognitive flexibility virtual environment can alter delusional perception by ex-posing the person to different scenarios that require them to question their assumptions, test their hypotheses, and revise their beliefs. Commonly used biosensors measure heart rate, skin con-ductance and body temperature in relation to different emotional states. Recently, there has been a major shift towards the use of neuroimaging techniques to better understand the pathophysiology of mental disorders. This is where the new wave of biosensor-integrated virtual reality (VR) sys-tems comes in.

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.

Veterinary science has benefitted from technological advancements in the past and will hopefully continue to do so, especially in the field of equine gait analysis. There is a need for rapid and easy to use technology that is accurate and portable, but at the same time is also readily interpretable. This manuscript presents two new approaches to equine gait analysis, both of which are commer-cial devices. The use of Acoustic MyoGraphy (AMG) has been proven in the field of muscle func-tion and performance as well as ligament health, but it can also provide details concerning gait when placed on the wall of the hoof of a horse. The TendibootTM system is a limb focused unit that can be easily attached, activated and used in a Veterinary clinic setting, rapidly providing gait details for equine diagnostic purposes. In conclusion this manuscript provides an insight into gait parameters from recent research trials that are novel and challenge current thinking.

Background: Virtual Reality (VR) is an emerging tool in the management of anxiety, one of the most disturbing symptoms of Alcohol Use Disorder (AUD), which often leads to relapse. Still, patients with Alcohol Use Disorder frequently have a history of Acute Symptomatic Seizures, and they are subsequently excluded from studies using VR because of the hypothesized fear of inducing photosensitive seizures. The first part of this narrative review explores the pathophysiological mechanisms of seizures associated with AUD, specifically acute symptomatic seizures. In contrast, the second part explores virtual reality’s safe use in seizure-prone individuals, highlighting that the current state-of-the-art is based on a biased per-ception and old epidemiological data from studies conducted on photosensitive seizures in the late 90s. VR exposure has yet to be reported as triggering seizures within known pharmacovigilance databases. Significance: The implications weigh heavily on VR research currently associated with this significant adverse event. Further studies are necessary to address the risk of seizures triggered by VR in patients predisposed to developing seizures, like alcohol use disorder patients with a history of acute symptomatic seizures. Such research is essential to ensure that the potential benefits of Virtual Reality as a tool for managing anxiety in individuals with alcohol use disorder and acute symptomatic seizures are not unduly restricted. Furthermore, AUD can also serve as an intervention model feasible to de-bias attitudes toward the current lack of evidence base concerning the significant adverse events of VR-induced seizures, therefore facilitating the clinical implementation of this unharnessed digital treatment interface.

This study investigated the effectiveness of virtual reality (VR) technology in table tennis education compared to traditional training methods. A 12-week randomized controlled trial was conducted with 120 participants divided equally between VR and traditional training groups. Performance metrics, learning motivation, and satisfaction were assessed at regular intervals. Results demonstrated significant advantages of VR training, with the VR group showing superior improvements in serve accuracy (23.5% vs. 15.8%, p < 0.001), rally endurance (increase of 8.2 vs. 5.7 shots, p < 0.01), and overall skill scores (18.7 vs. 13.2 points improvement, p < 0.001). The VR group also exhibited higher increases in learning motivation (23.5% vs. 12.8%, p < 0.001) and satisfaction (31.5% vs. 18.7%, p < 0.001). Subgroup analysis revealed particular benefits for novice players and younger participants. These findings suggest that VR technology offers a promising approach to enhance table tennis education, potentially revolutionizing sports training methodologies. Future research should focus on long-term skill retention and the optimization of VR training protocols.

The agricultural industry relies on physical fences to manage livestock. However, physical fences present some practical, financial, and ecological problems, that partly may be solved by virtual fencing. However, it is necessary for the livestock to be adapted to virtual fencing. This study aims to identify if adaptation to virtual fence can be improved through social facilitation between experienced cattle and the remaining herd. Moreover, which of the two different learning processes, a gradual or instant introduction to virtual fence is the most effective in associating warnings with impulses. Three pastures containing Angus (Bos taurus) will be used to examine these investigations; A, B and C. All investigations are conducted on the Danish Island of Fanø. Three methods of learning process were used, one gradual and two instant introductions to the virtual fence. The investigations had varying amounts of experienced cattle. Impulses and warnings were recorded during a learning period and the following observation period. To quantify if the cattle adapt to the warnings, impulses per warning are used. There was no evidence of improvement with the presence of experienced cattle for any pastures, indicating no social facilitation. Gradual introduction was found to be more beneficial than instant introduction. More standardized tests are necessary to discover the full effect of experienced cattle.

This research paper examines a cosmological model in flat space-time via $f(R,G)$ gravity where $R$ and $G$ are respectively the Ricci scalar and Gauss-Bonnet invariant. Our model assumes that $f(R,G)$ is an exponential function of $G$ combined with a linear combination of $R$. We scrutinize the observational limitations under a power law cosmology that relies on two parameters - $H_0$, the Hubble constant, and $q$, the deceleration parameter, utilizing the 57-point $H(z)$ data, 8-point BAO data, 1048-point Pantheon data, joint data of $H(z)$ + Pantheon, and joint data of $H(z)$ + BAO + Pantheon. The outcomes for $H_0$ and $q$ are realistic within observational ranges. We have also addressed Energy Conditions, $Om(z)$ analysis and cosmographical parameters like Jerk, Lerk and Snap. Our estimate of $H_0$ is remarkably consistent with various recent Planck Collaboration studies that utilize the $\Lambda$CDM model. According to our study, the power law cosmology within the context of $f(R,G)$ gravity provides the most comprehensive explanation for the important aspects of cosmic evolution.

Objectives: Aim to assess the perceptions of virtual learning among dental residents and faculty and employ Regulatory Focus Theory (RFT) to understand the impact of motivational orientations on virtual learning during COVID pandemic. Methods: 46 dental residents and 10 faculty in Upstate New York participated in the study (June -August 2021). Questionnaires were used to collect demographics, perceptions of virtual learning, burnout, and RFT types (promotion and prevention focus). Multiple regression analyses were used to examine factors associated with perceptions of virtual learning and burnout. Results: Overall, 70% of residents and 44% of faculty found virtual learning effective. Younger residents with less experience preferred virtual learning more than their older, experienced peers. Residents trained outside the U.S. and Canada favored in-person learning more than those trained within. Furthermore, residents with a higher promotion focus score found virtual learning more interactive for didactic courses. Additionally, 52% of residents experienced burnout, with a higher incidence among females (p=0.044). Conclusions: Virtual learning is well-received by dental residents and faculty, with potential for continued use post-pandemic. Future efforts should focus on creating an inclusive and supportive educational environment that meets the motivational and well-being needs of dental residents and faculty.

In GNSS/IMU integrated navigation systems, factors such as satellite occlusion and non-line-of-sight conditions can lead to degradation of satellite positioning results, Subsequently affecting the overall accuracy of the integrated navigation system. To address this issue and ef-fectively utilize historical pseudorange information from satellites, this paper proposes a graph optimization-based GNSS/IMU model with virtual constraints. These virtual constraints are con-structed using satellite ‘s position from previous time step, the rate of change of pseudoranges, and ephemeris data. This virtual constraint can serve as an alternative solution for individual satellites in case of signal anomalies, ensuring the integrity and continuity of the graph optimi-zation model. Additionally, this paper conducts an analysis of the graph optimization model constructed using these virtual constraints, comparing it with traditional integrated navigation graph optimization model, and analyzes and reconstructs the marginalization process based on these virtual constraints. The experimental results, compared with tightly coupled Kalman fil-tering and the original graph optimization method on a set of real-world data, demonstrate that the introduction of virtual pseudoranges maintains high positioning accuracy. The RMSE error between it and the original graph optimization remains within 5%, affirming the high feasibility of this approach.

Childhood overweight/obesity (OV/OB) is a major public health problem, of greater concern when accompanied with comorbidities such as hypertension and insulin resistance leading to metabolically unhealthy obesity (MUO). Aetiologic associations between meal patterns, OV/OB risk and MUO are limited. The aim of this systematic review was to explore associations between meal patterns and the risk of childhood OV/OB and MUO. Longitudinal studies and randomised controlled trials from PUBMED and Scopus published between January 2013 - April 2024 were retrieved. Twenty-eight studies were included, all of which reported on OV/OB risk; none on MUO risk. Regular consumption of breakfast and family meals and avoiding dining while watching TV may be protective factors against childhood OV/OB, whereas meal skipping (primarily breakfast) may be a detrimental factor. Mixed effects of meal frequency on OV/OB risk were observed; no effects of frequency of lunch or of fast-food consumption and of meals served at school were found. There was insufficient evidence to support the role of other patterns (meal timing, eating in other social contexts). Meals were mainly participant-identified, leading to increased heterogeneity. Research focusing on childhood MUO and improved methodological approach (e.g. harmonised definitions) regarding the assessment of meal patterns are highly warranted.

Technological advances made Virtual and Mixed Reality (VMR) accessible at our fingertips. However, only recently VMR has been explored for the teaching of biology. Here, we highlight how VMR applications can be useful in biology education, discuss about caveats related to VMR use that can interfere with learning, and look into the future of VMR applications in the field. We then propose that the combination of VMR with Machine Learning and Artificial Intelligence can provide unprecedented ways to visualise how species evolve in self-sustained immersive virtual worlds, thereby transforming VMR from an educational tool to the centre of biological interest.

This article presents an in-depth review of Virtual Power Plant (VPP), its organization in the energy system and its prospects in the face of the promising future of the increasing bidirectional complexity exposed in the current scenario. A new paradigm for the operations of modern power distribution and transmission systems requires greater grid flexibility that is accompanying an extensive change in the structure of electricity markets, the fruit of the development of the renewable industry and of the growing photovoltaic systems popularized, but in contrast due to the intermittent nature cause variable uncertainties in the power system. Innovative concepts like VPP are becoming a reality, establishing an efficient and effective mechanism. The objectives and components are described in a comprehensive way, and some of the most important are pointed out and presented in detail to contribute with a description of the energy systems and the implicit research needed for sustainability and resilience in the eminent energy scenario with this technology. In addition, the literature and studies of this technology already indicate a direction of this new tool as a promising solution to manage the uncertainties of the renewable energies.

Fractional flow reserve (FFR) is well recognized as a gold standard measure for the estimation of functional coronary stenosis. Technological progressions in image processing have empowered the reconstruction of three-dimensional models of the coronary arteries via both non-invasive imaging modalities, such as Coronary Computed Tomography Angiography (CCTA), and invasive coronary angiography or intravascular imaging. The application of computational fluid dynamics (CFD) techniques to coronary 3D anatomical models allows the virtual evaluation of the hemodynamic significance of a coronary lesion with high diagnostic accuracy in comparison to the invasive FFR using pressure wires. These opportunities providing hemodynamic information based on anatomy have given rise to a new era of functional angiography and coronary imaging. However, further validations are needed to overcome several scientific and computational challenges before these methods are applied in everyday clinical practice. This review aims to present all the data on the studies and methodologies that have been presented for the virtual estimation of FFR, and the diagnostic execution of the virtual tools for the hemodynamic assessment of coronary lesions compared to the invasive FFR.

Sensory integration is an essential function of human life, and its decline causes difficulties in the quality of life, especially in older adults. In this study, we proposed an arm-reaching task based on a virtual reality head-mounted display (VR-HMD) system to assess sensory integration in daily life, and examined whether reaching task performance was associated with age and resting-state functional connectivity (rsFC) between the brain regions of interest involved in sensory integration. We hypothesized that performance during a reaching task with multiple cognitive loadings would be affected by aging. The gap angle between the reaching hand and target positions was compared between older and middle-aged adults as a measure of sensory integration function. In addition, rsFC, which was significantly correlated with the gap angles of individual participants in the older adult group, was identified using resting-state functional magnetic resonance imaging data. The mean gap angle was significantly larger in the older adults than in the middle-aged group and was also significantly correlated with connections between the left primary motor area and the left inferior temporal gyrus, temporo-occipital part. Because the connectivity between the areas is known to be related to visuomotor integration, the results suggest the involvement of visuomotor integration in the decline of sensory integration function in old age and the validity of the gap angle during the proposed VR-HMD task as an index for the decline in function.

This paper examines the use of multisensory virtual reality (VR) as a novel approach in psychological therapy for autobiographical memory retrieval with benefits for cognitive enhancement, stress reduction etc. The research in this paper was done under Romanian Arut Research Grant no. 27/09/10/2023 ”Intelligent VR system for treating autobiographical/episodic memory deficits".  By simulating realistic multisensory experiences, VR technology offers an immersive environment that surpasses traditional therapeutic methods in effectiveness. Previous studies demonstrate improved outcomes in treating various psychological conditions (affective disorders and PTSD, specific phobias and age-related cognitive decline). Technological advancements in VR, such as olfactory integration cand contribute to the realism and therapeutic potential of these environments, the integration of various physical stimuli with VR holds promising potential psychological therapies and highlighting the need for further interdisciplinary research. In this pilot study we tested the efficacy of a new system for triggering autobiographical memory retrieval. For this we used images combined with odors in a congruent manner and offering participants the chance to interact with the VR environment by using 2 virtual hands. We evaluated the efficacy of this system using qualitative methods with emphasis on the evaluation of the emotions associated with memory recollection and the ease of triggering memories. All participants in our pilot study experienced intense emotions related to childhood or adolescence and the pleasant feelings they had during the experiment persisted even after it ended. This is an advancement to what exists currently and original research elements for our paper.

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.

The integration of robotic devices into healthcare settings for rehabilitation purposes represents a rapidly advancing field with significant benefits for both therapists and patients. However, standalone robot systems face limitations such as inefficient processing of patient data and logistical challenges for patients, such as travel time to rehabilitation centers. To address these shortcomings, this paper proposes the integration of cyber-physical systems into rehabilitation robotics. Cyber-physical systems leverage network connectivity and real-time data processing to enhance the efficiency and convenience of robot-based rehabilitation. By seamlessly integrating sensors, actuators, and computational algorithms, cyber-physical rehabilitation systems empower therapists to more effectively treat patients by providing actionable insights derived from comprehensive data analysis. This enables therapists to tailor treatment plans precisely to each patient’s unique needs, ultimately leading to improved outcomes. Additionally, cyber-physical rehabilitation systems facilitate remote monitoring and intervention, allowing therapists to oversee patient progress and make timely adjustments to treatment protocols without the need for in-person visits. This not only saves patients valuable time and resources but also ensures continuity of care, particularly for individuals residing in remote or underserved areas. Furthermore, cyber-physical rehabilitation systems enable collaborative decision-making by facilitating communication and information sharing among healthcare professionals, further enhancing the quality and efficacy of rehabilitation services. In summary, integrating cyber-physical systems into rehabilitation robotics represents a significant advancement in leveraging technology to optimize patient care and outcomes, promising to revolutionize rehabilitation therapy.

Dengue (DENV) and Zika (ZIKV) virus continue to pose significant challenges globally due to their widespread prevalence and severe health implications. Given the absence of effective vaccines and specific therapeutics, targeting of the highly conserved NS5 RNA-dependent RNA polymerase (RdRp) domain has emerged as a promising strategy. However, limited efforts have been made to develop inhibitors for this crucial target. In this study, we employed an integrated in silico approach utilizing combinatorial chemistry, docking, molecular dynamics simulations, MM/GBSA, and ADMET studies to target the allosteric N-pocket of DENV3-RdRp and ZIKV-RdRp. Using this methodology, we designed lycorine analogs with natural S-enantiomers (LYCS) and R-enantiomers (LYCR) as potential inhibitors of non-structural protein 5 (NS5) in DENV3 and ZIKV. Notably, 12 lycorine analogs displayed a robust binding free energy (&lt;-9.00 kcal/mol), surpassing that of RdRp-Ribavirin (&lt;-7.00 kcal/mol) along with promising ADMET score predictions (&lt;4.00), of which (LYCR728-210, LYCS728-210, LYCR728-212, LYCS505-214) displayed binding properties to both DENV3 and ZIKV targets. This study highlights the potential of non-nucleoside lycorine-based analogs with different enantiomers that may present different or even completely opposite metabolic, toxicological, and pharmacological profiles as promising candidates for inhibiting NS5-RdRp in ZIKV and DENV3, paving the way for further exploration for the development of effective antiviral agents.

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.

Genetic engineering has revolutionized our ability to modify microorganisms for various applications in agriculture, medicine, and industry. This review examines recent advances in genetic engineering techniques for bacteria, fungi, and oomycetes, with a focus on CRISPR-Cas systems. In bacteria, CRISPR-Cas9 has enabled precise genome editing, enhancing applications in antibiotic production and metabolic engineering. For fungi, despite challenges associated with their complex cell structures, CRISPR/Cas9 has advanced the production of enzymes and secondary metabolites. In oomycetes, significant plant pathogens, modified Agrobacterium-mediated transformation and CRISPR/Cas12a have contributed to developing disease-resistant crops. The review provides a comparative analysis of genetic engineering efficiencies across these microorganisms and addresses ethical and regulatory considerations. Future research directions include refining genetic tools to improve efficiency and expand applicability in non-model organisms. This comprehensive overview highlights the transformative potential of genetic engineering in microbiology and its implications for addressing global challenges in agriculture, medicine, and biotechnology.

This paper proposes an optimization method for the scheduling of a multi-energy virtual power plant supply-demand balance in the power market environment of Jiangxi Province. The objective of this method is to enhance the operational efficiency of the power grid, reduce energy costs, and facilitate economical and efficient energy distribution in the power market. The method comprehensively considers the characteristics and uncertainties of renewable energy sources such as solar and wind energy, and incorporates advanced multi-objective optimization algorithms. Additionally, real-time market price feedback is integrated to achieve accurate allocation of power supply and demand. Through a case study of a multi-energy virtual power plant in Jiangxi Province, this paper examines the optimal combination model for various energy sources within VPP, and analyzes the impact of different market environments on supply-demand balance. The results demonstrate that the proposed scheduling optimization method significantly improves economic benefits while ensuring grid stability. Compared with traditional power supply models, it reduces average electricity costs by 15% and increases renewable energy utilization efficiency by 20%.

A sustainable smart tourism ecosystem relies on building digital networks that link tourists to destinations. This study explores how web and immersive technologies, such as the VRRO platform, can improve tourism by offering interactive experiences to augment traditional travel. The study underscores the role of VRRO's design in enhancing user interaction and engagement, thereby encouraging the generation of user content and the development of a virtual tour network. An empirical analysis investigates user engagement, revealing that the platform is accessible to users regardless of their technological familiarity. It suggests a high likelihood of sustained use and recommendations. In conclusion, VRRO demonstrates how accessible and innovative technologies in tourism modernize travel experiences and significantly contribute to the evolution of the broader tourism ecosystem.

Selection is a fundamental interaction element in Virtual Reality (VR) and 3D user interfaces (UIs). Raycasting, one of the most common object selection techniques, has been known to have difficulties in selecting small or distant objects. Meanwhile, recent advancements in computer vision technology have enabled seamless vision-based hand tracking in consumer VR headsets, enhancing accessibility to freehand mid-air interaction and highlighting the need for further research in this area. This study proposed a new technique called TouchView which utilizes a virtual panel with a modern adaptation of the Through-the-lens metaphor to improve freehand selection for VR UI. TouchView enables faster and less demanding target selection by allowing direct touch interaction with the magnified object proxies reflected on the panel view. Repeated-measures ANOVA on the results of a follow-up user experiment on multitarget selection with 23 participants showed that TouchView outperformed the current market-dominating freehand raycasting technique, Hybrid Ray in terms of task performance, perceived workload, and preference. The user behavior was also analyzed to understand the underlying reasons for these improvements. The proposed technique can be used in VR UI applications to enhance the selection of distant objects, especially for cases with frequent view shifts.

Dengue virus is a global health problem most prevalent in tropical and subtropical regions. However, after the approval of two vaccines, Dengvaxia, TV003/TV005 of Takeda, for its prevention, problems were reported, like enhanced risks of infection or less efficiency of protection. Since then, more struggles have been in demand for the development of better vaccines. Here, we conducted a new design through an in-silico strategy. Initially, epitopes were chosen based on their antigenicity, immunogenicity, and binding affinity with MHC molecule, while excluded with allergenicity, toxicity and potential risk of antibody dependent enhancement. Subsequently, a core antigen was constructed with selected epitopes and linked with distinct adjuvant proteins to achieve three candidate vaccines, PSDV-1~3. PSDV-2 was chosen for further validation based on their advantage in physicochemical and structural properties. With a panel of simulations, this artificial protein showed tight binding with pattern recognition receptors, good stability, robust immune induction, and ultimately was confirmed as a high quality vaccine candidate. The plasmid for its recombinant expression was then designed accordingly. With our new design, one more choice was obtained for the effective protection from Dengue virus. Further experimental validations are still require to confirm it protection capacity and safety.

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.

Plant growth-promoting rhizobacteria (PGPR) are beneficial bacteria that play a crucial role in sustainable agriculture by enhancing plant growth through various mechanisms. This review examines the contributions of PGPR in improving nutrient availability, producing phytohormones, providing biocontrol against pathogens, and enhancing abiotic stress tolerance. By reducing the necessity for chemical fertilizers and pesticides, PGPR mitigate environmental impacts, enhance soil health, and support long-term agricultural productivity. However, challenges such as inconsistent performance across various soils, regulatory barriers, and limited farmer awareness hinder their widespread adoption. Recent advancements in nano-encapsulation technology, genetic engineering, and bioinformatics present promising solutions for overcoming these obstacles and enhancing PGPR efficacy. The incorporation of PGPR into biofertilizers, biopesticides, and integrated pest management (IPM) strategies offers a sustainable resolution to global agricultural challenges. This review addresses the current state of PGPR research, applications, and future directions for optimizing their use in promoting sustainable agriculture.

This study presents a systematic review to evaluate the effectiveness of virtual patients in enhancing clinical reasoning skills in medical education, utilizing a hybrid methodology that combines human reviewers and ChatGPT. By analyzing various studies involving conversational virtual patients, the review examines the impact of these digital tools on student learning outcomes and satisfaction. Consistent with previous systematic reviews, our findings suggest that conversational virtual patients can improve clinical competencies, particularly in history-taking and clinical reasoning. Regarding student feedback, satisfaction tends to be higher when virtual patients’ interactions are more realistic, often due to the use of artificial intelligence (AI) and natural language processing (NLP) in the simulators. Furthermore, the study compares the accuracy of AI-driven reviews with human assessments, revealing comparable results. This research highlights AI’s potential to complement human expertise in academic evaluations, contributing to more efficient and consistent systematic reviews in rapidly evolving educational fields.

There has been an increased focus on new technologies to monitor habitat use and behaviour of cattle, to develop a more sustainable livestock grazing system, without compromising animal welfare. The currently most used method for monitoring cattle behaviour is tri-axial accelerometer data from systems such as virtual fencing technology or bespoke monitoring technology. This method requires high frequency data, and as such, quickly drains contemporary systems of power making it unsuitable for long-term monitoring. In this paper, we explore the possibility of determining habitat preference and habitat utilisation patterns in cattle, using low frequency activity and location data. We do this by (1) calculating habitat selection ratios, (2) determining daily activity patterns and based on those, (3) inferring grazing and resting sites in a group of cattle wearing virtual fencing collars in a coastal setting with grey, wooded and decalcified dunes, humid dune slacks and salt meadows. We found that GPS data, and a measure of activity, combined with accurate mapping of habitats can be an effective tool in assessing habitat preference. The animals preferred salt meadows over the other habitats, with wooded dunes and humid dune slacks being the least preferred. We were able to identify daily patterns in activity. By comparing general trends in activity levels to existing literature, it was possible to somewhat infer resting and grazing behaviour in the different habitats. According to our inference of behaviour the herd predominantly used the salt meadows for resting and ruminating. The approach used in this study allowed us to use GPS location data for measuring the activity and combine it with accurate habitat mapping in a cheap and effective way, which can be an important tool for guiding management decisions.

The recent COVID-19 pandemic has showcased the implications of using virtual private networks (VPNs) as home-working is now common. Establishing the current state of knowledge on VPNs and their processes is vital. This corroborates an up to date understanding on the fundamentals of VPNs and their usage in today’s society; it informs on how to better use VPNs too. Insight into the security issues VPNs face and possible solutions to these allows for the identification of gaps for potential future research. Addressing these gaps would then indicate how to further improve VPNs, making sure VPNs are indeed beneficial to users.

The paper provides information on significant contamination of real laboratory water with hydrophilic microimpurities. This fact suggests that researchers are practically dealing with microdispersed systems. However, this fact is usually neglected in the discussions of the causes of the anomalous properties of water. We will show that, when exposed to various factors of physical nature, water demonstrates reactions of the same type, namely, increased pH and electrical conductivity, reduced redox potential and viscosity, and enhanced bioavailability. Each exposure is accompanied by the destruction of aggregates of the dispersed phase and its transition to a fine-dispersed state. The relationship between this phenomenon and the change in the physicochemical properties of water is discussed.

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.

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.

Appropriate techniques for promoting reading fluency are difficult to implement in the classroom. There is little time to provide students with individualized feedback on reading aloud or to moti-vate them to do so. In this context, VR can be beneficial for learning, to provide individualized feedback and for increasing learners' engagement. Studies analyzing established methods of lan-guage learning in school in VR seem to be lacking so far. Therefore, this study project was the first to analyze the acceptance of students towards the implementation of a concept of reading fluency training with students at a secondary school in VR. The study method was developed based on the Technology Acceptance Model. The VR environment developed is web-based and provides indi-vidual and collaborative opportunities for training reading fluency, giving, and receiving feed-back, and deepening content understanding of the reading texts. To analyze the acceptance of the VR environment, 5 guided interviews were conducted. The results show that despite technical challenges with the VR environment, students accepted and appreciated the reading fluency training in VR. The integration of established concepts of reading fluency training in foreign lan-guage classrooms has great potential as additional added value can be created to address the challenges of face-to-face instruction.

Virtual screening - predicting which compounds within a specified compound library bind to a target molecule, typically a protein - is a fundamental task in the field of drug discovery. Doing virtual screening well provides tangible practical benefits, including reduced drug development costs, faster time to therapeutic viability, and fewer unforeseen side effects. As with most applied computational tasks, the algorithms currently used to perform virtual screening feature inherent tradeoffs between speed and accuracy. Furthermore, even theoretically rigorous, computationally intensive methods may fail to account for important effects relevant to whether a given compound will ultimately be usable as a drug. Here we investigate the virtual screening performance of the recently released Gnina molecular docking software, which uses deep convolutional networks to score protein-ligand structures. We find, on average, that Gnina outperforms conventional empirical scoring. The default scoring in Gnina outperforms the empirical AutoDock Vina scoring function on 89 of the 117 targets of the DUD-E and LIT-PCBA virtual screening benchmarks with a median 1% early enrichment factor that is more than twice that of Vina. However, we also find that issues of bias linger in these sets, even when not used directly to train models, and this bias obfuscates to what extent machine learning models are achieving their performance through a sophisticated interpretation of molecular interactions versus fitting to non-informative simplistic property distributions.

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

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.

ABSTRACT: Background: Virtual Reality (VR) emerges as a promising non-pharmacological intervention for managing symptoms and providing distraction during chemotherapy. This study aims to assess VR's effectiveness on cancer-related symptoms, vital signs, and patients' perception of the chemotherapy in lung cancer patients. Methods: A quasi-experimental study was conducted on 100 patients. Participants were allocated into an intervention group (n = 55), which experienced immersive VR, and a comparison group (n = 45), which received usual care. Data were collected through questionnaires and checklists, including feedback on the VR experience, pain, vital signs, and common cancer symptoms, assessed through the Edmonton Symptom Assessment Scale. Results: VR had a significant impact on reducing the perception of the chemotherapy length. Patients reported high levels of satisfaction and tolerability. No adverse events were observed. VR did not have significant influence on pain intensity and vital signs. The only exceptions were oxygen saturation, where a significant difference (p = 0.02) was reported, and perception of chemotherapy duration. Conclusions: As a non-pharmacological intervention, VR proves beneficial in minimizing the perceived length of chemotherapy session for lung cancer patients, enhancing their overall treatment experience. The intervention showed to be a safe, feasible, and well-accepted distraction technique. Future research should explore VR's potential effects on a wider range of symptoms and evaluate its impact on long-term outcomes.

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.

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.

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.

The expansion of Open World Video Games (OWVGs) has seen the emergence of multiple new fictional worlds. This type of video game is characterized by total immersion in a world built for the players entertainment. What videogames developers want when players enter an OWVG is that they could feel like if they were open a door to an entirely new world and leave the real world behind. These virtual worlds manifest as a complement, an alternative, or the successor to the physical universe, and in some way continue the philosophical tradition of possible worlds begun by Leibniz. Accustomed to ‘surviving’ in hostile environments, millions of people continued to improve their skills in the midst of the COVID-19 pandemic while locked in their homes. Once the pandemic seems to start to be left behind, the paper analyzes the virtual worlds created by the video games and the relations between the pandemic and these fictional worlds.

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.

Falls are considered a significant cause of disability, pain, and premature deaths in older adults, often due to sedentary lifestyles and various risk factors. Combining immersive virtual reality (IVR) with physical exercise, or exergames, enhances motivation and personalizes training, effectively preventing falls by improving strength and balance in older people. IVR technology may increase the ecological validity of the assessments. The main goal of our study was to assess the feasibility of using a KAVE-based VR platform combining simulations of Levadas and a Cable Car to perform a balanced assessment and profiling of the older adult population for high risk-of-falls and the related user experience. A VR-based platform using a Wii balance board and a CAVE was developed to assess balance and physical fitness. Validated by the Biodex Balance System (BBS), 25 older adults participated in this study. The usability and presence were measured through the System Usability Scale and ITC-SOPI questionnaires, respectively. The IVR system showed a high presence and a good usability score of 75. Significant effects were found in the maximum excursion of the Centre of Pressure (COP) on the anterior-posterior axis during the Cable Car Simulation (CCS), correlating with BBS metrics. Multiple discriminative analysis models and the support vector machine classified fall risk with moderate to high accuracy, precision, and recall. The system accurately identified all high-risk participants using the Leave-One-Out method. This study suggests that an IVR-based platform based on simulations with high ecological validity can be used to assess physical fitness and identify individuals at a higher risk of falls.

Concrete is a heterogeneous material with a disordered material morphology that strongly governs the behavior of the material. In this contribution, we present a computational tool called the Concrete Mesostructure Generator (CMG) for the generation of ultra-realistic virtual concrete morphologies for mesoscale and multiscale computational modeling and simulation of concrete. Given an aggregate size distribution, realistic generic concrete aggregates are generated by a sequential reduction of a cuboid to generate a polyhedron with multiple faces. Thereafter, concave depressions are introduced in the polyhedron using gaussian surfaces. The generated aggregates are assembled into the mesostructure using a hierarchic random sequential adsorption algorithm. The virtual mesostructures are first calibrated using laboratory measurements of aggregate distributions. The model is validated by comparing the elastic properties obtained from laboratory testing of concrete specimens with the elastic properties obtained using computational homogenisation of virtual concrete mesostructures. Finally, a 3D-convolutional neural network is trained to directly generate elastic properties from voxel data.

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.

Music cultural heritage, as an important component of cultural heritage, possesses significant cultural value and inheritance significance. With the development of society and the passage of time, these precious traditional music cultural heritages inevitably face the dilemma of gradual depletion or even disappearance. In the digital age, effectively protecting and inheriting these music cultural heritages has become an urgent problem to be addressed. Therefore, this paper proposes an application method based on digital twin technology, exploring how to protect and inherit music cultural heritages through digital twin technology. By leveraging digital twin technology, a virtual museum dedicated to showcasing the richness and historical connotations of music cultures is created, preserving and simulating the soundscapes of historical music eras. Through the integration of audio archives, 3D modeling, and interactive displays, users can immerse themselves in the experience of historical music in the digital space. This paper evaluates the feasibility and cultural preservation value of this digital music history museum through the creation of music digital twin technology instances and user survey feedback, and discusses the prospects of digital twins in the field of music cultural heritage.

Myelolipoma is a benign, typically inert neoplasm of uncertain aetiology that is rarely reported in cats. Although commonly asymptomatic, in some cases, myelolipomas can cause abdominal discomfort or present with rupture and haemorrhage. Here, we describe a rare case of a splenic myelolipoma in a Domestic Long Hair cat in which, after extensive diagnostic investigations, clinical signs of hyporexia and weight loss were attributable to the presence of an intra-abdominal mass. The patient was treated by splenectomy and unexpectedly died during the post-operative period. Although splenectomy appears to be a sensible intervention in symptomatic patients, the optimal management of splenic myelolipomas in cats remains unknown. The risk-benefit ratio of surgical management needs to be carefully considered, and therapeutic intervention should be tailored individually to each patient.

Simulated crime scene investigation is an essential component of forensic science education, but its implementation poses challenges relating to cost, accessibility and breadth of experience. Virtual reality (VR) is an emerging technology which offers exciting prospects for teaching and learning, especially for imparting practical skills. We document here a multidisciplinary experimental study in which a bespoke VR crime scene app was designed and implemented, after which it was tested by both undergraduate student and staff/postgraduate student cohorts. Through both qualitative and quantitative analyses, we demonstrate that VR applications support learning of practical crime scene processing skills. VR-based practical sessions have the potential to add value to forensic science courses through offering cost-effective practical experience and the ability to work in isolation, in a variety of different scenarios. Both user groups reported high levels of satisfaction with the process and reports of adverse effects (motion sickness) were minimal. With reference to user feedback, we proceed to evaluate the scalability and development challenges associated with large-scale implementation of VR as an adjunct to forensic science education.

This paper investigates the effects of air void topology on hydraulic conductivity in asphalt mixtures with porosity in the range 14%-31%. Virtual asphalt pore networks were generated using the Intersected Stacked Air voids (ISA) method, with its parameters being automatically adjusted by the means of a differential evolution optimisation algorithm, and then 3D printed using transparent resin. Permeability tests were conducted on the resin samples to understand the effects of pore topology on hydraulic conductivity. Moreover, the pore networks generated virtually were compared to real asphalt pore networks captured via X-ray Computed Tomography (CT) scans. The optimised ISA method was able to generate realistic 3D pore networks corresponding to those seen in asphalt mixtures in term of visual, topological, statistical and air void shape properties. It was found that, in the range of porous asphalt materials investigated in this research, the high dispersion in hydraulic conductivity at constant air void content is a function of the average air void diameter. Finally, the relationship between average void diameter and the maximum aggregate size and gradation in porous asphalt materials was investigated.

This study investigates the impact of real-time emotional feedback on the quality of teamwork conducted over videoconferencing. We developed a framework that provides real-time feedback through a virtual mirror based on facial and voice emotion recognition. In an experiment with 28 teams (84 participants), teams collaborated over Zoom to set up a virtual Mars station using custom simulation software. Participants were divided into 14 experimental teams which were shown the virtual mirror, and 14 control teams without it. Team performance was measured by the improvement in the Mars simulation output quality. Our analysis using correlation, multilevel regression, and machine learning revealed that fewer interruptions but an increasing number over time correlated with higher performance. Higher vocal arousal and happiness also enhanced performance. We confirmed that female presence in teams boosts performance. SHAP values indicated that high variability in happiness, head movement, and positive facial valence—an “emotional rollercoaster”—positively predicted team performance. The experimental group outperformed the control group, suggesting that virtual mirroring improves virtual teamwork and that interrupting each other more, while speaking less, leads to better results.

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.

In the field of robotics education, introductory courses would ideally utilize heavy industrial arms for hands-on learning. This would provide students with valuable experience in joint programming, which involves direct control of each joint motor in the arm to accomplish desired path planning and differential movements. This practice requires consideration of the physical dynamics of the arm. However, the use of heavy industrial arms has several drawbacks. They are large and expensive, require specialized maintenance, can pose safety risks, and they typically do not allow for direct control of the joint motors. One solution is to use a small, lightweight, toy-like arm. While these are cost-effective and provide direct access to the joint motors without posing safety risks, their lightweight construction means they exhibit minimal dynamic behavior, which limits their educational value. Another solution involves a robotic arm simulator that uses a virtual arm. However, a virtual arm doesn't offer the same level of hands-on engagement and excitement as a physical arm. We propose a hybrid solution that combines a small physical arm with a virtual arm. This approach provides students with the experience of working with an industrial arm, but without the associated difficulties. We demonstrate how this approach successfully improved the completion rate of joint programming assignments, offering a promising solution for practical robotics education.

This paper explores benefits of using VR technologies in higher education. Theoretical part investigates classical education system and its features in order to compare advantages of using VR systems in education. VR technologies and its current state in industry and in education were explored as well as which branches of higher education uses these systems. Survey was conducted through online questionnaire where respondents (N = 55) gave their opinion on VR and the implementation of VR technologies in education. Three hypotheses related to the use of VR technology, student interest, and learning outcomes as well as the effectiveness, immersiveness and the effect of VR systems on the users were tested through 27 questions.

This case study explores social media discourses of a virtual ecovillage community based in Central Romania, in a Hungarian speaking region of Transylvania. The investigated virtual community embraces the idea of ecovillage as a local constructive answer to the challenges of the global ecological crisis, based on strategies of revitalizing local ethnic traditions, promoting sustainable development solutions, and innovations. Our key question is the relationship between tradition and innovation—as revealed by the discursive practices of the ecovillage Facebook group most active members. Using ecolinguistic as a frame of reference, the investigation unveiled the role social media played in fostering the formation of a virtual intentional community, and in clarifying the shared values of the group. We found that the local ecovillage is part of a larger regional and global movement, unfolding the organic connection between the Hungarian and the Romanian intentional communities, and the reframing of traditional values within innovative, sustainable everyday practices.

Multidisciplinary neurotechnology holds the promise of understanding and non-invasively treating neurodegenerative diseases. In this preclinical trial on Parkinson's disease (PD), we combined neuroscience together with the nascent field of medical virtual reality and generated several important observations. First, we established the Oculus Rift virtual reality system as a potent measurement device for parkinsonian involuntary hand tremors (IHT). Interestingly, we determined changes in rotation were the most sensitive marker of PD IHT. Secondly, we determined parkinsonian tremors can be abolished in VR with algorithms that remove tremors from patients' digital hands. We also found that PD patients were interested in and were readily able to use VR hardware and software. Together these data suggest PD patients can enter VR and be asymptotic of PD IHT. Importantly, VR is an open-medium where patients can perform actions, activities, and functions that positively impact their real lives - for instance, one can sign tax return documents in VR and have them printed on real paper or directly e-sign via internet to government tax agencies. Lastly, we generated a technical framework wherein movements in the real world can be measured side-by-side with those in virtual reality. With this framework, we observed anecdotal evidence of parkinsonian tremors being reduced in real life when our algorithms abolished digital hand tremors in VR.

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.

The past several decades have seen a shift in patient care towards digitalisation, which has ushered in a new era of health care delivery and improved sustainability and resilience of health systems, with positive impacts on both internal and external stakeholders. This study’s aim was to understand the role of digital virtual consultations in improving internal and external stakeholders’ health, as well as wellbeing among hospital doctors. A qualitative research approach was used with semi-structured online interviews administered to hospital doctors. The interviews showed that the doctors viewed digital virtual consultations as supplementary to in-person consultations, and as tools to reduce obstacles related to distance and time. If the necessary infrastructure and technology were in place, doctors would be willing to use these options. Implementing these technologies would improve the medical profession’s flexibility on the one hand; but it might affect doctors’ work–life balance if consultations extended beyond standard working hours.

Introduction: The combination of Virtual Screening (VS) techniques with in vivo screening in the zebrafish model is currently being used in tandem for drug development in a faster and more efficient way. Areas covered: We review the different virtual screening techniques, the use of zebrafish as a vertebrate model for drug discovery and the synergy that exists between them. Expert opinion: We highlight the advantages of combining virtual and zebrafish larvae screening for drug discovery. On the one hand, VS is a faster and cheaper tool for searching active compounds and possible candidates for therapy than in vivo screening when processing large compound libraries. On the other hand, zebrafish larvae form a vertebrate model which allows in vivo screening of large amounts of the compounds. Importantly physiology and chemical response are mostly conserved between zebrafish and mammals. The availability of the transgenic and mutant zebrafish lines allows an analysis of a specific phenotype upon treatment along with toxicity, off-target effect, side effects, and dosage. Advantages of VS, in vivo whole animal approach screening, and the screening combinations are also reviewed.

Human-Computer Interaction, including technology-aided instruction, is beginning to focus on virtual reality (VR) technology due to its ability to support immersive learning, teaching through simulation, and gamification of learning. These systems can deliver high-level multisensory learning experiences that are important in the teaching of many subjects, especially those involving abstract concepts or requiring spatial skills, such as organic chemistry. Haptic experiences with VR, however, remain a challenge. In addition, development have focused on general entertainment/gaming; VR systems in chemistry implement simulations of the chemistry laboratory and other advanced systems whereas those that support safe, game-like, immersive and multisensory learning of organic chemistry with haptics at pre-university education levels are scarce. We developed the VR Multisensory Classroom (VRMC) as an immersive learning environment within a VR head-mounted display, where learners employ hand movements to build hydrocarbon molecules and experience haptic feedback through gloves with built-in sensors and hand-tracking with the Leap Motion system. We report here the evaluation of the first prototype by learners from diverse backgrounds who reported on the ability of the VRMC to support high engagement, motivation, interest and organic chemistry learning as well as diverse learning styles. The VRMC is a novel VR classroom that supports immersive learning in molecular organic chemistry with haptics for multisensory learning.

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.

Hydroxyurea (Hu) has been a front-line therapeutic agent for myeloproliferative neoplasms (MPN) for many years and still enjoys the endorsement of experts in the field. However, several publications have reported sub-optimal response, the need for treatment interruption because of cytopenias and lack of sustained response. In all these studies, Hu was used as continuous therapy at a daily dose ranging from 500mg to 3000mg. At our Centre we have used Hu as intermittent therapy (akin to schedules used in patients with solid tumours) at 20-30mg/Kg doses, given as a single dose, twice or thrice weekly. We have consistently observed sustained responses without troublesome cytopenias. In this report we present our experience in 118 patients treated with intermittent Hu during the past 30 years (median follow-up 8.5 yrs): polycythemia vera – 29; essential thrombocythemia – 84; primary myelofibrosis – 5. Based on the pharmacokinetics of Hu and our experience, we speculate that the efficacy of intermittent Hu therapy without troublesome myelotoxicity over long periods of time is attributable to the following: i) higher plasma level from intake of Hu as a single dose; ii) higher uptake of Hu by cells with higher mitotic activity (i.e. the abnormal clone); and iii) unhindered, normal haemopoiesis on the drug free days each week. We hope that this article will generate interest and contemplation, leading to randomized clinical studies to compare the two dosage schedules (Continuous Vs Intermittent) in MPN patients.

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.

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.

Background: Regular moderate-vigorous intensity exercise is recommended for adults as it can improve longevity and reduce health risks associated with a sedentary lifestyle. However, there are barriers to achieving intense exercise that may be addressed using virtual reality (VR) as a tool to promote exercise intensity and adherence, particularly through visual feedback and competition. The purpose of this work is to compare visual feedback and competition within fully-immersive VR to enhance exercise intensity and user experience of exercise for young adults; and to describe and compare visual attention during each of the conditions. Methods: Young adults (21- 34 years old) bicycled in three 5-minute VR conditions (visual feedback, self-competition and competition against others). Exercise intensity (cycling cadence and % of maximum heart rate) and visual attention (derived from a wearable eye tracking sensor) were measured continuously. User experience was measured by an intrinsic motivation questionnaire, perceived effort and participant preference. A repeated measures ANOVA with paired t-test post-hoc tests was conducted to detect differences between conditions. Results: Participants exercised at a higher intensity and had higher intrinsic motivation in the two competitive conditions compared to visual feedback. Further, participants preferred the competitive conditions and only reached a vigorous exercise intensity during self-competition. Visual exploration was higher in visual feedback compared to self-competition. Conclusion: For young adults bicycling in VR, competition promoted higher exercise intensity and motivation compared to visual feedback.

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.

Background and Objectives: Daratumumab, a monoclonal antibody against CD38, has shown promising results in multiple myeloma (MM). We aimed to analyze its efficacy in newly diagnosed patients with MM. Materials and Methods: A search was conducted in PubMed, Cochrane, and Clinicaltrials.gov using the MeSH terms “daratumumab” or “Darzalex” and “multiple myeloma” covering the period until 2024. The Mantel-Haenzel formula was used to calculate the pooled risk ratio (RR), and the Generic Inverse Variance method was used to determine the pooled hazard ratio for disease progression, using RevMan version 5.4 at 95% confidence interval (CI). A P value of less than 0.05 was significant. Results: A total of 6 phase-III RCTs were analyzed. The use of daratumumab was associated with 39% fewer events of progression of disease or deaths in the TE group (RR= 0.61; 95% CI= 0.39 to 0.93; p=0.02) and 29% lower in the TIE group (RR= 0.71; 95% CI= 0.53 to 0.94; p=0.02). The hazard ratio for progression or death with daratumumab group versus control in both transplant eligible (TE) (HR= 0.44; 95% CI= 0.35 to 0.57; p&lt;0.00001) or transplant ineligible (TIE) (HR= 0.47; 95% CI= 0.38 to 0.59; p&lt;0.00001) group was significantly lower. Daratumumab significantly increased overall response rate (ORR) (RR= 1.20; 95% CI= 1.11 to 1.30 ; p&lt;0.00001) and complete response (CR) (RR= 1.34; 95% CI= 1.02 to 1.76; p=0.04) in the TIE group only. Conclusions: Daratumumab showed benefits in both TE and TIE patients with newly diagnosed multiple myeloma. It significantly reduced the risk of disease progression or death and improved clinical outcomes regarding ORR and CR, suggesting an effective treatment option in these patient groups.

Immersive virtual reality has the potential to motivate and challenge patients that need and want to relearn movements in the process of (neuro-)rehabilitation. The aims of this study were to evaluate the feasibility and users’ acceptance of an innovative immersive virtual reality system (head-mounted display) used in combination with robot assisted gait training in subjects suffering from neurological diseases. Fifteen participants tested a single session of immersive virtual reality by means of head-mounted display during a Lokomat gait session. Training parameters and safety indicators were collected and the acceptance was investigated among the participants and the therapists. The results suggest that the immersive virtual reality system is feasible with respect to safety and tolerance. Furthermore, the very positive overall acceptance of the system suggests that it has potential to be included in a robot assisted gait training session by means of Lokomat. Taken together, this study demonstrates the feasibility and acceptance of an innovative immersive virtual reality system in combination with a robot assisted gait training in subjects suffering from stroke and spinal cord injury, as well as their therapists.

This study explores consumer perceptions of virtual reality (VR) in marketing, aiming to understand how immersive technology impacts engagement and brand perception. As VR continues to evolve and integrate into various marketing strategies, it becomes crucial to examine its effectiveness and the factors influencing consumer attitudes. Through a detailed thematic analysis, this research identifies key themes such as familiarity with VR technology, immersion and engagement, technical quality, accessibility, personalization, storytelling, social interaction, purchase intentions, and brand perception. The findings reveal that familiarity with VR enhances enthusiasm and comfort, leading to more positive attitudes towards VR marketing. The immersive and multi-sensory nature of VR provides a significant advantage over traditional advertising methods, fostering stronger emotional connections and increasing memorability. However, the quality of the VR experience is critical; high-quality graphics and seamless interactions are essential for maintaining positive consumer perceptions. Technical issues, such as lag and motion sickness, can negatively impact the experience, especially for those less acquainted with VR technology. Accessibility remains a challenge, with limited access to VR headsets restricting the reach of VR marketing campaigns. Personalization of VR content is highly valued, though it must be balanced with ethical considerations related to data privacy. The power of storytelling in VR enhances engagement by allowing consumers to actively participate in narratives. Social interaction within VR experiences adds an extra layer of enjoyment. The study also highlights the practical applications of VR marketing in high-involvement sectors and underscores the need for continuous innovation and consumer feedback to maximize the technology's impact. Overall, VR holds significant potential to transform marketing practices by offering immersive, engaging, and memorable experiences that deepen consumer connections and drive positive outcomes.