Background and Objectives: Clinical trials are a critical step in the development of new medicines and medical devices, testing the efficacy and safety of new treatment regimens. However, if the results of clinical trials are not made public, the evidence base on interventions is incomplete and possibly distorted, which lead to suboptimal treatment choices and negatively affect public health. This study analyses and contrasts the laws and regulations governing clinical trial registration and reporting in China and the United States. Methods: We used desk research to compile, assess and compare current laws, regulations, compliance patterns, and enforcement mechanisms and actions in China and the United States (U.S.). Policy documents were downloaded from Chinese and U.S. government websites. A spreadsheet analysis was utilized for direct comparison. Results: Both China and the U.S. have laws and regulations governing clinical trial registration and reporting. Chinese legislation covers a broader range of trials. In the U.S. trial results must be disclosed to both the national regulator and the public, while Chinese law mandates disclosure to the regulator alone. Cross-country comparisons of regulatory compliance by trial sponsors are impossible due to the opacity of the Chinese data platform. Neither country effectively ensures that all clinical trial results are made public as required by the Declaration of Helsinki and recommended by the WHO. Interpretation: While neither country is perfect, both may be able to learn from each other. There is a major gap in the literature regarding the extent of non-publication of clinical trial results by sponsors operating in China.

Background and Objectives: In this current state, Type 2 Diabetes Mellitus (T2DM) is more prevalent in the population, and metformin is used as a first-line medication for treating it. There was up surge in the utilization of alternative therapies in the management of diabetes. Especially in diabetes, Herbal medicines are considered safe and reliable by majority of the population. Aim: The purpose of this research is aimed to estimate the safety and efficacy of Polyherbal Metabolite Compounds (PHMC) capsules in adults with T2DM. Materials and Methods: In this study, 60 T2DM patients aged 18-60 years were randomly assigned to Groups A (30) receiving Metformin 500 mg twice a day after food and Group B (30) receiving PHMC capsule 500 mg twice a day after food in a prospective, randomized and open-label clinical study. The in-silico simulation study was performed to selected plants major compounds on target protein Insulin-like Growth Factor-1 (1K3A). Result: The PHMC is found to be safe and effective in the management of T2DM. The FBS, PPBS and HbA1c were significantly lowered (p

Fundus image registration plays a crucial role in the clinical evaluation of ocular diseases, such as diabetic retinopathy and macular degeneration, necessitating meticulous monitoring. The alignment of multiple fundus images enables the longitudinal analysis of patient progression, widening the visual scope, or augmenting resolution for detailed examinations. Currently, prevalent methodologies rely on feature-based approaches for fundus registration. However, certain methods exhibit high feature point density, posing challenges in matching due to point similarity. This study introduces a novel fundus image registration technique integrating U-Net for the extraction of feature points employing FIVES for its training and evaluation, a novel and large dataset for blood vessels segmentation, prioritizing point distribution over abundance. Subsequently, the method employs medial axis transform and pattern detection to obtain feature points characterized by the Fast Retina Keypoint (FREAK) descriptor, facilitating matching for transformation matrix computation. Assessment of the vessel segmentation achieves 0.7559 for Intersection Over Union (IoU), while evaluation on the Fundus Image Registration Dataset (FIRE) demonstrates the method’s comparative performance against existing methods, yielding a registration error of 0.596 for area under the curve, refining similar earlier methods and suggesting promising performance comparable to prior methodologies.

For multi-sensor integrated systems, such as a mobile mapping system (MMS), data fusion at sensor-level, i.e., the 2D-3D registration between optical camera and LiDAR, is a prerequisite for higher level fusion and further applications. This paper proposes a line-based registration method for panoramic images and LiDAR point cloud collected by a MMS. We first introduce the system configuration and specification, including the coordinate systems of the MMS, the 3D LiDAR scanners, and the two panoramic camera models. We then establish the line-based transformation model for panoramic camera. Finally, the proposed registration method is evaluated for two types of camera models by visual inspection and quantitative comparison. The results demonstrate that the line-based registration method can significantly improve the alignment of the panoramic image and LiDAR datasets under either the ideal spherical or the rigorous panoramic camera model, though the latter is more reliable.

Image registration (IR) is a process that deforms images to align them with respect to a reference space, making it easier for medical practitioners to examine various medical images in a standardized reference frame, such as having the same rotation and scale. This document introduces image registration using a simple numeric example. It provides a definition of image registration along with a space-oriented symbolic representation. This review covers various aspects of image transformations, including affine, deformable, invertible, and bidirectional transformations, as well as medical image registration algorithms such as Voxelmorph, Demons, SyN, Iterative Closest Point, and SynthMorph. It also explores atlas-based registration and multistage image registration techniques, including coarse-fine and pyramid approaches. Furthermore, this survey paper discusses medical image registration taxonomies, datasets, evaluation measures, such as correlation-based metrics, segmentation-based metrics, processing time, and model size. It also explores applications in image-guided surgery, motion tracking, and tumor diagnosis. Finally, the document addresses future research directions, including the further development of transformers.

This study proposes a method for image matching between infrared(IR)-RGB images using a deep learning network to estimate the deformation field. We propose a deformation field generator (DFG) that estimates the deformation field of the transformation matrix to match each pixel or IR image to the RGB image. DFG is a network that receives IR and RGB images as input; the output size is two channels and has the sample resolution as the input image. By warping the IR image through a grid-sampler that warps the image according to the value of the deformation field, we can obtain a warped IR image that matches the RGB image. Additionally, to check whether the warped IR image matched the RGB image, the masking images detecting the segmentation of objects were photographed in two images. Without directly comparing IR and RGB images, we proposed mask loss that warps the IR mask image through the deformation field and grid sampler and then compares the warped IR mask image with the RGB mask image. Mask loss solves the spatial similarity comparison problem with multi-modality images, such as IR and RGB images, by comparing the mask image with the same modality image as the mask image.

Remote sensing image registration plays an important role in military and civilian fields, such as natural disaster damage assessment, military damage assessment and ground targets identification, etc. However, due to the ground relief variations and imaging viewpoint changes, non-rigid geometric distortion occurs between remote sensing images with different viewpoint, which further increases the difficulty of remote sensing image registration. To address the problem, we propose a multi-viewpoint remote sensing image registration method which contains the following contributions. (i) A multiple features based finite mixture model is constructed for dealing with different types of image features. (ii) Three features are combined and substituted into the mixture model to form a feature complementation, i.e., the Euclidean distance and shape context are used to measure the similarity of geometric structure, and the SIFT (scale-invariant feature transform) distance which is endowed with the intensity information is used to measure the scale space extrema. (iii) To prevent the ill-posed problem, a geometric constraint term is introduced into the L2E-based energy function for better behaving the non-rigid transformation. We evaluated the performances of the proposed method by three series of remote sensing images obtained from the unmanned aerial vehicle (UAV) and Google Earth, and compared with five state-of-the-art methods where our method shows the best alignments in most cases.

The aim of this randomized controlled clinical trial was to compare the 2-year clinical performance of resin composite restorations placed at non-caries cervical lesions (NCCL) with one-step self-etch, total-etch, and selective enamel etch & self-etch adhesive techniques. Thirty-two patients received three resin composite restorations each at NCCLs (Tetric EvoCeram/Ivoclar/Vivadent), bonded with a total-etch adhesive agent (ExciTE F/Ivoclar/Vivadent) and a self-etch (AdheSE One F/Ivoclar/Vivadent) without and with selective enamel etching. All restorations were evaluated by two examiners at baseline, 6-, 12-, 18- and 24-months post-operation regarding retention, caries occurrence, marginal adaptation, and marginal staining. A logistic regression analysis with generalized estimating equations was used. After 2 years, the retention rate was 86,8% for total-etch, 92.26% for self-etch, and 93.63% for selective enamel etching & self-etch. No caries were detected during all the restorations. Concerning marginal adaptation, the clinically perfect restorations were 26.9% for the total-etch technique, 16% for self-etch, and 25,9% for selective enamel etch & self-etch. All three adhesive strategies provided restorations with no significant differences in the retention rate and the marginal adaptation, whereas the total etch yielded better performance for marginal staining. All the restorations were assessed as clinically acceptable after 2 years.

Image registration has an imperative role in medical imaging. In this work, a grey-wolf optimizer (GWO) based non-rigid demons registration is proposed to support the retinal image registration process. A comparative study of the proposed GWO-based demons registration framework with cuckoo search, firefly algorithm, and particle swarm optimization- based demons registration is conducted. In addition, a comparative analysis of different demons registration methods, such as Wang’s demons, Tang’s demons, and Thirion’s demons which are optimized using the proposed GWO is carried out. The results established the superiority of the GWO-based framework which achieved 0.9977 correlation, and fast processing compared to the use of the other optimization algorithms. Moreover, GWO-based Wang’s demons performed better accuracy compared to the Tang’s demons and Thirion’s demons framework. It also achieved the best less registration error of 8.36×10^-5.

Multi-source image registration often suffered from great radiation and geometric differences. Specifically, gray scale and texture from similar landforms in different source images often show significantly different visual features. And these differences disturb the corresponding point extraction in the following image registration process. Considering that edges between heterogeneous images can provide homogeneous information and more consistent features can be extracted based on image edges, an edge consistency radiation-change insensitive feature transform (EC-RIFT) method is proposed in this paper. Firstly, the noise and texture interference are reduced by preprocessing according to the image characteristics. Secondly, image edges are extracted based on phase congruency, and an orthogonal Log-Gabor filter is performed to replace the global algorithm. Finally, the descriptors are built with logarithmic partition of the feature point neighborhood, which improves the robustness of descriptors. Comparative experiments on datasets containing multi-source remote sensing image pairs show that the proposed EC-RIFT method outperforms other registration methods in terms of precision and effectiveness.

Star image registration is the most important step in the application of astronomical image differencing, stacking and mosaicking, which requires high robustness, accuracy and real--time of the algorithm, but there is no high--performance registration algorithm in this field. In this paper, we propose a star image registration algorithm that relies only on radial module features (RMF) and rotation angle features (RAF), which has excellent robustness, high accuracy, and good real--time performance. The test results on a large amount of simulated and real data show that the comprehensive performance of the proposed algorithm is significantly better than the four classical baseline algorithms in the presence of rotation, insufficient overlapping area, false stars, position deviation, magnitude deviation and complex sky background, which is a more ideal star image registration algorithm.

Longitudinal image registration of pulmonary computed tomography (PCT) images may serve as an essential tool for investigating the relationship between radiation dose distribution and the occurrence and phenotype of radiation-induced lung disease (RILD). Although numerous longitudinal registration algorithms have been developed for PCT, most similarity-based approaches are not suitable for PCT involving RILD due to the complex tissue variation between two PCT images. Moreover, conventional feature-based approaches might fail to find a sufficient number of matched pairs of feature points due to the disparate lung deformation caused by breathing and RILD. To overcome the challenges resulting from RILD, component structure coherence point drift (CSCPD) was proposed to establish a deformation model by decomposing the chest into several components and matching them with individual parameters based on coherence point drift (CPD). Moreover, a regional vascular point matching (RVPM) algorithm was proposed to generate a vascular subtree and to substantially increase the number of corresponding pairs between two images. Eventually, the components were recomposed and aligned by a thin plate spline algorithm. A performance assessment on 15 pairs of PCT images of patients with RILD yielded recall and precision values of 0.85 and 0.89 for RVPM, respectively. Moreover, the target registration error of CSCPD with RVPM (2.3 ± 1.79) was significantly better than that of conventional CPD with RVPM (2.95 ± 1.89) and conventional CPD (5.04 ± 2.87). Therefore, the proposed registration system is robust enough to address the disparate deformation of lungs with RILD, and it improves registration accuracy within the parenchyma.

Direct georeferencing of airborne pushbroom scanner data usually suffers from the limited precision of navigation sensors onboard of the aircraft. The bundle adjustment of images and orientation parameters, used to perform geocorrection of frame images during the post-processing phase, cannot be used for pushbroom cameras without difficulties: it relies on matching corresponding points between scan lines, which is not feasible in the absence of sufficient overlap and texture information. We address this georeferencing problem by equipping our aircraft with both a frame camera and a pushbroom scanner: the frame images and the navigation parameters measured by a couple GPS/Inertial Measurement Unit (IMU) are input to a bundle adjustment algorithm; the output orientation parameters are used to project the scan lines on a Digital Elevation Model (DEM) and on an orthophoto generated during the bundle adjustement step; using the image feature matching algorithm Speeded Up Robust Features (SURF), corresponding points between the image formed by the projected scan lines and the orthophoto are matched, and through a least-squares method, the boresight between the two cameras is estimated and included in the calculation of the projection; finally, using Particle Image Velocimetry (PIV) on the gradient image, the projection is deformed into a final image that fits the geometry of the orthophoto. We apply this algorithm to five test acquisitions over Lake Geneva region (Switzerland) and Lake Baikal region (Russia). The results are quantified in terms of Root Mean Square Error (RMSE) between matching points of the RGB orthophoto and the pushbroom projection. From a first projection where the Interior Orientation Parameters (IOP) are known with limited precision and the RMSE goes up to 41 pixels, our geocorrection estimates IOP, boresight and Exterior Orientation Parameters (EOP) and produces a new projection which RMSE with the reference orthophoto is around two pixels.

Interferometric synthetic aperture radar (InSAR) and tomographic SAR measurement techniques are commonly used for the three-dimensional (3D) reconstruction of complex areas, while the effectiveness of these methods relies on the interferometric coherence among SAR images with minimal angular disparities. Radargrammetry exploits stereo image matching to determine the spatial coordinates of corresponding points in two SAR images, and acquire their 3D properties. The performance of the image matching process directly impacts the quality of the resulting digital surface model (DSM). However, the presence of speckle noise, along with dissimilar geometric and radiometric distortions, poses considerable challenges to achieve accurate stereo SAR image matching. To address the aforementioned challenges, this paper proposes a radargrammetric method based on composite registration of multi-aspect SAR images. The proposed method combines coarse registration using scale invariant feature transform (SIFT) with precise registration using normalized cross-correlation (NCC) to achieve accurate registration between multi-aspect SAR images with large disparities. Furthermore, the multi-aspect 3D point clouds are merged by the proposed radargrammetric 3D imaging method, resulting in 3D imaging of target scenes based on multi-aspect SAR images. For validation purpose, this paper presents a comprehensive 3D reconstruction of the Five-hundred-meter Aperture Spherical radio Telescope (FAST) by using Ka-band airborne SAR images. It does not necessitate prior knowledge of the target and is applicable to the detailed 3D imaging of large-scale areas with complex structures. In comparison to other SAR 3D imaging techniques, it reduces the requirements for orbit control and radar system parameters. To sum up, the proposed 3D imaging method with composite registration guarantees imaging efficiency while enhances the imaging accuracy of crucial areas with limited data.

Urban scene point cloud pose significant challenges for registration due to its large data volume, similar scenarios and dynamic objects. In this paper, we propose PCRMLP, a model for urban scene point cloud registration that achieves comparable registration performance to prior learning-based methods. Compared to previous works which focus on extracting features and estimating correspondence, the model estimates the transformation implicitly from concrete instances. An instance-level urban scene representation method is introduced to extract instance descriptors via semantic segmentation and DBSCAN, which enable the model to obtain robust instance features, filter dynamic objects and estimate transformation in a more logical manner. Then a lightweight network consisting of MLPs is employed to obtain transformation in an encoder-decoder manner. We validate the approach on KITTI dataset. Experimental results demonstrate that PCRMLP can obtain a satisfactory coarse transformation from instance descriptors just in 0.0028s. With a subsequent ICP refinement module, the proposed method achieves higher registration accuracy and computational efficiency than prior learning-based works.

With the advancement of photoelectric technology and computer image processing technology, the visual measurement method based on point clouds is gradually applied to the 3D measurement of large workpieces. Point cloud registration is a key step in 3D measurement, and its registration accuracy directly affects the accuracy of 3D measurements. In this study, we designed a novel MPCR-Net for multiple partial point cloud registration networks. First, an ideal point cloud was extracted from the CAD model of the workpiece and was used as the global template. Next, a deep neural network was used to search for the corresponding point groups between each partial point cloud and the global template point cloud. Then, the rigid body transformation matrix was learned according to these correspondence point groups to realize the registration of each partial point cloud. Finally, the iterative closest point algorithm was used to optimize the registration results to obtain a final point cloud model of the workpiece. We conducted point cloud registration experiments on untrained models and actual workpieces, and by comparing them with existing point cloud registration methods, we verified that the MPCR-Net could improve the accuracy and robustness of the 3D point cloud registration.

Alzheimer's disease (AD) is a stealthy and progressive neurological disorder that is a leading cause of dementia in the global elderly population, imposing a significant burden on both the elderly and society. Currently, the condition is treated with medications that alleviate symptoms. Nonetheless, these drugs may not consistently produce the desired results and can cause serious side effects. Hence, there is a vigorous pursuit of alternative options to enhance the quality of life for patients. Ginkgo biloba (GB), an herb with historical use in traditional medicine, contains bioactive compounds such as terpenoids (Ginkgolides A, B, and C), polyphenols, organic acids, and flavonoids (quercetin, kaempferol, and isorhamnetin). These compounds are associated with anti-inflammatory, antioxidant, and neuroprotective properties, making them valuable for cognitive health. A systematic search across three databases using specific keywords GB in AD and dementia yielded 1702 documents, leading to the selection of 15 clinical trials for synthesis. In eleven studies, GB extract/EGb 761® was shown to improve cognitive function, neuropsychiatric symptoms, and functional abilities in both dementia types. In four studies, however, there were no significant differences between the GB-treated and placebo groups. Significant improvements were observed in scores obtained from the Mini-Mental State Examination (MMSE), Short Cognitive Performance Test (SKT), and Neuropsychiatric Inventory (NPI). While the majority of synthesized clinical trials show Ginkgo biloba has promising potential in these conditions, more research is needed to determine optimal dosages, effective delivery methods, and appropriate pharmaceutical formulations. Furthermore, a thorough assessment of adverse effects, exploration of long-term use implications, and investigation into potential drug interactions are critical aspects that must be carefully evaluated in future studies.

This study examines the feasibility of using event-related potentials (ERPs) obtained from electroencephalographic (EEG) recordings as biomarkers for long-term memory item classification. Previous studies have identified old/new effects in memory paradigms associated with explicit long-term memory and familiarity. Recent advancements in convolutional neural networks (CNNs) have enabled the classification of ERP trials under different conditions and identification of features related to neural processes at the single-trial level. We employed this approach to compare three CNN models with distinct architectures using experimental data. Participants (N = 25) performed an association memory task while recording ERPs that were used for training and validation of the CNN models. The EEGNET-based model achieved the most reliable performance in terms of precision, recall, and specificity compared with the shallow and deep convolutional approaches. The classification accuracy of this model reached 70% for known items and 62% for unknown items. Good overall accuracy requires a trade-off between recall and specificity and depends on the architecture of the model and the dataset size. These results suggest the possibility of integrating ERP and CNN into online learning tools and identifying the underlying processes related to long-term memorization.

Abstract: The Micro-Electro-Mechanical System (MEMS) LiDAR point cloud in autonomous vehicles has a large deflection range, which results in slow registration speed and poor applicability. To maximize speed, an improved NDT (Normal Distribution Transform) method that integrates point cloud density features has been proposed. First, the point cloud is reduced using a modified voxel filter and a pass-through filter. Next, the ISS (Intrinsic Shape Signature) algorithm is utilized to analyze the point cloud features and extract keypoints, the 4PCS (4-Point Congruent Sets) algorithm is then employed to calculate the initial pose under the constraints of the keypoint set to complete the coarse registration. Finally, the self-adaptive segmentation model is constructed by using KD-tree to obtain the density features of keypoints, and the NDT algorithm is combined with this model to form an SSM-NDT algorithm, which is used for fine registration. Each algorithm was compared on the autonomous vehicle dataset PandaSet and actual collected data sets, the results show that the novel method increases the speed by at least 60% and takes into account good registration accuracy and strong anti-interference.

.Purpose: This paper presents a comparative analysis of state-of-the-art DIR algorithms in the context of head and neck squamous cell carcinoma (HNSCC) radiation therapy. Materials and Methods: We used a dataset of head and neck cancer patients within the Cancer Image Archive, which includes 31 patients with 3D CT image data from pre-treatment, mid-treatment, and post-treatment stages of radiotherapy. We applied DIR algorithms to two datasets, one for pre-treatment to mid-treatment registration and another for mid-treatment to post-treatment registration, by aligning one CT image to another CT image. To quantitatively analyze the patient data, we focused on the spinal cord, optic nerve, brain stem, cochlea, and PTV as the OAR datasets. To verify the DIR algorithm, we used two non-learning-based methods, SyN and NiftyReg, as well as three deep learning-based methods, Voxelmorph, Cyclemorph, and Transmorph. We trained a deep learning model by adjusting the ratio of the training dataset, validation dataset, and test dataset to 7:1:2. Results: The average DSCs of SyN and NiftyReg, the non-learning-based methods, were 0.74±0.06 and 0.70±0.12, respectively. The deep learning-based methods, Voxelmorph, Cyclemorph, and Transmorph, had average DSCs of 0.72±0.08, 0.68±0.11, and 0.69±0.13, respectively. The deep learning DIR algorithm produced transformed outputs of OAR/PTV in a shorter time than other models, including commercial and conventional mathematical algorithms (At Inference(sec/images), Voxelmorph: 0.36, Cyclemorph: 0.3, Transmorph: 5.1, SyN: 140, NiftyReg: 40.2). Conclusions: In conclusion, our study provides a comprehensive comparison of commercial DIR algorithms with traditional and deep learning-based DIR methods. Our results demonstrate that commercial DIR algorithms outperform traditional DIR methods in terms of accuracy and efficiency. However, we also show that deep learning-based DIR methods have the potential to achieve similar performance to commercial algorithms with proper training and optimization. Our findings suggest that both commercial and deep learning-based DIR methods have their respective advantages and limitations, and the choice of method should depend on the specific requirements of the clinical application. Overall, our study contributes to ongoing efforts to improve the accuracy and efficiency of DIR methods for better patient outcomes.

Background: One challenge in implant dentistry is to reduce marginal bone resorption to avoid long-term esthetic and biological complications. Sub-gingival implant placement has been suggested as a suitable strategy. Methods: 38 healthy patients were enrolled to receive bone level (BL – Control group) or 2 mm sub-crestal (SC - Test group) conical connection, platform-switched implants. An immediate tissue level abutment was used in the Test group by following a One Time Abutment (OTA) restorative procedure. Marginal Bone Modification (MBM) was calcu-latied on standardized radiographs at surgery (T0), loading (T1), and 6 months (T2) and 12 months after loading (T3), and cathegorised in Bone Loss (BL) if the resorption occurred below the implant neck and Bone Remodeling (BR) if above. Pocket probing depth (PPD), Bleeding on probing (BoP) and Plaque Index (PI) were also collected. Results: The mean MBM in the test group after 12 months was 0.61mm, compared to 0.52mm in the control group. However, no BL was observed in the test group, as the MBM completely occurred above the implant neck as BR, whilst in the control group MBM corresponded in total to BL. The average PPD was 2.38mm in the test group and 3.04mm in the control group after 12 months, BoP 50% and 43%, PI 33% and 19.44% respectively. Conclusions: Sub-crestal conical connection, platform-switched implants could be a suitable clinical choice to avoid BL with exposure of the treated implants surfaces.

Non-rigid registration presents a significant challenge in the domain of point cloud processing. The general objective is to model complex non-rigid deformations between two or more overlapping point clouds. Applications are diverse and span multiple research fields, including registration of topographic data, scene flow estimation, and dynamic shape reconstruction. To provide context, we begin with a general introduction to the topic of point cloud registration, including a categorization of methods. Next, we introduce a general mathematical formulation for point cloud registration and extend it to address non-rigid registration. A detailed discussion and categorization of existing approaches to non-rigid registration follows. We then introduce our own method where the usage of piece-wise tricubic polynomials for modeling non-rigid deformations is proposed. Our method offers several advantages over existing methods. These advantages include easy control of flexibility through a small number of intuitive tuning parameters, a closed-form optimization solution, and an efficient transformation of huge point clouds. We demonstrate our method through multiple examples that cover a broad range of applications, with a focus on remote sensing applications - namely, the registration of Airborne Laser Scanning (ALS), Mobile Laser Scanning (MLS), and Terrestrial Laser Scanning (TLS) point clouds. The implementation of our algorithms is open source and can be found on GitHub.

For Synthetic Aperture Radar (SAR) image registration, successive processes following feature extraction are required by both the traditional feature-based method and the deep learning method. Among these processes, the feature matching process—whose time and space complexity are related to the number of feature points extracted from sensed and reference images, as well as the dimension of feature descriptors—proves to be particularly time-consuming. Additionally, the successive processes introduce data sharing and memory occupancy issues, requiring an elaborate design to prevent memory leaks. To address these challenges, this paper introduces the OptionEM-based reinforcement learning framework to achieve end-to-end SAR image registration. This framework outputs registered images directly without requiring feature matching and calculation of the transformation matrix, leading to significant processing time savings. The Transformer architecture is employed to learn image features, while a correlation network is introduced to learn the correlation and transformation matrix between image pairs. Reinforcement learning, as a decision process, can dynamically correct errors, making it more efficient and robust compared to supervised learning mechanisms like deep learning. We present a hierarchical reinforcement learning framework combined with episodic memory to mitigate the inherent problem of invalid exploration in generalized reinforcement learning algorithms. This approach effectively combines coarse and fine registration, further enhancing training efficiency. Experiments conducted on three sets of SAR images, acquired by TerraSAR-X and Sentinel-1A, demonstrate that the proposed method’s average runtime is sub-second, achieving subpixel registration accuracy.

We report neutralization titer data against contemporary SARS-CoV-2 sublineages from an ongoing, open-label, phase 2/3 trial of a single 30-μg dose of monovalent Omicron XBB.1.5-adapted BNT162b2 vaccine. Healthy participants had previously received ≥3 doses of a US-authorized mRNA vaccine, with the most recent being a bivalent Omicron BA.4/BA.5-adapted vaccine administered ≥150 days before study vaccination. In this analysis, Omicron XBB.1.5, BA.2.86, and JN.1 serum neutralizing titers were assessed at baseline and 1 month after vaccination in a subset of ≥18-year-olds (N = 40) with evidence of previous SARS-CoV-2 infection. Immunogenicity was also evaluated in a demographically matched group of participants who received bivalent BA.4/BA.5-adapted BNT162b2 in another study (ClinicalTrials.gov Identifier: NCT05472038). The XBB.1.5-adapted BNT162b2 vaccine elicited higher XBB.1.5, BA.2.86, and JN.1 neutralizing titers than those elicited by bivalent BA.4/BA.5-adapted BNT162b2. Overall geometric mean fold rises in neutralizing titers from baseline to 1 month after vaccination were higher among participants who received XBB.1.5-adapted BNT162b2 than those who received bivalent BA.4/BA.5-adapted BNT162b2 for XBB.1.5 (7.6 vs 5.6), slightly higher for JN.1 (3.9 vs 3.5), and similar for BA.2.86 (4.8 vs 4.9). ClinicalTrials.gov Identifier: NCT05997290.

Older adults with obesity have an increased risk for cognitive decline and subsequent Alzheimer’s disease. Previous research has focused on the impact of individual nutrients and overall dietary patterns to improve cognitive function. The Brain and Body Health (BB-Health) study aims to demonstrate the feasibility of a multicomponent nutritional supplement (MCNS) and weight loss (WL) intervention for individuals with overweight and obesity who are not consuming a healthy diet. BB-Health is a parallel-group randomized placebo-controlled 2x2 factorial pilot trial comparing the MCNS, WL, and MCNS+WL with a Control group. Eligible participants are 55 to 85 years of age with a body mass index 27.0 to 39.9 kg/m2. Major exclusion criteria include type 2 diabetes, moderate or severe cognitive impairment, and self-reported healthy dietary pattern. The BB-Health feasibility trial is registered as NCT05542199 at clinicaltrials.gov. The BB-Health objectives are to report: 1) recruitment and enrollment, including pace and descriptive statistics of the study sample; 2) adherence to the administered interventions; 3) successful data collection and performance of outcome assessments, including evaluation of change in key outcomes over time that are powered for this pilot study; and 4) summary statistics on outcomes for use in planning a subsequent, larger trial. The outcomes of interest are age-sensitive cognitive assessments, cerebral hemodynamics, and related health parameters. All measurements are collected at baseline, 3-, 6-, and 12-month visits. If the BB-Health protocol demonstrates feasibility, the novel MCNS with and without a parallel WL intervention has potential to be administered in a confirmatory randomized trial to evaluate ability to prevent age-related cognitive decline and improve brain health. The BB-Health Feasibility Study could significantly contribute to our understanding of the influence of diet and weight management on cognitive health

The city of Lisbon, has any other capital of a European country, has a large number of issues while managing the waste and recycling containers spread throughout the city. This document presents the results of a study promoted by the Lisbon City Council for trialing LPWAN technology on the waste management vertical under the Lisbon Smart City initiative. Current waste management is done using GSM sensors, and the aim is to use LPWAN to reduce the costs, improve range and reduce provisioning times when changing the communications provider. After an initial study, LoRa was selected as the LPWAN of choice for the trials. The study is composed of multiple use cases at different distances, types of recycling waste containers, placements (underground and surface) and different kinds of waste level measurement LoRa sensors, deployed in order to assess the impact of the different use cases on the LoRa sensor usage. The results shown that the underground waste containers present the most difficult challenge, where the container itself imposes attenuation levels of 26dB on the link budget. The results promoted the deployment of a city wide LoRa network available to all departments inside the Lisbon City Council, and considering the network capacity the network, the network is also available to citizens to be used freely.

Chronic diseases are still known as incurable diseases, and we suspect that the medical research model is unfit for characterizing chronic diseases. In this study, we examined accuracy and reliability required for characterizing chronic diseases, reviewed implied presumptions in clinical trials and assumptions used in statistical analysis, examined sources of variances normally encountered in clinical trials, and conducted numeric simulations by using hypothetical data for several theoretical and hypothetical models. We found that the sources of variances attributable to personal differences in clinical trials can distort hypothesis test outcomes, that clinical trials introduce too many errors and too much inaccuracies that tend to hide weak and slow effects of treatments, and that the means of treatments used in statistical analysis have little or no relevance to specific patients. We further found that a large number of uncontrolled co-causal or interfering factors normally seen in human subjects can greatly enlarge the means and the variances of the experimental errors, and the use of high rejection criteria (e.g., low p values) further raises the chances of failing to find treatment effects. As a whole, we concluded that the research model using clinical trials is wrong on multiple grounds, under any of our realistic theoretical and hypothetical models, and that misuse of statistical analysis is most probably responsible for failure to identify treatment effects for chronic diseases and to detect harmful effects of toxic substances in the environment. We proposed alternative experimental models involving the use of single-person or mini optimization trials for studying low-risk weak treatments.

Objectives: To assess the short-term impact of a single global stretching session on plantar pressures and lumbar range of motion (RoM) over one week in sedentary university students. Design: A randomised controlled trial with two parallel groups. Participants: Sixty-four university students were randomly assigned to a stretching group or control group. The stretching group received a single session of global stretching and the control group remained seated for the same length of time as the stretching session. Main outcome measures: Lumbar RoM and plantar pressures were assessed before, immediately after, 48 hours after, and 7 days after intervention. Results: Group-by-time interaction was significant for lumbar lateral flexion (p = 0.044), right maximal pressure (p = 0.003), left maximal pressure (p = 0.008), right mean pressure (p = 0.025), left mean pressure (p = 0.002), and maximal pressure minus mean pressure in right foot (p = 0.007). The model with plantar pressures showed a significant difference for group-by-time interaction (p = 0.010).Conclusion: Global stretching seems to counteract the ill-effects of prolonged sitting up to seven days with respect to plantar pressure in standing without improving lumbar ROM

Mediterranean diet, featuring sourdough bread, shows promise in managing metabolic syndrome. This study explored the effects of two sourdough breads with differing fermentation times but similar nutritional profiles on inflammation, satiety, and gut microbiota composition in adults with metabolic syndrome. The double-blind clinical trial randomized participants to consume over two-months Elias Boulanger® long fermentation (48h) sourdough bread (EBLong) or Elias Boulanger® short fermentation (2h) sourdough bread (EBShort). We assessed clinical parameters, inflammatory- and satiety-related biomarkers; and richness and abundance of gut microbiota at baseline and follow-up. 31 individuals (mean age: 67, 55.7% female) participated. EBShort was associated with reduced soluble intercellular adhesion molecule (sICAM) levels, and irrespective of the adjudicated intervention, all participants had a decrease in sICAM and diastolic pressure relative to baseline (p<0.017). At follow-up, plasminogen activator inhibitor-1 (PAI-1) levels were lower in EBShort (-744 pg/mL; 95%CI: -282 to -1210 pg/mL) compared to EBLong. High-quality sourdough bread may offer mild benefits in blood pressure and inflammation for those with metabolic syndrome, however, only EBLong was associated to reduced Enterobacteriaceae abundance. Further research is needed to understand potential benefits and mechanisms of sourdough bread in managing metabolic syndrome and improving cardiovascular health.

The objective of this study was to review the study design and preliminary results of the Recovery trial and analyze the implementability of the Recovery trial by comparing it with the European Discovery trial.Method: The study design of the Recovery trial in the latest version of protocol was described and deeply analyzed to address the issue of implementation of the trial. A comparative analysis of study design and implementation between the UK Recovery trial and the European Discovery trial was conducted following the description.Results: The Recovery trial is a pragmatic, randomized, controlled, adaptive, open-label clinical trial. The study design of the Recovery trial was reported in the ISRCTN registry, the EU Clinical Trials Register and the U.S. National Library of Medicine ClinicalTrials.gov registry. Initially published on the 13^th March 2020, the study protocol of the Recovery trial has been updated five times at the time of this writing. More than 11,000 patients have been enrolled and 80% have completed the follow-up. Thousands of health care professionals at 175 Trusts in the UK have been involved. Conclusion: The Recovery trial applies a study design to address the issue of implementation in the context of the COVID-19 pandemic and emergency. It was conceptually pragmatic with a clear vision to address the top priority: the control of mortality and rational use of scarce resources. By contrast, the Discovery trial was designed as an intellectual exercise and consequently failed to address the issue of implementation in emergency.

The increasing prevalence of obesity and sedentary lifestyles has led to an increased incidence of metabolic syndrome (MetS) worldwide. In Taiwan, middle-aged women are at a greater risk of MetS, type 2 diabetes, and cardiovascular disease than men are because they have more subcutaneous fat and larger waist circumferences compared to men with equal visceral fat levels. This study investigated the effects of calorie restriction supplemented with fish oil (CRF) in middle-aged women with MetS. For 12 weeks, 75 eligible participants were randomly assigned either calorie restriction (CR) or CRF. Both dietary intervention groups were further divided into two age groups: ≤45 and >45 years. The changes in MetS severity, inflammatory status, iron status, and red blood cell fatty acid profile were evaluated. Seventy-one participants completed the trial. Both dietary interventions significantly ameliorated MetS and improved the participants’ inflammatory status. CR significantly increased total iron binding capacity, whereas CRF increased hepcidin levels. Furthermore, CRF significantly increased the n-6/n-3 and arachidonic acid/docosahexaenoic acid ratios. In conclusion, CR and CRF improved the anthropometric and MetS characteristics of early-middle aged women, including body weight, blood glucose levels, triglyceride levels, as well as the scores for the homeostasis model assessment of insulin resistance and quantitative insulin sensitivity cheque index. Dietary intervention was more effective in >45-year-old women than ≤45-year-old women.

Due to the retrognathic mandible, an orthodontist frequently observes skeletal class II malocclusion in growing patients. The preferred technique for analyzing and monitoring the temporomandibular joint alterations caused by the functional device is magnetic resonance imaging [MRI]. The study aimed to assess and compare changes in the articular disc's dimension and location before and following the use of various class II correctors to correct the class II molar relation using MRI technology. Methods: 39 adolescent patients aged 15-23 years old [24 girls and 15 boys] who were diagnosed with skeletal Class II division 1 malocclusion based on clearly defined criteria underwent treatment with either the power scope II [PS], Sabbagh Advanced Repositioning Appliance [SARA] and or Dynaflex [DF] with fixed appliances. For fixed functional treatment, the average length of treatment was 5-7 months. The changes in the articular disc dimension and position and condylar position were assessed. The study was done at the Department of Orthodontics at the College of Dentistry, Hawler Medical University in Erbil City. Results: Group DF has a significant effect on the condylar position index and posterior joint space on the closed mouth and disc length on both open and close mouth techniques, and in the group SARA, disc position, and condylar position index on closed mouth technique have shown that significant differences were observed. Conclusion: Class II malocclusions can be effectively corrected by fixed functional appliances. The statistical significance forward movement of the condyle in the glenoid fossa and the posterior movement of the articular disc concerning the condylar head was observed. The mechanism of action of functional appliances appears to include the forward migration of the C-GF complex.

Background/Objectives: The purpose of this study was to evaluate the relationship between 1-year mortality and health insurance benefit extension policy items in severe pneumonia pa-tients requiring mechanical ventilation using a South Korean nationwide cohort. Methods: A nationwide population-based retrospective study was conducted using the Korean National Health Insurance database. A total of 1,099 patients (542 patients in the health insurance benefit item group and 557 patients in the control group) were included. The primary outcome was 1-year mortality. Results: Among patients with health insurance benefit extension policy items, 203 patients (37.5%) were diagnosed with hemato-oncological disease, who were categorized as group A, and 339 patients (62.5%) were diagnosed with cerebrovascular, cardiovascular, or rare diseases, who were categorized as group B. Group B had lower 1-year mortality (50.7% vs. 62.5%, P

This study presents a method for the rapid and accurate generation of two-dimensional (2D) orthomosaic maps using selected image data collected by drone-captured video. The focus is on developing a real-time method capable of creating maps more quickly than image selection. The scale-invariant feature transform (SIFT) algorithm is applied to drone images to extract features in various scale regions. For feature point matching, a matching method based on the fast library for approximate nearest neighbors (FLANN) was adopted. A comparison of the computational speed of the FLANN with that of the k-nearest neighbors (KNN) and brute force matcher during the matching process revealed FLANN's superior capability for real-time data processing. The random sample consensus (RANSAC) algorithm was employed to enhance the accuracy of the matching by removing outliers, effectively identifying and eliminating mismatches, and reinforcing the reliability of feature point matching. The combination of SIFT, FLANN, and RANSAC algorithms demonstrates the capacity to process drone-captured image data in real time, facilitating the generation of precise 2D orthomosaic maps. The proposed method was assessed and validated using imagery obtained as the drone executed curvilinear and straight flight paths, confirming its accuracy and operational efficiency concurrently with the image capture process.

Background: Areca nut and betel quid (ANBQ) chewing is a widespread carcinogenic habit. The BENIT (ClinicalTrials.gov - NCT02942745) is the first known randomized trial designed for ANBQ chewers. Methods: We compared intensive behavioral treatment intervention condition (IC) with control condition (CC) in the BENIT and included a 5-stage early stopping rule. We report the primary analysis at stage 3. English literate adults in Guam and Saipan who self-identified as ANBQ chewers with tobacco were enrolled between August 2016 and August 2020. IC participants (n=88) received five in-person sessions over 22 days and a brochure containing quitting advice. CC participants (n=88) received only the brochure. Participants were assessed at baseline and day-22 follow-up. Self-reported chewing status at day-22 was determined by a composite of two survey items with disparate wording and response options for cross-verification. Results: Cessation rates were 38.6% (IC) and 9.1% (CC). Proportional hazards regression revealed a p=0.0058, which met the Stage 3 criteria for significance and an estimated reduction in ANBQ chewing for IC compared to the CC of 71% (95% CI: 41%-88%). Conclusion: Robust self-reported intervention effects at day-22 suggests that intensive cessation programs such as BENIT should be further developed and implemented on a larger scale.

Despite the expansion of financial institutions and proliferation of mobile financial services, reaching the unbanked and bringing them under formal financial services has become a policy concern in many developing countries. Due to the lack of financial accounts, unbanked people prefer informal, risky, and inconvenient mechanisms for receiving, sending and transferring money. Previous studies rely much on common intervention like no account maintenance and opening fees, easy documentation processes and money subsidies for opening financial accounts. This study aims to examine the impact of the motivational workshop on opening savings accounts through causality among the unbanked people in a setting where the respondents are unbanked despite having all the requirements and many institutional offers for opening savings accounts. We encouraged the unbanked people through a one-hour-long motivational workshop to open saving account. Based on our cross-sectional data and randomized controlled trial experiment among 505 unbanked Village Defense Party (VDP) members at Dhubil Union under Sirajganj in Bangladesh, we have the evidence that motivational workshop positively impacts opening ac-counts by 32.33 percent. However, the account opening rate differs in terms of respondent’s pref-erence for financial institutions. Our study also finds that unbanked people have the highest pref-erence for mobile financial services for opening accounts resulting in 15.33 percent. The result of the study has some policy implications for adopting effective strategies of financial access in many developing countries.

Immunosenescence refers to age-related alterations of the immune system function affecting both the humoral and cellular arm of immunity. Understanding immunosenescence and its impact on vaccination of older adults is essential since primary vaccine responses in older individuals can fail to generate complete protection, especially vaccines targeting infections with increased incidence among the elderly, such as the respiratory syncytial virus. Here, we review the clinical trials of both candidate and approved vaccines against respiratory syncytial virus (RSV), which include adults aged ≥50 years, with an emphasis on the evaluation of immunogenicity parameters. Currently, there are 10 vaccine candidates and 2 vaccines approved for the prevention of RSV in the older adult population. The number of registered clinical trials for this age group amounts to 32. Our preliminary evaluation of published results and interim analyses of the RSV vaccine clinical trials indicates efficacy in older adult participants, demonstrating immunity levels that closely resemble those of younger adult participants.

In this pilot study, 84 subjects with a history of poor oral hygiene were enrolled in an interventional, randomized, prospective, open-label controlled trial. The aim was to provide preliminary clinical data on the products, the recruitment monthly rate, and patient satisfaction to estimate resources for the main study, as well as descriptive data on oral microbiota rebalancing. The population was divided into five groups: 20 participants received delicate mint toothpaste, 12 mint toothpaste, 20 mint mouthwash, and 20 delicate mint toothpaste and mint mouthwash using a specifically custom-designed toothbrush. The 12 subjects in the control group continued to use their oral care products without changing their normal routine. The study duration was 28 days.All subjects tolerated the products well, and there were no adverse events. Recruitment capability and procedures allowed a realistic estimation for the future main trial. The products did not cause any changes in tooth color. The participants who completed the treatment consisting of delicate mint toothpaste, mint mouthwash, and the specifically custom-designed toothbrush showed the gingival sensitivity best results (p≤0.000). The products induced a statistically significant decrease in plaque in all treated groups (p≤0.000) and an improvement of gingival sensitivity (delicate mint toothpaste, p≤0.005; mint toothpaste, p≤0.015; and mint mouthwash, p≤0.015). All the products were effective in stabilizing the oral microbiota.The tested products showed an optimal safety profile. They also stabilized the biodiversity of the oral microbiota, making it less susceptible to microbial fluctuations than the control group.

Objectives: To compare the effects of high-velocity resistance training to slow-velocity re-sistance training on neuromuscular and functional parameters and to analyze the relationship between changes in walking speed and improvements in neuromuscular parameters following intervetions. Methods: 40 participants were randomly assigned to either a high-speed resistance training group (GHS, n = 18; age = 80.41 ± 10.12 years; BMI = 23.81 ± 3.45 kg/m²) or a low-speed resistance training group (GLS, n = 22; age = 82.89 ± 5.32 years; BMI = 23.81 ± 3.45 kg/m²). Before and after the interventions, gait speed (m/s) was assessed using a 10-minute walking test, and relative maximal force (Relative F max, N/kg) was evaluated during maximal voluntary isometric con-traction of the plantar flexors. From the force-time curve, early (0 – 50 ms) and late (100 – 200 ms) rates of force development (RFD) were extracted from the linear slopes (Δ force / Δ time). Results: Gait speed significantly improved in both groups (p < 0.05). However, the improvement was more pronounced in the GHS compared to the GLS (p < 0.05). Relative Fmax showed a more significant increase in the GLS than in the GHS (p < 0.05). Moreover, a significant 10% increase in early RFD in the GLS and a 20.1% increase in the GHS were observed (p < 0.05). The improvement in early RFD was greater in the GHS (p < 0.05). Additionally, late RFD improved significantly only in the GHS (+20.4%, p < 0.05). Conclusion: High-velocity resistance training appears particularly effective in improving the ability to rapidly generate force, which is essential for many daily activities re-quiring explosive movements and quick responses.

Early identification of viruses leads to more efficient disease management and control, and is extremely important. A possible new approach for creating virus sensors is the Electromagnetic echo effect (EMEE). An important feature is that the signal from EMEE is highly dependent on the state of the irradiated body. This makes it possible to control ongoing reactions, even if these reactions are invisible to the human eye or other equipment. This article shows the possibility of registering reaction occurring in the presence of an avian coronavirus causing infectious bronchitis, strain Massachusetts. The same methodology can be applied for other types of viruses as well.

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 &lt;5% of vaccinees. Main immunogenicity success endpoints were ≥4-fold anti-RBD IgG seroconversion or ≥20% increase in ACE2-RBD inhibitory antibodies in &gt;55% of vaccinees in Phase 1 and &gt;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 (&gt;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 &lt;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.

Patients with metastatic epidural spinal cord compression (MESCC) and favorable survival prognoses may benefit from radiation doses exceeding 10 x 3.0 Gy. In a multi-center phase 2 trial, patients receiving 15 x 2.633 Gy (41.6 Gy10) or 18 x 2.333 Gy (43.2 Gy10) were evaluated for local progression-free survival (LPFS), motor/sensory functions, ambulatory status, pain, distress, toxicity, and overall survival (OS). They were compared (propensity score adjusted Cox regression) to a historical control group (N=266) receiving 10 x 3.0 Gy (32.5 Gy10). In the phase 2-cohort, 50 (of 62 planned) patients were evaluable for LPFS. Twelve-month rates of LPFS and OS were 96.8% and 69.9%, respectively. Motor and sensory functions improved in 56% and 57.1% of patients, and 94.0% were ambulatory following radiotherapy. Pain and distress decreased in 84.4% and 78.0% of patients. Ten and two patients experienced grade 2 and 3 toxicities, respectively. Phase 2 patients showed significantly better LPFS than the control group (p = 0.039) and a trend for improved motor function (p = 0.057). Ambulatory and OS rates were not significantly different. Radiotherapy with 15 x 2.633 Gy or 18 x 2.333 Gy was well tolerated and appeared superior to 10 x 3.0 Gy.

Background: Large-cell neuroendocrine carcinoma presents significant treatment challenges owing to its rarity and limited therapeutic options. The LANCE study was designed to explore the survival benefits of incorporating atezolizumab in chemotherapy for metastatic LCNEC. Methods: In this non-randomized study, patients with metastatic LCNEC were treated with ei-ther standard chemotherapy plus atezolizumab or standard chemotherapy alone. The primary outcomes measured were progression-free survival (PFS) and overall survival (OS), with an ex-ploratory analysis of miR375 in plasma as a potential biomarker. Results: Of the 22 screened patients, 17 met the inclusion criteria and were stratified into the atezolizumab and chemotherapy (n=10) or chemotherapy alone(n=7) groups. After a median follow-up of 23.3 months, the 12-month survival rate for the atezolizumab group was 57.1% (95% CI: 32.6%-100%) and 45.7% at 24 months (95% CI: 22.4%-93.2%). In contrast, the chemotherapy group had a 14.3% survival rate at both 12 and 24 months (95% CI: 2.33%-87.7%). The log-rank test for survival showed a statistically significant difference in the atezolizumab-treated group (chi-squared = 4, df = 1, p = 0.04). A non-significant correlation was found between disease pro-gression and elevated levels of miR375. Conclusions: This pilot study suggests that atezolizumab combined with chemotherapy may be effective in treating metastatic LCNEC. The non-significant correlation between plasma miR375 levels and disease progression suggests its biomarker potential, warranting further validation research.

Shoulder tendinopathies produce pain and reduce functionality. The aim of this randomized clinical trial was to analyze the effects of Percutaneous electrolysis (PE), Percutaneous peripheral Nerve Stimulation (PNS) and eccentric exercise (EE), on pain (NPRS), strength, electromyographic activity, ultrasound characteristics of the tendon (echogenicity, thickness and hypervascularization) and functionality (DASH and SPADI) on individuals with supraspinatus tendinopathy. Participants (n=50) were divided into two groups, they received 4 treatment sessions, one per week, of PE and PNS (n=25) or 10 treatment sessions of TENS and US (n=25). Both groups performed EE program consisted of 3 sets of 10 repetitions of each of the 3 exercises, twice a day, during the 4 weeks. Follow-up was carried out at 4, 12 and 24 weeks after the start of the intervention. There are statistically significant differences in the analysis between groups (p&lt;0.001) in the post-treatment and follow-up measurements favorable to the PE+PNS+EE treatment on pain (NPRS), strength, supraspinatus electromyographic amplitude, ultrasound characteristics of the tendon (echogenicity, thickness and hypervascularization) and DASH and SPADI questionnaires. The combined treatment PE, PNS and EE is an effective option in the clinical management of tendinopathies, with positive results in the short and long term on the variables studied.

EUS–TA in unresectable pancreatic cancer requires not only a tissue diagnosis but also tissue collection in anticipation of comprehensive genomic profiling. However, the optimal puncture target remains controversial. Therefore, the Primary and Metastatic Lesions in Pancreatic Cancer (PRIMATE) study was designed to clarify the optimal target by comparing the success rates for meeting OncoGuide NCC Oncopanel (NOP) analysis criteria on pre-check primary and metastatic lesion specimens obtained during the same EUS–TA session in patients with invasive pancreatic ductal adenocarcinoma. In this ongoing prospective study, two specimens, each from primary and metastatic lesions, are obtained by EUS–TA (typically using a 19G fine-needle biopsy needle) in patients with invasive pancreatic ductal adenocarcinoma. The primary endpoint is the proportion of EUS–TA specimens that meet NOP analysis criteria during pre-check (i.e., tumor cellularity ≥ 20% and tissue area ≥ 4 mm2), which are then compared between primary and metastatic lesions. This study has been approved by the National Cancer Center Institutional Review Board (Research No. 2022-168). The results of this study will be reported at an international conference and published in an international peer-reviewed journal. The trial registration number is UMIN 000048966.

This study aimed to investigate the efficacy of manual therapy and exercise versus synchronized telerehabilitation with self-manual therapy and exercise in treating Subacromial Pain Syndrome (SAPS). Sixty individuals diagnosed with SPS, aged 18-50 years, were randomly assigned to home exercise (HE), manual therapy (MT), and telerehabilitation (TR) groups. Treatment protocols were administered over 8 weeks and included specific exercises and therapy interventions. Out-come measures included Visual Pain Scale (VAS), shoulder range of motion (ROM) via gonio-metric measurements, Quick Disability Arm-Shoulder-Hand Problems Survey (Q-DASH), and patient satisfaction. Results revealed that both MT and TR groups exhibited reduced pain, in-creased ROM, lower Q-DASH scores, and higher patient satisfaction compared to the HE group. However, no significant differences were found between MT and TR groups in pain levels, ROM, Q-DASH scores, or patient satisfaction. The study concludes that both telerehabilitation and manual therapy effectively alleviate pain and are well-received by patients with SPS. Addition-ally, manual therapy demonstrates superiority in enhancing functional levels compared to exer-cise-based interventions. (Registration: NCT05200130)

Background: Preserving health and physical fitness is critical to ensure independent living across the lifespan. Lower levels of physical fitness are associated with age-related cognitive decline and a higher prevalence of mild cognitive impairment (MCI). Thus, this study investigates the influence of a six-month dance intervention on selected measures of physical fitness in older adults with MCI. Methods: In this randomized controlled trial 55 patients with MCI were randomized into a sportive dance training (IG; n=26; Age: 70.7 +/- 5.6 years; 62% female) or an inactive control group (CG; n=24; Age: 69.1 +/- 6.8 years; 46% female).The dance group received two 90-minute dance training sessions per week over a duration of six-months, which focused on learning dance movement patterns. During the training sessions, heartrate was measured to control exercise intensity. Physical fitness was assessed using cardiopulmonary exercise testing (CPET), lower limb functional fitness via sit-to-stand test, handgrip strength and heart rate variability (HRV). Results: We observed that the dance intervention preserved the cardiorespiratory fitness as measured by maximal oxygen uptake (VO2max) during CPET, which decreased in the CG. Furthermore, participants in the IG demonstrated increases in leg and handgrip strength although not statistically significant. HRV displayed a nonsignificant decrease following the intervention. Conclusion: The results of this randomized controlled trial suggest that sportive dance training can preserve physical fitness in older adults with MCI. Although improvements in the other parameters were statistically non-significant, likely due to the small sample size, stabilizing muscular fitness and preventing age-related decline in older adults with MCI is important for maintaining functional independence.

Objective. To test the hypothesis that a session of unilateral tSMS over the dominant primary motor cortex (M1) in healthy subjects produces a transient decrease in manual dexterity. Methods. A triple-blinded randomized control trial was conducted in 40 healthy participants who were allocated to real- or sham-tSMS group. Each participant underwent one session of tSMS and were assessed before, immediately after, 15 minutes, and 40 minutes after stimulation. Outcome measures were Finger Tapping Test (FTT), 5-seconds FTT, nine Hole Peg Test, and the hand grip assessment. Results: Significant differences were found between groups 15 minutes after stimulation in favor of the tSMS group in the FTT (2.2 ± 0.99; CI= .18-4.22; d= .84p=.034), and 5-second FTT (4.2 ± 1.98; CI= .199-8.2, d= .68; p=.04). In the intragroup analysis, a significantly lower number of taps 15 minutes after stimulation was observed in sham group (3.3 ± 1.01; CI= .47-6.13; d= .42; p=.015), but not in the real stimulation group. Conclusion: A unilateral session of tSMS in the M1 of the dominant hemisphere of healthy individuals does not reduce manual dexterity or grip strength. This technique could have benefits on the motor performance of the arm contralateral to the stimulated motor cortex

This pilot randomized controlled trial (RCT) aimed to explore whether depression and anxiety could be reduced by psychiatric home healthcare supporters offering brief cognitive behavioral therapy for psychosis (CBTp) at home using a workbook for patients with schizophrenia. Eighteen patients with schizophrenia treated in a psychiatric home nursing service were randomly assigned to two groups: one group received CBTp in addition to usual care (CBTp + TAU group; n=8) and the other received only usual care (TAU group; n=8); 2 patients were excluded due to hospitalization or withdrawal of consent. Eight weekly CBTp sessions were conducted; anxiety/depression, quality of life, self-esteem, and overall functioning were assessed at baseline, week 9, and week 13. There was no significant difference in the primary evaluation; however, a significant improvement (p=0.014) was observed in the secondary evaluation of quality of life. The effect size was 0.95 for primary evaluation and 1.33 for the secondary evaluation, indicating a large effect. This study showed that nurses and occupational therapists can provide CBTp in psychiatric home care for patients with schizophrenia to potentially alleviate anxiety and depression compared to standard psychiatric home care alone. Therefore, larger RCTs with larger sample sizes are recommended.

As the world’s population age, Cognitive Frailty (CF) is becoming one of the most serious health problems and elucidating its biological mechanisms along with prevention and treatments becomes increasingly important also considering the associated health costs. This pilot study aims to investigate the potential cognitive and neuropsychological effects of a 5-week treatment with a therapy based on the regenerative properties of ozone (O3) in a cohort of patients stratified according to CF. We also study the potential effects of O3 on blood-based biomarkers indicative of specific biological systems that may be altered in CF. Seventy-five older persons have been recruited and randomly assigned to receive the active treatment (150cc of oxygen-O2-O3 mixture at the concentration of 30ug of O3 per cc of O2) or O2, or the placebo (air) for 5 weeks. The primary endpoint is a change in the scores of clinical scales from baseline (T0) to weeks 3 (T3), 9 (T9), 15 (T15) after treatment. The secondary endpoint is a change in biomarkers levels resulting from transcriptomics, proteomics and metabolomic patterns at the same times. This study will evaluate whether an intervention with the O2-O3 therapy could have potential cognitive, neuropsychological and biological effects on CF.

This study aimed to evaluate the safety and tolerability of STP1, a combination of ibudilast and bumetanide, tailored for the treatment of a specific subgroup of patients with Autism Spectrum Disorder (ASD), namely ASD Phenotype 1 (ASD-Phen1). We conducted a randomized, double-blind, placebo-controlled, parallel-group phase 1b study with two 14-day treatment phases (registered at clinicaltrials.gov as NCT04644003). Nine ASD-Phen1 patients were administered STP1, while three received a placebo. We assessed safety and tolerability, along with electrophysiological markers, such as EEG, Auditory Habituation, and Auditory Chirp Synchronization, to better understand STP1's mechanism of action. Additionally, we used several clinical scales to measure treatment outcomes. The results showed that STP1 was safe and well-tolerated, with electrophysiological markers indicating a significant and dose-related reduction of gamma power in the whole brain and in brain areas associated with executive function and memory. Treatment with STP1 also increased alpha 2 power in frontal and occipital regions and improved habituation and neural synchronization to auditory chirps. Although numerical improvements were observed in several clinical scales, they did not reach statistical significance. Overall, this study suggests that STP1 is safe and well-tolerated in ASD-Phen1 patients and shows indirect target engagement in ASD brain regions of interest.

A drug repositioning effort supported the possible use of the anti-HIV drug etravirine as a treatment for Friedreich Ataxia (FRDA). Etravirine increases frataxin protein and corrects the biochemical defects in cells derived from FRDA patients. Because of these findings, and since etravirine displays a favorable safety profile, we conducted this pilot open-label phase 2 clinical trial assessing the safety and potential efficacy of etravirine in FRDA patients. Thirty-five patients were stratified into 3 severity groups and randomized to etravirine 200 mg/day or 400 mg/day. They were treated for 4 months. Efficacy endpoints were represented by changes in peak oxygen uptake and workload as measured by incremental exercise test, SARA score, cardiac measures, measures of QoL and disability. Data were collected 4 months before the start of the treatment (T-4), at the start (T0), at the end (T4) and 4 months after the termination of the treatment (T+4). Etravirine was well tolerated. Etravirine completely stopped the progression of the SARA score during the 4-months treatment period, compared to the 4 months pre and post treatment. It increased peak workload, while the improvement of peak oxygen uptake was not statistically significant. No changes in the cardiac measures were observed. Health and QoL measures showed a worsening at the suspension of the drug. In this open trial etravirine significantly improved neurological function and was generally safe and reasonably tolerated. This suggests that etravirine represents a potential therapeutic agent in FRDA deserving testing in a randomized placebo controlled clinical trial.

The independence of commercial law and the independence of commercial trial are the key issues in the development of China's market economy, which is of great significance for maintaining the market order and protecting the rights and interests of consumers. With the development of China's market economy, the independence of commercial law and commercial trial has gradually become the focus of social attention. On the one hand, the independence of commercial law refers to the effective distinction between commercial law as a normative system and other laws, which has an independent social and economic basis and a unique role. On the other hand, the independence of commercial trial means that commercial trial has relatively independent space and procedures, which can effectively guarantee the fair settlement of commercial disputes.The independence of commercial law is reflected in many aspects, including commercial law ontology, normative structure and content, external relations and so on. Commercial law has the independent social and economic foundation and the unique role, and is the foundation of the development of market economy. The basic principles, adjustment objects, and system design of commercial law are independent, which makes commercial law play its unique role in social life. There are differences between commercial laws and other laws, such as civil law and economic law, in essence and in expression form, which makes commercial law irreplaceable.

The main question proposed in this research is if different types of organizational approach, adapted from rapidly changing disciplines — such as IT industry, and software engineering in particular — could help overcome this gap by shortening the response time needed to analyze advanced solutions in accordance with changed circumstances, thus allowing for architectural programming to obtain different positions in the timeline of project planning and realization. We propose a novel methodology of architectural design as a self-reliant instrument inspired by Agile Manifesto and some of its instantiations, most notably by the Scrum Framework.

Urinary tract infections (UTIs) are highly prevalent in long-term care facilities, constituting the most common infection in this setting. Our research focuses on analyzing clinical characteristics and antimicrobial prescriptions for UTIs in residents across nursing homes (NH) in Spain. This cross-sectional report is part of a before/after intervention study using a multifaceted approach based on the normalization process theory to improve healthcare quality provided by nursing staff in 34 NHs in Spain. In this study we present the results of the first audit including 719 UTI cases, with an average age of 85.5 years and 74.5% being women. Cystitis and pyelonephritis presented distinct symptom patterns. Notably, 6% of asymptomatic bacteriuria cases were treated. The prevalence of dipstick usage was 83%, raising concerns about overreliance, including in the 46 asymptomatic cases, leading to potential overdiagnosis and antibiotic overtreatment. Improved diagnostic criteria and personalized strategies are crucial for UTI management in NHs, emphasizing the need for personalized guidelines on management of UTIs, to mitigate indiscriminate antibiotic use in asymptomatic cases.

We aimed to directly compare the cost-effectiveness of the NELSON and NLST screening protocols, two trials influencing lung cancer screening implementation internationally. A decision-analytic model analyzing the cost-effectiveness of the NELSON protocols was manipulated to reflect the protocols of the NLST, while maintaining features specific to the Hungarian healthcare setting. In the NELSON protocol, there are three possible outcomes to the initial round of screening: positive, negative, or indeterminate, indicating an uncertain degree of suspicion for lung cancer. This pro-tocol differs from the NLST protocol, in which the only possible screening outcomes are positive or negative, with no indeterminate option. The NLST pathway for smokers aged 55-74 resulted in a 43 € increase in total average lifetime costs compared to the Hungarian screening pathway and re-sulted in a lifetime gain of 0.006 QALYs. The incremental costs and QALYs yield an ICER of 7875 €/QALY. Our results demonstrate that assigning any suspicious LDCT screen as a positive result (NLST protocol) rather than indeterminate (NELSON protocol) can yield a slight QALY gain that is worth the additional use of resources according to Hungary’s willingness to pay threshold. Our study provides insight on the cost-effectiveness, advantages, and disadvantages of various LDCT screening protocols for lung cancer and can assist other countries as they implement their screening programs.

Background: In this secondary analysis of the Supporting the Modification of Lifestyle In Lowered Emotional States (SMILES) randomised controlled trial, we investigated if the beneficial effects of a dietary intervention on clinical depression were driven, in part, by reducing the consumption of foods classified as ultra-processed.Methods: The SMILES trial enrolled 67 adults with major depressive disorder, randomly assigning them to either a 12-week modified Mediterranean dietary intervention or a social support control. Our analysis included 44 participants with non-missing dietary data and at least one valid Montgomery–Åsberg Depression Rating Scale (MADRS) assessment at 12 weeks of follow-up. The Nova food classification system was used to estimate the proportion of ultra-processed foods in the overall diet (percentage of grams) based on data from seven-day food diaries. We fitted linear regression models under blinded conditions to determine whether ultra-processed food intake-change from baseline to 12 weeks moderated the dietary intervention effects on depressive symptoms. We estimated mean differences in depressive symptoms along with ninety-five per cent confidence intervals (95%CIs).Results: For participants in the dietary intervention, there was an additional 2.5-point improvement in MADRS scores for each 10% reduction in the dietary share of ultra-processed foods compared to participants in the control group (between-group mean differences in depressive symptoms: −2.46, 95%CIs −4.71 to −0.20, p=0.039, η _p ² of 0.10).Conclusions: These preliminary findings suggest that the therapeutic benefit of a dietary intervention for depression may stem, at least in part, from reductions in the dietary share of ultra-processed foods.

Our objective was to evaluate whether pregnancy is prolonged by use of a proteomics-based maternal serum screening test followed by treatment interventions. This is a secondary analysis of the PREVENT-PTB randomized trial comparing screening with the PreTRM test versus no screening. The primary trial analysis found no significant between-group difference in preterm birth rate. Rather than considering a dichotomous outcome (preterm vs term), we treated gestational age at birth as a continuous variable using survival analysis. We also evaluated between-group difference in NICU length of stay and duration of respiratory support. Results indicated that pregnancy was significantly prolonged in subjects screened with PreTRM test compared to controls (adjusted hazard ratio 0.53, 95% confidence interval 0.36-0.78, P &lt;0.01). Newborns of screened subjects had significantly shorter NICU stay but no significant decrease in duration of respiratory support. In the PreTRM screen-positive group, interventions that were associated with pregnancy prolongation included care management and low-dose aspirin but not 17-hydroxyprogesterone caproate. We concluded that screening with the PreTRM test followed by interventions for screen-positive pregnancies can prolong pregnancy and reduce NICU-LOS.

Background: We evaluate the genetic and phenotypic features of a cohort of 12 Italian patients affected by Retinitis Pigmentosa (RP) associated with RP1 sequence variants.; Methods: Retrospective, single center study (Careggi Hospital, Florence), including a cohort of twelve Italian patients (Five male and seven female) affected by RP carrying pathogenic variants of the RP1 gene. A complete ophthalmic assessment and pedigree analysis was conducted with focus on the onset of disease symptoms, the patient’s age at the first diagnosis, the follow up duration and the possible presence of comorbidities; Results: The mean age at onset of symptoms was 31,0 ± 24,1 years old, with a mean follow-up period of 9,1± 2,4 years. The main symptoms at presentation were hemeralopia and visual field constriction. Fundus evaluation revealed a classic type of RP. Fundus autofluorescence (FAF), Optical Coherence Tomography (OCT), Electroretinogram (ERG), and visual field confirmed in most of the cases the typical features of classic retinitis pigmentosa.; (4) Conclusions: This single-center cohort of Italian patients provided information on the clinical and genetic features of RP1-associated RP. By comprehensively clarifying the genetic variations and their associated clinical manifestations, we can better tailor therapeutic interventions aimed at targeting specific genetic abnormalities. This ultimately promises to improve the prognosis and quality of life for individuals with RP-associated RP1.

Introduction: Emotional intelligence plays a critical role in nursing leadership, influencing organizational dynamics and patient care. However, there is limited understanding of the impact of Emotional Intelligence on leadership in Primary Health Care in the Greek context. Methods: A longitudinal experimental design assessed the effects of an educational intervention on EI and leadership among Greek Primary Health Care nurses. Questionnaires, including the Wong and Law Emotional Intelligence Scale (WLEIS) and Multifactor Leadership Questionnaire - form 5x (MLQ), were administered pre- and post-intervention. Results: The intervention group exhibited significant improvements in Emotional Intelligence and adoption of transformational leadership styles compared to the control group. Tables highlighted nuanced changes in leadership dynamics post-intervention. Conclusions: Educational interventions effectively enhance nurses' Emotional Intelligence and influence leadership styles, emphasizing the need for tailored professional development programs in nursing education.

Many clinical trials end uninformatively. Informativeness, in the context of clinical trials, defines whether a study’s results definitively answer its research questions with meaningful next steps. One subset of these trials are those focused on global health set in low-resource settings. Global health clinical trials benefitting people in low-resource settings are funded primarily by a limited number of large foundations, pharmaceutical firms (“industry”), and national governments. While clinical trial protocols are required to go through reviews in regulatory and ethical domains, outside of industry-funded trials, funders rarely require focused scientific design reviews. There are no documented standards and processes, or even best practices, for funders to perform scientific reviews after the funding commitment. Considering the investment in and standardization of ethical and regulatory reviews, and the prevalence of studies ending without clarity or never finishing, it may be that scientific reviews of trial designs with a focus on informativeness offer the best chance for improved outcomes and return on investments in clinical trials. A maturity model is a helpful tool for knowledge transfer to help grow capabilities in a new area, or for those looking to perform a self-assessment in an existing area. Such a model is offered for scientific design reviews of clinical trial protocols: a valuable and often-neglected governance step for funders or sponsors, among others. This maturity model includes 11 process areas and 5 maturity levels. Each of the 55 process area levels is populated with descriptions on a continuum toward an optimal state to improve trial protocols in the area of risk of failure. This tool allows for prescriptive guidance on next investments to improve attributes of post-funding reviews of trials, with a focus on informativeness.

The primary aim of this study is to investigate the relationship of the Mediterranean diet (MD) with metabolic syndrome (MetS) and its components in Caucasian subjects between 35 and 74 years. The secondary aim is to analyze sex differences. Methods: A cross‑sectional trial. This study utilized data from the EVA, MARK, and EVIDENT studies, a total of 3417 subjects with a mean age of 60.14±9.14 years (57% men). MetS was defined based on the Joint Scientific Statement National Cholesterol Education Program III. Waist circumference, blood pressure, fasting plasma glucose, and lipid profile were measured. Adherence to the MD was assessed with the 14-item Mediterranean Diet Adherence Screener (MEDAS) questionnaire used in the PREDIMED study. Good adherence was considered when the MD value was higher than the median value. Results: The mean value of the MEDAS questionnaire was 5.83±2.04; (Men 5.66±2.06 and women 6.04±1.99; p&lt;0.001). Adherence to the MD was observed by 38.6% (34.3% men and 40.3% women; p&lt;0.001). MetS was observed in 41.6% (39.0% men and 45.2%women p&lt;0.001). In the multiple regression analysis after adjusting for possible confounders, the mean MD value showed a negative association with the number of MetS components per subject (β=-0.336), and with the different components of MetS: Systolic blood pressure (β=-0.011), Diastolic blood pressure (β=-0.029), glycemia (β=-0.009), Triglycerides (β=-0.004), Waist circumference (β=-0.026), except with the HDL-cholesterol value which showed a positive association (β=0.021); (p&lt;0.001 in all cases). The adjusted logistic regression models showed that an increase in MDA decreases the probability of MetS (OR =0.56) and its components: blood pressure ≥130/85 mmHg (OR = 0.63), fasting plasma glucose ≥100 mg/dL (OR = 0.62); triglycerides ≥150 mg/dL (OR = 0.65); waist circumference ≥88 cm in women and ≥102 cm in men (OR = 0.74), and increases high-density lipoprotein cholesterol &lt;40 mg/dL in men or &lt;50 mg/dL in women (OR = 1.70); (p&lt;0.001 in all cases). The results by sex were similar, both in multiple regression and logistic regression. Conclusion: The results of this study suggest that a greater adherence to the Mediterranean diet decreases the probability of presenting Mets globally and by sex.

Background This study aimed to examine the acute effects of different pre-ST strategies on muscular performance and blood pressure (BP) responses in recreationally strength-trained women. Methods: Twelve overweight women with normal-to-elevated BP were recruited and performed six exper-imental protocols in a randomized order: 1) control protocol (CC) – BP assessed without exercises performed, 2) strength training (ST), 3) foam rolling warm-up followed by strength training (FR+ST), 4) specific warm-up followed by strength training (SW+ST), 5) aerobic exercise followed by strength training (AE+ST), and 6) stretching exercises followed by strength training (SE+ST). Strength training consisted of three sets at 80% of 10RM with a self-suggested rest interval between sets for bench press, back squat, bench press 45º, front squat, lat pull-down, leg press, shoulder press, and leg extension. Results: All experimental protocol had a lower total training volume, fa-tigue index, and repetitions performance in relation to ST (p

Background: Schizophrenia is a mental disorder associated with inflammatory and oxidative stress markers such as lactate; in addition, the rate of physical inactivity in this population is very high, which leads to physical and metabolic alterations. Aims: This study measured the effect of assisted physical exercise over lactate levels in schizophrenia. Methods: Stable outpatients with schizophrenia and a group of Healthy controls received two different programs of Physical exercise (Aerobic and Functional) in a clinical trial. Results: Patients had higher lactate compared to healthy controls before and after intervention, and had higher rate of lactate increase after activity. The finding of increased lactate in schizophrenia detected before and after physical exercise deserve further attention in biomarker studies and in the development of physical rehabilitation in schizophrenia, suggesting different profile of oxidative metabolism after physical exercise. Basal increased lactate may reflect mitochondrial dysfunction or metabolic dysregulation, and the higher rate of increase may reflect a different metabolic and oxidative process. Conclusion: The finding is in line with recent studies as surrogate of mitochondrial dysfunction in schizophrenia and points to the need of additional studies on mitochondrial activity in schizophrenia, and to additional care in the design of physical interventions in schizophrenia.

Background: Transcranial direct current stimulation (tDCS) is a neuromodulatory technique that delivers low levels of a constant current via scalp electrodes to specifically targeted areas of the brain. The effects of tDCS on whole-body exercise performance has been of interest in recent literature. The purpose of the current investigation was to investigate if tDCS, administered via Halo Sport, influences time trial performance in trained cyclists, and if changes in exercise performance are associated with prefrontal cortex (PFC) activation and/or muscle oxygenation (SmO2). Methods: Twelve recreationally trained cyclists volunteered to participate in two 10-kilometer time trials following 20 minutes of tDCS or a sham condition. Results: T-tests showed there was no significant difference in performance (time to completion) or physiological measures (BLa-, HR, SmO2, PFC oxygenation) between the Halo and sham conditions. Conclusions: These results indicate that the application of tDCS via Halo Sport does not induce changes in exercise performance or related physiological parameters during a 10-kilometer cycling time trial.

Background: Effectiveness of Anastrozole and levonorgestrel-releasing intrauterine device (LNG-IUD, Mirena®) in the treatment of endometriosis. Methods: Randomized clinical trial. Elegibility criteria: Endometriomas >3×4 cm, CA-125>35 U/mL and symptoms suggestive of endometriosis. Thirty-one women were randomized to anastrozole+Mirena®+Conservative Surgery(CS) (n=8), anastrozole+Mirena®+transvaginal ultrasound-guided puncture-aspiration(TUGPA) (n=7), Mirena®+CS (n=9), or Mirena®+TUGPA (n=7). Interventions: Anastrozole 1 mg/day and/or only Mirena® for 6 months. CS or TUGPA one month after starting medical treatment. Results: A significant improvement in symptoms during the treatment (difference of 43%, 95% CI 29.9-56.2) occurred, which was maintained at 1 and 2 years. It was more significant in patients treated with anastrozole. For CA-125, the most significant decrease was observed without anastrozole. After CS for endometriosis, a reduction of findings of endometriomas and long-term recurrences occurred, with or without anastrozole, although anastrozole seems to delay recurrences. At 4,2±1,7 years, 88% of the patients who underwent CS were asymptomatic, compared to only 21% if TUGPA was performed, with or without anastrozole (p=0.019). Conclusion: Dosing anastrozole for 6 months, starting one month before CS of endometriosis, reduces more significantly the painful symptoms and delays recurrences, but has no other significant advantages over the single insertion of LNG-IUD (Mirena®) during the same time.

Background: This study explored maternal gut, breast milk and infant gut microbiomes as possi-ble mediators of the observed effects of a relaxation intervention which reduced maternal stress and promoted infant weight gain. Methods: A randomized controlled trial was conducted in healthy Chinese primiparous mother-infant pairs. Mothers were randomly assigned to interven-tion group (IG, listening to relaxation meditation) or control group (CG). Outcomes were differ-ences in microbiome composition and diversity in maternal gut, breast milk and infant gut at 1- and 8-weeks between IG and CG, assessed by 16S rRNA gene amplicon sequencing of fecal and breastmilk samples. Results: 38 mother-infant pairs were included in this analysis (IG=19, CG=19). Overall microbiome community structure in the maternal gut was significantly different between IG and CG at 1-week and the difference was more significant at 8 weeks (Bray-Curtis distance R2=0.04 vs. R2=0.13). Post-intervention, the α-diversity was significantly lower in IG breast milk (observed features: CG=295 vs. IG=255, p=0.032); the Bifidobacterium genera presented higher relative abundance. In parallel, significantly higher α-diversity was observed in IG infant gut (observed features: CG=73 vs. IG=113, p

Background/Objectives: This study looks at how a kinematic chain exercise regimen that targets the lower, core, and upper body affects university shot put participants' shoulder muscle strength and throwing efficiency. This study fills an apparent research void on shot put training approaches by presenting a comprehensive kinematic chain workout program. It was anticipated that this method would improve performance the most, considering the complex biomechanical require-ments of the sport. Methodology: Athletes, seventy in age (19.87 ± 1.31 years), were assigned into two groups at random: experimental (n = 35) and control (n = 35). While the control group carried on with their usual training, the experimental group participated in an 8-week kinematic chain training program, pre- and post-training evaluations were carried out to evaluate shot put throwing ability, shoulder muscle strength, and participant satisfaction with the exercise regimen. Results: demonstrated that, when compared to the control group, the athletes in the kinematic chain program had a significantly improved throwing distance (p = 0.01) and shoulder muscle strength (p = 0.01). Furthermore, there was a significant difference (p = 0.005) in the athletes' satisfaction levels with the workout program among those in the experimental group. This implies that a kinematic chain-focused strategy improves performance and emphasizes the significance this type of training is for shot put athlete performance. Conclusion: As an improvement forward in sports science, the study's finding promotes the inclusion of kinematic chain workouts in shot put training programs and calls for more research on kinematic chain-based approaches in a variety of sports.

The study aimed to investigate the effect of climate change exposure on affect and pro-environmental behavioural intentions in a randomised controlled trial. An online survey was completed by 100 adult participants and included measures of affect and pro-environmental behavioural intentions pre- and post-exposure. Participants were randomly allocated to a group that saw a climate change video (n=55) or a group that saw a non-climate change video (n=45). The findings showed were that participants in the climate change group showed a significant increase in negative affect and pro-environmental behavioural intention scores post-video exposure compared to the non-climate change video group. This suggests that climate change video exposure negatively influences affect but also potentially increases the intention to act pro-environmentally. These findings have the potential to support policies and societal change, however further investigation into the type of contents, actual behaviour change, and impacts on diverse populations (e.g., minority groups) is needed that influences pro-environmental behaviours is required. Furthermore, to achieve a greater impact, future research should be conducted measuring actual pro-environmental behaviour change, including with those from diverse populations.

Background and objectives Osteoporotic vertebral compression fractures, particularly prevalent among the aging population, constitute a pressing global healthcare challenge. They often are unnoticed until severe pain and disability manifest, making them an underdiagnosed and undertreated condition. Patients who suffer from these fractures not only endure excruciating pain but also face diminished quality of life, impaired mobility, and the risk of respiratory compromise due to altered spinal alignment. The economic repercussions of vertebral compression fractures are substantial. Hospitalization costs, rehabilitation expenses, long-term care, and indirect costs related to lost productivity significantly burden healthcare systems and society at large , offering a promising avenue for enhancing patient outcomes and relieving the healthcare and societal financial strain posed by vertebral compression fractures. Kyphoplasty, a minimally invasive surgical technique, offers rapid pain relief, vertebral height restoration and improved function. Recognizing the importance of early intervention, this manuscript highlights the potential of kyphoplasty in mitigating both clinical and economic consequences. By addressing these fractures more effectively, kyphoplasty may potentially reduce long-term healthcare expenses and indirect costs. Material and Methods 66 randomized patients were divided into 2 treatment groups (kyphoplasty using single balloon and double balloon), analyzing radiographic and clinical parameters during 12 months of follow-up. Results Patients treated with double balloon obtained greater anterior and posterior vertebral height after reduction and a better local vertebral angle. Both groups of patients obtained clinical improvement after treatment (VAS and ODI), with no differences between the groups. Conclusion Patients treated with double balloon kyphoplasty had better radiographic results. This revision manuscript delves into the critical dimensions of these fractures, encompassing demographics, clinical consequences, challenges in diagnosis and management, and their profound economic impact. This manuscript serves to introduce an improved kyphoplasty technique to guide to the multifaceted nature of osteoporotic vertebral compression fractures and their management.

Depression and anxiety in cardiovascular disease worsen the prognosis of patients. Treatments for these disorders often provide limited improvement. The present study aimed to test, for the first time, the impact of educational technology on anxiety and depressive symptoms in patients participating in a cardiac rehabilitation program. A 12-month randomized controlled trial was conducted, in which 207 patients were randomly assigned to either the experimental (n=76) or control (n=69) groups. The intervention involved a structured patient education program provided by medical students who had undergone specially designed training in cardiac rehabilitation. The primary outcomes were death, hospitalization, heart failure, and recurrent myocardial infarction. The study also assessed anxiety and depression. A year later, the experimental group showed a statistically significant decrease in anxiety and depression on the HADS scale, with reductions of 2.0 and 1.9 points respectively (p&lt;0.05). The control group showed reductions of 1.5 and 1.2 points (p&lt;0.05). The difference in depression (HRDS) between the groups at 12 months was -1.29 in favor of the main group (95% CI, -0.7 to -1.88), and the standardized effect size (SMD) was 0.36 (95% CI, 0.03 to 0.69). No treatment-related adverse events were observed. The results suggest that educational interventions can have a positive impact on mental health. The study's strengths include a structured intervention, randomization, and long-term follow-up. Limitations include the lack of blinding of study participants and a relatively small sample size.

Background: The hypothesis is that a hypoxic-hyperoxic preconditioning (HHP) is associated with a protective effect on myocardial function by reducing endothelial damage and a beneficial effect on postoperative outcome in patients undergoing cardiac surgery with cardiopulmonary bypass (CPB). Methods: Patients (n=120) were randomly assigned to an HHP and a control group. A safe inhaled oxygen fraction for the hypoxic preconditioning phase (10-14% oxygen for 10 minutes) was determined by measuring the anaerobic threshold. At hyperoxic phase, 75-80% oxygen fraction was used during 30 minutes. Results: The cumulative frequency of postoperative complications was 14 (23.3%) in the HHP vs 23 (41.1%), p=0.041. The nitrate decreased after surgery by up to 20% in the HHP group and up to 38% in the control group. Endothelin-1 and nitric oxide metabolites were stable in HHP but remained low more than 24 h in control group. The endothelial damage markers appeared to be predictors of postoperative complications. Conclusion: The HHP with individual parameters based on the anaerobic threshold is a safe procedure, it can reduce the frequency of postoperative complications. The endothelial damage markers appeared to be predictors of postoperative complications.

This randomized trial compared pea protein, whey protein, and water-only supplementation on muscle damage, inflammation, delayed onset of muscle soreness (DOMS), and physical fitness test performance during a 5-day period after a 90-minute eccentric exercise bout in non-athletic, non-obese males (n=92, ages 18-55 years). The two protein sources (0.9 g protein/kg divided into three doses/day) were administered under double blind procedures. The eccentric exercise protocol induced significant muscle damage and soreness, and reduced bench press and 30-second Wingate performance. Whey protein supplementation significantly attenuated post-exercise blood levels for biomarkers of muscle damage compared to water-only, with large effect sizes for creatine kinase and myoglobin during the 4th and 5th days of recovery (Cohen's d &gt;0.80); pea protein versus water supplementation had an intermediate, non-significant effect (Cohen's d &lt;0.50); and no significant differences between whey and pea protein were found. Whey and pea protein compared to water supplementation had no significant effects on post-exercise DOMS and the fitness tests. In conclusion, high intake of whey protein for 5 days after intensive eccentric exercise mitigated efflux of muscle damage biomarkers, with intake of pea protein having an intermediate effect in part due to the 24% lower leucine amino acid content.

Depression is one of the most prevalent mental disorders worldwide. This study examined the effect of a spiritual connectivity intervention on individuals with depression in a randomized waitlist control trial. Fifty-seven participants with mild or moderate depressive symptoms were randomly assigned to either the intervention group (n=28) or the waitlist control group (n=29). The intervention comprised eight weekly sessions focusing on divine connection, forgiveness and freedom, suffering and transcendence, hope, gratitude, and relapse prevention. The outcome measures included depressive symptoms, anxiety, hope, meaning in life, self-esteem, and social support. Participants completed self-administered questionnaires at baseline (week 0), post-intervention (week 8), and at a 3-month follow-up (week 20). Repeated-measures ANOVA and one-way ANCOVA were used to compare the within-group and between-group differences in the changes in outcome variables. Participants in the intervention group showed significant improvements in depression, anxiety, spiritual experience, hope, self-esteem, and perceived social support after the intervention. Effect size statistics showed small to large differences (Cohen’s d, 0.308 to -1.452). Moreover, 85.71% of participants in the intervention group also experienced clinically significant reductions in PHQ-9 scores from baseline to immediate post-intervention. This study highlights the effectiveness of a low-cost, accessible intervention suitable for community implementation by clergy and faith-based organizations.

Appropriate supplementation of vitamin D can affect infections, allergy, and mental and behavioral development. This study aimed to assess the effectiveness of monitored vitamin D supplementation in a population of preterm infants. 109 preterm infants (24 0/7–32 6/7 weeks of gestation) were randomized to receive 500 IU vitamin D standard therapy (n=55; approximately 800-1000 IU from combined sources) or monitored therapy (n=54; with an option of dose modification). 25(OH)D concentrations were measured at birth, 4 weeks of age, and 35, 40, and 52±2 weeks of post-conceptional age (PCA). Vitamin D supplementation was discontinued in 23% of infants subjected to standard treatment due to increased potentially toxic 25(OH)D concentrations (&gt;90 ng/mL) at 40 weeks of PCA. A significantly higher infants’ percentage in the monitored group had safe vitamin D levels (20–80 ng/mL) at 52 weeks of PCA (p=0.017). We observed increased vitamin D levels and abnormal ultrasound findings in five infants. Biochemical markers of vitamin D toxicity were observed in two patients at 52 weeks of PCA in the control group. Inadequate and excessive amounts of vitamin D can lead to serious health problems. Supplementation with 800–1000 IU of vitamin D prevents deficiency and should be monitored to avoid overdose.

In the context of the COVID-19 Pandemic, the use of surgical masks has become the new normal. The use of these devices in exercise and medical situations has been advocated with the purpose of reducing contagions, but some concerns exist regarding its safety. We performed maximal treadmill stress tests in 12 healthy young subjects, with and without surgical mask use, and measured exercise capacity, oxygen saturation (rest, peak exercise and post-exercise) and electrocardiographic changes. Exercise capacity and Oxygen saturation levels decreased in peak exercise vs rest in a statistically significant manner when mask was used. ECG changes, although not significant, were present in 3 subjects when mask was used and disappeared when the test was made unmasked. We conclude that masked exercise has the potential to cause decreased exercise load and oxygen saturation and potentially cause diagnostic errors in medical exams.

The present study explored the effects of a Second-generation mindfulness-based intervention known as Flow Meditation (Meditación-Fluir) in the improvement of life habits. A sample of university students (n = 51) in Spain were randomly assigned to a seven-week mindfulness treatment or a waiting list control group. Results showed that compared to the control group, individuals in the mindfulness group demonstrated significant improvements across all outcome measures, including healthy eating habits (balanced diet, intake rate, snacking between meals, decrease in consumption by emotional states negative, increased consumption by negative emotional states, amount of consumption, meal times, consumption of low-fat products), tobacco, alcohol and cannabis consumption, and resting habits. There were differences between males and females in some of these variables and a better effect of the treatment was evident in the females of the experimental group as compared to males. The Flow Meditation program shows promise for fostering healthy life habits, thus decreasing behaviors related to maladaptive eating, tobacco, alcohol and drug consumption, as well as negative resting habits, in university students. This mindfulness program can significantly contribute in the treatment of eating disorders and addictions, wherein negative emotional states and impulsivity are central features of the condition.

Abstract Psychiatric care in Spain has experienced relevant changes both in the legislative and conceptual frameworks. This new approach advocates for the combination of carrying out mental health promotion, prevention of alterations and early diagnosis and treatment, enhancing actions against stigma and emphasising the attention on the most vulnerable groups, like childhood and youth. For that, it has seen fit to perform a nursing intervention on Education and Promotion of mental health for teachers and counsellors of a secondary school located in Valencia, with the general objective of assessing their impact on stigma. Non-randomised clinical trial in which a nursing intervention on Education and Promotion of mental health was performed. Pre-intervention tools: multiple choice test validated by a group of experts; pre and post-intervention: AQ-27 (stigma attribution); in order to check its acceptance, satisfaction surveys were used. The inferential analysis included the Wilcoxon Test (pre and post AQ-27) and the Pearson Correlation Test for the quantitative variables of interest. Sample (n=22): women aged 47.96 ± 10.12 years with 18.64 ± 10.34 years of work experience. The predominant stigmatising attitude before and after intervention was “Coercion”. The ones with lower score were “Segregation” and “Anger”. The p-values obtained in the Wilcoxon Test were statistically significant (p-value <0.05) except for “pre and post Responsibility” and “pre and post Pity”. The following constructs of interest were faced: “Age” vs “Fear” (r= -0.48, moderate), “Professional experience” and “Fear” (r= -0.46, moderate) and “Help” and “Psychosis test” (r= 0.51, severe). The overall satisfaction score was 9/10. Despite the scores obtained in “Coercion” and “Psychosis”, the intervention was useful for reducing stigma in the sample.

We compared the efficacy of a tailored and a targeted intervention designed to increase clinical breast exam (CBE), mammography, and genetic services/testing among young breast cancer survivors (YBCS) (diagnosed <45 years old) and their blood relatives. A two-arm cluster randomized trial recruited a random sample of YBCS from the Michigan cancer registry and up to two of their blood relatives. Participants were stratified according to race and randomly assigned as family units to the tailored (n=637) or the targeted (n=595) intervention. Approximately 40% of participants were Black; 12% YBCS and 27% relatives were living in more than 20 different U.S. States. Higher screening rates were reported by YBCS (CBE p=0.05; mammography p=0.04) and relatives (CBE p<0.01; mammography p=0.04) in the tailored arm, and by White/Other YBCS (CBE p=0.02) and relatives (CBE p<0.01; mammography p=0.03). YBCS genetic testing rates increased from 22% to 26% (p=0.11). Black YBCS and relatives reported higher self-efficacy and intention for genetic testing, and higher satisfaction and intervention acceptance. The tailored intervention improved CBE and mammography uptake - despite having minimal contact with participants. Professional referrals will improve genetic testing uptake. Intervention materials increased self-efficacy and satisfaction for Black women but could not overcome multiple access barriers.

Background: Alzheimer's Disease (AD) is a progressive and incurable condition that prompts the exploration of interventions to slow its advancement and enhance the quality of life. The cortical brain waves could have a role in the process of executive function deterioration, increasing dementia symptoms. Objective: To interrogate the effects of physical exercise, and non-invasive brain stimulation, both in electrophysiological behavior of the brain, the executive functions, and dementia symptoms in older adults with AD. Methods: One hundred and sixteen older adults were grouped (n=22 each): GAE (AD, PMED+NIBS), GCP (AD, PMED), GCN (AD, NIBS), GCS (control, no intervention). Binaural beats were used as a non-invasive brain stimulation, physical exercise, or both, were applied during 16 weeks. Pre/post measurements included Alpha Band, and SMR Rhythms, executive functions, and dementia symptoms. Results: GCS showed no significant changes (p>0.05). GCN and GCS slightly enhanced inhibitory control (p>0.05) and working memory (p>0.05). In contrast, GCP and GAE improved executive function (p

Background: The protocol described in this paper is part of a research project coordinated 1 between three Spanish universities where a technology aimed at improving the quality of life of 2 people suffering from cerebral palsy will be developed. Part of the technology developed will consist 3 of developing an interface and a series of applications to increase motivation for daily physical activity. 4 The basis of these developments is based on the measurement of the emotional state of the subjects. 5 Methods: The experimental protocol is designed with two objectives, on the one hand to identify the 6 emotional state through physiological signals, and on the other to determine whether music can be 7 a motivating factor to promote physical activity. It has been specifically designed for subjects with 8 cerebral palsy taking into account the special characteristics of this population. These are people with 9 whom it is difficult to use questionnaires to have a basis to contrast with the measured physiological 10 signals, so measurements must be taken in carefully chosen daily life situations Discussion: As results 11 we hope to obtain which physiological parameters are the most robust to measure the emotional state 12 and how to design rehabilitation and physical activity promotion routines that are motivating, in 13 addition to being able to avoid risk factors during the performance of these routines. Trial registration: 14 NCT05621057. https://clinicaltrials.gov/ct2/show/NCT05621057

Introduction: Psoriasis is an inflammatory skin disease. The objective was to elaborate a cream with natural products and salicylic acid. Hypothesis: ¿Will the topical cream made from natural products reduce the characteristic clinical signs of psoriasis? Methodology: Quasi-experimental clinical trial, in 100 healthy volunteer subjects, five formulations of the new product were prepared and applied to each 20 healthy subjects. The universe was 270 patients with different type of dermatology disease, 120 volunteer patients were selected with Psoriasis, of which he creams was applied to 60 volunteer patients with mild and moderate psoriasis were no randomly administered the full formulation of the new product at TMC Hospital. The database for this study is in the Figshare and Dryad repository. Outcome: In healthy subjects showed that 99% had no side effects. In psoriasis patient mild and moderate psoriasis at TMC Hospital was evaluated the results before and after treatment with the new formulation, Using T Student for paired tests, in the clinical variables, as well as the PASI index and the SBA, the alternative hypothesis was proved, the new formula is effective in the control post treatment of psoriasis (p=0.000). Discussion: The new formulation showed greater efficacy after 10 days treatment. This cream is recommended as an alternative and complementary therapy for psoriasis, since it did not show secondary reactions in healthy subjects, so its effectiveness was demonstrated in this study. A new population study is recommended by regions in Ecuador: coast, highlands, Amazon and Galapagos Island, to evaluate the response to treatment.

BACKGROUND: The National Lung Screening Trial (ILST) and the NELSON study showed that lung cancer-specific mortality can be reduced by 20-24% using low-dose computed tomography (LDCT) screening in high-risk populations, due to an increase in early-stage diagnoses. RESEARCH QUESTION: How much lung cancer-related direct costs may be reduced using a LDCT screening programme based on the ILST protocol in a public healthcare system?STUDY DESIGN AND METHODS: Cost analysis of lung cancer screening (LCS) vs. usual care in the framework of the retail price of the Catalan public healthcare system. The LCS group included costs of screening (ILST protocol), treatment cost according to weighted average distribution of TNM staging in the NLST and NELSON trials, lung cancer detection rate (CDR) and smoking cessation intervention. The usual care group included treatment costs based on distribution of TNM staging registered in the Spanish index hospital. RESULTS: In the usual care group, treatment costs were €91,959. In the 5-year duration of the LCS programme, the average expected costs per subject were €1,342 (range €1,054-1,832 depending on malignancy in detected nodules) for screening and €32,431 for treatment, with an expected reduction of €952 based on an average CDR of 1.6%. The decrease in cost resulting from stage shift offsets 70.6% of the costs of the screening programme. INTERPRETATION: Baseline 5-year LCS costs are low according to the ILST protocol. In the Catalan public healthcare system, the expense reduction from the stage shift due to the LCS programme compensates a substantial part of its costs.

Like 18F-FDG, 99mTc-1-thio-D-glucose (99mTc-TG) also binds to GLUT receptors. The aim of this Phase I study was to evaluate the safety, biodistribution and dosimetry of 99mTc-TG. Twelve lym-phoma patients were injected with 729±102 MBq 99mTc-TG. Whole-body planar imaging was per-formed in 10 patients at 2, 4, 6 and 24 h after injection. In all 12 patients SPECT/CT (at 2 h) and SPECT (at 4 and 6 h) imaging was performed. Vital signs and possible side effects were monitored during imaging and up to 7 days after injection. 99mTc-TG injections were well tolerated and no side effects or alterations in blood and urine analyses data were observed. The highest absorbed dose was in the kidneys and urinary bladder wall, followed by the adrenals, prostate, bone mar-row, lungs, myocardium, ovaries, uterus, liver and gall bladder wall. 99mTc-TG SPECT/CT re-vealed foci of high activity uptake in the lymph nodes of all nine patients with known nodal le-sions. Extranodal lesions were detected in all nine cases. In one patient, a lesion in the humerus head, which was not detected by CT, was visualized using 99mTc-TG. Potentially, 99mTc-TG SPECT can be considered as an additional diagnostic method for imaging GLUT receptors in lymphoma patients.

This multi-center, single-blinded, randomized controlled study assessed the efficacy of phased exercise rehabilitation programs in patients who underwent a total knee arthroplasty (TKA) and investigated suitable exercise types, intensities, and frequencies for patients undergoing postoperative rehabilitation. Between January and March 2018, 494 patients who had undergone TKA were treated at two medical centers. Patients were randomized and allocated to the rehabilitation group (n=330) or the control group (n=164; treated with postoperative care). The 100-mm Visual Analogue Scale (VAS), Western Ontario and McMaster Universities Arthritis Index (WOMAC), range of motion, and Short-Form 36 (SF-36) scores were assessed and compared between the two groups. The average WOMAC score was 84.40±15.20 in the rehabilitation group and 108.30±3.90 in the control group (p=0.009). The mean VAS score was 2.54±0.16 in the rehabilitation group and 2.87±0.31 in the control group (p=0.024). Furthermore, the range of motion was 125.02±6.20 in the rehabilitation group and 116.40±1.40 in the control group (p=0.017). The mean SF-36 score was 105.40±21.50 in the rehabilitation group and 83.70±5.01 in the control group (p=0.043). This study suggests that the phase rehabilitation program could be more effective at improving pain, knee function, and quality of life than condition postoperative care after TKA.

The aim of this document is to provide practical guidance on the choice of target difference used in the sample size calculation of a randomised controlled trial (RCT). Guidance is provided with a definitive trial, one that seeks to provide a useful answer, in mind and not those of a more exploratory nature. The term “target difference” is taken throughout to refer to the difference that is used in the sample size calculation (the one that the study formally “targets”). Please see the glossary for definitions and clarification with regards other relevant concepts. In order to address the specification of the target difference, it is appropriate, and to some degree necessary, to touch on related statistical aspects of conducting a sample size calculation. Generally the discussion of other aspects and more technical details is kept to a minimum, with more technical aspects covered in the appendices and referencing of relevant sources provided for further reading.The main body of this guidance assumes a standard RCT design is used; formally, this can be described as a two-arm parallel-group superiority trial. Most RCTs test for superiority of the interventions, that is, whether or not one of the interventions is superior to the other (See Box 1 for a formal definition of superiority, and of the two most common alternative approaches). Some common alternative trial designs are considered in Appendix 3. Additionally, it is assumed in the main body of the text that the conventional (Neyman-Pearson) approach to the sample size calculation of an RCT is being used. Other approaches (Bayesian, precision and value of information) are briefly considered in Appendix 2 with reference to the specification of the target difference.

In recent decades, there has been a rising demand for anti-aging interventions aimed at postponing or potentially reversing indicators of skin aging. The use of collagen-based nutraceutical supplements has gained popularity as they have shown promise in enhancing skin health and reducing signs of aging. The aim of this randomized, placebo-controlled, blinded study was to investigate the effects of 2.5 g COLLinstant® LMW, a novel cosmeceutical containing low molecular weight (≤ 1000 Da) collagen peptides, on skin aging and health. The trial was conducted in 80 healthy women aged 30 years and older. They received a daily oral dose of either the food supplement (n = 40) or placebo (n = 40) for six weeks. Skin assessment was performed based on validated objective methods, such as Visioface 1000D (skin wrinkling), cutometry (elasticity and fatigue) and corneometry (skin hydration) at baseline (T0), and at week 6 (T6). After 6 weeks, participants that received collagen had significant improvements in biometric skin wrinkle parameters from baseline, with a reduction in volume by 46%, in area by 44%, and in depth by 9%, along with a greater increase in skin moisturization (by 34%) than those in the placebo group (p &lt; 0.001). The food supplement did not significantly modify skin firmness or fatigue and had only slight beneficial effects on skin elasticity. The investigational product was well tolerated. The observed effects aligned closely with the subjective assessments reported by study participants. The study provides substantiated evidence supporting the efficacy of low molecular weight collagen peptides in restoring altered skin biometric parameters, as objectively assessed. Thus, regular supplementation with this nutraceutical may contribute to achieving smoother and more radiant skin.

Objective. To evaluate serum neuronal and inflammatory biomarkers in asphyctic newborns treated with hypothermia alone or hypothermia plus melatonin, and whether biomarkers correlate with neurodevelopmental outcomes. Design. This is a pilot multicentre, randomised, controlled, double blind clinical trial. Neuronal glial fibrillary acidic protein (GFAP), granulocyte-macrophage colony-stimulating factor (GM-CSF), and inflammatory cytokines (interleukin (IL)-1, IL-2, IL-7 and IL-13) were measured in serum samples at hospital admission (T0), 24 hours (T1), 72 hours (T2) and 7-10 days of age (T3). Neurodevelopmental outcomes (Bayley Scales of Infant and Toddler Development-III scales, Gross Motor Function Classification System (GMFCS) and the Tardieu scale) were performed at 6 and 18 months. Setting: Level 3 neonatal intensive care unit. Patients and interventions: 25 newborns were recruited. The treated patients received a daily dose of intravenous melatonin, 5 mg per kg body weight, for 3 days. Results. After adjusting the data for severity, in the group treated with melatonin, there is a decrease in plasma levels of GM-CSF, IL-2 and IL-13 at T1 compared to placebo, as well as, at T2, in GM-CSF concentrations, as well as IL-7 and IL-13 at T3. Evolutionarily, we found a significant decrease in GM-CSF concentrations in the treatment group compared to placebo, with no differences for the rest of the biomarkers. It is noteworthy that the sustained decrease in GM-CSF and inflammatory cytokines IL-2, IL-7 and IL-13 correlated with better neurodevelopmental outcomes at 6 and 18 months. Conclusions. In neonates with hypoxic-ischemic encephalopathy, the addition of iv melatonin to hypothermia therapy affects the plasma concentration of biomarkers in the first week of life, with a high correlation with long-term neurological prognosis.

Lymphoma diagnoses in the U.S. are substantial, with an estimated 89,380 new cases in 2023, necessitating innovative treatment approaches. Phase 1 clinical trials play a pivotal role in this context. We developed a binary predictive model to assess trial adherence to expected average durations, analyzing 1,089 completed Phase 1 lymphoma trials from clinicaltrials.gov. Using machine learning, the Random Forest model demonstrated high efficacy with an accuracy of 0.7248 and ROC-AUC of 0.7701 for lymphoma trials. Importantly, this model maintained an accuracy of 0.7405 when applied to lung cancer trials, showcasing its versatility. A key insight is the correlation between higher predicted probabilities and extended trial durations, offering nuanced insights beyond binary predictions. Our research contributes to enhanced clinical research planning and potential improvements in patient outcomes in oncology.

Emerging evidence has shown that microRNAs play pivotal roles in wound healing. MicroRNA-21 (miR-21) was previously found to upregulate in order to fulfill an anti-inflammation role for wounds. Exosomal miRNAs have been identified and explored as essential markers for diagnostic medicine. However, the role of exosomal miR-21 in wounds has yet to be well studied. In order to facilitate the early management of poorly healing wounds, we developed an easy-to-use, rapid, paper-based microfluidic-exosomal miR-21 extraction device to determine wound prognosis in a timely manner. We isolated and then quantitatively examined exosomal miR-21 in wound fluids from normal tissues, acute and chronic wounds. Eight improving wounds displayed lower levels of exosomal miR-21 expression after wound debridement. However, four instances of increased exosomal miR-21 expression levels were notably associated with patients with poor healing wounds despite aggressive wound debridement, indicating a predictive role of tissue exosomal miR-21 for wound outcome. Paper-based nucleic acid extraction device provides a rapid and user-friendly approach for evaluating exosomal miR-21 in wound fluids as a means of monitoring wounds. Our data suggest that tissue exosomal miR-21 is a reliable marker for determining current wound status.

Background: this RCT assesses the 18 months clinical outcomes after regenerative therapy of periimplantitis lesions using either an electrolytic method (EC) to remove biofilms or a combination of powder spray and electrolytic method (PEC). Materials and Methods: Twenty-four patients (24 implants) suffering from periimplantitis were randomly treated by EC or PEC followed by augmentation and submerged healing. Probing pocket depth (PPD), Bleeding on Probing (BoP), suppuration and standardized radiographs were assessed before surgery (T0), 6 months after augmentation (T1), 6 (T2) and 12 (T3) months after replacement of the restoration. Results: Mean of PPD changed from 5.8 ± 1.6 mm (T0) to 3.1 ± 1.4 mm (T3). While BoP and suppuration at T0 was 100 % BoP decreased at T2 to 36.8 % and at T3 to 35.3 %. Suppuration could be found 10.6% at T2 and 11.8% at T3. Radiologic bone level measured from the implant shoulder to the first visible bone to implant contact was 4.9 ± 1.9 mm at me-sial and 4.4 ± 2.2 mm at distal sites (T0) and 1.7 ± 1.7 mm and 1.5 ± 17 mm at T3. Conclusions: Significant radiographic bone fill and improvement of clinical parameters were demonstrated 18 months after therapy.

To compare surgical and refractive outcomes between phacotrabeculectomy (P-Trab) and phaco with Ex-PRESS (P-Ex-PRESS) for glaucoma at 6-month follow-up. This prospective randomized controlled trial included 81 eyes; 43 (53%) and 38 (47%) were assigned to the P-Ex-PRESS and P-Trab groups, respectively. Refraction, intraocular pressure (IOP), and best-corrected visual acuity were measured. Refractive change was described by analyzing the magnitude of the cylinder, and polar analysis assessed the change in trend of astigmatism [with-the-rule, against-the-rule (ATR), oblique] evaluating mean astigmatism in centroid form. All patients showed statistically significant postsurgical decrease in IOP (P&lt;0.05). There were no differences neither between the groups for postoperative IOP or visual outcomes, nor in astigmatism before or after surgery (P=0.61, P=0.74). In both groups, the mean pre- and postoperative astigmatism was ATR and OBL, respectively. Pre- and postoperative centroids in the P-Ex-PRESS group were 0.44±1.32 D at 177˚ and 0.35±1 D at 8˚, respectively, (P=0.5) and in the P-Trab group, 0.16±1.5 D at 141˚ and 0.39±1.38 D at 29˚, respectively (P=0.38). Both P-Ex-PRESS and P-Trab showed comparable antihypertensive efficacy in treating open-angle glaucoma in a 6-month period. Pre- and postoperative astigmatism did not differ between groups. The groups showed comparable results for final visual acuity.

Feline sporotrichosis is an endemic disease with high occurrence in Brazil. Itraconazole (ITZ), remains the drug of choice for treating this disease in cats, despite the increasing reports of therapeutic failure. A controlled, randomized clinical trial was performed on 166 naive cats with sporotrichosis to assess the effectiveness and safety of the combination therapy (ITZ+KI) com-pared with ITZ monotherapy. Cats were randomly allocated in two treatment groups: G1 - ITZ 100 mg/cat/day and G2 - ITZ 100mg/cat/day + KI 2.5-20 mg/kg/day. Cats treated in G2 presented 77% more risk of reaching clinical cure (a positive effect) than those treated in G1, even when controlled by negative predictors. The survival curves of the two treatment protocols indicates that clinical cure was achieved faster in G2. An increase in the KI dose was necessary in 28 cats due to persistence of clinical signs. Adverse reactions were equally frequent in both groups and manageable with a temporary drug suspension and/or a hepatoprotective therapy. The combination therapy was associated with a higher cure rate and a shorter treatment time, suggesting that ITZ+KI arises as a better option for treating feline sporotrichosis and should be considered as the first-line treatment in the presence of negative predictors.

This investigation delves into an examination of the growth dynamics observed in Central Taiwan Science Park (CTSP) and Silicon Glen in Scotland, with a specific focus on their energy, environmental, and economic management. The aim is to predict and evaluate the latest advancements and applications of technology. In terms of energy, CTSP focuses on Taiwan's supply security and green transformation challenges, while Silicon Glen emphasizes Scotland's wind energy generation technologies. Both regions are committed to the development of renewable energy and smart grids. Regarding environmental aspects, CTSP and Silicon Glen prioritize environmental protection and sustainable development by implementing measures for environmental monitoring. In terms of economic management, CTSP, and Silicon Glen serve as key technology industry hubs This investigation delves into an examination of the growth dynamics observed in Central Tai-wan Science Park (CTSP) and Silicon Glen in Scotland, with a specific focus on their energy, environmental, and economic management. The aim is to predict and evaluate the latest advancements and applications of technology. In terms of energy, CTSP focuses on Taiwan's supply security and green transformation challenges, while Silicon Glen emphasizes Scotland's wind energy generation technologies. Both regions are committed to the development of renewable energy and smart grids. Regarding environmental aspects, CTSP and Silicon Glen prioritize environmental protection and sustainable development by implementing measures for environmental monitoring. In terms of economic management, CTSP, and Silicon Glen serve as key technology industry hubs in Taiwan and Scotland, respectively, attracting numerous high-tech and startup enterprises. Various means facilitate the growth of industries and foster innovations in different industrial spheres. Important factors contributing to this growth include policy support, availability of research materials, and provision of infrastructure. This research paper compares the successful case studies of two industrial parks, along with their environmental and economic management strategies. It explores the management principles that ensure the sustainable development and economic growth of industrial parks, aiming to assist decision-makers and relevant stakeholders in evaluating the sustainable development planning of industrial parks.

To assess the clinical efficacy of a novel organic olive oil-based denture adhesive and its effect on Candida Albicans growth in maxillary edentulous individuals wearing complete dentures. Individuals were selected from two Dental Schools in Portugal and Spain. Twenty-eight complete dentures were relined, following a standardized protocol. The novel product (Test) was compared with a commercialized adhesive (Control) and Vaseline (Placebo) randomly assigned in a cross-study design. The retention resistance was measured with a Gnathometer and a dynamometer, the patient related outcome evaluations with a 5-points questionnaire and the Candida albicans growth in a Sabouraud dextrose agar (SDA) medium in order to evaluate differences between the placebo and experimental product. Twenty-three participants were included. Dynamometer evaluation showed significant differences between not using a denture adhesive and using either (experimental, p = .03; control, p = .04), no significant differences between the two adhesives (p &gt; .05). In the subjective analysis, the experimental adhesive showed a significantly longer effectiveness (p = .001); the control reported better results at taste (p = .03) in chewing (p = .001). The test adhesive showed better (p &lt; .001) Candida albicans growth inhibition. The experimental adhesive showed longer effectiveness than the control and placebo with a better inhibition capacity for the growth of Candida albicans, patients reported better abilities for speech, chewing, taste and retirement in the control adhesive.

Background Posttraumatic stress disorder (PTSD) is a complex condition that represents a significant burden in terms of individual disability and societal costs. Despite decades of research investigating treatment options, PTSD remains a major cause of quality-of-life impairment. We hypothesized that patients with PTSD might benefit from peripheral somatosensory stimulation (PSS) therapy. Methods Six adult patients with clinically diagnosed PTSD were enrolled to undergo daily PSS therapy over a 4-week period. Patients completed two surveys evaluating satisfaction with treatment and overall well-being (Survey 1) and severity of PTSD symptoms (Survey 2). Survey 1 was completed weekly during the course of the study. Survey 2 was based on the 9-question National Stressful Events Survey PTSD Short Scale (NSESSS) and was completed as a baseline prior to initiation of therapy and then at the conclusion of the trial. All data were analyzed by an independent statistician. Results Six male patients were enrolled in the study; all completed the trial. All patients demonstrated a decrease in symptoms within one week of initiation of therapy. This benefit was sustained and appeared to further improve over the course of the trial. For Survey 1, the overall median scores demonstrated a significant time-dependent improvement across measurement times (p < 0.001). For Survey 2, patients had statistically significant improvements from baseline regarding feelings of being emotionally upset and being overly alert. Results from a cumulative link mixed model demonstrated that treatment yielded a 38.2-fold higher likelihood of transitioning from a higher PTSD score at baseline to a lower (improved) score at week 4. No adverse events were described by the patients. Conclusions PSS stimulation appeared to improve symptoms in all six patients with PTSD symptoms in this trial. Patients had unanimous and clinically meaningful improvement in overall PTSD symptoms with treatment. By week 4, all patients responded that they enjoyed the treatment and would like to keep their device. We suggest that further investigation into the potential usefulness of PSS therapy in patients with PTSD is warranted.

A single paragraph of about 200 words maximum. Electroencephalography (EEG) accumulates the electrical activities of human brain. It is an easy and cost effective tool to characterize motor imagery (MI) task used in brain computer interface (BCI) implementation. The MI task is represented by short time trial of multichannel EEG. In this paper, the raw EEG is decomposed into a finite set of narrowband signals obtained from individual EEG channels using Fourier transformation based bandpass filter. Each of the subband signals represents narrowband rhythmic components which characterize the brain activities related to motor imagery. The subband signals are arranged to extent the dimension of EEG trial in spatial domain. The spatial features are extracted from the set of extended trials using common spatial pattern (CSP). An optimum number of features are used to classify the motor imagery tasks represented by EEG trials. Artificial neural network is used to classify MI tasks. The performance of the proposed method is evaluated using two publicly available benchmark datasets. The experimental results show that it performs better than the recently developed algorithms.

Recent wastewater testing suggests the poliovirus is reemerging, raising questions about the efficacy of the current inactivated polio vaccine and mass vaccination to eradicate poliomyelitis. The present study reassessed reported outcomes from the placebo-control study of the 1954 Salk inactivated poliomyelitis vaccine field trial, which studied a population of 1,829,916 U.S. school children from the first three grades. The placebo-control study of the trial reported that the polio vaccine was 80% to 90% effective in reducing cases of laboratory confirmed paralytic poliomyelitis, 60% to 70% effective against type 1 of the virus, and greater than 90% effective against types 2 and 3 of the poliovirus. However, these outcomes are reported as relative risk reductions, and the absolute risk reductions of the 1954 polio vaccine field trial were never reported to the public. The present paper’s analysis reveals to the public for the first time that the inactivated poliomyelitis vaccine's absolute risk reduction of laboratory confirmed paralytic poliomyelitis in the placebo-control study is 0.01% to 0.02%, an extraordinarily low clinical effect that impugns the Salk polio vaccine’s reported effectiveness. Furthermore, absolute risk reductions for the three poliovirus types are 0.01%, 0.00%, and 0.01%, respectively. Outcome reporting bias in the 1954 inactivated poliomyelitis vaccine field trial casts doubt on eradication of the poliovirus through mass vaccination.

The study's objective was to assess the impact of Mediterranean diet/lifestyle interventions for weight loss on Positive airway pressure (PAP) adherence, Body mass index (ΒΜΙ), sleepiness, and blood pressure measurements (BP) in patients with obstructive sleep apnea (OSA). We designed a randomized, controlled trial, including overweight and obese patients with moderate-to-severe OSA, randomized to standard care (SCG, n=37) and Mediterranean diet group (MDG, n=37). SCG received healthy lifestyle advice, while MDG underwent a 6-month behavioral intervention aiming to enhance weight loss and adherence to Mediterranean diet. PAP adherence, BMI, Epworth Sleepiness Scale (ESS) and BP measurements were evaluated pre- and post-intervention. Post-intervention PAP use was higher in MDG compared to SCG (6.1 vs 5.4, p=0.02). Diet/lifestyle intervention was one of the most significant predictive factors for PAP adherence (OR = 5.458, 95% CI = 1.144-26.036, p=0.03). The SCG demonstrated a rise in BMI, while the MDG displayed a decline (0.41 vs -0.75, p=0.02). The MDG also demonstrated a substantial reduction in adjusted SBP (-5.5 vs 2.8, p=0.014) and DBP (-4.0 vs 2.5, p=0.01). Ultimately, incorporating a dietary/lifestyle intervention with standard care yields superior PAP adherence, BMI, and BP measurements in contrast to standard care alone, underscoring the potential benefits of allocating increased time and support within the MDG group. Trial registry: ClinicalTrials.gov; No.: NCT05881824; URL: www.clinicaltrials.gov.

Background: Evidence supports a causal relationship between circadian disturbance and impaired glucose homeostasis. Method: To determine the effect of a nursing educational intervention on improving healthy sleep, a parallel, open-label clinical trial in subjects with Impaired Fasting Glucose (IFG) or Type 2 Diabetes Mellitus (T2DM) and 18 and older was performed. Study variables were sex, age, fasting glucose, glycated hemoglobin A1c (HbA1c), Pittsburgh Sleep Quality Index (PSQI), sleep duration and efficiency, BMI, antidiabetic treatment and diet and physical exercise. An individual informative educational intervention was carried out following a bidirectional feedback method. It was intended to develop skills to improve sleep through 9 simple tips. An analysis of covariance was performed on all the mean centered outcome variables controlling for the respective baseline scores. Results: After the intervention, in the experimental group, PSQI dropped, the duration and quality of sleep increased. Further, a decrease in fasting glucose and in HbA1c levels was observed. Conclusion: The proposed intervention has proven to be effective to improve sleep quality, time, and efficiency and in only 3 months, to achieve a decrease in fasting glucose and HbA1c levels. These findings support the importance of sleep and circadian rhythms education focused on improving in T2DM or IFG.